На главную К списку выставокАрхив выставок

Протеасомы и трансплантология

Журнальные статьи

1. 009715
"ИНДУКТОР РЕГЕНЕРАЦИИ ТЕТРАДЕКАПЕПТИД (TEKKRRETVEREKE) АКТИВИРУЕТ MAPK-КИНАЗНЫЙ СИГНАЛЬНЫЙ ПУТЬ В NIH/3T3 ФИБРОБЛАСТАХ Чулкина М.М., Лебедева Е.С., Пичугин А.В., Холмухамедов Э.Л., Атауллаханов Р.И. Иммунология. 2017. Т. 38. № 4. С. 172-179. "

Ранее мы сообщали, что индуктор заживления эрозий, язв и ран тетрадекапептид TEKKRRETVEREKE (иммуномодулирующий препарат Гепон) вызывает дифференцировку фибробластов в миофибробласты, а также увеличивает подвижность клеток в модели повреждения монослоя [1]. В данной работе мы сравнили сигнальные события в фибробластах линии NIH/3T3 при их активации тетрадекапептидом и естественным стимулятором фибробластов TGF-?1. В клетках линии NIH/3T3 мы исследовании активацию канонического (SMAD) и неканонического (МАРК) сигнальных путей, а также изменение транскрипции генов ?-sma, col1?1, tgf-?1, связанных с дифференцировкой фибробластов. Показано, что тетрадекапептид так же, как цитокин TGF-?1, активирует транскрипцию генов ?-sma и col1?1. В отличие от TGF-?1, тетрадекапептид не индуцировал транскрипцию мРНК гена tgf-?1. TGF-?1 индуцировал в NIH/3T3 фибробластах фосфорилирование транскрипционного фактора SMAD2. Напротив, тетрадекапептид TEKKRRETVEREKE не активировал канонический сигнальный путь, фосфорилирования SMAD2 не происходило. Оба активатора фибробластов - TGF-?1 и тетрадекапептид - индуцировали сильную и быструю активацию неканонического МАРК-киназного сигнального пути, что проявлялось в фосфорилировании ERK1/2 киназы в первые минуты и последующей её транслокации в ядро. Таким образом, индуктор заживления эрозий, язв и ран тетрадекапептид TEKKRRETVEREKE активирует фибробласты иначе, нежели цитокин TGF-?1. Оба индуктора активируют MAPK-киназный сигнальный путь и транскрипцию генов ?-sma и col1?1, но только TGF-?1 активирует канонический SMAD-сигнальный путь и транскрипцию гена tgf-?1.

https://elibrary.ru/item.asp?id=29988043

2. Aleksova J. et al. Serum phosphorus levels and fracture following renal transplantation // Clin. Endocrinol. 2017. Vol. 87, № 2. P. 141–148.

PurposeIncreased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression and mineral and bone disorders.(1) Low serum phosphorus levels occur post-transplantation; however, its relationship with fracture risk has not been evaluated. The purpose of this study was to evaluate risk factors for fracture in RTRs at a single tertiary referral centre. MethodsA retrospective cross-sectional analysis of 146 patients (75M, 71F) who had been referred for dual energy X-ray densitometry (DXA) post-renal transplantation was performed. Aetiology of end stage kidney disease (ESKD), duration of dialysis, parathyroidectomy history, immunosuppression regimen, bone mineral density (BMD), biochemistry and fractures were documented. Statistical analyses included univariable and multivariable regression. ResultsThe mean age of patients was 54years and mean time post-transplantation 6.7years. A total of 79 fractures occurred in 52 patients (35%), with 40 fractures occurring post-transplantation. Ankle/foot fractures were most common (48%). Lower serum phosphorus levels and declining femoral neck (FN) T-score and were associated with fractures in both univariable and multivariable regression analyses after adjusting for age, gender, weight, estimated glomerular filtration rate and pre-transplant history of fracture (P=.011 and P=.042 respectively). The relationship between serum phosphorus and fracture remained significant independent of FN T-score, parathyroid hormone levels, parathyroidectomy status and prednisolone use. ConclusionFracture was common post-renal transplantation. Lower serum phosphorus levels and declining FN T-scores were associated with fractures. The mechanism of this previously unreported observation requires further evaluation in prospective studies.

http://dx.doi.org/10.1111%2Fcen.13363

3. Bhat M., Watt K.D. Mammalian target of rapamycin inhibition after solid organ transplantation: can it, and does it, reduce cancer risk? // Clin. Transplant. 2015. Vol. 29, № 7. P. 654–663.

The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been increasingly used as immunosuppressants for recipients of solid organ transplants. Over the years, potential advantages unique to this class of immunosuppressants have been recognized, including chemoprevention by virtue of their antiproliferative effects. Prevention of malignancy after transplant through mTOR inhibitor-based immunosuppression may have a specific practical application in transplant recipients with preexisting malignancy including hepatocellular carcinoma or cholangiocarcinoma. This review will reveal how the biochemistry of the mTOR pathway, as it pertains to chemoprevention, can support a clinical role for mTOR inhibitors in the prevention of malignancies, recurrent or de novo, after solid organ transplantation in selected patients.

http://dx.doi.org/10.1111%2Fctr.12559

4. Borentain P. et al. Successful treatment with sofosbuvir of fibrosing cholestatic hepatitis C after liver transplantation in an HIV-HCV-coinfected patient // Antivir. Ther. 2015. Vol. 20, № 3. P. 353–356.

Fibrosing cholestatic hepatitis is a severe form of post-liver transplantation HCV recurrence. Fibrosing cholestatic hepatitis is characterized by its early onset and severe prognosis in HIV-infected patients. We report the case of an HIV-HCV genotype-4 coinfected patient successfully treated with a combination of sofosbuvir and ribavirin. After 4 weeks of treatment we observed a resolution of HCV recurrence related symptoms associated with a normalization of liver biochemistry and dramatic decrease of HCV viral load. This case illustrates the efficiency and tolerance of a sofosbuvir-based anti-HCV interferon-free regimen in post-liver HCV recurrence. Because of the absence of drug interactions between sofosbuvir and antiretroviral treatment or calcineurin inhibitors, its administration in HIV-HCV-coinfected liver transplanted patients is very promising.

http://dx.doi.org/10.3851%2FIMP2841

5. Buneeva O.A. et al. Quantitative affinity interaction of ubiquitinated and non-ubiquitinated proteins with proteasome subunit Rpn10 // Biochem.-Moscow. 2017. Vol. 82, № 9. P. 1042–1047.

Recent proteomic profiling of mouse brain preparations using the ubiquitin receptor, Rpn10 proteasome subunit, as an affinity ligand revealed a representative group of proteins bound to this sorbent (Medvedev, A. E., et al. (2017) Biochemistry (Moscow), 82, 330-339). In the present study, we investigated interaction of the Rpn10 subunit of proteasomes with some of these identified proteins: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase, and histones H2A and H2B. The study revealed: (i) quantitative affinity interaction of the proteasome subunit immobilized on a Biacore-3000 optical biosensor cuvette with both the GAPDH (K (d) = 2.4 center dot 10-6 M) and pyruvate kinase (K (d) = 2.8 center dot 10(-5) M); (ii) quantitative high-affinity interaction of immobilized histones H2A and H2B with the Rpn10 subunit (Kd values of 6.5 center dot 10(-8) and 3.2 center dot 10(-9) M, respectively). Mass spectrometric analysis revealed the presence of the ubiquitin signature (GG) only in a highly purified preparation of GAPDH. We suggest that binding (especially high-affinity binding) of non-ubiquitinated proteins to the Rpn10 proteasome subunit can both regulate the functioning of this proteasomal ubiquitin receptor (by competing with ubiquitinated substrates) and promote activation of other pathways for proteolytic degradation of proteins destined to the proteasome.

http://dx.doi.org/10.1134%2FS0006297917090073

6. Calvino J. et al. Advanced glycation end products (AGEs) estimated by skin autofluorescence are related with cardiovascular risk in renal transplant // PLoS One. 2018. Vol. 13, № 8. P. e0201118.

Background Advanced glycation end products (AGEs) accumulation, a measure of cumulative metabolic stress, constitute a novel pathogenic mechanism involved in aging, diabetes, cardiovascular (CVD) and chronic kidney disease (CKD). Despite removal of uremic toxins and AGEs after a successful renal transplant (RT), CVD remains the leading cause of mortality. We hypothesized that AGEs measurement by Skin Autofluorescence (SAF) might be useful even after a successful RT and thus reflect the high cardiovascular risk burden of these patients. Methods 189 stable RT (61% men, aged 56 +/- 13.0 years), CKD stages 1-4 and >12 months since RT were enrolled. Variables collected comprised comorbid history, medication use, smoking habit, routine biochemistry, subclinical atheromatosis by ankle-brachial-index (ABI) and allograft resistivity index (RI), 24-h ABPM, anthropometry and handgrip strength. AGEs were measured by SAF and expressed in arbitrary units (AU). Vascular age was estimated by Koetsier's formula (SAF-0.83/0.024) and expected 10-years cardiovascular death risk was calculated with the REGICOR score. Results Mean SAF was 3.00 +/- 0.83 AU and estimated vascular age 90 +/- 34.7 years (30 years above biological age). SAF was higher among men (3.10 +/- 0.91 vs 2.81 +/- 0.66), diabetic nephropathy (3.49 +/- 0.75 vs 2.96 +/- 0.83) and steroid users (3.14 +/- 0.86 vs 2.71 +/- 0.69). We observed a positive correlation of SAF with night-systolic blood pressure (r = 0.25, p = 0.001), parathormone (r = 0.20, p<0.01), phosphate (r = 0.28, p<0.001) and negative with hemoglobin (r = -0.29, p<0.001), CKD-EPI (r = -0.32, p<0.001), albumin (r = -0.17, p<0.05), and dynamometry (r = -0.20, p<0.01). Subclinical vascular atheromatosis (ABI and RI) as well as the REGICOR scale (r = 0.35 p<0.001) were also correlated with SAF. In multivariable analysis age, gender, steroid use, serum phosphate and handgrip strength remained independently associated with SAF. Conclusions SAF levels are elevated in RT patients and correlate with CVD risk. Besides age and male sex, our results suggest that phosphate overload, steroid use and nutritional status are important factors linking to AGEs accumulation.

http://dx.doi.org/10.1371%2Fjournal.pone.0201118

7. Dumitrescu G. et al. Thromboelastometry: Relation to the severity of liver cirrhosis in patients considered for liver transplantation // Medicine (Baltimore). 2017. Vol. 96, № 23. P. e7101.

