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Abstract Testicular impairment is a common complication of Diabetes mellitus (DM). Zinc Oxide Nanoparticles (ZnO NPs) are a novel agent for Zn delivery with antidiabetic and antioxidant activities. However, few reports were recorded on it. The current study aimed to investigate the possible ameliorating effect of ZnO NPs treatment on testicular tissues alterations in streptozotocin (STZ)-induced diabetic rats. Therefore, thirty mature male Wistar rats were divided into three main groups: Control group (n = 18) was subdivided equally into three subgroups (negative control, vehicle and ZnO NPs), Diabetic group (n = 6) and ZnO NPs-treated diabetic group (n = 6). Induction of diabetes was done by a single intraperitoneal injection of STZ (60 mg/kg bw). The rats were orally treated by ZnO NPs (10 mg/kg bw) for 30 constitutive days. At the end of the experiment, blood glucose and serum testosterone levels were measured. Also, testicular tissues were obtained for histopathological investigations and immunohistochemical staining with anti-PCNA (proliferating cell marker), anti-ssDNA (apoptotic cell marker), anti-SOX9 (Sertoli cell marker), anti-Stella (spermatogonia marker), anti-STRA8 (preleptotene and early-leptotene spermatocytes marker), anti-DMC1 (leptotene and zygotene spermatocytes marker), anti-Dnmt3a (a marker for cells under DNA methylation) and anti-α-SMA (peritubular myoid cell marker). The biochemical analysis revealed that diabetes resulted in a significant elevation in blood glucose level and a reduction in serum testosterone level. Moreover, histopathological investigations revealed disorganized seminiferous epithelium and sever hyalinization with vacuolization of the testicular interstitium containing Leydig cells. The immunohistochemical findings support spermatogenesis impairment in the diabetic group. However, ZnO NPs treatment restores architecture of seminiferous epithelium and Leydig cells. Furthermore, more PCNA, SOX9, Stella, STRA8, DMC1 and Dnmt3a immunopositive cells with an improvement of peritubular α-SMA immunopositive expression, as well as few ssDNA-immunopositive cells were detected in the seminiferous epithelium. This study suggested the possible protective role of orally administered ZnO NPs on testicular alterations in the STZ-induced diabetic group via steroidogenesis and spermatogenesis enhancement. In addition, further researches are acquired for evaluation mechanism of ZnO NPs treatment via oral or parenteral routes in a dose-dependent manner to identify the more effective route and dose in the treatment of testicular diabetic complications. [ABSTRACT FROM AUTHOR]

Functional hematopoiesis is governed by the bone marrow (BM) niche, which is compromised by radiotherapy, leading to radiation induced BM failure. The aim of this study was to demonstrate the radiation induced pathological remodeling of the niche and the efficacy of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in restoring hematopoiesis via improvement of the niche. Thirty male Wistar rats were equally assigned to three groups: control (CON), irradiated (IR), and IR+hUCB‐MSCs. Biochemical, histopathological and immunohistochemical analyses were performed to detect collagen type III and IV, Aquaporin 1+ sinusoidal endothelial cells and immature hematopoietic cells, CD11c+ dendritic cells, Iba1+ macrophages, CD9+ megakaryocytes, Sca-1+, cKit+, CD133 and N-cadherin+ hematopoietic stem and progenitor cells, CD20+, Gr1+ mature hematopoietic cells, in addition to ki67+ proliferation, Bcl-2+ anti-apoptotic, caspase-3+ apoptotic, TNF-α+ inflammatory cells. Histoplanimetry data were statistically analyzed using the one-way analysis of variance followed by the post hoc Duncan's test. Moreover, Pearson's correlation was used to assess the correlation between various parameters. In comparison to the IR group, the IR+hUCB-MSCs group showed restored cell populations and extracellular collagen components of the BM niche with significant increase in hematopoietic stem, progenitor, mature and proliferating cells, and a considerable decrease in apoptotic and inflammatory cells. Furthermore, highly significant correlations between BM niche and blood biochemical, histopathological, and immunohistochemical parameters were observed. hUCB-MSCs restored functional hematopoiesis through amelioration of the BM niche components via reduction of oxidative stress, DNA damage, inflammation, and apoptosis with upregulation of cellular proliferation. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Ovariectomized menopausal rat model was used to investigate the effects of menopause on the sublingual salivary gland (SSG) and the potential therapeutic effect of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). Thirty rats were equally divided into three groups: sham-operated (SHAM), ovariectomized (OVX), and ovariectomized stem cells injected (OVX+ hUCB-MSCs). Expressions of α-SMA, AQP1, Sca-1, PCNA, ssDNA, and caspase-3 were determined. Homing of hUCB-MSCs was detected by fluorescence microscopy and examination of immunostained sections for human CD105 and CD34 was performed. Morphometric data were statistically analyzed using the Kruskal–Wallis test followed by Scheffé's method. Correlation of AQP1 with Sca-1-positive sublingual stem cells was also analyzed. In the SSGs of the OVX group, ballooned mucus acinar cells, atrophied serous cells, and a decreased number and height of duct lining cells were observed. The interstitial spaces were edematous, and the blood vessels were congested. The significant decrease in the positive area % of α-SMA and AQP1, the number of Sca-1-positive sublingual stem cells, and proliferating cells was associated with a significant increase in apoptotic cells. The OVX+hUCB-MSCs group showed significant structural improvement, manifested by the normal appearance of mucus and serous acini, as well as the number and height of striated duct cells. A significant increase in the positive area % of α-SMA and AQP1 and the number of proliferating and Sca-1-positive sublingual stem cells was observed. Interestingly, a significantly positive Pearson's correlation between the area % of AQP1 and the number of Sca-1-positive sublingual stem cells was also recorded. Our results indicated a positive effect of hUCB-MSCs therapy for SSG pathology in a post ovariectomy rat model as evidenced by an improvement in the histologic architecture, upregulation of the immunostained area % of α-SMA and AQP1, increase in the number of Sca-1-positive sublingual stem cells and proliferating cells, and downregulation of apoptotic cells. [ABSTRACT FROM AUTHOR]

Immunosenescence is the decline of the host immune system due to aging, resulting in various complications. The splenic lymphoid nodule is the pivotal compartment involved in immunosenescence. In this study, we investigated the important changes in the splenic immune cell populations of aged rats (18–24 months) in comparison with young rats (3–5 months). We, also, studied the effects of aging on the activities of total superoxide dismutase (T-SOD) and malondialdehyde (MDA) levels in spleen of both groups, besides the changes of the splenic architecture. Furthermore, immunohistochemical staining was performed to detect the aging effects in T cells, B cells, macrophages, granulocytes, mast cells, proliferating cells, apoptotic cells, and cells positive for interleukin-1β (IL-1β), interleukin-6 (IL-6), and Toll-like receptor 4 (TLR4). The aged rats had significantly lower spleen/body weight ratios and smaller splenic nodules, indicating a decline in general immunity in them. With aging, T-SOD activities were decreased, while MDA levels were increased, exhibiting that oxidative stress increases in spleens. In addition, the aged group also had significantly fewer T and B cells, macrophages, granulocytes, IL-6 and TLR4 immuno-positive cells, and proliferating cells in the periarterial lymphatic sheaths, marginal zone, and lymphoid follicles compared with the young group. On the other hand, the number of mast cells and apoptotic cells was significantly increased with age. Therefore, we can conclude that cellular immunity and humoral immunity were crumpled with age. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is the most widespread inflammatory arthropathy, which causes severe disability. It is highly important to ameliorate the side effects caused by different drugs used to treat RA. Therefore, this study assessed the potential role of β-caryophyllene (BCP) in treating adjuvant-induced arthritis (AIA), increasing the efficacy of methotrexate (MTX) and/or leflunomide (LEF), and ameliorating their side effects. AIA was induced in rats by injecting complete Freund's adjuvant. The rats were divided into different groups such as sham group; control group; monotherapy groups, including BCP (300 mg/kg), MTX (1 mg/kg), and LEF (10 mg/kg); and combined groups, including MTX + BCP, LEF + BCP, MTX + LEF, and MTX + LEF + BCP groups. Monotherapy with BCP or MTX or LEF as well as MTX + LEF significantly reduced paw thickness and arthritic index; the histopathological changes in hind paw joints were recovered; and oxidative stress and tumor necrosis factor-alpha (TNF-α) levels in arthritic rats were reduced. The co-administration of BCP and MTX and/or LEF significantly improved the therapeutic efficacy of MTX and/or LEF and significantly reduced the myelosuppressive and hepatotoxic effects of MTX and/or LEF. Taken together, BCP could be used with MTX and/or LEF for the treatment of RA to reduce the side effects of the drugs and increase their efficacy. [ABSTRACT FROM AUTHOR]