Impact of varied immunosuppressive agents and post-transplant diabetes mellitus on prognosis among diverse transplant recipients (experimental studies).

The success of solid organ transplantation (SOT) and the use of immunosuppressive agents offer hope to patients with end-stage diseases. However, the impact of post-transplant diabetes mellitus (PTDM) on SOT patients has become increasingly evident. In our study, we utilized the Scientific Registry of Transplant Recipients (SRTR) database to investigate the association between PTDM and patient survival in various types of organ transplantations, including liver, kidney, intestinal, heart, lung, and combined heart-lung transplantations (all P <0.

Intragraft B cell differentiation during the development of tolerance to kidney allografts is associated with a regulatory B cell signature revealed by single cell transcriptomics.

Mouse kidney allografts are spontaneously accepted in select, fully mismatched donor-recipient strain combinations, like DBA/2J to C57BL/6 (B6), by natural tolerance. We previously showed accepted renal grafts form aggregates containing various immune cells within 2 weeks posttransplant, referred to as regulatory T cell-rich organized lymphoid structures, which are a novel regulatory tertiary lymphoid organ. To characterize the cells within T cell-rich organized lymphoid structures, we performed single-cell RNA sequencing on CD45 sorted cells from accepted and rejected renal grafts from 1-week to 6-months posttransplant.

Adjuvant conditioning induces an immunosuppressive milieu that delays alloislet rejection through the expansion of myeloid-derived suppressor cells.

Advances in immunosuppression have been relatively stagnant over the past 2 decades, and transplant recipients continue to experience long-term morbidity associated with immunosuppression regimens. Strategies to reduce or eliminate the dosage of immunosuppression medications are needed. We discovered a novel administration strategy using the classic adjuvant alum to condition murine islet transplant recipients, known as adjuvant conditioning (AC), to expand both polymorphonuclear and monocytic myeloid-derived suppressive cells (MDSCs) in vivo.

Novel intragraft regulatory lymphoid structures in kidney allograft tolerance.

Intragraft events thought to be relevant to the development of tolerance are here subjected to a comprehensive mechanistic study during long-term spontaneous tolerance that occurs in C57BL/6 mice that receive life sustaining DBA/2 kidneys. These allografts rapidly develop periarterial Treg-rich organized lymphoid structures (TOLS) that form in response to class II but not to class I MHC disparity and form independently of lymphotoxin α and lymphotoxin β receptor pathways. TOLS form in situ in the absence of lymph nodes, spleen, and thymus.

Kidney-induced systemic tolerance of heart allografts in mice.

In swine and nonhuman primates, kidney allografts can induce tolerance of heart allografts, leading to their long-term, immunosuppression-free survival. We refer to this phenomenon as kidney-induced cardiac allograft tolerance (KICAT). In this study, we have developed a murine model for KICAT to determine the underlining cellular/molecular mechanisms.

PARP-1 inhibitor-AG14361 suppresses acute allograft rejection via stabilizing CD4+FoxP3+ regulatory T cells.

Acute allograft rejection is the most common complication in organ transplantation leading to organ loss. Treg cells play an important role in preventing acute rejection, but they are unstable and easily lose function. Poly(ADP-ribose) polymerase 1(PARP-1) is involved in the differentiation stabilization of Treg cells, it has been suggested that PARP-1 inhibition could prevent acute rejection and prolong allograft survival.

Plasmacytoid Dendritic Cell-driven Induction of Treg Is Strain Specific and Correlates With Spontaneous Acceptance of Kidney Allografts.

Background: DBA/2J kidney allografts, but not heart allografts, are spontaneously accepted indefinitely in C57BL/6 (B6) mice, through regulatory tolerance mechanism dependent on Foxp3 cells. In contrast, B6 kidneys are rejected within a week in DBA/2J recipients. We hypothesized that the tolerogenic difference of the kidneys might be due to differences in number or function of plasmacytoid dendritic cells (pDCs), because these cells are potent inducers of Foxp3 cells.

Recruited T cells promote the bladder cancer metastasis via up-regulation of the estrogen receptor β/IL-1/c-MET signals.

Clinical data indicates that T cells can be recruited to bladder cancer (BCa), yet the impact of T cells on BCa progression remains unclear. In the present study, we found that T cells were recruited more to BCa tissues than to the surrounding normal bladder tissues. Results from an in vitro co-culture system also found that BCa recruited more CD4 T cells than did normal bladder cells.

Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell renal cell carcinoma progression.

Objectives: Clear cell renal cell carcinoma (ccRCC) is characterized histologically by accumulation of cholesterol esters, cholesterol and other neutral lipids. Lysosomal acid lipase (LAL) is a critical enzyme involved in the cholesterol ester metabolism. Here, we sought to determine whether LAL could orchestrate metabolism of cholesterol esters in order to promote ccRCC progression.

microRNA-495 promotes bladder cancer cell growth and invasion by targeting phosphatase and tensin homolog.

Accumulating evidence has linked deregulation of microRNA-495 (miR-495) to tumorigenesis; however, its function in tumor progression is controversial. This work was undertaken to explore the expression and biological roles of miR-495 in bladder cancer. The expression of miR-495 was examined in 67 pairs of bladder cancer and adjacent normal bladder tissues.

The platelet isoform of phosphofructokinase contributes to metabolic reprogramming and maintains cell proliferation in clear cell renal cell carcinoma.

Metabolic alterations underlying clear cell renal cell carcinoma (ccRCC) progression include aerobic glycolysis, increased pentose phosphate pathway activity and reduced oxidative phosphorylation. Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L, M, and P isoforms with different tissue distributions. The mRNA level of the platelet isoform of phosphofructokinase (PFKP) is reported to be up-regulated in ccRCC patients.

Differential microRNA expression in aristolochic acid-induced upper urothelial tract cancers ex vivo.

Aristolochic acid (AA) is a carcinogenic, mutagenic and nephrotoxic compound commonly isolated from members of the plant family of Aristolochiaceae (such as Aristolochia and Asarum) and used in Chinese herbal medicine. Use of AA and AA‑containing plants causes chronic kidney disease (CKD) and upper urinary tract carcinoma (UUC); however, the underlying mechanism remains to be defined. miRNAs regulate a number of biological processes, including cell proliferation, differentiation and metabolism.

Inguinal and subinguinal micro-varicocelectomy, the optimal surgical management of varicocele: a meta-analysis.

Conventional meta-analyses have shown inconsistent results for the efficacy of various treatments of varicoceles. Therefore, we performed a multiple-treatment meta-analysis to assess the effectiveness and safety of 10 methods of varicocelectomy and embolization/sclerotherapy. We systematically reviewed 35 randomized controlled trials and observational studies, from 1966 to August 5, 2013, which compared any of the following treatments for varococeles: laparoscopic, retroperitoneal, open inguinal and subinguinal varicocelectomy, microsurgical subinguinal and inguinal varicocelectomy, percutaneous venous embolization, Tauber antegrade sclerotherapy, retrograde sclerotherapy and expectant therapy (no treatment).