The severity of liver disease is assessed by scoring systems, which include the conventional coagulation test prothrombin time-the international normalized ratio (PT-INR). However, PT-INR is not predictive of bleeding in liver disease and thromboelastometry (ROTEM) has been suggested to give a better overview of the coagulation system in these patients. It has now been suggested that coagulation as reflected by tromboelastomety may also be used for prognostic purposes. The objective of our study was to investigate whether thrombelastometry may discriminate the degree of liver insufficiency according to the scoring systems Child Pugh and Model for End-stage Liver Disease (MELD).Forty patients with chronic liver disease of different etiologies and stages were included in this observational cross-sectional study. The severity of liver disease was evaluated using the Child-Pugh score and the MELD score, and blood samples for biochemistry, conventional coagulation tests, and ROTEM were collected at the time of the final assessment for liver transplantation. Statistical comparisons for the studied parameters with scores of severity were made using Spearman correlation test and receiver-operating characteristic (ROC) curves.Spearman correlation coefficients indicated that the thromboelastometric parameters did not correlate with Child-Pugh or MELD scores. The ROC curves of the thromboelastometric parameters could not differentiate advanced stages from early stages of liver cirrhosis.Standard ROTEM cannot discriminate the stage of chronic liver disease in patients with severe chronic liver disease.

http://dx.doi.org/10.1097%2FMD.0000000000007101

8. Foschi A. et al. Autoimmunity after liver transplantation: a frequent event but a rare clinical problem // Clin. Transplant. 2015. Vol. 29, № 2. P. 161–166.

Autoantibodies are frequently detected after liver transplantation (LT), but their role is unclear. This study was designed to address three points: autoantibody prevalence pre-LT and over time up to five yr after LT, identification of possible predictors of autoantibody formation, and correlation between autoantibodies and graft dysfunction. To these aims, we retrospectively evaluated 92 consecutive LT recipients for whom prospectively stored frozen sera were available for autoantibodies assessment by immunofluorescence. The overall autoantibody prevalence resulted significantly higher after LT than before LT (64% vs. 27%, p<0.001 and 35.9% vs. 8.7%, p<0.001 considering cutoff titer of 1:80 and 1:160, respectively). Recipient gender, donor age and gender, and indication for LT and main immunosuppressant (cyclosporine vs. tacrolimus) were not associated with the presence of autoantibodies. Patients with graft dysfunction had a significantly higher autoantibody prevalence irrespective of the etiology of liver injury as compared to those patients with persistently normal liver biochemistry, but only for cutoff titers 1:160 (p=0.004). No cases of de novo autoimmune hepatitis were observed. In conclusion, autoantibodies are very frequently detected after LT also at high titers and their association with graft dysfunction likely represents an aspecific indicator of liver injury.

http://dx.doi.org/10.1111%2Fctr.12498

9. Fung J. et al. Long-Term Outcomes of Entecavir Monotherapy for Chronic Hepatitis B After Liver Transplantation: Results up to 8 Years // Hepatology. 2017. Vol. 66, № 4. P. 1036–1044.

Long-term antiviral prophylaxis is required to prevent hepatitis B recurrence for patients with chronic hepatitis B after liver transplantation. We determined the long-term outcome of 265 consecutive chronic hepatitis B liver transplant recipients treated with entecavir monotherapy without hepatitis B immune globulin. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. The median duration of follow-up was 59 months. The cumulative rates of hepatitis B surface antigen (HBsAg) seroclearance were 90% and 95% at 1 and 5 years, respectively. At 1, 3, 5, and 8 years, 85%, 88%, 87.0%, and 92% were negative for HBsAg, respectively, and 95%, 99%, 100%, and 100% had undetectable hepatitis B virus (HBV) DNA, respectively. Fourteen patients remained persistently positive for HBsAg, all of whom had undetectable HBV DNA. There was no significant difference in liver stiffness for those who remained HBsAg-positive compared to those who achieved HBsAg seroclearance (5.5 versus 5.2 kPa, respectively; P 5 0.52). The overall 9-year survival was 85%. There were 37 deaths during the follow-up period, of which none were due to hepatitis B recurrence. Conclusion: Long-term entecavir monotherapy is highly effective at preventing HBV reactivation after liver transplantation for chronic hepatitis B, with a durable HBsAg seroclearance rate of 92%, an undetectable HBV DNA rate of 100% at 8 years, and excellent long-term survival of 85% at 9 years.

http://dx.doi.org/10.1002%2Fhep.29191

10. Jordan K. et al. Gastrointestinal Toxicity, Systemic Inflammation, and Liver Biochemistry in Allogeneic Hematopoietic Stem Cell Transplantation // Biol. Blood Marrow Transplant. 2017. Vol. 23, № 7. P. 1170–1176.

Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-regulating cytokines during the early post-transplantation period. We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning. Alanine aminotransferase (ALT), total bilirubin levels, and international normalized ratio were measured longitudinally until 3 months after the transplantation and related to levels of inflammatory markers (C-reactive protein [CRP], IL-6, and IL-10) and to plasma citrulline as a marker of intestinal toxicity during the first 3 weeks after HSCT. The majority of patients experienced ALT levels above the normal range (45 U/L) with significant increases at 3 months after HSCT. Increased levels of total bilirubin were observed in 26% during the 3-month period. Citrulline levels decreased significantly to a nadir at day 7 (B = .23; 95% confidence interval [CI], .12 to .35; P < .0001), but citrulline levels at nadir were not associated with parameters of liver toxicity. However, a faster reconstitution of mucosa with higher citrulline levels at day +21 correlated with lower bilirubin levels 3 months after HSCT (r = -.26, P = .034) and increased overall survival (hazard ratio, .88; 95% CI, .79 to .97; P = .008). Increased levels of CRP and IL-6 at day 7 after HSCT correlated positively with ALT and bilirubin, and in the multivariate analysis, IL-6 at day 7 appeared to be the only predicting risk factor for increased mean bilirubin during the early post-transplantation phase (B = .01; 95% CI, .01 to .02; P = .001) as well as maximum levels of bilirubin (B = .3; 95% CI, .12 to .48; P = .001) and occurrence of sinusoidal obstruction syndrome during the first 3 months after HSCT (odds ratio, 1.003; 95% CI, 1.001 to 1.005; P = .002). The results of this study indicate that liver toxicity after HSCT is associated with an increased inflammatory response mounted during the phase of maximal gastrointestinal toxicity in the early phase after transplantation.

http://dx.doi.org/10.1016/j.bbmt.2017.03.021

11. Kaji K. et al. DNMT1 Is a Required Genomic Regulator for Murine Liver Histogenesis and Regeneration // Hepatology. 2016. Vol. 64, № 2. P. 582–598.

DNA methyltransferase 1 (DNMT1) is an essential regulator maintaining both epigenetic reprogramming during DNA replication and genome stability. We investigated the role of DNMT1 in the regulation of postnatal liver histogenesis under homeostasis and stress conditions. We generated Dnmt1 conditional knockout mice (Dnmt1(Delta alb)) by crossing Dnmt1(fl/fl) with albumin-cyclization recombination transgenic mice. Serum, liver tissues, and primary hepatocytes were collected from 1-week-old to 20-week old mice. The Dnmt1(Delta alb) phenotype was assessed by histology, confocal and electron microscopy, biochemistry, as well as transcriptome and methylation profiling. Regenerative growth was induced by partial hepatectomy and exposure to carbon tetrachloride. The impact of Dnmt1 knockdown was also analyzed in hepatic progenitor cell lines; proliferation, apoptosis, DNA damage, and sphere formation were assessed. Dnmt1 loss in postnatal hepatocytes caused global hypomethylation, enhanced DNA damage response, and initiated a senescence state causing a progressive inability to maintain tissue homeostasis and proliferate in response to injury. The liver regenerated through activation and repopulation from progenitors due to lineage-dependent differences in albumin-cyclization recombination expression, providing a basis for selection of less mature and therefore less damaged hepatic progenitor cell progeny. Consistently, efficient knockdown of Dnmt1 in cultured hepatic progenitor cells caused severe DNA damage, cell cycle arrest, senescence, and cell death. Mx1-cyclization recombination-driven deletion of Dnmt1 in adult quiescent hepatocytes did not affect liver homeostasis. Conclusion: These results establish the indispensable role of DNMT1-mediated epigenetic regulation in postnatal liver growth and regeneration; Dnmt1(Delta alb) mice provide a unique experimental model to study the role of senescence and the contribution of progenitor cells to physiological and regenerative liver growth.

http://dx.doi.org/10.1002%2Fhep.28563

12. Kaxiras A. et al. Cyclosporin A, but not tacrolimus, negatively affects the hepatic extraction fraction of hepatobiliary scintigraphy in liver transplant recipients // EJNMMI Res. 2014. Vol. 4. P. 1–8.

