- Apigenin prevents metabolic syndrome in high-fructose diet-fed mice by Keap1-Nrf2 pathway. [Journal Article]
- BPBiomed Pharmacother 2018; 105:1283-1290
- Chronic dietary high fructose leads to various kinds of undesirable metabolic effects. Apigenin, a naturally occurring plant flavone, is plentiful in fruits and vegetables. The aim of this study was ...
Chronic dietary high fructose leads to various kinds of undesirable metabolic effects. Apigenin, a naturally occurring plant flavone, is plentiful in fruits and vegetables. The aim of this study was to identify the protective effects of apigenin on metabolic syndrome and elucidate potential underlying mechanisms. The animal model was established by 4-weeks high fructose feeding. Insulin resistance was estimated by oral glucose tolerance test and homeostasis model assessment-insulin resistance index. Liver function was evaluated by serum AST and ALT, hepatic histopathological alternation, and lipid accumulation in the liver. The alterations of lipid profile was evaluated by TG, TC, LDL-C and HDL-C levels in serum. Administration of apigenin exerted beneficial effects through improving insulin resistance, alleviating liver injury, and inhibiting the alterations of lipid profile in high fructose-fed mice. In addition, apigenin potently facilitated the accumulation of Nrf2 nuclear translocation and accompanied by increasing HO-1 and NQO1 protein expressions, which are responsible for attenuating oxidative stress. Molecular docking results demonstrated that potential interaction of apigenin with the Nrf2-binding site in the Keap1 protein. In summary, we demonstrated that apigenin prevented high fructose-induced metabolic syndrome probably by inhibiting binding of Keap1 to Nrf2, and thus Nrf2 nuclear translocation, subsequently resulting in increased the expressions of anti-oxidative genes including HO-1 and NQO1.
- Protective aptitude of Periploca hydaspidis Falc against CCl4 induced hepatotoxicity in experimental rats. [Journal Article]
- BPBiomed Pharmacother 2018; 105:1117-1132
- In the present study the antioxidant capacity of Periploca hydaspidis was assessed through various in vitro assays and by the hepatoprotective potential on CCl4 induced toxicity in rat. Phytochemical...
In the present study the antioxidant capacity of Periploca hydaspidis was assessed through various in vitro assays and by the hepatoprotective potential on CCl4 induced toxicity in rat. Phytochemical analysis of different extracts of P. hydaspidis indicated existence of various phytochemical classes. HPLC-DAD analysis of methanol extract indicated the existence of rutin, gallic acid and caffeic acid. Total phenolic (TPC) and total flavonoid content (TFC) exhibited significant (p < 0.05) correlation with 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide, hydroxyl ion, inhibition of β-carotene oxidation, iron chelation, reducing power and total antioxidant capacity. In hepatic sample of rat, CCl4 administration increased (p < 0.05) the level of nitrite, hydrogen peroxide (H2O2), thiobarbituric acid reactive substances (TBARS) whereas a decline was recorded in antioxidant enzymes; superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and in reduced glutathione (GSH). Concentration of alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) and globulin increased (p < 0.05) whereas level of total protein and albumin decreased in serum of CCl4 treated rats. Level of pro-inflammatory cytokines; tumor necrosis factor-α (TNF-α), tumor growth factor-β1 (TGF-β1) and resistin was increased (p < 0.05) in serum whereby anti-inflammatory markers; interleukin-10 (IL-10), adiponectin and nuclear factor erythroid 2- related factor 2 (Nrf-2) decreased (p < 0.05) in hepatic tissues of CCl4 treated rats. DNA damages and histopathological alterations were induced with administration of CCl4 to rat. The altered levels of various parameters provoked by CCl4 toxicity restored towards the control level by the methanol extract of P. hydaspidis in a dose dependent manner. These results suggested the presence of antioxidant and anti-inflammatory phyto-constituents in methanol extract of P. hydaspidis.
- Current advances of pharmacological properties of 7-chloro-4-(phenylselanyl) quinoline: Prevention of cognitive deficit and anxiety in Alzheimer's disease model. [Journal Article]
- BPBiomed Pharmacother 2018; 105:1006-1014
- This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) at a dose of 1 mg/kg in memory impairment and anxiety in an Alzheimer's disease (AD) model induced by amyloid β-pept...
