Background During the last few decades, patients worldwide have been interested in using alternative medicine in treating diseases to avoid the increased side effects of chemical medications. Green coffee is unroasted coffee seeds that have higher amounts of chlorogenic acid compared to roasted coffee. Green coffee was successfully used to protect against obesity, Alzheimer disease, high blood pressure and bacterial infection. Methods This study aimed to investigate the probable protective activity of the green coffee methanolic extract, silymarin and their combination on CCl4-induced liver toxicity in male rats. Thirty Sprague – Dawley male albino rats were divided into 5 groups; control negative (G1) just got the vehicle (olive oil) and the other four groups received CCl4 dissolved in olive oil through an intraperitoneal injection and were divided into untreated control positive group (G2), the third group (G3) was treated with green coffee methanolic extract, the fourth group (G4) was treated with silymarin, and the fifth group (G5) was treated with a combination of green coffee methanolic extract and silymarin. Results In the positive control group treated with CCl4 (G2), the CCl4-induced toxicity increased lipid peroxidation, IL-6, kidney function parameters, liver function enzymes, total cholesterol, triglycerides and low-density lipoproteins, and decreased irisin, antioxidants, CYP450 and high-density lipoprotein levels. Hepatic tissues were also injured. However, treating the injured rats in G3, G4 and G5 significantly improved the altered parameters and hepatic tissues. Conclusions Green coffee methanolic extract, silymarin, and their combination succeeded in protecting the male rats against CCl4 hepatotoxicity due to their antioxidant activity. Effect of green coffee methanolic extract mixed with silymarin in G5 was more efficient than that of green coffee methanolic extract in G3 or silymarin in G4.

Carbon tetrachloride (CCl 4 ) causes severe injury to the body particularly the liver and the kidney. The aim of the present study was testing the probable hepatonephro protective effect of Moringa oleifera seed methanolic extract against CCl 4 toxicity in male rat. 24 male rats were divided into 4 groups (n=6); the first group (G1) was the negative control group, rats of the other three groups were injected with CCl 4 twice a week. Rats of the second group (G2) were kept without treatment as positive CCl 4 group, the third group (G3) received a daily dose of M. oleifera methanolic extract and the fourth group (G4) received a silymarin dose as a positive treated group. The HPLC analysis of M. oleifera seed methanolic extract revealed that it is rich in ascorbic and oleic acids. Rats of the CCl 4 positive control group showed an increase in kidney and liver injury markers, interleukin-6, bilirubin and lipid peroxidation, and a decrease in antioxidants activity and total protein. In addition, liver and kidney tissues showed drastic histopathological changes. Treating the CCl 4 hepatonephrotoxicity in G3 and G4 with either M. oleifera seed methanolic extract or silymarin, respectively significantly alleviated all altered biochemical and histological changes approaching the normal values. M. oleifera methanolic extract revealed more protection to liver and kidney in G3 than silymarin in G4. This protecting activity of M. oleifera seed methanolic extract against CCl 4 hepatonephrotoxicity may be ascribed to its high content of phenols and flavonoids, in addition to ascorbic acid and oleic acid.

In a recent study, the treatment of different human cancer cell lines in vitro with ethylene diamine tetra-acetic acid (EDTA) showed a promising anticancer activity which could be a novel promising approach for cancer treatment. The aim of this study is to address the ability of EDTA to enhance the antitumor efficacy of the low dose of cisplatin (Cis) treatment in Ehrlich ascetic carcinoma (EAC) bearing mice. Sixty female albino mice were divided into six groups. The 1 st group of mice was served as a negative control. 2 nd -6 th groups were inoculated intraperitoneal (i.p) with 2×10 6 EAC cells/mouse. After one day of inoculation, the 2 nd , 3 rd and 4 th groups were injected daily for 6 days (early treatment) with phosphate buffer saline, low dose of Cis and Cis/EDTA, respectively. After six days, the 5 th and 6 th groups were injected with the low dose of Cis and Cis/EDTA for 6 consecutive days (late treatment), respectively. At day 14, all groups of mice were sacrificed, sera were collected for biochemical assessment, HIGHLIGHTS• EDTA enhanced the antitumor efficacy of the low dose of Cisplatin.• Low dose of Cisplatin did not inhibit tumor growth • Co-treatment with EDTA delayed and decreased tumor growth.• EDTA decreased the toxicity of Cisplatin. 2 El-Naggar, S.A.; et al.

Adolescent idiopathic scoliosis is the most prevalent spine deformity and the molecular mechanisms underlying its pathophysiology remain poorly understood. We have previously found a differential impairment of melatonin receptor signaling in AIS osteoblasts allowing the classification of patients into three biological endophenotypes or functional groups (FG1, FG2 and FG3). Here, we provide evidence that the defect characterizing each endophenotype lies at the level of Gαi proteins leading to a systemic and generalized differential impairment of Gi-coupled receptor signaling. The three Gαi isoforms exhibited a selective serine phosphorylation patterns for each AIS endophenotype resulting in a differential reduction in Gαi protein activity as determined by cellular dielectric spectroscopy and small interfering RNA methods. We found that one endophenotype (FG2) with phosphorylated Gαi 1 and Gαi 2 was consistently associated with a significantly high risk of spinal deformity progression when compared to the other two endophenotypes (FG1 and FG3). We further demonstrated that each endophenotype is conserved among affected family members. This study expands our understanding of the mechanism underlying the Gi-coupled receptor signaling dysfunction occurring in AIS and provides the first evidence for its hereditary nature. Collectively, our findings offers a new perspective on Gαi hypofunctionality in a human disease by revealing specific serine phosphorylation signatures of Gαi isoforms that may facilitate the identification of AIS patients at risk of spinal deformity progression.

