Due to the easier availability of transgenic mice and reagents, the mouse orthotopic liver transplantation model offers significant advantages in liver transplantation research. However, technical challenges have limited its broader application. The most challenging steps of the procedure include manual anastomosis of the suprahepatic vena cava, cuff anastomosis of the portal vein, and maintaining the anhepatic phase within 20 minutes. This study aims to provide detailed solutions to overcome these bottlenecks and introduces a modified magnetic device to facilitate safer and more efficient cuff anastomosis. We also describe the learning curve for beginners to achieve a 30-day survival rate exceeding 90% in mouse orthotopic liver transplantation. We demonstrate that mouse orthotopic liver transplantation can be mastered within 8 months of continuous practice, with 7-day and 30-day survival rates improving from 0% to 96.7% and 0% to 93.3%, respectively. The entire procedure can be completed within 80 minutes. We believe these technical improvements will provide more practical guidance for mouse liver transplantation.

The BK virus has become a substantial threat to transplanted kidneys. Yet, the present understanding of the clinical course and postoperative management of BK virus infections remains inadequate. Here, we report a case of a male transplant recipient with rapid graft loss due to BK virus-associated nephropathy after the second renal transplant, who had previously experienced failure of his first kidney allograft for the same reason. The posttransplant period was uneventful until serum creatinine rose to 2.30 mg/dL on postoperative day 59. Puncture biopsy was postponed because of swelling in the transplanted kidney, and acute rejection was considered as a source of the swelling because the repetitive results of blood BK virus DNA tests were negative. Methylprednisolone 500 mg was administered empirically for 3 days, followed by a 5-day course of anti-thymocyte globulin 100 mg. On postoperative day 83, SV40 T-antigen antibody immunostaining confirmed the diagnosis of BK virus nephropathy. However, it took only 28 days for this patient to progress from abnormal kidney function to the loss of the secondary transplanted kidney, and dialysis was initiated on postoperative day 87. To our knowledge, this is the first report of BK virus resulting in acute failure of a transplanted kidney. An early biopsy is crucial, and a negative test for viremia is not sufficient to exclude the recurrence of BK virus.

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with few effective treatments. In its pathogenesis, damage-associated molecular patterns are released and recognized by Toll-like receptors (TLRs); all TLRs except TLR3 transduce signals through MyD88. Research has shown that autophagy participates in the progression of pulmonary fibrosis, and MyD88 is closely associated with autophagy. However, whether targeting MyD88 can affect fibrosis progression by regulating autophagy during lung fibrosis remains unclear. Materials and Methods: TJ-M2010-5 (TJ-5) is a small molecular derivative of aminothiazole that inhibits MyD88 homodimerization. A bleomycin-induced pulmonary fibrosis model in mice was established, and a human lung fibroblast cell line MRC-5 was cultured, and the mechanism of fibrosis induced by TGF-β1 was studied. TJ-5 and the autophagy inhibitor 3-MA were used to intervene. Results: Our study indicated that TJ-5 suppressed fibrosis foci formation and collagen deposition in fibrotic lungs, effectively increased the survival rate of bleomycin-stimulated mice from 40.0% to 80.0%, and repressed lung fibroblast activation in vitro. Subsequently, TJ-5 could trigger autophagy, as indicated by increased autophagosomes, LC3B-II and Beclin-1 promotion, and p62 degradation. Moreover, inhibition of TJ-5-induced autophagy by 3-MA reversed the anti-fibrosis effect of TJ-5. Furthermore, the autophagy-related pathways PI3K/AKT/mTOR and MAPK/mTOR were inhibited under TJ-5 intervention. Conclusions: Our findings demonstrated that the mechanism of TJ-5 in alleviating lung fibrosis was through triggering MyD88-related autophagy, and TJ-5 may be therapeutically useful for the clinical treatment of IPF.

