Electrostimulation suppresses allograft rejection via promoting lymphatic regulatory T cell migration mediated by lymphotoxin - lymphotoxin receptor ß signaling.

Conventional immunosuppressants that suppress allograft rejection cause various side effects. Although regulatory T cells (Tregs) are essential for allograft survival, the limited efficacy of Treg therapy demands improvement. Thus, it is imperative to seek new approaches to enhancing Treg suppression. Low-intensity electrostimulation (ES) has been shown to exert antiinflammatory effects without causing major adverse reactions. However, it remains unknown whether and how ES regulates alloimmunity. Here, we found that regional ES delayed murine skin allograft rejection and promoted long-term allograft survival induced by an mTOR inhibitor, rapamycin. ES also extended islet allograft survival. Mechanistically, ES enhanced the expression of lymphotoxin α (LTα) on Tregs after transplantation. Blockade of lymphotoxin ß receptor-mediated nonclassical NFκB signaling suppressed lymphatic Treg migration and largely reversed the effects of ES on allograft survival. Moreover, ES failed to extend allograft survival when recipients lacked LTα/lymph nodes or if transferred Tregs lacked LTα. Therefore, ES promoted the lymphatic migration of CD4+Foxp3+ Tregs by upregulating their surface expression of LTα. Finally, ES augmented expression of LTα on murine or human Tregs, but not conventional T cells, while promoting their calcium influx in vitro. This ES-mediated upregulation of LTα relied on calcium influx. Thus, our findings have unveiled novel mechanisms underlying ES-mediated immunoregulation.

Endoplasmic reticulum stress signaling modulates ischemia/reperfusion injury in the aged heart by regulating mitochondrial maintenance.

Aging is associated with an increased risk of myocardial ischemia/reperfusion injury (IRI). With an increasing prevalence of cardiovascular diseases such as coronary arteriosclerosis in older people, there has been increasing interest in understanding the mechanisms of myocardial IRI to develop therapeutics that can attenuate its damaging effects. Previous studies identified that abnormal mitochondria, involved in cellar senescence and oxidative stress, are the master subcellular organelle that induces IRI. In addition, endoplasmic reticulum (ER) stress is also associated with IRI. Cellular adaptation to ER stress is achieved by the activation of ER molecular chaperones and folding enzymes, which provide an important link between ER stress and oxidative stress gene programs. In this review, we outline how these ER stress-related molecules affect myocardial IRI via the crosstalk of ER stress and mitochondrial homeostasis and discuss how these may offer promising novel therapeutic targets and strategies against age-related cardiovascular diseases.

Sirtuin 3 in renal diseases and aging: From mechanisms to potential therapies.

The longevity protein sirtuins (SIRTs) belong to a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases. In mammals, SIRTs comprise seven members (SIRT1-7) which are localized to different subcellular compartments. As the most prominent mitochondrial deacetylases, SIRT3 is known to be regulated by various mechanisms and participate in virtually all aspects of mitochondrial homeostasis and metabolism, exerting significant impact on multiple organs. Notably, the kidneys possess an abundance of mitochondria that provide substantial energy for filtration and reabsorption. A growing body of evidence now supports the involvement of SIRT3 in several renal diseases, including acute kidney injury, chronic kidney disease, and diabetic nephropathy; notably, these diseases are all associated with aging. In this review, we summarize the emerging role of SIRT3 in renal diseases and aging, and highlights the intricate mechanisms by which SIRT3 exerts its effects. In addition, we highlight the potential therapeutic significance of modulating SIRT3 and provide valuable insights into the therapeutic role of SIRT3 in renal diseases to facilitate clinical application.

Methyl eugenol protects the kidney from oxidative damage in mice by blocking the Nrf2 nuclear export signal through activation of the AMPK/GSK3ß axis.

