Objective: To elucidate the molecular mechanisms of the potent anti-obesity effect of Moringa oleifera Lam. (M. oleifera) ethanolic extract and to clarify the link between these mechanisms and the associated metabolic and vascular risks in the experimental model of visceral obesity. Methods: M. oleifera ethanolic extract was orally administered at 600 mg/kg body weight in obese female rats daily for 12 weeks. At the end of treatment, body weight was deter-mined, and the atherogenic index, coronary artery index, glucose level, insulin resistance status, liver and kidney functions were assessed. Also, the mRNA of leptin, adiponectin and resistin in visceral adipose tissue was determined by quantitative real time-PCR. Results: The results showed that M. oleifera extract down-regulated mRNA expression of leptin and resistin, while it up-regulated adiponectin gene expression in obese rats relative to untreated obese control counterparts. This amelioration of genes expression was paralleled by a reduction in body weight and improvement of the atherogenic index and coronary artery index, as well as glucose level and insulin resistance value without adverse effects on liver or kidney functions, versus the untreated obese control ones. Conclusions: It is reasonable to assume that the anti-obesity, anti-atherogenic and anti-diabetic properties of M. oleifera are mechanistically achieved via working directly on the adipokines of the visceral adipose tissue. Therefore, M. oleifera may be a good thera-peutic candidate for the symptoms of metabolic syndrome.

BACKGROUND AND OBJECTIVES: Insulin secretion entirely depends on Ca²⁺ influx and sequestration into endoplasmic reticulum (ER) of β-cells, performed by Sarco-ER Ca²⁺-ATPase 2b (SERCA2b). In diabetes, SERCA2b is decreased in the β-cells leading to impaired intracellular Ca²⁺ homeostasis and insulin secretion. Adipose mesenchymal stem cells (AMSCs) play a potential role in transplantation in animal models. The present study aimed at investigating and comparing the therapeutic effect of non-transfected AMSCs and SERCA2b gene transfected AMSCs on the pancreas of induced diabetes type 1 in rat. METHODS AND RESULTS: 58 adult male albino rats were divided into: Donor group: 22 rats, 2 for isolation, propagation and characterization of AMSCs and SERCA2b transfected AMSCs, in addition 20 for isolated islet calcium level assessment. Group I (Control Group): 6 rats, Group II (Diabetic Group): 10 rats, 50 mg streptozotocin (STZ) were injected intraperitoneal (IP), Group III (AMSCs Group): 10 rats, 1×10⁶ AMSCs were injected intravenous and Group IV (SERCA2b transfected AMSCs Group): 10 rats, 1×10⁶SERCA2b transfected AMSCs were injected as in group III. Groups I, II, III and IV were sacrified 3 weeks following confirmation of diabetes. Serological, histological, morphometric studies and quantitative polymerase chain reaction (qPCR) were performed. Nuclear, cytoplasmic degenerative and extensive fibrotic changes were detected in the islets of group II that regressed in groups III and IV. Isolated islet calcium, blood glucose, plasma insulin and qPCR were confirmative. CONCLUSIONS: AMSCs and SERCA2b gene transfected AMSCs therapy proved definite therapeutic effect, more obvious in response to SERCA2b gene transfected AMSCs.
Adult ; Animals ; Blood Glucose ; Calcium ; Cytoplasm ; Endoplasmic Reticulum ; Homeostasis ; Humans ; Insulin ; Male ; Mesenchymal Stromal Cells ; Models, Animal ; Pancreas ; Plasma ; Polymerase Chain Reaction ; Rats ; Stem Cells ; Streptozocin ; Tissue Donors

BACKGROUND/AIMS: Cellulitis is a common infection in patients with liver cirrhosis. We aimed to compare risk factors, microbial aspects, and outcomes of cellulitis in compensated and decompensated hepatitis C virus (HCV)-related cirrhosis. METHODS: Six hundred twenty consecutive HCV-related cirrhotic patients were evaluated for cellulitis. Demographic and clinical data were evaluated, along with blood and skin cultures. Severity of cirrhosis was assessed using Child-Pugh score. In-hospital mortality was assessed. RESULTS: Seventy-seven (12.4%) cirrhotic patients had cellulitis (25 with compensated and 52 with decompensated disease). Smoking and venous insufficiency were risk factors of cellulitis in compensated cirrhosis. Leg edema, ascites, hyperbilrubinemia and hypoalbuminemia were risk factors in decompensated cirrhosis. Gram-positive bacteria (Staphylococcus spp. and Streptococcus pyogenes) were the infective organisms in compensated patients, while gram negative bacteria (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were the predominant organisms in decompensated cirrhosis. Fungi (Candida albicans and Aspergillus niger) were detected in 3 decompensated cases. In-hospital mortality in patients with cellulitis was 27.3%, approaching 100% in decompensated patients with gram-negative cellulitis. Prolonged hospitalization, higher model for end-stage liver disease (MELD)-Na score, septic shock, local complication, and recurrent cellulitis were predictors of mortality. CONCLUSIONS: Cellulitis in compensated cirrhosis is different from that of decompensated patients regarding microorganisms, pathogenesis, and prognosis. Cellulitis has a poor prognosis, with mortality rates approaching 100% in decompensated patients with gram-negative cellulitis. Stratifying patients according to severity of cirrhosis is important to identify the proper empirical antibiotic and to decide the proper means of care.
Ascites ; Aspergillus ; Cellulitis ; Edema ; Fibrosis ; Fungi ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Hepacivirus ; Hepatitis C ; Hepatitis ; Hospital Mortality ; Hospitalization ; Humans ; Hypoalbuminemia ; Klebsiella pneumoniae ; Leg ; Liver Cirrhosis ; Liver Diseases ; Mortality ; Prognosis ; Pseudomonas ; Risk Factors ; Shock, Septic ; Skin ; Smoke ; Smoking ; Streptococcus ; Venous Insufficiency