INTRODUCTION:Trace elements in the environment are considered significant risk factors for chronic liver disease. However, the impact of blood metal levels on the incidence of liver fibrosis or cirrhosis has not been fully assessed. Our study investigated the correlation between metal mixture exposure and liver fibrosis/cirrhosis as well as the mediating effect between non-alcoholic fatty liver disease (NAFLD) and liver fibrosis/cirrhosis. METHODS:We conducted a cross-sectional study using the National Health and Nutrition Examination Survey database from 2017 to 2020. Transient elastography was used to identify NAFLD and liver fibrosis or cirrhosis. Various statistical models have been applied to evaluate the relationship between blood metal mixtures and liver fibrosis/cirrhosis. The role of metal mixtures in NAFLD-associated liver fibrosis/cirrhosis was explored using a mediation analysis. RESULTS:In the fully adjusted logistic models, selenium was negatively correlated with liver fibrosis [odds ratio (OR) = 0.219, P = 0.039) and cirrhosis (OR = 0.007, P = 0.003). In the weighted quantile sum and quantile-based g-computation models, selenium showed the highest contribution to liver fibrosis (0.544 and 0.578) and cirrhosis (0.538 and 0.630, respectively). Bayesian kernel machine regression and restricted cubic splines models indicated an L-shaped association between selenium and liver fibrosis/cirrhosis. Selenium negatively mediated the relationship between NAFLD and liver fibrosis/cirrhosis according to the mediation analysis (-3.4% and -13.3%). CONCLUSIONS:Selenium shows an L-shaped relationship with liver fibrosis and cirrhosis and plays a negative mediating role in the association between NAFLD and liver fibrosis/cirrhosis. Blood selenium is a promising biomarker for chronic liver diseases, and supplemental selenium intake might contribute to the prevention and management of liver fibrosis/cirrhosis.

Chronic kidney disease (CKD) is now an unquestionable progressive condition that affects more than 10% of the general population worldwide, and has emerged as one of the most important causes of global mortality. It is clear that the prevalence of CKD among the aging population is significantly elevated. It involves a broad range of complex and poorly understood concerns in older adults such as frailty, malnutrition, sarcopenia, and even cognitive and mental dysfunction. In kidneys, renal function such as glomerular filtration, urine concentration and dilution, and homeostasis of sodium and potassium, can be influenced by the aging process. In addition, it is worth noting that CKD and end-stage kidney disease patients often have accompanying activation of immune system and inflammation, involving both the innate and adaptive immune system. Based on this background, in this review article we attempt to summarize the epidemiological characteristics of CKD in the aging population, discuss the immunological mechanisms in aging-related CKD, and furnish the reader with processes for the therapy and management of elderly patients with CKD.

Purpose: This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) to assess the kidneys' quality before procurement.Methods: This prospective study included 74 donors and 148 recipients of kidneys.119 kidneys underwent quantitative analysis.Before organ procurement, potential kidney donors underwent CEUS, though organ procurement involved a zero-point puncture biopsy.CEUS parameters of the renal cortex and medulla were evaluated, including rise time (RT), time to peak (TTP), the area under the curve (AUC), wash-in slope (WIS), peak intensity (PI), and mean transit time (MTT).Donors' kidneys were classified based on their pathological.Additionally, short-term clinical indicators of renal recipients were collected and analyzed to determine whether the patients had delayed recovery of renal allograft function.Results: This experiment included 148 cases of kidney information, divided into two groups based on the Remuzzi score of the kidneys.However, 29 kidneys were excluded from the quantitative analysis due to loss or low quality of CEUS images.Comparing the time-intensity curve (TIC) of renal cortical region of interest (ROI), we found that the group with lower pathological scores exhibited higher PI (P=0.002),AUC(P=0.003), and WIS (P=0.009).TIC comparison results for renal medulla ROI revealed that the group with lower pathological scores had higher PI (P=0.010),AUC (P=0.023), and WIS (P=0.024).Conclusions: This study highlighted the potential of CEUS as a non-invasive, safe, and real-time examination method that correlates with the Remuzzi score and renal pathology.Therefore, it can be used as a prospective preoperative non-invasive evaluation method for the donor's kidney.