Disrupted redox homeostasis contributes to renal ischemia-reperfusion (IR) injury. Abundant natural products can activate nuclear factor erythroid-2-related factor 2 (Nrf2), thereby providing therapeutic benefits. Methyl eugenol (ME), an analog of the phenolic compound eugenol, has the ability to induce Nrf2 activity. In this study, we investigated the protective effects of ME against renal oxidative damage in vivo and in vitro. An IR-induced acute kidney injury (AKI) model was established in mice. ME (20 mg·kg-1·d-1, i.p.) was administered to mice on 5 consecutive days before IR surgery. We showed that ME administration significantly attenuated renal destruction, improved the survival rate, reduced excessive oxidative stress and inhibited mitochondrial lesions in AKI mice. We further demonstrated that ME administration significantly enhanced Nrf2 activity and increased the expression of downstream antioxidative molecules. Similar results were observed in vitro in hypoxia/reoxygenation (HR)-exposed proximal tubule epithelial cells following pretreatment with ME (40 µmol·L-1). In both renal oxidative damage models, ME induced Nrf2 nuclear retention in tubular cells. Using specific inhibitors (CC and DIF-3) and molecular docking, we demonstrated that ME bound to the binding pocket of AMPK with high affinity and activated the AMPK/GSK3ß axis, which in turn blocked the Nrf2 nuclear export signal. In addition, ME alleviated the development of renal fibrosis induced by nonfatal IR, which is frequently encountered in the clinic. In conclusion, we demonstrate that ME modulates the AMPK/GSK3ß axis to regulate the cytoplasmic-nuclear translocation of Nrf2, resulting in Nrf2 nuclear retention and thereby enhancing antioxidant target gene transcription that protects the kidney from oxidative damage.

Early graft loss due to acute thrombotic microangiopathy accompanied by complement gene variants in living-related kidney transplantation: case series report.

BACKGROUND: Recently, early graft loss has become very rare in living-related kidney transplantation (LKT) as a result of decreased risk of hyperacute rejection and improvements in immunosuppressive regimens. Post-transplant acute thrombotic microangiopathy (TMA) is a rare, multi-factorial disease that often occurs shortly after kidney transplantation and is usually resistant to treatment with dismal renal outcomes. The complement genetic variants may accelerate the development of TMA. However, the complement genetic test was seldom performed in unknown native kidney disease recipients scheduled for LKT. CASE PRESENTATION: We reported three cases of unknown native kidney diseases who had fulminant TMA in the allograft shortly after LKT. Both the donors and the recipients were noted to carry complement genetic variants, which were identified by genetic testing after transplantation. However, all recipients were refractory to treatment and had allograft loss within 3 months after LKT. CONCLUSION: This case series highlights the suggestion to screen complement gene variants in both the donors and the recipients with unknown native kidney diseases scheduled for LKT.

[Effect of methyl eugenol on hypoxia/reoxygenation injury of human renal tubular epithelial cells and its mechanism].

This study aimed to investigate the effect of methyl eugenol(ME) on hypoxia/reoxygenation(H/R)-induced injury of human renal tubular epithelial HK-2 cells and its mechanism. The viability of HK-2 cells cultured with different concentrations of ME and exposed to H/R was detected by cell counting kit-8(CCK-8) assay. The effect of ME on the morphology of HK-2 cells was observed under an inverted microscope. The content of intracellular reactive oxygen species in different groups was detected after 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA) fluorescence staining. Cell apoptosis was determined by flow cytometry. Changes in mitochondrial membrane potential were monitored by JC-1 dye. The concentrations of nuclear factor erythroid 2 related factor 2(Nrf2), heme oxygenase-1(HO-1), and nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4) were measured by Western blot, followed by the assay of Nrf2 concentration changes in cytoplasm and nucleus by confocal fluorescence staining. The results showed that when the concentration of ME was 0-40 µmol·L~(-1), the activity of HK-2 cells was not affected. Compared with the model group, ME enhanced the activity of HK-2 cells and the cell morphology was normal. As revealed by further experiments, ME inhibited the release of reactive oxygen species and the decline in mitochondrial membrane potential of HK-2 cells after H/R injury, promoted Nrf2/HO-1 expression and Nrf2 translocation to the nucleus, and down-regulated the expression of Nox4, thereby significantly reducing apoptosis. This protective effect of ME could be reversed by the specific Nrf2 inhibitor ML385. These findings have preliminarily proved that ME effectively protected HK-2 cells against H/R injury, which might be related to its promotion of Nrf2/HO-1 signaling pathway and inhibition of Nox4. Such exploration on the possible mechanism of ME in the treatment of renal ischemia-reperfusion injury(IRI) and protection of organ function from the perspective of antioxidant stress has provided reference for related research on the treatment of acute kidney injury with traditional Chinese medicine.