This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) at a dose of 1 mg/kg in memory impairment and anxiety in an Alzheimer's disease (AD) model induced by amyloid β-peptide (Aβ) (fragment 25-35) in mice. The involvement of acetylcholinesterase (AChE) activity and lipid peroxidation in hippocampus and cerebral cortex was evaluated. Male Swiss mice were pretreated with 4-PSQ (1 mg/kg, intragastrically (i.g.), daily) for fourteen days. Thirty minutes after the first treatment with 4-PSQ, the animals received a single injection of Aβ (3 nmol/3 μl/per site, intracerebroventricular (i.c.v.)). Mice were submitted to the behavioral tasks (open-field, elevated plus maze, Barnes maze, object recognition and location, and step-down inhibitory avoidance tests) from the fifth day onwards. On the fifteenth day, blood was removed for analysis of biochemical markers (glucose, triglycerides, urea, aspartate (AST) and alanine (ALT) aminotrasferases), and cerebral cortex and hippocampus for determination of AChE activity and thiobarbituric acid reactive species (TBARS) levels. Aβ caused memory impairment, anxiogenic behavior, increased AChE activity in the cerebral structures and TBARS levels in the cerebral cortex. 4-PSQ was effective to protect against behavioral changes, AChE activity and TBARS levels. In conclusion, 4-PSQ protected against learning and memory impairment and anxiety in a mouse model of AD induced by Aβ, and anticholinesterase and antioxidant actions are involved in the pharmacological effect of the compound.
- Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [Review]
- JCJ Cancer Res Clin Oncol 2018 Jul 17
- CONCLUSIONS: PD-1/PD-L1 inhibitors are generally safer and better tolerated than chemotherapy for patients with NSCLC with regard to summary toxic events, detailed toxic symptoms and hematologic toxicities. However, PD-1/PD-L1 inhibitors can generate a unique spectrum of irAEs, and several of them can be severe and even life-threatening. Clinicians should be aware of the risk of these AEs, as they may have a potentially negative impact on the patients' quality of life and survival outcome.
- Interferon Regulatory Factor 1 Activates Autophagy to Aggravate Hepatic Ischemia-Reperfusion Injury by Increasing High Mobility Group Box 1 Release. [Journal Article]
- CPCell Physiol Biochem 2018 Jul 17; 48(1):328-338
- CONCLUSIONS: IRF-1 activates autophagy to aggravate hepatic IRI by increasing HMGB1 release.
- HULC and 7SL RNA expression levels in patients with Crimean-congo hemorrhagic fever. [Journal Article]
- JMJ Med Virol 2018 Jul 17
- Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the Crimean-Congo hemorrhagic fever virus (CCHFV). Long non-coding RNAs (lncRNAs) are generally classified as transcripts long...
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the Crimean-Congo hemorrhagic fever virus (CCHFV). Long non-coding RNAs (lncRNAs) are generally classified as transcripts longer than 200 nucleotides (nt). The various lncRNAs expressed in infected cells are responsible for regulating the expression of viral and host genes. This is the first study to investigate hepatocellular carcinoma up-regulated long non-coding RNA (HULC) and 7SL RNA expression levels in CCHF patients. Blood samples were taken from 100 individuals (60 patients and 40 controls) and total RNA isolation was performed. Quantitative polymerase chain reaction (qPCR) was performed using the SYBR Green method to determine HULC and 7SL RNA expression levels in the study population. Compared the patient and control groups, HULC was upregulated statistically significant (p=0.04) and 7SL RNA was downregulated (p=0.93) in patients. Also there was a statistically significant difference between fatal cases and surviving patients for HULC and 7SL RNA (p<0.01 and p=0.03, respectively). In addition, HULC expression was increased statistically significant in fatal cases compared surviving patients in terms of clinical parameters such as aspartate aminotransferase (AST) (p<0.01), alanine aminotransferase (ALT) (p<0.01), international normalized ratio (INR) (p=0.05), prothrombin time (PT) (p=0.01), active partial thromboplastin time (aPTT) (p<0.01), and lactate dehydrogenase (LDH) (p<0.01). These findings highlighted that HULC and 7SL RNA could be important mediators for studying pathogenesis of CCHF and significant therapeutic targets of the disease. This article is protected by copyright. All rights reserved.
- The association between obesity and dengue virus (DENV) infection in hospitalised patients. [Journal Article]
- PlosPLoS One 2018; 13(7):e0200698
- Both obesity and DENV infections are growing public health concerns that have far-ranging socioeconomic effects, especially in developing countries. Despite the increasing prevalence of these conditi...