BACKGROUND:Acute vascular rejection (AVR) and systemic inflammation in xenograft recipients (SIXR) negatively impact the xenografts survival, and novel immunosuppressants are required to improve survival outcomes. We previously reported that TJ-M2010-5, a myeloid differentiation factor 88 (MyD88) inhibitor, exerts excellent anti-rejection effects in allogeneic transplantation. The aim of the present study was to evaluate the efficacy of TJ-M2010-5 in preventing AVR and SIXR and to investigate whether combined treatment of TJ-M2010-5 with anti-CD154 antibody (MR1) could prolong xenograft survival furthermore.METHODS:A model involving heart transplantation from Sprague-Dawley rats to BALB/c mice was established in vivo, and the xenografts developed typical AVR. Bone marrow-derived dendritic cells and macrophages were cultured to study the underlying mechanisms induced by rat cardiomyocyte lysate stimulation in vitro.RESULTS:TJ-M2010-5 monotherapy prolonged xenograft survival, although combination treatment with MR1 further enhanced the anti-AVR and anti-SIXR effects with about 21 days graft survival, compared to monotherapy. TJ-M2010-5 reduced dendritic cell and macrophage activation induced by xenotransplantation, downregulated CD80/CD86 expression, suppressed B-cell activation and anti-donor antibody generation, reduced pro-inflammatory cytokine production and tissue factor expression, and attenuated epigenetic modifications underlying interleukin-6 and tumor necrosis factor-α production in macrophages by inhibiting nuclear factor kappa B nuclear translocation.CONCLUSIONS:TJ-M2010-5 attenuated AVR and SIXR and contributed to xenograft survival by inhibiting dendritic cell and macrophage activation. A dual-system inhibition strategy combining TJ-M2010-5 with anti-CD154 antibody achieved better results in xenotransplantation.

Renal transplantation is one of the primary approaches for curing end-stage kidney disease. With advancements in immunosuppressive agents, the short-term and long-term survival rates of transplanted kidneys have significantly improved. However, infections associated with potent immunosuppression have remained a persistent challenge. Among them, BK virus (BKV) reactivation following renal transplantation leading to BK virus-associated nephropathy (BKVAN) is a major cause of graft dysfunction. However, we still face significant challenges in understanding the pathogenesis, prevention, diagnosis, and treatment of BKVAN. These challenges include: 1. The mechanism of BKV reactivation under immunosuppressive conditions has not been well elucidated, leading to difficulties in breakthroughs in clinical research on prevention, diagnosis, and treatment. 2. Lack of proper identification of high-risk individuals, and effective personalized clinical management strategies. 3.Lack of early and sensitive diagnostic markers. 4. Lack of direct and effective treatment options due to the absence of specific antiviral drugs. The purpose of this review is to summarize the current status and cutting-edge advancements in BKV-related research, providing new methods and perspectives to address future research challenges.