Background: Hepatobiliary scintigraphy using Tc-99m-mebrofenin has been used as an investigation to study liver function after liver transplantation (LTx). Hepatic extraction fraction (HEF) is a measurement of the hepatic extraction efficiency and hepatic extraction rate. With the purpose of evaluating a possible diverging effect of cyclosporin A (CSA) and tacrolimus (TAC) on the HEF, we compared the HEF with biochemical and histological parameters in LTx patients receiving either CSA or TAC. Methods: Thirty-nine adult patients who underwent LTx due to hepatitis C virus (HCV) cirrhosis were evaluated. All patients underwent a 3-month and 1-year follow-up that included hepatobiliary scintigraphy and biochemistry tests. Liver biopsy was performed at 1 year. These clinical parameters were compared between the two groups, TAC (n = 15) and CSA (n = 24). Results: The average HEF was significantly lower in the CSA group compared to the TAC group both at 3 months and 1 year after LTx. The liver biochemistry tests, average donor and recipient age, average cold ischemia time (CIT), and a clearance were comparable in the two groups. The TAC group had more inflammation than the CSA group. Moreover, three patients who converted from CSA to TAC increased their HEF values. Conclusions: CSA-treated patients presented a lower HEF value on hepatobiliary scintigraphy in spite of comparable liver function by traditional measurements indicating a decrease on HEF values by CSA.

http://dx.doi.org/10.1186%2Fs13550-014-0073-z

13. Lee J.N. et al. Proteasome inhibitors induce auditory hair cell death through peroxisome dysfunction // Biochem. Biophys. Res. Commun. 2015. Vol. 456, № 1. P. 269–274.

Even though bortezomib, a proteasome inhibitor, is a powerful chemotherapeutic agent used to treat multiple myeloma (MM) and other lymphoma cells, recent clinical reports suggest that the proteasome inhibitor therapy may be associated with severe bilateral hearing loss. We herein investigated the adverse effect of proteasome inhibitor on auditory hair cells. Treatment of a proteasome inhibitor destroys stereocilia bundles of hair cells resulting in the disarray of stereocilia in the organ of Corti explants. Since proteasome activity may be potentially important for biogenesis and function of the peroxisome, we tested whether proteasome activity is necessary for maintaining functional peroxisomes. Our results showed that treatment of a proteasome inhibitor significantly decreases both the number of peroxisomes and expression of peroxisomal proteins such as PMP70 and Catalase. In addition, we also found that proteasome inhibitor impairs the import pathway of PTS1-peroxisome matrix proteins. Taken together, our findings support recent clinical reports of hearing loss associated with proteasome inhibition. Mechanistically, peroxisome dysfunction may contribute to hair cell damage and hearing loss in response to the treatment of a proteasome inhibitor.

http://dx.doi.org/10.1016%2Fj.bbrc.2014.11.070

14. McGorum B.C. et al. Proteomic Profiling of Cranial (Superior) Cervical Ganglia Reveals Beta-Amyloid and Ubiquitin Proteasome System Perturbations in an Equine Multiple System Neuropathy // Mol. Cell. Proteomics. 2015. Vol. 14, № 11. P. 3072–3086.

Equine grass sickness (EGS) is an acute, predominantly fatal, multiple system neuropathy of grazing horses with reported incidence rates of approximate to 2%. An apparently identical disease occurs in multiple species, including but not limited to cats, dogs, and rabbits. Although the precise etiology remains unclear, ultrastructural findings have suggested that the primary lesion lies in the glycoprotein biosynthetic pathway of specific neuronal populations. The goal of this study was therefore to identify the molecular processes underpinning neurodegeneration in EGS. Here, we use a bottom-up approach beginning with the application of modern proteomic tools to the analysis of cranial (superior) cervical ganglion (CCG, a consistently affected tissue) from EGS-affected patients and appropriate control cases postmortem. In what appears to be the proteomic application of modern proteomic tools to equine neuronal tissues and/or to an inherent neurodegenerative disease of large animals (not a model of human disease), we identified 2,311 proteins in CCG extracts, with 320 proteins increased and 186 decreased by greater than 20% relative to controls. Further examination of selected proteomic candidates by quantitative fluorescent Western blotting (QFWB) and subcellular expression profiling by immunohistochemistry highlighted a previously unreported dysregulation in proteins commonly associated with protein misfolding/aggregation responses seen in a myriad of human neurodegenerative conditions, including but not limited to amyloid precursor protein (APP), microtubule associated protein (Tau), and multiple components of the ubiquitin proteasome system (UPS). Differentially expressed proteins eligible for in silico pathway analysis clustered predominantly into the following biofunctions: (1) diseases and disorders, including; neurological disease and skeletal and muscular disorders and (2) molecular and cellular functions, including cellular assembly and organization, cell-to-cell signaling and interaction (including epinephrine, dopamine, and adrenergic signaling and receptor function), and small molecule biochemistry. Interestingly, while the biofunctions identified in this study may represent pathways underpinning EGS-induced neurodegeneration, this is also the first demonstration of potential molecular conservation (including previously unreported dysregulation of the UPS and APP) spanning the degenerative cascades from an apparently unrelated condition of large animals, to small animal models with altered neuronal vulnerability, and human neurological conditions. Importantly, this study highlights the feasibility and benefits of applying modern proteomic techniques to veterinary investigations of neurodegenerative processes in diseases of large animals.

http://dx.doi.org/10.1074%2Fmcp.M115.054635

15. Moghadasali R. et al. Autologous transplantation of mesenchymal stromal cells tends to prevent progress of interstitial fibrosis in a rhesus Macaca mulatta monkey model of chronic kidney disease // Cytotherapy. 2015. Vol. 17, № 11. P. 1495–1505.

Background aims. Chronic kidney disease (CKD) attributed to cisplatin is well documented. Mesenchymal stromal cells (MSCs) are proven to be renotropic. Although they have been shown to improve function in CKD and reduce fibrosis in different experimental rodent models, their efficiency in primates is unknown. The present study aimed to evaluate the prevention of CKD and reduction of fibrosis in monkeys treated with MSCs after cisplatin nephrotoxicity. Methods. We induced CKD in adult rhesus Macaca mulatta monkeys by means of intravenous administration of cisplatin. Autologous MSCs were transplanted by means of intrarenal arterial injections to assess the adverse effects of cisplatin in two CKD models: preventative and stable. Preventative CKD monkeys (n = 3) underwent cell transplantation 4 days after the cisplatin injection. The stable CKD monkeys (n = 2) underwent cell transplantation 6 months after the cisplatin injection. Non-treated (n = 4) and normal saline injected animals (n = 3) comprised the control and vehicle groups, respectively. We followed the animals for survival rate, serum biochemistry, urine analysis and histopathological indices. Results. In the preventive CKD model, MSC transplantation tended to improve some renal functions but significantly reduced the histopathologic score compared with the vehicle and control groups. In the stable CKD model, MSCs did not ameliorate renal function or pathological score. Conclusions. These results suggest that MSCs tend to delay progression of CKD and fibrosis but do not reduce established interstitial fibrosis in this unique primate model of cisplatin induced nephrotoxicity.

http://dx.doi.org/10.1016%2Fj.jcyt.2015.06.006

16. Morozov A.V., Karpov V.L. Biological consequences of structural and functional proteasome diversity // Heliyon. 2018. Vol. 4, № 10. P. e00894.

Cell homeostasis and regulation of metabolic pathways are ensured by synthesis, proper folding and efficient degradation of a vast amount of proteins. Ubiquitin-proteasome system (UPS) degrades most intracellular proteins and thus, participates in regulation of cellular metabolism. Within the UPS, proteasomes are the elements that perform substrate cleavage. However, the proteasomes in the organism are diverse. Structurally different proteasomes are present not only in different types of cells, but also in a single cell. The reason for proteasome heterogeneity is not fully understood. This review briefly encompasses mammalian proteasome structure and function, and discusses biological relevance of proteasome diversity for a range of important cellular functions including internal and external signaling.

http://dx.doi.org/10.1016/j.heliyon.2018.e00894

17. Pereira-Neves A. et al. Characterisation of 20S Proteasome in Tritrichomonas foetus and Its Role during the Cell Cycle and Transformation into Endoflagellar Form // PLoS One. 2015. Vol. 10, № 6. P. e0129165.

Proteasomes are intracellular complexes that control selective protein degradation in organisms ranging from Archaea to higher eukaryotes. These structures have multiple proteolytic activities that are required for cell differentiation, replication and maintaining cellular homeostasis. Here, we document the presence of the 20S proteasome in the protist parasite Tritrichomonas foetus. Complementary techniques, such as a combination of whole genome sequencing technologies, bioinformatics algorithms, cell fractionation and biochemistry and microscopy approaches were used to characterise the 20S proteasome of T. foetus. The 14 homologues of the typical eukaryotic proteasome subunits were identified in the T. foetus genome. Alignment analyses showed that the main regulatory and catalytic domains of the proteasome were conserved in the predicted amino acid sequences from T. foetus-proteasome subunits. Immunofluorescence assays using an anti-proteasome antibody revealed a labelling distributed throughout the cytosol as punctate cytoplasmic structures and in the perinuclear region. Electron microscopy of a T. foetus-proteasome-enriched fraction confirmed the presence of particles that resembled the typical eukaryotic 20S proteasome. Fluorogenic assays using specific peptidyl substrates detected presence of the three typical peptidase activities of eukaryotic proteasomes in T. foetus. As expected, these peptidase activities were inhibited by lactacystin, a well-known specific proteasome inhibitor, and were not affected by inhibitors of serine or cysteine proteases. During the transformation of T. foetus to endoflagellar form (EFF), also known as pseudocyst, we observed correlations between the EFF formation rates, increases in the proteasome activities and reduced levels of ubiquitin-protein conjugates. The growth, cell cycle and EFF transformation of T. foetus were inhibited after treatment with lactacystin in a dose-dependent manner. Lactacystin treatment also resulted in an accumulation of ubiquitinated proteins and caused increase in the amount of endoplasmic reticulum membranes in the parasite. Taken together, our results suggest that the ubiquitin-proteasome pathway is required for cell cycle and EFF transformation in T. foetus.

http://dx.doi.org/10.1371%2Fjournal.pone.0129165

18. Piotrowski P.C. et al. Neurologic complications in kidney transplant recipients // Folia Neuropathol. 2017. Vol. 55, № 2. P. 86–109.