Concha bullosa (CB) is a pneumatic cavitation inside a concha in the nasal cavity. It is one of the most widely recognized nasal variations and is mostly found in the middle concha. CB is divided according to its site into three types; lamellar, bulbous and extensive. The goal of our study was to estimate the prevalence of CB among Saudi adult population and its association with sinusitis by using multidetector computed tomography (MDCT). This was a retrospective study carried out over a three-year period on 879 adult Saudi patients aged 18 years or older, referred for MDCT assessment of paranasal sinuses. Males were 540 and females were 339. Patients with facial congenital anomalies or nasal trauma were excluded from our study. CB was prevalent in both males and females among Saudi population (55.4%, 55.7%) respectively. Bilateral CB (55.5%) was more frequent than unilateral (44.5%). Extensive CB (44.0%) was the most frequent type. Sinusitis was associated more in patients with CB (48.0%) versus those who have no CB (5.9%). In conclusion, CB was prevalent among Saudi population and the most frequently recorded is the extensive type. Furthermore, the most common type associated with sinusitis was extensive CB (49.6%).

Concha bullosa (CB) is a pneumatic cavitation inside a concha in the nasal cavity. It is one of the most widely recognized nasal variations and is mostly found in the middle concha. CB is divided according to its site into three types; lamellar, bulbous and extensive. The goal of our study was to estimate the prevalence of CB among Saudi adult population and its association with sinusitis by using multidetector computed tomography (MDCT). This was a retrospective study carried out over a three-year period on 879 adult Saudi patients aged 18 years or older, referred for MDCT assessment of paranasal sinuses. Males were 540 and females were 339. Patients with facial congenital anomalies or nasal trauma were excluded from our study. CB was prevalent in both males and females among Saudi population (55.4%, 55.7%) respectively. Bilateral CB (55.5%) was more frequent than unilateral (44.5%). Extensive CB (44.0%) was the most frequent type. Sinusitis was associated more in patients with CB (48.0%) versus those who have no CB (5.9%). In conclusion, CB was prevalent among Saudi population and the most frequently recorded is the extensive type. Furthermore, the most common type associated with sinusitis was extensive CB (49.6%).

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.
Acetaminophen ; therapeutic use ; Adult ; Carcinoma, Hepatocellular ; Disease Progression ; Drug Therapy, Combination ; Enzyme Inhibitors ; Glutathione ; Glycolysis ; Hexokinase ; Humans ; L-Lactate Dehydrogenase ; Lactic Acid ; Lung Neoplasms ; secondary ; Male ; Melanoma ; drug therapy ; Necrosis ; Neovascularization, Pathologic ; Pleural Neoplasms ; secondary ; Prognosis ; Pyruvates ; adverse effects ; therapeutic use ; Treatment Outcome

Objective To elucidate the molecular mechanisms of the potent anti-obesity effect of Moringa oleifera Lam. (M. oleifera) ethanolic extract and to clarify the link between these mechanisms and the associated metabolic and vascular risks in the experimental model of visceral obesity. Methods M. oleifera ethanolic extract was orally administered at 600 mg/kg body weight in obese female rats daily for 12 weeks. At the end of treatment, body weight was determined, and the atherogenic index, coronary artery index, glucose level, insulin resistance status, liver and kidney functions were assessed. Also, the mRNA of leptin, adiponectin and resistin in visceral adipose tissue was determined by quantitative real time-PCR. Results The results showed that M. oleifera extract down-regulated mRNA expression of leptin and resistin, while it up-regulated adiponectin gene expression in obese rats relative to untreated obese control counterparts. This amelioration of genes expression was paralleled by a reduction in body weight and improvement of the atherogenic index and coronary artery index, as well as glucose level and insulin resistance value without adverse effects on liver or kidney functions, versus the untreated obese control ones. Conclusions It is reasonable to assume that the anti-obesity, anti-atherogenic and anti-diabetic properties of M. oleifera are mechanistically achieved via working directly on the adipokines of the visceral adipose tissue. Therefore, M. oleifera may be a good therapeutic candidate for the symptoms of metabolic syndrome.