Background:While immunosuppressive regimens have improved outcomes in solid organ transplantation, non-immune factors have also been identified as contributors to graft prognosis. Age, gender, hormones, heredity, and other diseases have been recognized to affect organ transplantation. However, the causal relationship between blood lipids and graft dysfunction remains unverified in human clinical investigations. In this study, we employed two-sample Mendelian randomization (MR) to examine the causality between different types of blood lipids and graft dysfunction following organ and tissue transplantation.Methods:We conducted a two-sample MR study using available genome-wide association summary data from the online database MRBASE (http://app.mrbase.org/), which encompasses over 11 billion associations between genetic factors and health-related outcomes, enabling researchers to explore various potential determinants of poor health. The exposure factors included four types of blood lipids: high-density lipoprotein, low-density lipoprotein, cholesterol, and triglycerides. For each exposure factor, three databases were selected for analysis. The outcome factor was the failure and rejection of transplanted organs and tissues. All databases consisted of European population samples, without specific subgroups. The related studies were conducted between 2016 and 2022, and the "TwoSampleMR" R package was employed for variant selection.Results:A total of 13 sample groups were collected and analyzed. The results revealed a causal association between blood lipids and graft dysfunction following organ and tissue transplantation. Specifically, the two-sample MR analysis confirmed that low-density lipoprotein and cholesterol levels were significant risk factors for increased graft dysfunction risk after transplantation. Moreover, high-density lipoprotein potentially reduced the risk of allograft dysfunction, while triglycerides possibly elevated the risk.Conclusions:Our recent study provides the initial confirmation that blood lipids may initiate causal pathological processes leading to graft dysfunction after organ and tissue transplantation.

Background. With the development of medical technology and increased surgical experience, the number of patients receiving liver transplants has increased. However, restoration of liver function in patients is limited by the occurrence of hepatic ischemia-reperfusion injury (IRI). Previous studies have reported that the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway and pyroptosis play critical roles in the development of hepatic IRI. Methods. A mouse model of segmental (70%) warm hepatic IRI was established using BALB/c mice in vivo. The mechanism underlying inflammation in mouse models of hepatic IRI was explored in vitro using lipopolysaccharide- and ATP-treated bone marrow-derived macrophages. This in vitro inflammation model was used to simulate inflammation and pyroptosis in hepatic IRI. Results. We found that a MyD88 inhibitor conferred protection against partial warm hepatic IRI in mouse models by downregulating the TLR4/MyD88 signaling pathway. Moreover, TJ-M2010-5 (a novel MyD88 inhibitor, hereafter named TJ-5) reduced hepatic macrophage depletion and pyroptosis induction by hepatic IRI. TJ-5 treatment inhibited pyroptosis in bone marrow-derived macrophages by reducing the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells, decreasing the release of high-mobility group box-1, and promoting endocytosis of lipopolysaccharide-high-mobility group box-1 complexes. Conclusions. Inhibition of MyD88 may protect the liver from partial warm hepatic IRI by reducing pyroptosis in hepatic innate immune cells. These results reveal the mechanism underlying the development of inflammation in partially warm hepatic IRI and the induction of cell pyroptosis.

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.

This review summarizes the clinical data of one pediatric liver transplant recipient and two adult kidney transplant recipients with posterior reversible encephalopathy syndrome(PRES)at Tongji Hospital of Huazhong University of Science & Technology.The relevant clinical characteristics of recipients are discussed for providing reference for clinical diagnoses and treatments.

目的 探讨肾移植术后多瘤病毒相关性肾病(PyVN)的临床病理学特征及预后.方法 回顾性分析 44 例肾移植术后确诊PyVN患者的临床资料,分析患者穿刺原因及病理学诊断时间.按Banff 2018 标准进行组织学分级,比较各级患者临床资料及病理特征.分析患者血、尿BK病毒DNA载量及移植肾功能.比较各组患者的预后情况,分析影响预后的危险因素.结果 患者病理诊断PyVN距肾移植手术时间为16(8,29)个月,血清肌酐升高为穿刺的主要原因.44例患者中,PyVN 1 级19例、2级21例、3级4例,各组光学显微镜下病毒包涵体阳性率差异无统计学意义(P=0.148),2 级患者炎症细胞浸润、间质纤维化、肾内多瘤病毒载量均多于或高于 1 级患者,3 级患者炎症细胞浸润及肾内多瘤病毒载量多于或高于 1 级患者,3 级患者肾内多瘤病毒载量多于或高于 2 级患者,差异均有统计学意义(均为P<0.05/3).确诊时 39 例患者具有血、尿BK病毒DNA载量检测记录,其中 38 例尿BK病毒阳性,30 例血BK病毒阳性.患者确诊PyVN时血清肌酐较术后 1 个月升高,末次随访时血清肌酐较确诊PyVN时升高,差异均有统计学意义(P<0.001、P=0.049).不同级别PyVN患者术后1 个月血清肌酐差异无统计学意义(P=0.554),确诊时 2 级患者血清肌酐水平高于 1 级患者(P=0.007).肾移植术后1、3、5年移植肾累积存活率分别为95％、69％、62％,不同分级PyVN间移植肾存活率差异有统计学意义,分级越高,存活率越低(P=0.014).单因素和多因素Cox回归分析提示肾内多瘤病毒载量、确诊时血清肌酐水平为移植肾失功的独立危险因素(均为P<0.05).结论 PyVN多发生在肾移植术后 2 年内,临床表现以血清肌酐升高、BK病毒血症和BK病毒尿症为主,术后常规监测BK病毒有利于早期诊断并保护移植肾,Banff 2018 分级标准可有效预测移植肾预后.