Transplantology experiences continuous growth and kidney transplantation is the most frequently transplanted solid organ. Metabolic, cardiovascular, infectious or kidney function-related aspects are widely recognised and are of key interest for transplant doctors. Neurological complications seen in these patients, although known, are less covered in the literature. According to some reports, neurologic symptoms are experienced by almost 9 per 10 transplant recipients. The intensity, severity and type of abnormalities may vary, and most frequently the complications seem to be associated with a direct or indirect effect of immunosuppressive medications, including their direct effect on cells, on blood vessels, and susceptibility to infections. Increasing age of transplant recipients and relaxation of transplantation eligibility criteria enriches the population with patients already compromised, with a higher present risk of stroke, neuropathy, malignancy etc. Research on and introduction to clinical practice of new agents like belatacept, proteasome inhibitors, or modified release formulations of tacrolimus, changes the picture and type of abnormalities within the nervous or neuromuscular system but does not eliminate them. Thus, it seems justified to remind the society of the whole array of neurologic complications they can see in their practice despite advances in the field.

http://dx.doi.org/10.5114%2Ffn.2017.68577

19. Pyart R. et al. UK Renal Registry 20th Annual Report: Chapter 3 Demographic and Biochemistry Profile of Kidney Transplant Recipients in the UK in 2016: National and Centre-specific Analyses // Nephron. 2018. Vol. 139. P. 75–104.

There was a 5% increase in overall renal transplant numbers from 2015 to 2016, with an increase in kidney transplants from donors after brainstem death (9%), donors after cardiac death (13%) but a fall from living donors (-3%). In 2016, death-censored renal transplant failure rates in prevalent patients were similar to previous years at 2.4% per annum. Transplant patient death rates were similar at 2.5 per 100 patient years. The median age of incident and prevalent renal transplant patients in the UK was 51.4 and 54.3 years respectively. The median eGFR of prevalent renal transplant recipients was 52.2 ml/min/1.73 m(2). The median eGFR of patients one year after transplantation was 57.2 ml/min/1.73 m post live transplant, 52.4 ml/min/1.73 m(2) post brainstem death transplant and 48.4 ml/min/1.73 m(2) post circulatory death transplant. In 2016, 13.1% of prevalent transplant patients had eGFR <30 ml/min/1.73 m(2). The median decline in eGFR slope beyond the first year after transplantation was -0.7 ml/min/ 1.73 m(2)/year. In 2016, malignancy (23%) replaced infection (22%) as the commonest cause of death in patients with a functioning renal transplant. Data completeness for attainment of blood pressure targets remained variable between centres.

http://dx.doi.org/10.1159%2F000490961

20. Rockel B. et al. Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes // Biochem. Biophys. Res. Commun. 2014. Vol. 450, № 2. P. 991–997.

The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 265 proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts are very similar, Flag-CSN pulldowns are a proper alternative to CSN preparation from erythrocytes.

http://dx.doi.org/10.1016/j.bbrc.2014.06.093

21. Seto W.-K. et al. Hepatitis B Reactivation in Occult Viral Carriers Undergoing Hematopoietic Stem Cell Transplantation: A Prospective Study // Hepatology. 2017. Vol. 65, № 5. P. 1451–1461.

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg-negative, anti-HBc-positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (>= 10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg-negative, anti-HBc-positive, of whom 62 were recruited and monitored for a median of 48 (4-104) weeks. The 2-year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8-100) weeks. Multivariate analysis showed that age >= 50 years (P = 0.004, hazard ratio = 8.2) and chronic graft-versus-host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft-versus-host disease, compared with the remaining patient cohort, had a significantly lower 2-year cumulative HBV reactivation rate (5.6% versus 65.0%, P=5 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. Conclusion: HBsAg-negative, anti-HBc-positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age >= 50 years and chronic graft-versus-host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.)

http://dx.doi.org/10.1002%2Fhep.29022

22. Shahidi N., Azalgara V.M., Yoshida E. Use of Monitoring Gamma-Glutamyl Transpeptidase Levels After Liver Transplant: A Longitudinal Retrospective Analysis of a Single-Center’s Experience // Exp. Clin. Transplant. 2016. Vol. 14, № 3. P. 317–322.1.

Objectives: Recently, gamma-glutamyl transpeptidase has garnered increased attention as a diagnostic tool in the early identification of liver disease. However, its value in liver transplant is largely unknown, as the disease processes leading to abnormal gamma-glutamyl transpeptidase levels and the expected temporal trends in gamma-glutamyl transpeptidase levels during the period after liver transplant remain unclear. Materials and Methods: Between January 2010 and August 2013, consecutive patients who underwent liver transplant at Vancouver General Hospital (Vancouver, Canada) were assessed longitudinally up to 1 year after liver transplant. A "gamma-glutamyl transpeptidase event" was defined as 2 abnormal gamma-glutamyl transpeptidase values (exceeding sex-specific limits of normal, at 55 U/L for female and 80 U/L for male patients) >= 1 week apart. Results: Our study included 147 liver transplant recipients. The median gamma-glutamyl transpeptidase level on day 1 after liver transplant was 73 U/L, which peaked to 435 U/L during the first month after liver transplant and returned to within normal parameters by 1 year. In total, there were 282 gamma-glutamyl transpeptidase events, with biliary complications (22%), acute rejection (16%), and hepatitis C virus recurrence (10%) being the most common causes. In 39% of events, no cause was identified. When attempting to identify a disease-associated event, if gamma-glutamyl transpeptidase was the initial liver biochemistry test to double in value, it had 42% sensitivity and 40% specificity. Comparatively, if gamma-glutamyl transpeptidase was the initial liver biochemistry test to become abnormal, it had 3% sensitivity and 93% specificity. Conclusions: Although gamma-glutamyl transpeptidase almost universally becomes abnormal after liver transplant, a specific pathologic cause was not commonly identified. Interpreting the characteristics of gamma-glutamyl transpeptidase elevation has limited use for identifying the underlying reason for its elevation.

http://dx.doi.org/10.6002%2Fect.2015.0224

23. Singh V. et al. Apigenin manipulates the ubiquitin-proteasome system to rescue estrogen receptor-beta from degradation and induce apoptosis in prostate cancer cells // Eur. J. Nutr. 2015. Vol. 54, № 8. P. 1255–1267.

To investigate apigenin (5,7,4-trihydroxyflavone), a dietary flavonoid with proteasome-inhibitory activity (desired for the management of multiple types of cancers), against FDA-approved anticancer proteasome inhibitor bortezomib in context to its effects on the tumor suppressor estrogen receptor-beta (ER-beta) in prostate cancer cells. Prostate cancer (PC-3) cells were treated with either apigenin or bortezomib, and proliferation inhibition was correlated with proteasomal biochemistry, ER-degradation and cell apoptosis. Apigenin specifically inhibited only chymotrypsin-like activity of proteasome without affecting trypsin and caspase-like activities, which was in contrast to the non-specific inhibition of all the three activities by bortezomib. Apigenin selectively increased the protein levels of ER-beta at 1.8 and 10.0 A mu M (without affecting mRNA levels) and preferentially accumulated ubiquitinated ER-beta over ER-alpha in PC-3. Apigenin-treated cells exhibited increased ER-beta interactions with ubiquitin-protein ligase E6AP, downregulated PSMA5 (alpha-5 subunit for assembly of 20S proteasome) without affecting PSMB1 (beta-1 subunit), PSMB2 (beta-2 subunit) and PSMB5 (beta-5 subunit, whose overexpression by bortezomib causes drug resistance) of proteasome at mRNA levels. Caspase-3 activation in PC-3 by apigenin was dependent on caspase-8 activity but independent of mitochondrial membrane depolarization. The deubiquitinase USP14 activity, which antagonizes degradation of proteins via proteasome, was significantly increased by apigenin treatment. Apigenin selectively inhibits proteasomal degradation of tumor suppressor ER-beta by specifically inhibiting chymotrypsin-like activity of proteasome, preventing its assembly via PSMA5 and inhibiting USP14 enzyme activity in prostate cancer cells, resulting in cancer cell apoptosis. Unlike bortezomib, apigenin's actions are subtle, precise, mechanistically distinct and capable of abstaining drug resistance.

http://dx.doi.org/10.1007/s00394-014-0803-z

24. Sriuttha W. et al. Ex vivo and in vivo characterization of cold preserved cartilage for cell transplantation // Cell Tissue Banking. 2016. Vol. 17, № 4. P. 721–734.

Due to the inconvenient and invasive nature of chondrocyte transplantation, preserved cartilage has been recognized as an alternative source of chondrocytes for implantation. However, there are major concerns, in particular, the viability and quality of the chondrocytes. This study investigated the biochemistry and molecular characterization of chondrocytes isolated from preserved cartilage for purposes of transplantation. Ex vivo characterization was accomplished by storing human cartilage at either 4 or -80 A degrees C in a preservation medium. Microscopic evaluation of the preserved cartilage was conducted after 1, 2, 3 and 6 weeks. The chondrocytes were isolated from the preserved cartilage and investigated for proliferation capacity and chondrogenic phenotype. Transplantation of chondrocytes from preserved cartilage into rabbit knees was performed for purposes of in vivo evaluation. The serum cartilage degradation biomarker (WF6 epitopes) was evaluated during the transplantation procedure. Human cartilage preserved for 1 week in a 10 % DMSO chondrogenic medium at 4 A degrees C gave the highest chondrocyte viability. The isolated chondrocytes showed a high proliferative capacity and retained chondrogenic gene expression. Microscopic assessment of the implanted rabbit knees showed tissue regeneration and integration with the host cartilage. A decreased level of the serum biomarker after transplantation was evidence of in vivo repair by the implanted chondrocytes. These results suggest that cartilage preservation for 1 week in a 10 % DMSO chondrogenic medium at 4 A degrees C can maintain proliferation capacity and the chondrogenic phenotype of human chondrocytes. These results can potentially be applied to in vivo allogeneic chondrocyte transplantation. Allogeneic chondrocytes from preserved cartilage would be expected to maintain their chondrogenic phenotype and to result in a high rate of success in transplanted grafts.

http://dx.doi.org/10.1007%2Fs10561-016-9577-2

25. Sugihara K. et al. Recovery pattern of non-protein respiratory quotient and non-esterified fatty acids after liver resection // Nutrition. 2014. Vol. 30, № 4. P. 443–448.