Bone Marrow-Derived Mesenchymal Stem Cells Protect Islet Grafts Against Endoplasmic Reticulum Stress-Induced Apoptosis During the Early Stage After Transplantation.

Early loss of grafted islets is the main obstacle to achieve favorable outcomes of islet transplantation. Mesenchymal stem cells are known to have a protective effect; however, its mechanism remains unclear. We hypothesized that bone marrow-derived mesenchymal stem cells (BMSCs) can protect grafted islets against endoplasmic reticulum stress (ERS)-induced apoptosis. In syngeneic streptozocin-induced diabetic BALB/c mice, islet grafts decreased blood glucose levels; however, the effect was not fully functional from the immediate post-transplant phase. ß-Cell apoptosis was proven on days 1 and 3 after transplantation. Ultra-structural evidence of ERS was observed along with increased expressions of marker protein BIP and apoptosis-related protein CHOP. In contrast, BMSC co-transplantation maintained glucose hemostasis, inhibited apoptosis and alleviated ERS. In ex vivo culture, BMSCs improved viability of islets and decreased apoptosis. Increased ERS were observed in cultured islets exposed to hypoxia, but not in the islets cocultured with BMSCs. Furthermore, cocultured BMSCs protected islets against ERS-induced apoptosis as well as improved their insulin secretion, and BMSCs alleviated ERS by improving Myc expression through both stromal cell-derived factor 1 signal and contact effect. In conclusion, BMSCs protected the grafted islets against ERS-induced apoptosis during the early stage after transplantation. This study opens a new arena for ERS-targeted therapy to improve outcomes of islet transplantation. Stem Cells 2018;36:1045-1061.

Immunoregulatory effects of sirolimus vs. tacrolimus treatment in kidney allograft recipients.

The difference in immunoregulatory effects between sirolimus and tacrolimus on kidney transplantation remains unclear. In this study, a total of 18 living-donor-related kidney transplant recipients received sirolimus (n=8) or tacrolimus (n=10) treatment. Kidney function, acute rejection, peripheral blood CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs), CD19(+)CD5(+)CD1d(+) regulatory B cells (Bregs), and panel reactivity antibody were analyzed after one and three years. Th1/2 cell polarization was also determined at one year. The proportion of Tregs in the recipients receiving tacrolimus significantly decreased to 3.69% and 2.49% at one and three years, respectively, compared to 6.59% in controls, whereas the proportion in the recipients receiving sirolimus remained at 6.67% and 5.66%, respectively. However, no differences in kidney function, acute rejection, proportion of Bregs, panel reactivity antibody, or the frequencies of Th1/2 cells were identified. In conclusion, unlike tacrolimus, sirolimus maintains the proportion of Tregs in kidney transplant recipients.

Genetic and pharmacological targeting of XBP1 alleviates hepatic ischemia reperfusion injury by enhancing FoxO1-dependent mitophagy.