Background: Cerebral ischemia-reperfusion injury (CIRI) inevitably occurs after vascular recanalization treatment for ischemic stroke. The accompanying inflammatory cascades have a major impact on outcome and regeneration after ischemic stroke. Evidences have demonstrated that TLR/MyD88/NF-κB signaling contributes to CIRI. This study aimed to investigate the druggability of MyD88 in the central nervous system (CNS) and the neuroprotective and anti-neuroinflammatory effects of the MyD88 inhibitor TJ-M2010-5 on CIRI.Methods: A middle cerebral artery occlusion (MCAO) model was used to simulate CIRI in mice. BV-2 cells were stimulated with oxygen glucose deprivation/reoxygenation (OGD/R) or lipopolysaccharide, and SH-SY5Y cells were induced by OGD/R in vitro. Neurological deficit scores and cerebral infarction volumes were evaluated. Immunofluorescence staining was performed to measure neuronal damage and apoptosis in the brain. The anti-neuroinflammatory effect of TJ-M2010-5 was evaluated by analyzing the expression of inflammatory cytokines, activation of microglia, and infiltration of peripheral myeloid cells. The expression of proteins of the MyD88/NF-κB and ERK pathway was detected by Simple Western. The concentrations of TJ-M2010-5 in the blood and brain were analyzed by liquid chromatography-mass spectrometry.Results: The cerebral infarction volume decreased in mice treated with TJ-M2010-5, with the most prominent decrease being approximately 80% of the original infarction volume. Neuronal loss and apoptosis were reduced following TJ-M2010-5 treatment. TJ-M2010-5 inhibited the infiltration of peripheral myeloid cells and the activation of microglia. TJ-M2010-5 also downregulated the expression of inflammatory cytokines and inhibited the MyD88/NF-κB and ERK pathway. Furthermore, TJ-M2010-5 showed good blood-brain barrier permeability and no neurotoxicity.Conclusion: TJ-M2010-5 has an excellent therapeutic effect on CIRI as a novel CNS drug candidate by inhibiting excessive neuroinflammatory responses.

Objective This study investigated the composition of pathogenic microorganisms, clinical features, and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor (DD) kidneys. Methods We retrospectively studied the clinical data of the DD kidney transplant recipients with donor-associated infection at Tongji Hospital, Wuhan, China from January 1, 2015 to December 31, 2018, related recipients and corresponding donors. We collected the entire results of pathogenic microorganisms cultured from these related ruptured kidneys and then analyzed their distribution and differences. Results A total of 1440 kidney transplants from DD were performed in our center. The total incidence of infective artery rupture in kidney transplants was about 0.76% (11/1440), and the annual incidence ranged from 0.25% to 1.03%. The microbial culture results revealed that 11 recipients suffered from infective artery rupture and 3 recipients who accepted the kidney from same donor had the donor-associated pathogens, including 9 fungal strains (28.1%) and 23 bacterial strains (71.9%). There were 4 recipients infected with multi-drug-resistant Staphylococcus and Klebsiella pneumoniae from the above 11 recipients, of which, 10 recipients underwent graft loss, and one died of septic shock. The microbial cultures of the remaining 3 recipients who received appropriate anti-infective regimens turned negative eventually, and the patients were discharged successfully without significant complications. Conclusion Renal recipients with infections derived from DDs were at high risk of artery rupture, graft loss, or even death. Appropriate anti-infective treatment is essential to reduce the incidence of artery rupture and mortality.