Objective: Perioperative nutritional care is important to maintain preoperative and postoperative nutritional status. However, few reports have investigated energy metabolism after hepatectomy. The aim of this study was to determine differences in energy metabolism, blood biochemistry, and nutritional status before and after liver resection in patients with hepatocellular carcinoma (HCC) and healthy living donors for liver transplantation. Methods: Eighteen hospitalized patients with HCC group and 13 living donors for liver transplantation (donor group) were enrolled in this study. The donor group was divided into two groups on the basis of age; Y-donor group (age <40 y, n = 7), and O-donor group (age >= 40 y, n = 6). Energy metabolism was measured by indirect calorimetry at preoperative day and postoperative day (POD) 7 and 14, and blood biochemistry was also examined. Results: Recovery of non-protein respiratory quotient (npRQ) and blood biochemical data such as total bilirubin, aspartate aminotransferase and alanine aminotransferase levels were observed in Y-donor group on POD 14. However, although biochemical data improved in the HCC and O-donor group, npRQ remained unchanged on POD 14. Conclusions: Improvement of npRQ took longer than blood biochemical data in patients with HCC and older donors. Because the recovery of npRQ is associated with donor age, careful nutritional management may be required for a longer time depending on the pathophysiological condition of each patient after hepatectomy.

http://dx.doi.org/10.1016%2Fj.nut.2013.09.012

26. Wareham N.E. et al. The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients // J. Cancer Res. Clin. Oncol. 2018. Vol. 144, № 8. P. 1569–1580.

Emerging EBV DNAemia in plasma is considered an early sign of post-transplant lymphoproliferative disorder (PTLD). The aim of this study was to quantify the extent of benefit from screening for EBV DNAemia to detect emerging PTLD among solid organ (SOT) or hematopoietic stem cell transplant recipients (HSCT). We used receiver operating characteristic (ROC) curves for assessing ability of models to predict PTLD. Among 2642 recipients transplanted between January 2004 and December 2014, 79 (3%) developed PTLD. EBV DNAemia was observed in 331/1784 recipients (18.6%, 95% CI 16.8-20.4) with measured EBV DNA. The area under the curve (AUC) of the ROC of EBV DNAemia to identify persons with subsequent PTLD was 72% (95% CI, 64-79%) among SOT and 59% (51-68%) among HSCT. Including clinical predictors such as age, gender, transplant year and type, high-risk EBV serostatus, and routine biochemistry in addition to EBV DNAemia increased AUC to 83% (75-90%) among SOT and 84% (79-89%) among HSCT. Among HSCT, including additional factors such as T-cell-depleting treatment, acute graft vs. host disease and donor match increased AUC to 85% (78-91%). We constructed a model to better predict PTLD compared to EBV DNA screening alone which could have clinical implications.

http://dx.doi.org/10.1007%2Fs00432-018-2674-9

27. Watson C.J.E. et al. Observations on the ex situ perfusion of livers for transplantation // Am. J. Transplant. 2018. Vol. 18, № 8. P. 2005–2020.

Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels. Lactate clearance occurred within 3hours in 46 of 47 perfusions, and glucose rose initially during perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary nonfunction. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified three livers that developed cholangiopathy (peak pH < 7.4) from those that did not (pH > 7.5). In the 11 research livers where it could be studied, bile pH > 7.5 discriminated between the 6 livers exhibiting >50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25-50% necrosis had a maximum pH 7.46. Liver viability during normothermic perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance, and maintenance of acid-base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of posttransplant ischemic cholangiopathy. The authors describe a series of ex situ normothermic liver perfusions in which they examine biochemical markers of hepatocyte and cholangiocyte biochemistry in an effort to predict posttransplant viability.

http://dx.doi.org/10.1111%2Fajt.14687

28. Wolf F. et al. Biosynthesis of the beta-Lactone Proteasome Inhibitors Belactosin and Cystargolide // Angew. Chem.-Int. Edit. 2017. Vol. 56, № 23. P. 6665–6668.

Belactosins and cystargolides are natural product proteasome inhibitors from Actinobacteria. Both feature dipeptidic backbones and a unique beta-lactone building block. Herein, we present a detailed investigation of their biosynthesis. Identification and analysis of the corresponding gene clusters indicated that both compounds are assembled by rare single-enzyme amino acid ligases. Feeding experiments with isotope-labeled precursors and in vitro biochemistry showed that the formation of the beta-lactone warhead is unprecedented and reminiscent of leucine biosynthesis, and that it involves the action of isopropylmalate synthase homologues.

http://dx.doi.org/10.1002%2Fanie.201612076

29. Zhou W. et al. Diabetogenic agent alloxan is a proteasome inhibitor // Biochem. Biophys. Res. Commun. 2017. Vol. 488, № 2. P. 400–406.

Alloxan has been used as a diabetogenic agent to induce diabetes. It selectively induces pancreatic beta-cell death. The specific toxicity, however, is not fully understood. In this study, we observed the effect of alloxan on proteasome function. We found that alloxan caused the accumulation of ubiquitinated proteins in NRK cells through the inhibition of the proteolytic activities of the proteasome. Biochemistry experiments with purified 26S and 20S proteasomes revealed that alloxan directly acts on the chymotrypsin- and trypsin-like peptidase activities. These results demonstrate that alloxan is a proteasome inhibitor, which suggests that its specific toxicity toward beta-cell is at least in part through proteasome inhibition.

http://dx.doi.org/10.1016%2Fj.bbrc.2017.05.065

30. Ziff O.J. et al. Impact of seasonality on the dynamics of native Vitamin D repletion in long-term renal transplant patients // Clin. Kidney J. 2017. Vol. 10, № 3. P. 411–418.

Background: Renal transplant recipients (RTRs) are often Vitamin D (VitD) depleted as a result of both chronic kidney disease and mandated sun avoidance behaviours. Repleting VitD may be warranted, but how, and for how long, is unknown, as is the impact of seasonality on the success of repletion. We investigated the impact of seasonality on VitD status following VitD repletion in a large cohort of stable, long-termRTRs. Methods: Serum 25-hydroxyvitamin D [25(OH)D] concentrations and bone biochemistry parameters were analysed from 102 VitD repletion courses in 98 RTRs that had undergone VitD repletion. Repletion was delivered over 6 months with either 240 000 IU colecalciferol if pre-repletion serum VitD was between 20 and 50 nmol/L, or with 360 000 IU if VitD was < 20 nmol/L. Twelve months post-repletion 25(OH) D and parathyroid hormone (PTH) were available for 75 patients. Results: At baseline, 25(OH)D was 20.1 +/- 1.0 nmol/L, increasing to 65.4 +/- 1.8 nmol/L following repletion (+7.55 nmol/L/month, P<0.0001). Twelve months post-repletion and after no further VitD administration, 25(OH)D fell to 35.4 +/- 1.8 nmol/L (14.2 +/- 0.7 ng/mL; - 2.50 nmol/L/month, P< 0.0001). PTH followed the opposite trend with baseline, repletion-end and post-repletion values being 144.2 +/- 12.0, 109.6 +/- 7.5 and 129.2 +/- 11.4 ng/L, respectively. VitD repletion during the summer was associated with significantly higher at repletion-end 25(OH)D compared with any other time of year [summer 80.9 +/- 4.0, autumn 64.1 +/- 3.0 (P = 0.002), winter 48.9 +/- 3.0 (P< 0.001), spring 63.8 +/- 2.5 nmol/L (P< 0.001)]. There was no hypercalcaemia during repletion and renal transplant function remained stable without any evidence of allograft rejection. Conclusions: VitD repletion can safely and effectively be achieved in the majority of chronic stable RTRs using a 6-month bolus intermediate-dose schedule. Winter repletion is associated with an inadequate response in 25(OH)D; however, all patients experience a post-repletion fall towards deficiency in the absence of maintenance supplementation, irrespective of the season of repletion.

http://dx.doi.org/10.1093%2Fckj%2Fsfw136

31. 04617X
Акунеева Т.В. ВЗАИМОДЕЙСТВИЕ ИММУНОЦИТОВ КОЖИ В ПРОЦЕССЕ РЕПАРАТИВНОЙ РЕГЕНЕРАЦИИ В РАНЕ // Российский иммунологический журнал. 2017. Т. 11(20). № 2. С. 148-150.