Hepatic ischemia reperfusion (I/R) injury is a common clinical complication. X-box binding protein 1 (XBP1), as a critical regulator of the endoplasmic reticulum stress, has been implicated in a variety of diseases. In this study, we aimed to investigate the effects and the underlying mechanism of XBP1 in the progression of hepatic I/R injury. Hepatocyte-specific XBP1 knockout mice, multiple viral delivery systems and specific pharmacological inhibitors were applied in vivo in a partial hepatic I/R injury mouse model and in vitro in a cell model of hypoxia-reoxygenation (H/R) injury. Mitophagy and autophagic flux were evaluated and fluorescence resonance energy transfer (FRET) as well as immunoprecipitation were performed. The results demonstrated that reperfusion for 6 h represented a critical timepoint in hepatic I/R injury and resulted in significant intracellular mitochondrial dysfunction; led to the breakdown of hepatocytes accompanied by the highest expression levels of XBP1. Hepatocyte-specific XBP1 knockout alleviated hepatic I/R injury via enhanced mitophagy, as demonstrated by the reduction in hepatocellular damage/necrosis and increased expression of mitophagy markers. Mechanistically, XBP1 interacted with FoxO1 directly and catalyzed the ubiquitination of FoxO1 for proteasomal degradation. Targeting XBP1 by genetic or pharmacological techniques potentiated the protein levels of FoxO1, further promoting the activity of the PINK1/Parkin signaling pathway, thus augmenting mitophagy and exerting hepatoprotective effects upon I/R injury. In conclusion, the inhibition of XBP1 potentiated FoxO1-mediated mitophagy in hepatic I/R injury. Specific genetic and pharmacological treatment targeting XBP1 in the perioperative 6 h prior to reperfusion exerted beneficial effects, thus providing a novel therapeutic approach.

XBP1 Modulates the Aging Cardiorenal System by Regulating Oxidative Stress.

X-box binding protein 1 (XBP1) is a unique basic-region leucine zipper (bZIP) transcription factor. Over recent years, the powerful biological functions of XBP1 in oxidative stress have been gradually revealed. When the redox balance remains undisturbed, oxidative stress plays a role in physiological adaptations and signal transduction. However, during the aging process, increased cellular senescence and reduced levels of endogenous antioxidants cause an oxidative imbalance in the cardiorenal system. Recent studies from our laboratory and others have indicated that these age-related cardiorenal diseases caused by oxidative stress are guided and controlled by a versatile network composed of diversified XBP1 pathways. In this review, we describe the mechanisms that link XBP1 and oxidative stress in a range of cardiorenal disorders, including mitochondrial instability, inflammation, and alterations in neurohumoral drive. Furthermore, we propose that differing degrees of XBP1 activation may cause beneficial or harmful effects in the cardiorenal system. Gaining a comprehensive understanding of how XBP1 exerts influence on the aging cardiorenal system by regulating oxidative stress will enhance our ability to provide new directions and strategies for cardiovascular and renal safety outcomes.

Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation.

Introduction: Porcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear. Methods: We retrospectively analyzed 12 kidney transplant recipients receiving pALG, and additional recipients receiving rabbit anti-human thymocyte immunoglobulin (rATG), basiliximab, or no induction therapy as a comparison group. Results: pALG showed high binding affinity to peripheral blood mononuclear cells (PBMCs) after administration, immediately depleting blood lymphocytes; an effect that was weaker than rATG but stronger than basiliximab. Single-cell sequencing analysis showed that pALG mainly influenced T cells and innate immune cells (mononuclear phagocytes and neutrophils). By analyzing immune cell subsets, we found that pALG moderately depleted CD4+T cells, CD8+T cells, regulatory T cells, and NKT cells and mildly inhibited dendritic cells. Serum inflammatory cytokines (IL-2, IL-6) were only moderately increased compared with rATG, which might be beneficial in terms of reducing the risk of untoward immune activation. During 3 months of follow-up, we found that all recipients and transplanted kidneys survived and showed good organ function recovery; there were no cases of rejection and a low rate of complications. Discussion: In conclusion, pALG acts mainly by moderately depleting T cells and is thus a good candidate for induction therapy for kidney transplant recipients. The immunological features of pALG should be exploited for the development of individually-optimized induction therapies based on the needs of the transplant and the immune status of the patient, which is appropriate for non-high-risk recipients.

XBP1 modulates endoplasmic reticulum and mitochondria crosstalk via regulating NLRP3 in renal ischemia/reperfusion injury.