Liver fibrosis is the result of most chronic inflammatory liver damage and seriously endangers human health. However, no drugs have been approved to treat this disease. Previous studies showed that the Toll‐like receptors (TLRs)/myeloid differentiation factor-88 (MyD88)/nuclear factor-κB (NF-κB) pathway plays a key role in liver fibrosis. TJ-M2010-5 is a self-developed small molecule MyD88 inhibitor, which has been proven to have a good protective effect in a variety of inflammatory disease models. In the present study, to investigate the anti-fibrotic effect of TJ-M2010-5, mice were injected with carbon tetrachloride (CCl4) in vivo and LX2 cells (a human hepatic stellate cell line) were treated with TGF-β1 in vitro to induce liver fibrosis. In vivo studies showed that TJ-M2010-5 attenuated the CCl4-induced liver damage, collagen accumulation, and the activation of hepatic stellate cells by inhibiting the nuclear transfer of NF-κB. Moreover, in vitro experiments of LX2 cells stimulated with TGF-β1 further indicated that the NF-κB pathway is involved in the development of liver fibrosis. TJ-M2010-5 significantly inhibited the proliferation and activation of LX2 cells. In addition, TJ-M2010-5 upregulated the expression of bone morphogenetic protein and membrane-bound inhibitor (BAMBI) in LX2 cells by blocking the activation of MyD88/NF-κB, thereby inhibiting the phosphorylation of Smad2/3 and the expression of collagen I (COL1A1) induced by TGF-β1. In conclusion, this study illustrates the anti-hepatic fibrosis effect of TJ-M2010-5 and provides a new treatment method for liver fibrosis.

Cardiac arrhythmias (CAs) are generally caused by disruption of the cardiac conduction system; interleukin-2 (IL-2) is a key player in the pathological process of CAs. This study aimed to investigate the molecular mechanism underlying the regulation of IL-2 and the sodium channel current of sodium voltage-gated channel beta subunit 3 (SCN3B) by miR-190a-5p in the progression of CAs. ELISA results suggested the concentration of peripheral blood serum IL-2 in patients with atrial fibrillation (AF) to be increased compared to that in normal controls; fluorescence in situ hybridization indicated that the expression of IL-2 in the cardiac tissues of patients with AF to be upregulated and that miR-190a-5p to be downregulated. Luciferase reporter assay, quantitative real-time-PCR, and whole-cell patch-clamp experiments confirmed the downregulation of IL-2 by miR-190a-5p and influence of the latter on the sodium current of SCN3B. Overall, miR-190a-5p suppressed the increase in SCN3B sodium current caused by endogenous IL-2, whereas miR-190a-5p inhibitor significantly reversed this effect. IL-2 was demonstrated to be directly regulated by miR-190a-5p. We, therefore, concluded that the miR-190a-5p/IL-2/SCN3B pathway could be involved in the pathogenesis of CAs and miR-190a-5p might acts as a potential protective factor in pathogenesis of CAs.

Cardiac fibrosis is a significant global health problem associated with almost all types of heart disease. Extensive cardiac fibrosis reduces tissue compliance and contributes to adverse outcomes, such as cardiomyocyte hypertrophy, cardiomyocyte apoptosis, and even heart failure. It is mainly associated with pathological myocardial remodeling, characterized by the excessive deposition of extracellular matrix (ECM) proteins in cardiac parenchymal tissues. In recent years, a growing body of evidence demonstrated that microRNAs (miRNAs) have a crucial role in the pathological development of cardiac fibrosis. More than sixty miRNAs have been associated with the progression of cardiac fibrosis. In this review, we summarized potential miRNAs and miRNAs-related regulatory mechanisms for cardiac fibrosis and discussed the potential clinical application of miRNAs in cardiac fibrosis.

