Liver disease remains a significant global health problem. Increased caffeine consumption has been associated with a lower prevalence of chronic liver disease. This study aimed to investigate the modifying effects of caffeine on liver injury induced by thioacetamide (TAA) administration in male rats and the possible underlying mechanisms. Forty adult male rats were equally classified into four groups: control group, received only tap water; caffeine-treated group, received caffeine (37.5 mg/kg per day); TAA-treated group, received intraperitoneal (i.p.) TAA (200 mg/kg b.w.) twice a week; and caffeine + TAA-treated group, received combined TAA and caffeine in the same previous doses. After eight weeks of treatment, blood samples were collected for biochemical analysis and liver specimens were prepared for histological and immunohistochemical studies and for assessment of oxidative stress. TAA induced liver toxicity with elevated liver enzymes and histological alterations, fatty changes, apoptosis, and fibrosis evidenced by increased immunohistochemical reaction to matrix metalloproteinase-9 (MMP-9) and collagen type IV in hepatocytes. Also, the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in serum were significantly elevated. Co-treatment with caffeine and TAA restored normal liver structure and function. Caffeine provided an anti-fibrogenic, anti-inflammatory, and antioxidant effect that was associated with recovery of hepatic histological and functional alterations from TAA-induced hepatotoxicity.

We examined the effect of placenta-derived MSCs (PDMSCs) injection intraregionally and intraperitoneally on healing of induced full thickness mice skin wounds; moreover, the mechanisms by which MSCs exert their effects were also studied. Sixty female mice were divided into three groups after induction of full thickness skin wound; untreated group, wounded mice were injected with MSCs derived from human placenta intraperitoneally or intraregionally. Skin biopsies were obtained 7 and 12 days after wound incision for histological examinations, detection of vascular endothelial growth factor (VEGF) by ELISA, and estimation of expression of mouse ICAM-1, Integrin b1, Integrin b3 genes and human albumin and GAPDH genes by reverse transcription polymerase chain reaction. Human placenta derived-MSCs treated groups showed accelerated wound healing than non-treated group. VEGF, Integrin b1, and Integrin b3 levels were significantly increased in the intraregionally and intraperitoneally treated mice as compared to non-treated group at day 7 after wound induction. ICAM-1 showed significant decrease in its expression in treated groups compared with non-treated group. Interestingly, the intraperitoneal MSCs injections showed better results than intraregional one. PDMSCs accelerate full thickness skin wound healing and the intraperitoneal MSCs injections are more effective than intraregional one. MSCs promote wound healing through release of proangiogenic factors as VEGF, increase healing promoting factors as integrin b1 and b3, and decrease proinflammatory cytokines as ICAM-1. V C 2015 IUBMB Life, 67(9): [701][702][703][704][705][706][707][708][709] 2015

Currently, azoospermia is one of the most common diseases of male infertility. Stem cell research is the new hope for novel therapy with a higher degree of safety and lower cost. This study aimed to investigate the effect of umbilical cord blood-derived stem cells (" and mesenchymal "UCB-MSCs") and mono-cell layer implanted into the induced azoospermic mice testis. Stem cells were isolated from umbilical cord blood and CD34+ve cells were separated from negative one by Mini MACs column. At 5th week after single injection of busulfan, stained mesenchymal (CD34-ve), hematopoietic stem cells (CD34+ve) and their conjugate (mono-cell layer) were injected locally into testis. At the end of the study, MSCs group showed that mRNA levels of genes related to meiosis (Vasa, SCP3, and PgK2) were increased with significant decrease of FSH and LH levels, compared to control group. Histologically, most of the tubules restored normal architecture. In contrast, HSCs and mono-cell layer groups showed statically insignificant change of FSH, LH, and gene expression, compared to control group. Histologically, distorted seminiferous tubules, with reduction in sperm content, and interstitial mononuclear cellular infiltration were seen. There was significant increase in the optical density of PCNA immune reaction in MSCs group than azoospermia, HSCs, and mono-cell layer, while there was non-significant difference between MSCs and control group. The present study suggested that injection of MSCs into chemotherapeutic-induced azoospermia in mice improved testicular failure; histologically and functionally, by restoration of spermatogenic gene expression while HSC and mono-cell layer showed no effect on spermatogenesis added to that mono-cell layer may induce testicular tissue damage.

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Stem cell therapy is considered as a promising approach in the treatment of myocardial infarction (MI). This study was designed as a comparison of human umbilical cord blood (HUCB)-derived CD341 and HUCB-derived MSCs for the repair of cardiac tissue by induction of the angiogenesis. Forty-eight male rats were randomized into four groups: sham-operated group, MI group, MSCs-treated group, and CD341 cellstreated group. After 4 weeks, the rats were sacrificed. All sections from left ventricles of all groups were subjected to hematoxylin & eosin, Masson's trichrome, and immunohistochemical stains (CD133, CD44, and a-smooth muscle actin). RNA was extracted for gene expression of the angiogenic markers. A significant reduction of the infarct size and the amplitude of T-wave in the CD341 cells-treated group when compared with the MSCs-treated group were determined. Histologically, the MI group showed scar tissue, congested blood capillaries around the infarcted area, some necrotic cells, and inflammatory cells. Administration of either MSCs or CD341 cells had a therapeutic potential to induce regenerative changes in the myocardium with better results in CD341cells-treated group. Quantitative RT-PCR analysis revealed a significant increase in the expression of vascular endothelial growth factor (VEGF), VEGFR-2, Ang-1, and Tie-2 and a significant decreased expression of Ang-2 in stem cells transplanted groups when compared with the noncell transplanted hearts. A significant increase of VEGF, VEGFR-2, Ang-1, and Tie-2 expression in the group receiving CD341 cells than those receiving MSCs was found. Finally, there was an upregulation of both human VEGF and human hypoxia-inducible factor 1a in the infarcted hearts treated by CD341 cells than that treated by MSCs. We first revealed a superior efficacy of CD341 cells when compared with MSCs in induction of regenerative changes in the MI model. Both cell therapies may repair the damaged heart tissue primarily by secretion of proangiogenic factors that induce the angiogenesis and activate the angiogenesis signaling pathway. V C 2016 IUBMB Life, 68(5): [343][344][345][346][347][348][349][350][351][352][353][354] 2016