Immunomodulatory Functions of Adipose Mesenchymal Stromal/Stem Cell Derived From Donors With Type 2 Diabetes and Obesity on CD4 T Cells.

For adipose stromal/stem cell (ASCs)-based immunomodulatory therapies, it is important to study how donor characteristics, such as obesity and type 2 diabetes (T2D), influence ASCs efficacy. Here, ASCs were obtained from 2 groups, donors with T2D and obesity (dASCs) or nondiabetic donors with normal-weight (ndASCs), and then cultured with anti-CD3/CD28-stimulated allogeneic CD4 T cells. ASCs were studied for the expression of the immunomodulators CD54, CD274, and indoleamine 2, 3 dioxygenase 1 (IDO) in inflammatory conditions. CD4 T cells cultured alone or in cocultures were assessed to evaluate proliferation, activation marker surface expression, apoptosis, the regulatory T cells (Tregs; CD4+ CD25high FOXP3+) frequency, and intracellular cytokine expression using flow cytometry. Modulation of T-cell subset cytokines was explored via ELISA. In inflammatory conditions, the expression of CD54, CD274, and IDO was significantly upregulated in ASCs, with no significant differences between ndASCs and dASCs. dASCs retained the potential to significantly suppress CD4 T-cell proliferation, with a slightly weaker inhibitory effect than ndASCs, which was associated with significantly reduced abilities to decrease IL-2 production and increase IL-8 levels in cocultures. Such attenuated potentials were significantly correlated with increasing body mass index. dASCs and ndASCs comparably reduced CD4 T-cell viability, HLA-DR expression, and interferon-gamma production and conversely increased CD69 expression, the Tregs percentage, and IL-17A production. Considerable amounts of the immunomodulators prostaglandin E2 (PGE2) and IL-6 were detected in the conditioned medium of cocultures. These findings suggest that ASCs obtained from donors with T2D and obesity are receptive to the inflammatory environment and able to modulate CD4 T cells accordingly.

Natural antioxidants enhance the power of physical and mental activities versus risk factors inducing progression of Alzheimer's disease in rats.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is exacerbated by social isolation (SI) and protein malnutrition (PM). Antioxidants, physical and mental activities (Ph&M) can maintain cognitive functions and protect against dementia. OBJECTIVE: To investigate the impact of Epigallocatechin-3-gallate (EGCG), Vitamin E (VE), Vitamin C (VC), and Selenium (Se), in enhancing the potential effect of Ph&M versus SI&PM as risk factors in the progression of AD in rats. METHODS: Aluminum chloride (70 mg/kg, I.P for 5 weeks) was used to induce AD in rats that either normally fed or socially isolated and protein malnourished (SI&PM). Simultaneously, rats were weekly exposed to Ph&M either alone or in combination with EGCG (10 mg/kg, I.P), VC (400 mg/kg, P.O), VE (100 mg/kg, P.O), and Se (1 mg/kg, P.O). RESULTS: The combination protocol of EGCG, VE, VC, and Se together with Ph&M significantly increased brain monoamines, superoxide dismutase (SOD), total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF) in AD, SI&PM and SI&PM/AD groups. Additionally, this regimen significantly mitigated brain acetylcholine esterase (ACHE), ß-amyloid (Aß), Tau protein, ß-secretase, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and Interleukin 1ß (IL-1ß) as well as DNA fragmentation. These biochemical findings were supported by the histopathological examinations of brain tissue. CONCLUSION: The combination protocol of antioxidants with Ph&M activities mitigated SI&PM-induced progressive risk of AD.

The potential effect of methylseleninic acid (MSA) against γ-irradiation induced testicular damage in rats: Impact on JAK/STAT pathway.