Background: The acute ischemia-reperfusion injury that occurs after an ischemic stroke is almost inevitable. In treating ischemic stroke, the prevention and treatment of cerebral ischemia-reperfusion injury (CIRI) is an undeniable difficulty clinically. Despite increasing studies being done on the subject, medicines showing effective neurological improvements after reperfusion is still minimal. This study aims to investigate the effects of a self-developed MyD88 inhibitor (TJ-M2010-5) on CIRI and its mechanism. Methods: The middle cerebral artery occlusion (MCAO) model was used to simulate CIRI in mice. BV-2 cells were cultured for the mechanism study by LPS stimulation in vitro. Neurological deficit score and cerebral infarction volume were studied. Immunofluorescence staining was used to measure neuronal damage and apoptosis in the brain. The anti-inflammation effect of TJ-M2010-5 was evaluated by analyzing the expression of inflammatory cytokines, activation of microglia and infiltration of peripheral myeloid cells. The expression of TLR4/Myd88/NF-κB signaling pathway protein was detected by Simple Western. The concentrations of TJ-M2010-5 in blood and brain were analyzed by LC-MS methods. Results: The cerebral infarction volume decreased in mice treated with TJ-M2010-5, with the most prominent decrease in approximately 80% of the original infarction volume. Moreover, the downregulation of apoptosis and NeuN protein expression in the brain of infarction area further indicated that neuronal damage was alleviated. TJ-M2010-5 treatment also reduced the infiltration ratio of peripheral myeloid cells in the cerebral infarction area and increased the proportion of inactive microglia. The inflammatory cytokines decreased after TJ-M2010-5 treatment in infarction area and supernatant. TJ-M2010-5 downregulated the expression of iNOS and inhibited TLR4/MyD88/NF-κB signaling pathway in vivo and in vitro. In addition, TJ-M2010-5 could freely pass through the blood-brain barrier. Conclusions: TJ-M2010-5 has shown to have an excellent therapeutic effect on CIRI by inhibiting TLR4/Myd88/NF-κB signaling pathway to decrease excessive inflammatory response, showing the potential to change the history that there is no effective medicine for the treatment of CIRI. and also has the potential to be utilized in brain neuroinflammatory diseases.

Objective:To summarize the medium-term outcomes of single kidney transplantation from senile deceased donors aged above 65 years.Methods:Forty-three kidney recipients from donors aged above 65(old-aged donor group, OAD) and 43 kidney recipients of the same age and gender from donors aged 18 to 49 years(standard-criteria donor group, SCD) were retrospectively reviewed.The survival outcomes of patients and grafts, renal functions, the incidence of delayed graft function(DGF)and other complications were recorded within the 3-year follow-up post-transplantation.Results:The 3-year patient survival rates were 95.3% both in OAD and SCD and the 3-year death-censored graft survival rates 92.7% and 97.6% respectively.The serum levels of creatinine were significantly higher in OAD than that in SCD( P<0.05). And lower estimated glomerular filtration rate(eGFR)was found in OAD as compared with SCD( P<0.05). No significant difference existed in the incidence of DGF(OAD 20.9% and SCD 18.6%, P>0.05), acute rejection (OAD 4.7% and SCD 2.3%, P>0.05)or proteinuria(OAD 27.9%and SCD 14.0%, P>0.05). Conclusions:Single kidney transplantation from old-aged deceased donors may achieve excellent medium-term survival outcomes of patients and grafts.It can expand the donor pool though kidney functions were not as good as those of SCD.