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Objective: Malignancy following renal transplantation remains inconsistent with the reported safety of kidney donation during the long-term follow-up.Methods: We conducted searches of the published literature which included healthy participants, recipients, living kidney donors (LKDs), and the availability of outcome data for malignancy. Eight from 938 potentially relevant studies were analyzed by means of fixed-effects model or random-effects model, as appropriately.Results: In 48,950 participants, the follow-up range was 18 months to 20 years, and the mean age of the subjects was approximately 41 years. The incidence rate with 95% confidence interval (CI) for malignancy after kidney transplantation was 0.03 (0.01–0.05) in recipients and 0.03 (0.1–0.07) in LKDs, giving a pooled incidence rate of 0.03 (95% CI 0.02–0.04). LKDs contrasted nondonors by the overall odds ratio and 95% CI for total cancer of 2.80 (2.69–2.92).Conclusions: Kidney transplantation was associated with an increased risk of cancer during a long-term follow-up. Long-term risk for cancer in LKDs and kidney recipients should be monitored. [ABSTRACT FROM AUTHOR]

Autoimmune diabetes is a disorder of immune homeostasis that leads to targeted insulin-secreting islet β cell destruction characterized by insulitis. Human amylin (hA) is an important neuroendocrine hormone co-secreted with insulin by pancreatic β cells. Here, we report hA immune-modulatory action through inducing regulatory T cells. We ex vivo-treated human peripheral blood mononuclear cells (hPBMCs) with hA for 24 h and counted CD4+Foxp3+ regulatory T cells (Treg) using flow cytometry. Diabetic status was monitored and splenic Treg were measured in non-obese diabetic (NOD) male mice. NOD mice were intraperitoneally injected once daily with hA (n = 25) or solvent for control (n = 25) for 7 months continuously. Spleen tissues were collected at the end of intervention and processed for flow cytometry and Western blot. We found a 2.9-fold (p < 0.05) increase of CD4+Foxp3+ Treg in hPBMCs treated with 10 nmol/L hA compared with negative control. Incidence of diabetes in hA-treated NOD mice decreased 44% (p = 0.045) in the 6th month and 57% (p = 0.0002) in the 7th month. Meanwhile, the hA treatment induced a 1.5-fold increase of CD4+Foxp3+ Treg from mouse splenocytes (p = 0.0013). Expression of transforming growth factor-β (TGF-β) and toll-like receptor-4 (TLR-4) were upregulated in hA-treated mice. Human amylin might protect against autoimmune diabetes via the induction of CD4+Foxp3+ Treg, which suggests a novel approach to improve autoimmune conditions. [ABSTRACT FROM AUTHOR]

Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis. [ABSTRACT FROM AUTHOR]

Vinegar is a traditional remedy for ailments including diabetes. This study was conducted to investigate the beneficial effects of vinegar in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were orally administered with white rice vinegar (WRV, 2 ml/kg body weight per day, n = 6) or with an equal volume of drinking water ( n = 6) for 1 month. Fasting and random blood glucose was measured from tail vein samples. Body weight, 24-h food and water intake were monitored 1 week and 1 month after STZ injection. Fasting serum insulin concentrations were assayed using ELISA. Pancreatic beta- and alpha-cell proportions were measured using immunofluorescence microscopy. Periodic acid Schiff staining was performed to access glycogen contents and histological changes in liver tissues. Compared with control animals, the WRV-treated rats had less weight loss, lower fasting and random blood glucose, higher fasting serum insulin and higher beta-cell proportion. The WRV treatment also improved fatty changes and glycogen storages in the liver of STZ rats. Oral intake of WRV improved fasting hyperglycemia and body weight loss through attenuating insulin deficiency, pancreatic beta-cell deficit, and hepatic glycogen depletion and fatty changes in STZ-induced diabetic rats. [ABSTRACT FROM AUTHOR]