The functional status of mitochondria and the endoplasmic reticulum are central to renal ischemia/reperfusion injury (IRI). X-box binding protein 1 (XBP1) is an important transcription factor in endoplasmic reticulum stress. NLR family pyrin domain containing-3 (NLRP3) inflammatory bodies are closely related to renal IRI. In vivo and in vitro, we examined the molecular mechanisms and functions of XBP1-NLRP3 signaling in renal IRI, which influences ER-mitochondrial crosstalk. In this study, mice were subjected to 45 min of unilateral renal warm ischemia, the other kidney resected, and reperfusion was performed for 24 h in vivo. In vitro, murine renal tubular epithelial cells (TCMK-1) were exposed to hypoxia for 24 h and reoxygenation for 2 h. Tissue or cell damage was evaluated by measuring blood urea nitrogen and creatinine levels, histological staining, flow cytometry, terminal deoxynucleotidyl transferase-mediated nick-end labeling, diethylene glycol staining, and transmission electron microscopy (TEM). Western blotting, immunofluorescence staining, and ELISA were used to analyze protein expression. Whether XBP1 regulates the NLRP3 promoter was evaluated using a luciferase reporter assay. Kidney damage was reduced with decreasing blood urea nitrogen, creatinine, interleukin-1ß, and interleukin-18 levels. XBP1 deficiency reduced tissue damage and cell apoptosis, protecting the mitochondria. Disruption of XBP1 was associated with reduced NLRP3 and cleaved caspase-1 levels and markedly improved survival. In vitro in TCMK-1 cells, XBP1 interference inhibited caspase-1-dependent mitochondrial damage and reduced the production of mitochondrial reactive oxygen species. The luciferase assay showed that spliced XBP1 isoforms enhanced the activity of the NLRP3 promoter. These findings reveal that XBP1 downregulation suppresses the expression of NLRP3, a potential regulator of endoplasmic reticulum mitochondrial crosstalk in nephritic injury and a potential therapeutic target in XBP1-mediated aseptic nephritis.

Sirolimus in combination with low-dose extended-release tacrolimus in kidney transplant recipients.

Introduction: Many challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival. Methods: This retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months. Results: There was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection (p = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m2 vs. 56.97 ± 19.23 ml/min/1.73 m2, p < 0.05). The medication adherence at 12 months after conversion was superior to before conversion (p = 0.002). Discussion: Our findings suggest that an immunosuppressive regimen of SRL combined with low-dose ER-TAC is no less effective and safe than standard immunosuppressive regimens for renal transplant recipients and may improve graft renal function and medication adherence.

Values of Donor Serum Lipids and Calcium in Predicting Graft Function after Kidney Transplantation: A Retrospective Study.

OBJECTIVE: Delayed graft function (DGF) and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor. As "non-traditional" risk factors, serum biomarkers of donors, such as lipids and electrolytes, have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts. This study aimed to examine the value of these serum biomarkers for prediction of renal graft function. METHODS: The present study consecutively collected 306 patients who underwent their first single kidney transplantation (KT) from adult deceased donors in our center from January 1, 2018 to December 31, 2019. The correlation between postoperative outcomes [DGF and abnormal serum creatinine (SCr) after 6 and 12 months] and risk factors of donors, including gender, age, body mass index (BMI), past histories, serum lipid biomarkers [cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (DL)], and serum electrolytes (calcium and sodium) were analyzed and evaluated. RESULTS: (1) Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level (≥2 mg/dL) at 6 and 12 months after KT (P<0.05); (2) The donor's BMI was significantly correlated with the incidence rate of DGF after KT (P<0.05); (3) For serum lipids, merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT [P<0.05, OR (95% CI): 0.425 (0.202-0.97)]; (4) The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT [P<0.05, OR (95% CI): 0.184 (0.045-0.747) and P<0.05, OR (95% CI): 0.114 (0.014-0.948), respectively]. CONCLUSION: The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT, in addition to the donor's age, BMI and pre-existing hypertension.