Проведен эксперимент на 20 половозрелых кроликах с целью уточнения роли иммуноцитов в репаративной регенерации кожи в условиях гнойно-инфицированной раны. Понимание роли иммунокомпетентных клеток в процессах регенерации в ране и образовании рубцовой ткани возможно, может способствовать поиску новых подходов к терапии, связанной с воздействием на иммунные механизмы для профилактики образования рубцов.

https://elibrary.ru/item.asp?id=29826631

32. 040949
Волков А.В., Антонов Е.Н., Васильев А.В., Бухарова Т.Б., Эшмотова Г.К., Попов В.К., Вихрова Е.Б., Минаева С.А., Капанадзе Г.Д., Фатхудинова Н.Л., Ревякин А.О., Гольдштейн Д.В. ВЛИЯНИЕ ПРОТИВОВОСПАЛИТЕЛЬНЫХ ПРЕПАРАТОВ НА РЕГЕНЕРАЦИЮ КОСТНОЙ ТКАНИ ПРИ ТРАНСПЛАНТАЦИИ МУЛЬТИПОТЕНТНЫХ МЕЗЕНХИМАЛЬНЫХ СТРОМАЛЬНЫХ КЛЕТОК // Д.В. Биомедицина. 2014. № 4. С. 17-24.

https://elibrary.ru/item.asp?id=23572016

33. 040991
Готье С.В. ТРАНСПЛАНТОЛОГИЯ XXI ВЕКА: ВЫСОКИЕ ТЕХНОЛОГИИ В МЕДИЦИНЕ И ИННОВАЦИИ В БИОМЕДИЦИНСКОЙ НАУКЕ // Вестник трансплантологии и искусственных органов. 2017. Т. 19. № 3. С. 10-32.

Представлен обзор основных направлений исследований и наиболее значимых результатов, полученных в последние годы в Федеральном научном центре трансплантологии и искусственных органов, включая трансплантацию сердца, трансплантацию легких, эволюцию трансплантации печени, трансплантацию почки. В статье также рассмотрены перспективные разработки в области создания искусственных органов - систем вспомогательного кровообращения - и регенеративной медицины, нано- и клеточных технологий, создание биоискусственных органов.

https://elibrary.ru/item.asp?id=29987148

34. 00789X
Зайкова Ю.Я., Евтеева И.Н., Цимоха Л.С. ПРОТЕАСОМЫ И ИХ ВОЗМОЖНАЯ РОЛЬ ВО ВНЕКЛЕТОЧНОМ ПРОСТРАНСТВЕ // Цитология. 2013. Т. 55. № 11. С. 753-760.

Представлен обзор литературы, касающейся исследований внеклеточных протеасом и их возможных функций. Убиквитин-протеасомная система (УПС) отвечает за большую часть регулируемого протеолиза в клетке. 26S протеасома является центральным протеолитическим звеном УПС и представляет собой мультисубъединичный белковый комплекс, состоящий из коровой 20S протеасомы и ассоциированный с ней одним или двумя 19S регуляторными комплексами. Обнаружено, что протеасомы присутствуют во внеклеточном пространстве — в альвеолярном секрете, спинномозговой жидкости и в плазме крови. Внеклеточные протеасомы имеют аналогичную внутриклеточным частицам цилиндрическую структуру и обладают тремя типами пептидазной активности, специфическими для протеасом. Внеклеточные протеасомы присутствуют как у здоровых, так и у больных людей. Обнаружено, что у пациентов, страдающих от аутоиммунных заболеваний, злокачественных новообразований, сепсиса или травмы, концентрация внеклеточных протеасом в крови повышается, что коррелирует с прогрессированием заболевания и имеет как диагностическое, так и прогностическое значение.

https://elibrary.ru/item.asp?id=20410576

35. Захарова А.С., Вагина Е.С. ТРАНСПЛАНТОЛОГИЯ: ЮРИДИЧЕСКИЕ АСПЕКТЫ МЕДИЦИНСКОЙ ПРОБЛЕМЫ XXI ВЕКА // Духовная ситуация времени. Россия XXI век. 2015. № 1 (4). С. 44-45.

В статье рассматривается и анализируется понятие трансплантологии и юридическая возможность ее осуществления применительно к России и зарубежным странам. Затрагиваются вопросы правового регулирования трансплантологии международными нормативно-правовыми актами, а так же законодательством Российской Федерации.

https://elibrary.ru/item.asp?id=23528219

36. 042126
ИТОГИ 7-Й НАУЧНО-ПРАКТИЧЕСКОЙ КОНФЕРЕНЦИИ "МОСКОВСКАЯ ТРАНСПЛАНТОЛОГИЯ: ЖИЗНЬ ПОСЛЕ ТРАНСПЛАНТАЦИИ" // Трансплантология. 2017. Т. 9. № 2. С. 99-100.

https://elibrary.ru/item.asp?id=29381486

37. 042126
ИТОГИ 8-Й НАУЧНО-ПРАКТИЧЕСКОЙ КОНФЕРЕНЦИИ С МЕЖДУНАРОДНЫМ УЧАСТИЕМ "МОСКОВСКАЯ ТРАНСПЛАНТОЛОГИЯ. НАУЧНАЯ ШКОЛА ПО ТРАНСПЛАНТАЦИИ ПЕЧЕНИ" Трансплантология. 2018. Т. 10. № 3. С. 173-174.

https://elibrary.ru/item.asp?id=35655870

38. 040402
Камышный А.М. ВЛИЯНИЕ ЭКСПЕРИМЕНТАЛЬНОГО ГЕСТАЦИОННОГО ДИАБЕТА НА ЭКСПРЕССИЮ ИММУННОЙ СУБЪЕДИНИЦЫ ПРОТЕАСОМЫ LMP-2 И АУТОИММУННОГО РЕГУЛЯТОРА AIRE В ТИМУСЕ // Патогенез. 2014. Т. 12. № 2. С. 45-50.

Исследовались особенности экспрессии белка AIRE и иммунной субъединицы протеасомы LMP-2 в тимусе у потомства крыс с экспериментальным гестационным диабетом (ЭГД). Для определения AIRE и LMP-2 были применены методы иммуногистохимии и двойной иммунофлюоресценции с использованием моноклональных антител к AIRE, LMP-2, СD4-антигену и цитокератинам крысы. Установлено, что у потомства крыс с ЭГД наблюдаются изменения уровня экспрессии LMP-2 и AIRE в тимусе, что может оказывать влияние на представительство панкреатических антигенов и их процессинг, являясь факторами риска развития аутоиммунной патологии у потомства.

https://elibrary.ru/item.asp?id=24183923

39. 002190
Карпова Я.Д., Божок Г.А., Алабедалькарим Н.М., Люпина Ю.В., Астахова Т.М., Легач Е.И., Шарова Н.П. ПРОТЕАСОМЫ И ТРАНСПЛАНТОЛОГИЯ: СОВРЕМЕННОЕ СОСТОЯНИЕ ПРОБЛЕМЫ И ПОИСК ПЕРСПЕКТИВНЫХ НАПРАВЛЕНИЙ // Известия Российской академии наук. Серия биологическая. 2017. № 3. С. 218-227.

Проведен обзор фундаментальных исследований структуры и функций множественных форм протеасом. Дано описание протеасом печени, выполняющей функции первичного лимфоидного органа в эмбриональном периоде, обладающей неспецифическим локальным иммунитетом и обеспечивающей развитие толерантности к пищевым и другим чужеродным антигенам на протяжении всей жизни. Отмечены роль отдельных форм протеасом печени в трансплантологии и возможность использования их в качестве маркеров приживления эндокринных тканей.

https://elibrary.ru/item.asp?id=29431323

40. 000617
Карпова Я.Д., Люпина Ю.В., Алабедалькарим Н.М., Легач Е.И., Божок Г.А., Шарова Н.П. ИЗМЕНЕНИЕ СОДЕРЖАНИЯ МОНОНУКЛЕАРНЫХ КЛЕТОК ПЕЧЕНИ, ЭКСПРЕССИРУЮЩИХ ИММУННЫЕ ПРОТЕАСОМЫ, ПРИ ТРАНСПЛАНТАЦИИ ТКАНИ ЯИЧНИКОВ В ЗАВИСИМОСТИ ОТ ДОНОР-РЕЦИПИЕНТНЫХ РАЗЛИЧИЙ У КРЫС // Бюллетень экспериментальной биологии и медицины. 2018. Т. 165. № 6. С. 732-736.

Приживление аллотрансплантатов ткани яичников у аутбредных крыс Вистар и крыс инбредной линии Август на фоне индукции донор-специфической толерантности сопровождалось увеличением содержания мононуклеарных клеток в печени, экспрессирующих иммунную субъединицу LMP2 протеасом, к 37-м суткам после трансплантации по сравнению с нулевыми сутками. Отторжение трансплантата, напротив, было связано с уменьшением количества LMP2+-клеток в печени крыс обеих линий в этот период. Разница в содержании этих клеток и приживаемость трансплантата были выше у крыс Вистар. Количество мононуклеарных клеток печени, экспрессирующих иммунную субъединицу LMP7 протеасом, не изменялось у крыс обеих линий к 37-м суткам по сравнению с нулевыми сутками. Таким образом, уровень иммунных протеасом с субъединицей LMP2 в мононуклеарных клетках печени, по-видимому, связан с тонкими механизмами регуляции иммунных реакций и смещения их в сторону приживления или отторжения трансплантата.

https://elibrary.ru/item.asp?id=35055269

41. 000617
Карпова Я.Д., Люпина Ю.В., Астахова Т.М., Степанова А.А., Ерохов П.А., Абрамова Е.Б., Шарова Н.П. ИММУННЫЕ ПРОТЕАСОМЫ В РАЗВИТИИ ИММУННОЙ СИСТЕМЫ КРЫСЫ // Биоорганическая химия. 2013. Т. 39. № 4. С. 400.

В сыворотке крови больных плоскоклеточным раком головы и шеи на стадии T1N0М0 выявлено увеличение сывороточной активности протеасом по сравнению с пациентами с хроническими заболеваниями гортани и гортаноглотки, что свидетельствует о перспективности использования определения химотрипсинподобной активности сыворотки крови для дифференциальной диагностики, определения групп риска, оценки степени дифференцировки опухоли.

https://elibrary.ru/item.asp?id=27656301

42. 041195
Кочарян Е.З., Федоров Д.Н., Ахмедов Ш.М., Жидков И.Л., Ситниченко Н.В., Мухамедов И.Т., Корвяков В.С., Меланьин В.Д., Лекишвили М.В., Зелянин А.С., Бурмистрова Т.В. СРАВНИТЕЛЬНОЕ ИЗУЧЕНИЕ РЕГЕНЕРАЦИИ ТЕМЕННЫХ КОСТЕЙ КРОЛИКА ПОСЛЕ ПЛАСТИКИ ДЕФЕКТА ПЕРФООСТОМ, КОЛЛАПАНОМ-Д, АЛЛО- И АУТОХРЯЩОМ // Клиническая и экспериментальная морфология. 2016. № 4 (20). С. 43-48.