This study suggested that methylseleninic acid (MSA) could respond to the inflammatory signaling associated with ionizing radiation-induced testicular damage. Mature male rats were divided into four groups: negative control, whole body γ-irradiated (IRR) (5 Gy), MSA (0.5 mg/kg, daily for nine consecutive days), and MSA+ IRR groups. MSA increased serum testosterone level and testicular glutathione peroxidase (GPx) as well as decreased the percentage of sperm abnormalities. Radiation prompted inflammatory signaling in the testes through increasing phospho-janus kinase1 (p-JAK1), phospho-signal transducers and activators of transcription 3 (p-STAT3) protein expressions. This induced increment in the inflammatory markers including nuclear factor- kappa B (NF-κB) and interleukin-1beta (IL-1ß) levels. Also, radiation induced elevation of nitric oxide (NO) and malondialdhyde (MDA) levels with consequent reduction in testicular reduced glutathione level (GSH) and superoxide dismutase (SOD) activity. MSA significantly counteracted the radiation effect on testicular nuclear factor erythroid-2-related factor-2 (Nrf2) and suppressor of cytokine signaling (Socs3) protein expressions. In summary, this investigation proposed that MSA preserved spermatogenesis through increasing testosterone levels and GPx activity. Additionally, it diminished testicular inflammation by increasing of Nrf2 and Socs3 levels leading to reducing of p-JAK1, p-STAT3 and NF-κB levels. Histopathological examination results of testicular tissues showed a coincidence with the biochemical analysis.

α-Lipoic acid and amlodipine/perindopril combination potentiate the therapeutic effect of mesenchymal stem cells on isoproterenol induced cardiac injury in rats.

Cardiac injury is a dangerous disease and become a greater issue in the forthcoming decades. The ultimate goal is to prevent the progression of heart failure and apoptotic processes. Cardiac tissue may regenerate itself but to certain extent depending on the number of resident stem cells that is limited. Thus, research had been focused on bone marrow derived stem cells (BM-MSCs) as a promising therapy in different types of tissues, including the heart. This study is designed not only to assess the therapeutic effect of BM-MSCs but also to improve their therapeutic effect in combination with antioxidant α-lipoic acid (ALA) and antihypertensive therapeutic drug form (AP) against isoproterenol-induced cardiac injury and compared with that of BM-MSCs alone. Cardiac injury was induced in 70 male rats by Isoproterenol (ISO was injected s.c. for four consecutive days). Experimental animals were divided into six ISO-treated groups beside a control non treated one. The six ISO-treated groups were divided into: ISO group, ISO+BM-MSCs group, ISO+ALA group, ISO+AP group, ISO+ALA+AP group and ISO+ALA+AP+BM-MSCs group, the last five groups were treated with the examined materials after one week of ISO injection. Isoproterenol significantly increased serum CK-MB, LDH activities, Troponin1 and TNF-α. Oxidative stress is evidenced by the increased MDA, NO and Caspase-3 activity associated with significant reduction of GSH content and SOD activity in cardiac tissue. Furthermore, mRNA expression of NFκB and iNOS were significantly up regulated and eNOS mRNA expression was down regulated. Administration of BM-MSCs, ALA and AP alone significantly mitigated the induced cardiac injury. Concomitant administration of ALA and AP after BM-MSCs induced a more pronounced improving effect on cardiac functions. In conclusion, the concomitant administration of ALA and AP after BM-MSCs infusion increases the cellular antioxidant levels of cardiac tissue that improves the repairing function of BM-MSCs.

Enhanced therapeutic benefit of quercetin-loaded phytosome nanoparticles in ovariectomized rats.

Quercetin, a dietary flavonol phytoestrogen, has many health benefits but it is poorly absorbed when administered orally. To improve its bioavailability, we prepared quercetin-loaded phytosome nanoparticles (QP) using the thin film hydration method. The prepared nano-formulations were characterized using different techniques. Transmission electron microscopy revealed the homogeneously spherical, well and uniformly dispersed, nano-sized nature of QP. Dynamic light scattering measurements of QP (70 ± 7.44 nm) also confirmed this. Stability of the formed nanoparticles was established via zeta potential determination. The prepared QP exhibited very high encapsulation efficiency (98.4%). The estrogenic activity of QP, concerning inflammation, oxidative stress, bone, lipid profile, blood glucose level and weight gain, was investigated in ovariectomized rat model using 10 and 50 mg/kg/day oral doses for 4 weeks. Treatment with QP showed significant increase in serum calcium, inorganic phosphorus and glutathione content. Whereas, it significantly decreased serum alkaline phosphatase, acid phosphatase, malondialdehyde level, tumor necrosis factor-alpha and glucose level and improved lipid profile. Consequently, the results obtained confirm the superiority of QP over free quercetin at the same doses as a promising hormone replacement therapy.