Role of the PI3K/Akt signaling pathway in liver ischemia reperfusion injury: a narrative review.

OBJECTIVE: To explore the role of phosphatidylinositol-3-kinase/protein kinase B and alpha serine/threonine protein kinase PI3K/PKB (also known as PI3K/Akt) signaling pathway in liver ischemia reperfusion injury. BACKGROUND: The PI3K/Akt signaling pathway is one of the major signal transduction pathways that regulates numerous cellular activities in vivo. The main functions of this pathway include induction of stem cell differentiation and metastasis, promotion of cell proliferation, inhibition of apoptosis, and regulation of tissue inflammation, tumor growth, and invasion. Liver ischemia reperfusion injury is an inevitable clinical problem that can occur during liver transplantation, liver resection, and various circulatory shock events, and it is one of the primary reasons for postoperative liver dysfunction, and poor disease outcome and patient prognosis. In recent years, it has been found that PI3K/Akt signaling pathway is closely related to liver ischemia reperfusion injury. METHODS: In this review, a large number of relevant literatures were collected to explain the biological basis of PI3K/Akt signaling pathway and its role in liver ischemia reperfusion injury. The review was based on a PubMed search using the terms "liver ischemia reperfusion injury", "PI3K/Akt signaling pathway", and "PI3K/Akt signaling pathway AND liver ischemia reperfusion injury", so as to understand the complex interaction between them. CONCLUSIONS: Activated PI3K/Akt signaling pathway can exert anti-inflammatory, antioxidant stress, anti-apoptosis and autophagy regulation effects through downstream related targeted pathways and proteins, thus alleviating liver ischemia-reperfusion injury. Therefore, the regulation of PI3K/Akt signaling pathway is expected to become an effective targeted pathway for clinical prevention and alleviation of liver ischemia reperfusion injury.

Prevention of alloimmune rejection using XBP1-deleted bone marrow-derived dendritic cells in heart transplantation.

BACKGROUND: Genetically modified dendritic cells (DCs) modulate the alloimmunity of T lymphocytes by regulating antigen presentation. METHODS: We generated mice with specific deletion of the X-box-binding protein 1 (XBP1) allele in bone marrow cells and cultured bone marrow-derived DCs (Xbp1-/- BMDCs) from these animals. We then tested the phenotype of Xbp1-/- BMDCs, evaluated their capability to activate allogeneic T cells and investigated their mechanistic actions. We developed a mouse model of allogeneic heart transplantation in which recipients received PBS, Xbp1-/- BMDCs, a suboptimal dose of cyclosporine A (CsA), or Xbp1-/- BMDCs combined with a suboptimal dose of CsA to evaluate the effects of Xbp1-/- BMDC transfusion on alloimmunity and on the survival of heart allografts. RESULTS: The deletion of XBP1 in BMDCs exploited the IRE1-dependent decay of TAPBP mRNA to reduce the expression of MHC-I on the cell surface, altered the capability of BMDCs to activate CD8+ T cells, and ultimately suppressed CD8+ T-cell-mediated allogeneic rejection. The adoptive transfer of Xbp1-/- BMDCs inhibited CD8+ T-cell-mediated rejection. In addition, XBP1-deficient BMDCs were weak stimulators of allogeneic CD4+ T cells despite expressing high levels of MHC-II and costimulatory molecules on their cell surface. Moreover, the adoptive transfer of Xbp1-/- BMDCs inhibited the production of circulating donor-specific IgG. The combination of Xbp1-/- BMDCs and CsA treatment significantly prolonged the survival of allografts compared to CsA alone. CONCLUSIONS: The deletion of XBP1 induces immunosuppressive BMDCs, and treatment with these immunosuppressive BMDCs prevents alloimmune rejection and improves the outcomes of heart transplantation. This finding provides a promising therapeutic target in combating transplant rejection and expands knowledge of inducing therapeutic DCs.

[Histopathologic analysis of 1500 renal allograft biopsies].

