Follicular dendritic cells.

Follicular dendritic cells (FDCs) are unique accessory immune cells that contribute to the regulation of humoral immunity. They are multitasker cells essential for the organization and maintenance of the lymphoid architecture, induction of germinal center reaction, production of B memory cells, and protection from autoimmune disorders. They perform their activities through both antigen-driven and chemical signaling to B cells. FDCs play a crucial role in the physiological regulation of the immune response. Dis-regulation of this immune response results when FDCs retain antigens for years. This provides a constant antigenic stimulation for B cells resulting in the development of immune disorders. Antigen trapped on FDCs is resistant to therapeutic intervention causing chronicity and recurrences. Beyond their physiological immunoregulatory functions, FDCs are involved in the pathogenesis of several immune-related disorders including HIV/AIDS, prion diseases, chronic inflammatory, and autoimmune disorders. FDCs have also been recently implicated in rare neoplasms of lymphoid and hematopoietic tissues. Understanding FDC biology is essential for better control of humoral immunity and opens the gate for therapeutic management of FDC-mediated immune disorders. Thus, the biology of FDCs has become a hot research area in the last couple of decades. In this review, we aim to provide a comprehensive overview of FDCs and their role in physiological and pathological conditions.

Hydrogen sulfide renal protective effects: possible link between hydrogen sulfide and endogenous carbon monoxide in a rat model of renal injury.

Hydrogen sulfide (H2S), along with nitric oxide (NO) and carbon monoxide (CO), proved to have renoprotective effects in various renal diseases. Therefore, this study investigated the renoprotective effect of H2S, in a renal injury model, and its crosstalk with other gasotransmitters such as CO. Thirty-two adult rats were divided into four groups: control, gentamicin (GEN)-treated, GEN + sodium hydrosulfide (NaHS), and GEN + NaHS + zinc protoporphyrin (ZnPP) groups. GEN was used to induce renal injury, NaHS is a water-soluble H2S, and ZnPP is a selective heme oxygenase-1 (HO-1) inhibitor used to inhibit CO synthesis in vivo. NaHS improved kidney functions in the GEN group as evidenced by significantly lower levels of renal injury markers: serum urea, creatinine, uric acid, urinary albumin excretion, and urinary albumin/creatinine. Moreover, NaHS administration to the GEN-treated group significantly lowered renal levels of NO and tumor necrosis factor-α with an increase in total antioxidant, HO-1, and interleukin-10 levels. Furthermore, NaHS administration downregulated the GEN-induced overexpression of the renal inducible nitric oxide synthase (iNOS) and upregulated the suppression of endothelial nitric oxide synthase (eNOS) with improvement in the histological examination and periodic acid Schiff (PAS) staining. However, this improvement in kidney function produced by NaHS was reduced by combination with ZnPP but still improved as compared with the GEN-treated group. The renoprotective effects of H2S can be through its effects on renal tissue antioxidants, pro-inflammatory and anti-inflammatory cytokines, and expression of eNOS and iNOS which can be partially dependent on CO pathway via induction of HO-1 enzyme.

Antioxidant, anti-inflammatory, and anti-apoptotic effects of zinc supplementation in testes of rats with experimentally induced diabetes.

One of the major obstacles that males with diabetes may confront is subfertility or infertility. Thus, the present study investigated the effect of co-administration of metformin and zinc (Zn) on the testes of streptozotocin-induced diabetic rats. Male albino rats were randomly divided into 4 groups: control group; untreated diabetic group; diabetic + metformin group, in which diabetic rats were treated orally with metformin (250 mg/kg) once daily for 4 weeks; and diabetic + metformin + Zn group, in which diabetic rats were treated orally with metformin in combination with Zn (10 mg/kg) once daily for 4 weeks. Concomitant administration of metformin and Zn produced a significant decrease in serum levels of glucose and insulin and testicular levels of malondialdehyde and tumor necrosis factor α. Additionally, there was a significant increase in serum levels of Zn, testosterone, and follicle-stimulating hormone, as well as testicular total antioxidant capacity and anti-apoptotic protein Bcl-2, when compared with both the diabetic and metformin-treated diabetic groups. Moreover, co-administration of Zn and metformin significantly improved testicular histopathology, with a significant reduction in percent area of collagen fibers and nuclear factor kappa B (p65) immunoreactivity and a significant increase in seminiferous tubule diameter and connexin 43 immunoreactivity as compared with the diabetic and metformin-treated diabetic groups. In conclusion, the combination of Zn and metformin was an efficacious and safe alternative treatment, as it had superior antihyperglycemic efficacy and provided additional benefits over metformin alone in rats with type 2 diabetes.

Protective effect of C-peptide on experimentally induced diabetic nephropathy and the possible link between C-peptide and nitric oxide.

Diabetic nephropathy one of the major microvascular diabetic complications. Besides hyperglycemia, other factors contribute to the development of diabetic complications as the proinsulin connecting peptide, C-peptide. We described the role of C-peptide replacement therapy on experimentally induced diabetic nephropathy, and its potential mechanisms of action by studying the role of nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its production by NG-nitro-l-arginine methyl ester (L-NAME). Renal injury markers measured were serum urea, creatinine, tumor necrosis factor alpha, and angiotensin II, and malondialdehyde, total antioxidant, Bcl-2, and NO in renal tissue. In conclusion, diabetic induction resulted in islet degenerations and decreased insulin secretion with its metabolic consequences and subsequent renal complications. C-Peptide deficiencies in diabetes might have contributed to the metabolic and renal error, since C-peptide treatment to the diabetic rats completely corrected these errors. The beneficial effects of C-peptide are partially antagonized by L-NAME coadministration, indicating that NO partially mediates C-peptide effects.