Аллогенные трансплантаты - перфоост, аллохрящ, а также искусственный материал коллапан-Д вызывают выраженную иммунную реакцию, вследствие которой происходит их деструкция, резорбция и замещение костной тканью. В то же время аутохрящ сохраняется практически в полном объеме, что позволяет использовать его при необходимости ревизии костных стенок полостей, например среднего уха. Замещение коллапана-Д происходит медленнее по сравнению с перфоостом.

https://elibrary.ru/item.asp?id=29946241

43. 000617
Кузина Е.С., Кудряева А.А., Мальцева Д.В., Белогуров А.А. ПЕПТИДИЛАЛЬДЕГИД, СПЕЦИФИЧЕСКИ ВЗАИМОДЕЙСТВУЮЩИЙ С ИММУНОСУБЪЕДИНИЦЕЙ ПРОТЕАСОМЫ B1I: ЭФФЕКТЫ IN VITRO И IN VIVO // Бюллетень экспериментальной биологии и медицины. 2016. Т. 161. № 1. С. 80-83.

Исследовано влияние b1i-специфического пептидилальдегида IPSI-001 на протеасому из клеток млекопитающих. В концентрациях менее 1 мкМ данный ингибитор эффективно подавлял иммунопротеасому и лишь незначительно снижал химотрипсинподобную активность конститутивной протеасомы. Интраперитонеальное введение данного ингибитора мышам линии C3H/He в дозе 100 мг/кг не приводило к значимым физиологическим и поведенческим изменениям, что свидетельствует о значительном терапевтическом потенциале данного соединения в терапии нейродегенеративных нарушений аутоиммунной природы.

https://elibrary.ru/item.asp?id=25284832

44. 000231
Лебедева А.И., Муслимов С.А., Щербаков Д.А. ИССЛЕДОВАНИЕ СПЕКТРА ПРО- И ПРОТИВОВОСПАЛИТЕЛЬНЫХ ЦИТОКИНОВ ПРИ РЕГЕНЕРАЦИИ СКЕЛЕТНОЙ МЫШЕЧНОЙ ТКАНИ ПОСЛЕ ПРИМЕНЕНИЯ АЛЛОГЕННЫХ ТРАНСПЛАНТАТОВ // Морфология. 2014. Т. 145. № 3. С. 113-114.

https://elibrary.ru/item.asp?id=30056561

45. Ли А.В. ТРАНСПЛАНТОЛОГИЯ: ПРОБЛЕМА ДЕФИЦИТА ДОНОРСКИХ ОРГАНОВ И АЛЬТЕРНАТИВНЫЕ ПУТИ ЕЕ РЕШЕНИЯ // Бюллетень медицинских интернет-конференций. 2014. Т. 4. № 11. С. 1181.

Вопрос о пересадке донорских органов и (или) тканей является одним из остро обсуждаемых во всем мире. Среди множества проблем трансплантологии нам хотелось бы обратить внимание на проблему дефицита донорских органов. Очевидно, что она индуцирует ряд других проблем, например, растущее утверждение механистического взгляда на тело человека как на машину, состоящую из «запчастей». Более того, не следует забывать, что вследствие дефицита донорских органов возник новый сегмент преступности – криминальный рынок человеческих органов.Если мы обратим внимание на состояние отечественной трансплантологии, то увидим, что проблема нехватки трансплантационного материала в России более чем актуальна. К тому же, по мнению Министерства здравоохранения, а также главного трансплантолога России Готье С. В. закон о трансплантологии от 1992 года “во многом устарел и стал тормозом развития нашей отрасли”. В связи с этим Минздрав РФ готовит законопроект на эту тему, который должен решить ряд проблем как медицинского, так и этико-правового характера.Альтернативными методами решения проблем нехватки донорских органов сейчас может являться замена нерабочего органа искусственным, использование стволовых клеток, а также замещение человеческих органов органами животных.Таким образом, необходимо более активно использовать альтернативные методы решения проблемы дефицита органов, помогая тем самым миллионам людей. Следует констатировать, что в современных дискуссиях по проблеме нехватки органов обычно муссируется идея о насущной необходимости морально-правовой системы, которая облегчала бы процесс изъятия органов от человека. На наш взгляд это слишком односторонне и акцент должен быть смещен в сторону поиска новых и интенсивного развития и внедрения существующих альтернатив трансплантации. В перспективе это позволит не только решить проблему дефицита донорских органов, но и избежать этически нежелательного механистического взгляда на человеческое тело.

https://elibrary.ru/item.asp?id=22860028

46. 000513
Люпина Ю.В., Богатырев М.Е., Орлова А.Ш., Марюхнич Е.В., Казанский Д.Б., Шарова Н.П. ПРОТЕАСОМЫ В ГОЛОВНОМ МОЗГУ МЫШЕЙ, НОКАУТНЫХ ПО 2-МИКРОГЛОБУЛИНУ // Биохимия. 2013. Т. 78. № 10. С. 1436-1447.

Молекулы ГКГ I играют важную роль в синаптической пластичности нервной системы млекопитающих. Протеолитические комплексы (протеасомы) образуют олигопептиды, презентируемые на поверхности клеток в составе молекул ГКГ I, и, помимо этого, регулируют многочисленные клеточные процессы. Исследованы особенности функционирования протеасом и связанные с ними сигнальные пути и сделана оценка экспрессии NeuN и gFAP в различных отделах головного мозга у мышей, нокаутных по ?2-микроглобулину, составной части молекул ГКГ I. Обнаружено, что фронтальная кора и ствол, структуры с разным соотношением экспрессии NeuN и gFAP, характеризуются противоположными изменениями в пулах протеасом при постоянном общем уровне протеасом у B2m-нокаутных мышей по сравнению с контрольными животными. В коре B2m-нокаутных мышей повышены ХТП-активность, экспрессия иммунной субъединицы LMP7 и регулятора РА28 протеасом, в то время как в стволе эти показатели снижены. Содержание сигнальных молекул nNOS и HSP70 в коре B2m-нокаутных мышей также повышено, а в стволе – снижено, что указывает на возможное контролирование ими экспрессии субъединицы LMP7 и регулятора РА28. Изменения в пуле протеасом стриатума B2m-нокаутных мышей сходны с таковыми в стволе. Вместе с тем, мозжечок характеризуется отличной от всех структур картиной функционирования протеасом. В нем повышена экспрессия иммунных субъединиц LMP7, LMP2 и регулятора РА28, но понижена экспрессия регулятора РА700. В большинстве отделов головного мозга B2m-нокаутных мышей обнаружен дефицит NeuN и gFAP. Таким образом, выявленные нарушения в структурах головного мозга, а также отсутствие в нем молекул ГКГ I компенсируются повышенной экспрессией иммунных субъединиц и регулятора РА28 протеасом в коре и мозжечке. По-видимому, это способствует образованию пептидов, важных для межклеточных взаимодействий, и поддержанию пластичности нервной системы у B2m-нокаутных мышей.

https://elibrary.ru/item.asp?id=20417621

47. 042215
Люпина Ю.В., Орлова А.Ш., Карпова Я.Д., Астахова Т.М., Шарова Н.П. ПРОТЕАСОМЫ И МОЛЕКУЛЫ ГЛАВНОГО КОМПЛЕКСА ГИСТОСОВМЕТИМОСТИ В РАЗВИТИИ ГОЛОВНОГО МОЗГА У МЛЕКОПИТАЮЩИХ // Медицинская иммунология. 2015. Т. 17. № S. С. 42.

https://elibrary.ru/item.asp?id=24498980

48. 000617
Маклакова И.Ю., Гребнев Д.Ю. ВЛИЯНИЕ СОЧЕТАННОЙ ТРАНСПЛАНТАЦИИ МУЛЬТИПОТЕНТНЫХ МЕЗЕНХИМНЫХ СТРОМАЛЬНЫХ И ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК НА РЕГЕНЕРАЦИЮ ГЕМОПОЭТИЧЕСКОЙ ТКАНИ // Бюллетень экспериментальной биологии и медицины. 2017. Т. 163. № 1. С. 73-77.

Изучено влияние аллогенной сочетанной трансплантации плацентарных мультипотентных мезенхимных стромальных и гемопоэтических стволовых клеток на регенерацию миелоидной ткани и селезенки после острой кровопотери у лабораторных мышей. Сочетанная трансплантация данных видов клеток в физиологических условиях не влияет на содержание цитогенетически измененных клеток в костном мозге, в то время как после острой кровопотери вызывает их снижение. Сочетанное введение мультипотентных мезенхимных стромальных и гемопоэтических стволовых клеток обеспечивает активацию эритропоэза и гранулоцитопоэза. В селезенке происходит уменьшение основных морфометрических и цитологических показателей белой пульпы, что может быть обусловлено иммуносупрессивным действием мультипотентных мезенхимных стромальных клеток.

https://elibrary.ru/item.asp?id=27656294

49. 043453
Маклакова И.Ю., Гребнев Д.Ю., Ястребов А.П. ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ ВЛИЯНИЯ СОЧЕТАННОЙ ТРАНСПЛАНТАЦИИ МУЛЬТИПОТЕНТНЫХ МЕЗЕНХИМАЛЬНЫХ СТРОМАЛЬНЫХ КЛЕТОК И ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК НА РЕГЕНЕРАЦИЮ ЭПИТЕЛИЯ КИШЕЧНИКА В УСЛОВИЯХ ВОЗДЕЙСТВИЯ ЭКСТРЕМАЛЬНЫХ ФАКТОРОВ // Успехи геронтологии. 2016. Т. 29. № 3. С. 433-436.