OBJECTIVE: To summarize the histopathological features of posttransplant complications for renal allografts and evaluate the biopsy values. METHODS: Between January 1997 and May 2010, a total of 1712 percutaneous renal allograft biopsies were performed in 1500 kidney transplants and diagnostic procedures for staining, classification and staging had been performed according to the Banff 1997 and 2005 Schema. RESULTS: There were 213 (14.2%) cases of acute T cell-mediated rejection post transplantation in 1500 kidney transplants. Meanwhile there were 36 (2.4%) cases of acute antibody-mediated rejection. Chronic T cell-mediated rejection and chronic antibody-mediated rejection were 251 (16.7%) cases and 45 (3.0%) cases, respectively. Acute CNI-nephrotoxicity and chronic CNI-nephrotoxicity were 106 (7.1%)cases and 251 (16.7%) cases, respectively. Relapsed or new nephropathy were 6 (0.4%) cases. Chronic CNI-nephrotoxicity is the most common cause of allograft dysfunction in the long survival recipients. CONCLUSION: Percutaneous renal allograft biopsy is valuable for the diagnosis of various posttransplantation complications.

[Histopathological study of 268 hepatic allograft biopsies].

OBJECTIVE: To observe the histopathological features of posttransplant complications for hepatic allografts and evaluate their biopsy values. METHODS: From January 1999 to May 2011, a total of 268 percutaneous hepatic allograft biopsies were conducted in 207 recipients and the diagnostic procedures for staining, classification and staging performed according to the Banff schema and Chinese Schema on hepatic allograft rejection. RESULTS: Among them, there were ischemia/reperfusion injury (n = 26, 9.7%), acute T cell-mediated rejection (n = 83, 31.0%), acute antibody-mediated rejection (n = 12, 4.5%), chronic posttransplantation rejection (n = 31, 11.6%), immunosuppressive-induced liver injury (n = 70, 26.1%) and recurrent diseases (n = 18, 6.7%). Acute T cell-mediated rejection and drug-induced liver injury were two most common causes of allograft dysfunctions. CONCLUSION: Percutaneous hepatic allograft biopsy is valuable for the diagnosis and evaluation of various posttransplantation complications.

Muscle multiorgan crosstalk with MG53 as a myokine for tissue repair and regeneration.

Through stress and injury to tissues, the cell membrane is damaged and can lead to cell death and a cascade of inflammatory events. Soluble factors that mitigate and repair membrane injury are important to normal homeostasis and are a potential therapeutic intervention for regenerative medicine. A myokine is a type of naturally occurring factors that come from muscle and have impact on remote organs. MG53, a tripartite motif-containing family protein, is such a myokine which has protective effects on lungs, kidneys, liver, heart, eye, and brain. Three mechanisms of action for the beneficial regenerative medicine potential of MG53 have been identified and consist of 1) repair of acute injury to the cellular membrane, 2) anti-inflammatory effects associated with chronic injuries, and 3) rejuvenation of stem cells for tissue regeneration. As such, MG53 has the potential to be a novel and effective regeneration medicine therapeutic.

Long-Term Clinical and Immunological Impact of Severe COVID-19 on a Living Kidney Transplant Recipient - A Case Report.

The long-term impact of COVID-19 on transplant recipients remains unknown. We describe the case of a 30-year-old male kidney transplant recipient from Wuhan, China that was treated for severe COVID-19 in February 2020. He suffered an acute lung and renal injury and required systemic treatment including adjustment of his immunosuppressant regime. He was followed up to 1-year after discharge. No chronic lung fibrosis or deterioration of his pulmonary function was observed. Despite COVID-19 mediated damage to his renal tubular cells, no transplant rejection occurred. His immunological profile demonstrated both cellular anti-SARS-CoV-2 reactivity and specific humoral immunity, indicating that it is beneficial for the transplanted patients to be immunized with SARS-CoV-2 virus vaccine. This case will help guide clinical decision making for immunocompromised individuals that become infected with SARS-CoV-2.