Tanshinone IIA (Tan IIA), a natural product from herb Salvia miltiorrhiza Bunge, has potential anti-tumor activity. The aim of this study was to pinpoint the molecular mechanisms underlying Tan IIA-induced cancer cell apoptosis. Human hepatoma BEL-7402 cells treated with Tan IIA underwent assessment with MTT assay for cell viability, 10-day culture for colony formation, flow cytometry and fluorescence microscopy for apoptosis and cell cycle analysis. Changes in intracellular [Ca] and mitochondrial membrane potential (∆ψ) reflected the calcium-dependent apoptosis pathway. RT-PCR was used to detect gene expression of Bad and metallothionein 1A (MT 1A). Cytotoxicity of Tan IIA was tested in human amniotic mesenchymal stem cells (HAMCs). Tan IIA exhibited dose-dependent and time-dependent anticancer effects on BEL-7402 cells through apoptosis and G/G arrest. Cells treated with Tan IIA increased their intracellular calcium, decreased their mitochondrial membrane potential and induced Bad and MT 1A mRNA expression. No adverse effects of Tan IIA were found in HAMCs. In conclusion, these results indicate that Tan IIA-induced cancer cell apoptosis acts via activation of calcium-dependent apoptosis signaling pathways and upregulation of MT 1A expression. [ABSTRACT FROM AUTHOR]

This longitudinal study addressed the sequential events and metabolic consequences of lipid partitioning following uninephrectomy. Adult male Sprague-Dawley rats were randomized into sham operation ( n = 15) or left uninephrectomy (UNX, n = 18). At 1 and 3 months post nephrectomy, three rats from each group were killed for histopathological examination of adipocyte differentiation and lipid accumulation. Renal protein expression of the lipogenic peroxisome proliferator-activated receptor-γ (PPAR-γ), HMG-CoA reductase (HMGCR), and adiponectin receptor was detected by Western blot and immunofluorescence microscopy. Blood lipids, glucose, insulin, and renal functions were longitudinally measured up to 10 months after operation. The UNX rats progressively developed lipodystrophy of subcutaneous and visceral adipose depots with failure of adipocyte differentiation and lipid storage, followed by blood lipid elevation and ectopic lipid deposition with cellular lipid peroxidation, and renal adipogenesis with chronic inflammatory infiltration. Despite having standard diet, normal food consumption and normal body weight, the uninephrectomized rats with defective lipid partitioning manifested a myriad of homeostatic disturbances including insulin resistance, hyperglycemia, adiponectin resistance, and upregulation of PPAR-γ and HMGCR. Abnormal lipid partitioning from adipose depots to circulation and non-adipose tissues and non-adipocytic cells contributes to homeostatic disturbances and lipogenic activation. [ABSTRACT FROM AUTHOR]

In skeletal muscle cells, insulin stimulates cytoskeleton actin remodeling to facilitate the translocation of glucose transporter GLUT4 to plasma membrane. Defect of insulin-induced GLUT4 translocation and actin remodeling may cause insulin resistance. Free fatty acids cause insulin resistance in skeletal muscle. The aim of this study was to investigate the effects of fatty acids on glucose transport and actin remodeling. Differentiated L6 muscle cells expressing c-myc epitope-tagged GLUT4 were treated with palmitic acid, linoleic acid and oleic acid. Surface GLUT4 and 2-deoxyglucose uptake were measured in parallel with the morphological imaging of actin remodeling and GLUT4 immunoreactivity with fluorescence, confocal and transmission electron microscopy. Differentiated L6 cells showed concentration responses of insulin-induced actin remodeling and glucose uptake. The ultrastructure of insulin-induced actin remodeling was cell projections clustered with actin and GLUT4. Acute and chronic treatment with the 3 fatty acids had no effect on insulin-induced actin remodeling and GLUT4 immunoreactivity. However, insulin-mediated glucose uptake significantly decreased by palmitic acid (25, 50, 75, 100 μmol/L), oleic acid (180, 300 μmol/L) and linoleic acid (120, 180, 300 μmol/L). Oleic acid (120, 300 μmol/L) and linoleic acid (300 μmol/L), but not palmitic acid, significantly decreased insulin-mediated GLUT4 translocation. These data suggest that fatty acids inhibit insulin-induced glucose transport associated with actin remodeling in L6 muscle cells. [ABSTRACT FROM AUTHOR]