Изучали влияние сочетанной трансплантации мультипотентных мезенхимальных стромальных и гемопоэтических стволовых клеток на регенерацию эпителия кишечника в условиях воздействия экстремальных факторов. Получено, что в физиологических условиях и в условиях воздействия экстремальных факторов сочетанная трансплантация плацентарных мультипотентных мезенхимальных стромальных и гемопоэтических стволовых клеток у зрелых и старых животных сопровождается увеличением содержания эпителиоцитов крипт тощей кишки. В физиологических условиях у зрелых животных этот эффект реализуется через повышение пролиферативной активности эпителиоцитов, у старых животных - через ингибирование апоптоза. В условиях воздействия экстремальных факторов увеличение содержания клеточной популяции крипт у зрелых животных достигается за счет повышения пролиферативной активности и угнетения апоптоза эпителиоцитов, а в старом организме - за счет ингибирования апоптоза.

https://elibrary.ru/item.asp?id=26744147

50. Мухамедов И.И., Болатбеков Б.А., Баймагамбетов А.К., Джошибаев С. ТОРАКОСКОПИЧЕСКОЕ ЗАКРЫТИЕ ДЕФЕКТА МЕЖЖЕЛУДОЧКОВОЙ ПЕРЕГОРОДКИ СЕРДЦА: ПЕРВЫЙ ОПЫТ НАУЧНО-КЛИНИЧЕСКОГО ЦЕНТРА КАРДИОХИРУРГИИ И ТРАНСПЛАНТОЛОГИИ // Вестник Казахского Национального медицинского университета. 2016. № 4. С. 77-81.

Цель исследования - оценить результаты торакоскопичекой коррекции дефекта межжелудочковой перегородки. За период с июня 2015 по декабрь 2016 года изучены 8 пациентов, всем проведена полная торакоскопическая коррекция. Все операций были выполнены успешно. Послеоперационных осложнений не наблюдалось, конверсий в стандартный метод не было, без признаков остаточного шунта. Все пациенты были удовлетворены косметическим эффектом. Наш первый опыт торакоскопического закрытия дефекта межжелудочковой перегородки является осуществимым и безопасным. Данный метод может быть применен в клинической практике.

https://elibrary.ru/item.asp?id=32403862

51. 04617X
Нигматуллин Р.Т., Гизатуллина Э.Р., Мотыгуллин Б.Р. РОЛЬ МОНОЦИТАРНО-МАКРОФАГАЛЬНОЙ СИСТЕМЫ В ДИНАМИКЕ ЗАМЕСТИТЕЛЬНОЙ РЕГЕНЕРАЦИИ ПРИ ТРАНСПЛАНТАЦИИ ЭЛАСТИНОВОГО БИОМАТЕРИАЛА // Российский иммунологический журнал. 2017. Т. 11(20). № 2. С. 179-182.

В статье представлены результаты морфологических исследований при подкожной трансплантации двух видов эластинового биоматериала: структурированного и диспергированного (патент № 2440148). Эксперименты выполнены на крысах породы Вистар (n=59). Трансплантируемые биоматериалы подвергаются поэтапной резорбции с формированием соединительнотканного регенерата. При этом клетки макрофагального и фибробластического дифферонов выступают как единая морфофункциональная система, обязательным элементом которой являются гигантские многоядерные клетки. В зависимости от структуры биоматериала выделены два гистотопографических типа заместительной регенерации: фронтальный для структурированного и диффузно-локунарный - для диспергированного.

https://elibrary.ru/item.asp?id=29826641

52. 000231
Нигматуллин Р.Т., Щербаков Д.А., Мухаметов А.Р., Гизатуллина Э.Р. ТРАНСПЛАНТАЦИЯ ЭЛАСТИНОВОГО БИОМАТЕРИАЛА КАК ЭКСПЕРИМЕНТАЛЬНАЯ МОДЕЛЬ ЗАМЕСТИТЕЛЬНОЙ РЕГЕНЕРАЦИИ // Морфология. 2014. Т. 145. № 3. С. 140-141.

https://elibrary.ru/item.asp?id=30056645

53. 040402
Пальцын А.А., Свиридкина Н.Б. О РЕГЕНЕРАЦИИ МОЗГА (ЛЕКЦИЯ I) // Патогенез. 2017. Т. 15. № 4. С. 74-80.

В лекции рассматриваются общие вопросы регенерации мозга при патологических изменениях его в старости. Такие же изменения развиваются в мозге при многих самых распространенных болезнях современного человечества: атеросклероз, гипертоническая болезнь, воспалительные заболевания, диабет, рак, инсульт, саркопения, деменция. На большинстве территорий мозга нет постнатального обновления нейронов. На части этих территорий число нейронов в течение жизни остается неизменным, на других - уменьшается. В зонах постнатального нейрогенеза его скорость с возрастом снижается. Пропорционально возрасту уменьшается объем белого вещества, диаметр дендритов, нарастает демиелинизация. Уменьшается число синапсов и прочность синаптических контактов. Снижается скорость экспрессии генов и, прежде всего, генов, ответственных за клеточные коммуникации. Всё перечисленное действует в одном направлении, а именно нарушает суть нервной системы - нарушает связи. Решившись приняться за такую тему, как «Мозг, Старость, Регенерация» авторы пытались написать понятно и интересно для врачей и биологов любой специальности.

https://elibrary.ru/item.asp?id=32362009

54. 040949
Пронина Г.И., Корягина Н.Ю., Ревякин А.О., Капанадзе Г.Д., Степанова О.И., Курищенко Ж.О., Петрова Н.В. ВЛИЯНИЕ ТРАНСПЛАНТАЦИИ СТВОЛОВЫХ КЛЕТОК МЫШЕЙ НА РЕГЕНЕРАЦИЮ КОНЕЧНОСТЕЙ АКСОЛОТЛЕЙ // Биомедицина. 2015. № 4. С. 43-50.

Для изучения регенерации была ампутирована часть передней конечности аксолотлей до локтевого сустава. Выявлено, что ксенотрансплантация экспериментальным аксолотлям стволовых клеток мышей-доноров ускоряет регенерацию удаленных конечностей.

https://elibrary.ru/item.asp?id=26330252

55. 042215
Шарова Н.П., Карпова Я.Д., Божок Г.А., Астахова Т.М., Ерохов П.А., Алабедалькарим Н.М., Устиченко В.Д., Легач Е.И., Люпина Ю.В. ПРОТЕАСОМЫ ПЕЧЕНИ В РАННЕМ ОНТОГЕНЕЗЕИ РАЗВИТИИ ТОЛЕРАНТНОСТИ К ТРАНСПЛАНТАТУ // Медицинская иммунология. 2017. Т. 19. № S. С. 105.

https://elibrary.ru/item.asp?id=29758142

56. Шевченко О.П., Волкова Е.А. 30 ЛЕТ НАУЧНОЙ СПЕЦИАЛЬНОСТИ "ТРАНСПЛАНТОЛОГИЯ И ИСКУССТВЕННЫЕ ОРГАНЫ" (К 30-ЛЕТИЮ ДИССЕРТАЦИОННОГО СОВЕТА ПРИ ФЕДЕРАЛЬНОМ НАУЧНОМ ЦЕНТРЕ ТРАНСПЛАНТОЛОГИИ И ИСКУССТВЕННЫХ ОРГАНОВ ИМЕНИ АКАДЕМИКА В.И. ШУМАКОВА) // Вестник трансплантологии и искусственных органов. 2016. Т. 18. № 1. С. 6-8.

https://elibrary.ru/item.asp?id=25813820

57. 040991
Шевченко О.П., Стаханова Е.А. КЛИНИЧЕСКАЯ ТРАНСПЛАНТОЛОГИЯ, ИСКУССТВЕННЫЕ ОРГАНЫ, РЕГЕНЕРАТИВНАЯ МЕДИЦИНА -ТРИ СОСТАВЛЯЮЩИЕ ОДНОЙ НАУЧНОЙ СПЕЦИАЛЬНОСТИ (VIII ВСЕРОССИЙСКИЙ СЪЕЗД ТРАНСПЛАНТОЛОГОВ) // Вестник трансплантологии и искусственных органов. 2016. Т. 18. № 4. С. 6-10.

https://elibrary.ru/item.asp?id=28089497

58. 040991
Шевченко О.П., Цирульникова О.М., Стаханова Е.А., Улыбышева А.А. СОВРЕМЕННАЯ ТРАНСПЛАНТОЛОГИЯ: ПАМЯТНЫЕ ДАТЫ И НОВЕЙШИЕ ДОСТИЖЕНИЯ // Вестник трансплантологии и искусственных органов. 2017. Т. 19. № 4. С. 6-10.

https://elibrary.ru/item.asp?id=32352356

59. 042272
Юшков Б.Г. КЛЕТКИ ИММУННОЙ СИСТЕМЫ И РЕГУЛЯЦИЯ РЕГЕНЕРАЦИИ //Бюллетень сибирской медицины. 2017. Т. 16. № 4. С. 94-105.

Предложена теория иммунологической регуляции регенерации тканей. Дана оценка роли макрофагов, лимфоцитов, тучных клеток, тромбоцитов, эндотелиоцитов в восстановлении структуры функционального элемента поврежденного органа. Обсуждаются механизмы взаимодействия клеток иммунной системы в процессе регенерации. Представлены основные факторы, определяющие дифференцировку стволовых клеток. В качестве одного из компонентов восстановительного процесса рассматривается апоптоз.

https://elibrary.ru/item.asp?id=32521313

На главную К списку выставокАрхив выставок