AD-MSCs and BM-MSCs Ameliorating Effects on The Metabolic and Hepato-renal Abnormalities in Type 1 Diabetic Rats.

Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.

N,N'-Diphenyl-1,4-phenylenediamine Antioxidant's Potential Role in Enhancing the Pancreatic Antioxidant, Immunomodulatory, and Anti-Apoptotic Therapeutic Capabilities of Adipose-Derived Stem Cells in Type I Diabetic Rats.

Mesenchymal stem cells (MSCs) are considered to be a promising therapeutic protocol for diabetes mellitus (DM) management. The latter is attributed to their differentiation potentiality to pancreatic ß-cells, angiogenesis, and immune-modulatory capabilities by releasing various paracrine factors. Interestingly, antioxidant co-administration increased the MSCs' hypoglycemic and regenerative activities. Thus, this study aims to evaluate the therapeutic implication of type 1 DM after the co-administration of adipose tissue-derived-MSCs (AD-MSCs) and N,N'-d iphenyl-1,4-phenylenediamine (DPPD), compared to the single injection of either of them alone. In our four week long experiment, six rat groups were used as control, DPPD (250 mg/kg, i.p.), STZ-diabetic (D), D+DPPD, D+AD-MSCs (1 × 106 cell/rat, i.p.), and D+AD-MSCs+DPPD groups. Within this context, a single injection of AD-MSCs or DPPD into diabetic rats showed significant pancreatic anti-inflammatory, immunomodulation, antioxidant, and anti-apoptotic capacities, superior to AD-MSCs injection. However, AD-MSCs and DPPD co-administration into diabetic rats manifested the highest hypoglycemic and pancreatic regenerative activities in managing diabetes compared to the single shot of AD-MSCs or DPPD. These results highlight the synergetic role of DPPD as an antioxidant in enhancing AD-MSCs' therapeutic applications.

Protective Role of Juniperus phoenicea L. Leaves Extract against Gamma-irradiation-induced Oxidative Stress.

BACKGROUND AND OBJECTIVE: Radiation exposure can cause several harmful effects in biological systems due to free radical production. Several antioxidants have been tested as potential hepatoprotective agents against ionizing radiation as they lower oxidative stress in normal cells induced by Reactive Oxygen Species (ROS). The present study was conducted to evaluate the possible ameliorative effects of Juniperus phoenicea L. MATERIALS AND METHODS: Aqueous leaves extract on different biochemical and histopathological parameters against whole body gamma-irradiation-induced oxidative stress, organ dysfunction and metabolic disturbances in experimental Swiss Albino rats. After a single dose of gamma-radiation (6 Gy), there was a significant reduction in albumin, total protein and globulin levels and a significant increase in the liver enzymes (ALT, AST, ALP and GGT) and lipid profile parameters (cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) in gamma-irradiated rats unlike in normal controls. RESULTS: The gamma-irradiated rats pre-treated with J. phoenicea leaf extracts, however, showed a significant increase in albumin, total protein and globulin levels and a significant reduction in liver enzymes and lipid profile parameters as opposed to the untreated ones. The gamma-irradiated rats showed toxic changes in the liver, whereas, the rats pre-treated with J. phoenicea leaves extract demonstrated a protective effect. Additionally, gamma- irradiation caused myocardial degenerative changes, interstitial edema between muscle fibers, necrosis and inflammatory cells infiltration and fibrotic and cellular damages to the heart, but J. phoenicea leaves extract were found to ameliorate the gamma-irradiation-induced changes in the heart. CONCLUSION: The results suggested that treatment with J. phoenicea leaves extract is possibly safe and can ameliorate gamma-irradiation-induced oxidative damage and tissue injury in rats. The leaves of J. phoenicea could serve as a potential source of therapeutic antioxidants.

Screening of SHOX gene sequence variants in Saudi Arabian children with idiopathic short stature.

PURPOSE: Short stature affects approximately 2%-3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene (SHOX) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations. METHODS: We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. RESULTS: A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX. CONCLUSION: In Saudi Arabia ISS patients, rather than SHOX, it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.

Biogenesis of extracellular microfibrils: Multimerization of the fibrillin-1 C terminus into bead-like structures enables self-assembly.

Microfibrils are essential elements in elastic and nonelastic tissues contributing to homeostasis and growth factor regulation. Fibrillins form the core of these multicomponent assemblies. Various human genetic disorders, the fibrillinopathies, arise from mutations in fibrillins and are frequently associated with aberrant microfibril assembly. These disorders include Marfan syndrome, Weill-Marchesani syndrome, Beals syndrome, and others. Although homotypic and heterotypic fibrillin self-interactions are considered to provide critical initial steps, the detailed mechanisms for microfibril assembly are unknown. We show here that the C-terminal recombinant half of fibrillin-1 assembles into disulfide-bonded multimeric globular structures with peripheral arms and a dense core. These globules are similar to the beaded structures observed in microfibrils isolated from tissues. Only these C-terminal fibrillin-1 multimers interacted strongly with the fibrillin-1 N terminus, whereas the monomers showed very little self-interaction activity. The multimers strongly inhibited microfibril formation in cell culture, providing evidence that these recombinant assemblies can also interact with endogenous fibrillin-1. The C-terminal self-interaction site was fine-mapped to the last three calcium-binding EGF domains in fibrillin-1. These results suggest a new mechanism for microfibril formation where fibrillin-1 first oligomerizes via its C terminus before the partially or fully assembled bead-like structures can further interact with other beads via the fibrillin-1 N termini.