The possible renal and hepatic toxicities of ethylenediaminetetraacetic acid (EDTA) in bean cooking media were studied using 100 male albino mice. Two sublethal doses of EDTA were used to explore their toxic effects; 20 mg/kg and 200 mg/kg, which corresponded to 1/100th and 1/10th of LD50, respectively. Accordingly, the toxicity study was performed using 50 mice, divided into five groups ( n = 10/group) as follows: group 1 (Gp1) served as a negative control and was orally administered normal saline; group 2 (Gp2) was administered the bean cooking medium; group 3 (Gp3) was administered EDTA (200 mg/kg); group 4 (Gp4) was administered bean cooking medium containing 20 mg/kg of EDTA; and group 5 (Gp5) was administered bean cooking medium containing 200 mg/kg of EDTA. The results showed no significant changes in liver and kidney functions in Gp2 while Gp3, Gp4, and Gp5 exhibited significant increases in adverse liver and kidney function markers. Hematocrit values were significantly decreased in Gp3 and Gp5, while the total white blood cells counts were significantly decreased in Gp3 and significantly increased in Gp5. The number of platelets was decreased in Gp3, Gp4, and Gp5. The blood levels of sodium (Na+), iron (Fe2+), and calcium (Ca2+) were decreased in Gp3, Gp4, and Gp5 due to the chelating effects of EDTA. The hepatic and renal architectures were disorganized in Gp3, Gp4, and Gp5 with some hemorrhagic manifestations in livers and kidneys of mice. These results demonstrate that EDTA in bean cooking is harmful in mice under the conditions of this study, and the potentially harmful effects in humans supports restricting its use.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and fibromyalgia (FM) are two chronic complex diseases with overlapping symptoms affecting multiple systems and organs over time. Due to the absence of validated biomarkers and similarity in symptoms, both disorders are misdiagnosed, and the comorbidity of the two is often unrecognized. Our study aimed to investigate the expression profiles of 11 circulating miRNAs previously associated with ME/CFS pathogenesis in FM patients and individuals with a comorbid diagnosis of FM associated with ME/CFS (ME/CFS + FM), and matched sedentary healthy controls. Whether these 11 circulating miRNAs expression can differentiate between the two disorders was also examined. Our results highlight differential circulating miRNAs expression signatures between ME/CFS, FM and ME/CFS + FM, which also correlate to symptom severity between ME/CFS and ME/CFS + FM groups. We provided a prediction model, by using a machine-learning approach based on 11 circulating miRNAs levels, which can be used to discriminate between patients suffering from ME/CFS, FM and ME/CFS + FM. These 11 miRNAs are proposed as potential biomarkers for discriminating ME/CFS from FM. The results of this study demonstrate that ME/CFS and FM are two distinct illnesses, and we highlight the comorbidity between the two conditions. Proper diagnosis of patients suffering from ME/CFS, FM or ME/CFS + FM is crucial to elucidate the pathophysiology of both diseases, determine preventive measures, and establish more effective treatments.

Heavy metals intoxication causes several health problems that necessitate finding new protective and therapeutic approaches. This study aimed to evaluate the impact of Musa sp. leaves extract (MLE) on hepato-renal toxicities induced by cadmium (Cd) in male mice. The phytochemical screening, metal chelating activity (MCA), and the median lethal dose (LD50) of MLE were determined. Fifty CD-1 male mice were used and intraperitoneally (i.p.) injected with MLE (1000 to 5000 mg/kg b.wt) for MLE LD50 determination. Another 50 mice were used for evaluating the effect of MLE on Cd toxicity. Blood samples were collected for hematological, liver, and kidney functions assessments. Liver tissue homogenates were used for determination of oxidant/antioxidant parameters. Liver and kidney tissues were harvested for histopathological and molecular investigations. MLE showed potent in vitro antioxidant activities. The MCA and LD50 of the MLE were 75 µg/mL and 3000 mg/kg b.wt, respectively. MLE showed beneficial therapeutic activity against hepato-renal toxicities in Cd-intoxicated mice, evidenced by improving the hematological, biochemical, histopathological, and molecular alterations.

Objective: the present research was focused to evaluate the date palm resistance to osmotic stress exerted by three concentrations of poly ethylene glycol 6000 in three months seedlings as reflected by the change in phenolic and flavonoid content and the activity of catalase, peroxidase and polyphenol oxidase. Materials and Methods: The phenolic and flavonoid content and the target enzyme's activity was estimated at four time points; 0,1,3,7 days. Results and Discussion: The phenolic and flavonoid content as well as the activity of catalase, peroxidase and polyphenol oxidase were increased by increasing the poly ethylene glycol and the treatment period. Conclusion: Phenolic and flavonoids are non-enzymatic antioxidants with high scavenging potential to the free radical produced from the oxidative stress resulted from the drought tolerance in date palm seedlings. In addition, the increase in the enzymatic activity of catalase, peroxidase and polyphenol oxidase under drought stress is very important to get rid of the free radicals and the reactive oxygen species.