Both obesity and DENV infections are growing public health concerns that have far-ranging socioeconomic effects, especially in developing countries. Despite the increasing prevalence of these conditions, there is a scarcity of data investigating the potential relationships between these two entities. Our study aims to examine the influence of obesity on various clinical and laboratory parameters amongst patients with DENV infections. A total of 335 hospitalized patients aged >12 years who were DENV non-structural protein 1 (NS1) antigen-positive were enrolled in this study. Clinical and laboratory variables were compared between patients with and without obesity. Multivariate analysis showed that the following admission clinical findings and laboratory results were independently associated with obesity; chills and rigors (AOR:2.653, 95% CI: 1.286-5.474), higher temperature (AOR:1.485, 95% CI: 1.080-2.042), higher systolic BP (AOR:1.057, 95% CI:1.037-1.078), raised haematocrit (AOR: 1.953, 95% CI: 1.010-3.778), elevated creatinine (AOR:3.504, 95% CI:1.351-9.008) and elevated ALT (AOR: 4.146, 95% CI:1.878-9.154). Obesity was found to be significantly associated with hospitalization >3 days (AOR: 1.990, 95% CI: 1.134-3.494) and the presence of increasing haematocrit with decreasing platelets (AOR: 2.134, 95% CI = 1.235-3.688). Serial assessment of laboratory data revealed that peak haematocrit was significantly higher and nadir platelets levels were significantly lower in obese patients. Both peak and admission levels of leukocyte counts, AST, ALT and creatinine were significantly higher in the obese group. Conversely, both admission and nadir albumin levels were lower for the obese group, although only nadir albumin levels achieved statistical significance. These findings support closer clinical monitoring of obese patients who present with DENV infections, as this patient cohort may possess an increased tendency towards developing more severe clinical manifestations of DENV infections as compared to non-obese patients.
- [Effect of Rutin on Liver Function and Morphology in Type 1 Diabetes Mice Induced by Streptozotocin]. [Journal Article]
- SDSichuan Da Xue Xue Bao Yi Xue Ban 2018; 49(3):384-387
- CONCLUSIONS: Rutin may improve the liver function and reduce the damage of liver tissue in STZ-induced type 1 diabetic mice.
- Crosstalk between GSK-3, c-Fos, NFκB and TNF-α signaling pathways play an ambitious role in Chitosan Nanoparticles Cancer Therapy. [Journal Article]
- TRToxicol Rep 2018; 5:723-727
- Nanotechnology is a promising era of medicine for developing targeted drug delivery system. Chitosan nanoparticles (CNPs) have attracted increasing attention for their wide applications as anticancer...
Nanotechnology is a promising era of medicine for developing targeted drug delivery system. Chitosan nanoparticles (CNPs) have attracted increasing attention for their wide applications as anticancer drugs. This article is concerned with the therapeutic index of chitosan nanoparticles against diethyl nitrosamine (DEN) induced hepatocellular carcinoma (HCC). HCC was induced in rats via repeated DEN administration in a dose of 200 mg/kg BW IP, 2 weeks later rats received (2 ml/kg BW) CCl4 orally for 2 months followed by daily treatment with chitosan nanoparticles in an oral dose of 12 mg/kg for 1 month. Then the gene expression of glycogen synthase kinase-3 (GSK-3), (c-FOS), nuclear factor kappa-B (NFκB) and tumor necrosis factor- α (TNF-α) were reported in rats sera and the correlation between GSK-3, C-Fos, NFƘB and TNF-α and liver tumorigenesis was investigated. The results elucidated that DEN significantly increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Marked increments in serum malondialdehyde (MDA) and nitric oxide (NOx) levels along with a slight reduction of glutathione (GSH) level were evidenced in HCC. Liver injury triggered an inflammatory response by enhancing the mRNA gene expression of NFκB and TNF-α. DEN effectively activated apoptotic markers GSK-3 and c-FOS. Oral administration of CNPs alleviated the oxidative, inflammatory and apoptotic hazards induced via DEN. The histopathological examination reinforced these results. The present study highlights the anti-inflammatory and anti-apoptotic potentials of CNPs against DEN-induced HCC.
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- Effects of 3 Rodent Beddings on Biochemical Measures in Rats and Mice. [Journal Article]
- JAJ Am Assoc Lab Anim Sci 2018 Jul 16
- Components of bedding might interact with experimental treatments and affect the outcome of various experiments. Herewe studied the biochemical effects of 3 rodent bedding materials that are commonly...
Components of bedding might interact with experimental treatments and affect the outcome of various experiments. Herewe studied the biochemical effects of 3 rodent bedding materials that are commonly used in Egypt. Male and female rats and mice were assigned randomly into 4 single-sex and single-species groups (10 animals per group). Three types of bedding-rice straw, wheat straw, and pine wood shavings-were evaluated. After 4 wk, animals were euthanized, and biochemical parameterswere measured. In male and female rats given wood shavings, serum ALT activity and malondialdehyde concentration increased whereas catalase activity decreased compared with levels in the wheat straw group. In contrast, ALT activity and malondialdehyde concentrations decreased but CAT activity increased in rats housed on rice straw compared with wheat straw. Serum AST and ALT activities increased in male and female mice exposed to rice straw, whereas the malondialdehyde concentration increased and catalase decreased in the wood shavings group relative to the wheat straw group. In mice exposed to wheat straw, AST and ALT activities and malondialdehyde concentrations decreased and CAT activity increased compared with the other groups. Because our results showed that exposure to wood shavings affects some biochemical parameters of rats and mice, we do not recommend its use as laboratory animal bedding. We consider that, of the materials tested, rice straw bedding is the best bedding material for rats, whereas wheat straw is best for mice.