This study assessed the fertility potential of methanol leaf extract of Glyphaea brevis (MGB) in rats exposed to 1,4-Dinitrobenzene (DNB), an environmental reprotoxicant. Male Wistar rats were orally ...exposed to 50 mg/kg DNB and administered 750 mg/kg MGB, 1500 mg/kg MGB or 300 mg/kg vitamin E for 21 days after 48 h of DNB exposure. Determination of serum reproductive hormone levels by enzyme-linked immunosorbent assays, evaluation of hematologic profile, computer-assisted sperm analyses (CASA) of sperm kinematics and morphology, assessment of testicular and spermatozoan antioxidant systems, and histopathological evaluation of reproductive tissues were performed. HPLC-DAD analysis identify Glyphaeaside C as the major component of the extract. In rats toxified with 50 mg/kg DNB, testicular and epididymal weights, serum levels of luteinizing hormone, testosterone and follicle-stimulating hormone, and packed cell volume, haemoglobin concentration, and white blood cell counts were decreased. There was altered sperm kinematics which reflected in increased sperm abnormalities. Treatment with the Glyphaeaside C -enriched MGB counteracted all DNB-induced changes and corrected DNB-induced aberrations in kinematic endpoints. Also, testicular and epididymal antioxidant systems were disrupted and there was damage to tissue histoarchitecture. Furthermore, our molecular docking study revealed that Glyphaeaside-C exhibited high binding affinities to the binding pocket of some free radical generating enzymes. Conclusively, the results indicated that Glyphaeaside C-enriched extract of Glyphaea brevis leaf enhanced the quality of semen and improved the functional capabilities of spermatozoa following exposure of rats to DNB which could translate to enhanced fertility.
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•Identification of Glyphaeaside C the active component of the G. brevis leaf extract.•The extract preserved testicular DNA integrity.•Extract improved the antioxidant system in the testis and epididymis following 1,4 dinitrobenzene exposure.•Glyphaeaside C-enriched MGB improved semen quality and sperm motility.•Glyphaeaside C has string binding sites for myeloperoxidase, xanthine oxidase, NADP(H) oxidase and nitric oxide synthase.
Doxorubicin (DOX) is an anticancer agent for treating solid and soft tissue malignancies. However, the clinical use of DOX is restricted by cumulative, dose-dependent cardiotoxicity. Therefore, the ...present study aimed to assess the cardioprotective effects of
P. ginseng
C. A. Mey, febuxostat, and their combination against DOX-induced cardiotoxicity. Thirty-five Sprague Dawley male rats were used in this study. The animals were randomly divided into five groups, with seven rats per group. The control group received normal saline, the induced group received DOX only, and the treated group received
P. ginseng
, febuxostat, and their combination before DOX treatment. Biomarkers of acute cardiac toxicity were assessed in each group. Results showed that treatment with the combination of febuxostat and
P. ginseng
before DOX led to a significant improvement in the biomarkers of acute DOX-induced cardiotoxicity. In conclusion, the combination of
P. ginseng
and febuxostat produced more significant cardioprotective effects against DOX-induced cardiotoxicity when compared to either
P. ginseng
or febuxostat when used alone. The potential mechanism of this combination was mainly mediated by the anti-inflammatory and antioxidant effects of
P. ginseng
and febuxostat.
Background and Objectives: Vitamin D supplementation plays a key effect in lowering cytokine storms among COVID-19 patients by influencing the activity of the renin-angiotensin system and the ...production of the angiotensin-2 converting enzyme. The study was conducted to explore the effect of high-dose intramuscular vitamin D in hospitalized adults infected with moderate-to-severe SARS-CoV-2 in comparison with the standard of care in the COVID-19 protocol. Materials and Methods: Two groups of patients were compared in this prospective randomized controlled trial as the vitamin D was administered orally to group 1 (alfacalcidol 1 mcg/day) and intramuscularly to group 2 (cholecalciferol 200,000 IU). One hundred and sixteen participants were recruited in total, with fifty-eight patients in each group. Following the Egyptian Ministry of Health’s policy for COVID-19 management, all patients received the same treatment for a minimum of five days. Results: A significant difference was recorded in the length of hospital stay (8.6 versus 6.8 days), need for high oxygen or non-invasive mechanical ventilator (67% versus 33%), need for a mechanical ventilator (25% versus 75%), clinical improvement (45% versus 55%), the occurrence of sepsis (35% versus 65%), and in the monitored laboratory parameters in favor of high-dose vitamin D. Moreover, clinical improvement was significantly associated with the need for low/high oxygen, an invasive/non-invasive mechanical ventilator (MV/NIMV), and diabetes, while mortality was associated with the need for MV, ICU admission, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and the occurrence of secondary infection. Conclusions: Our study showed that high-dose vitamin D was considered a promising treatment in the suppression of cytokine storms among COVID-19 patients and was associated with better clinical improvement and fewer adverse outcomes compared to low-dose vitamin D.
Atherosclerotic ischemic coronary artery disease (CAD) is a significant community health challenge and the principal cause of morbidity and mortality in both developed and developing countries for ...all ethnic groups. The progressive chronic coronary atherosclerosis is the main underlying cause of CAD. Although enormous progress occurred in the last three decades in the management of cardiovascular diseases, the prevalence of CAD continues to increase worldwide, indicating the need for discovery of deeper molecular insights of CAD mechanisms, biomarkers, and innovative therapeutic targets. Recently, several research groups established that microRNAs essentially regulate various cardiovascular development and functions, and a deregulated cardiac enriched microRNA profile plays a vital role in the pathogenesis of CAD and its biological aging. Numerous studies established that over- or downregulation of a single miRNA gene by ago-miRNA or anti-miRNA is enough to modify the CAD disease process, significantly prevent age-dependent cardiac cell death, and markedly improve cardiac function. In the light of more recent experimental and clinical evidences, we briefly reviewed and discussed the involvement of miRNAs in CAD and their possible diagnostic/therapeutic values. Moreover, we also focused on the role of miRNAs in the initiation and progression of the atherosclerosis plaque as the strongest risk factor for CAD.
COVID-19 is caused by the SARS-CoV-2 virus, which has afflicted more than 245.37 million individuals worldwide and resulted in more than 4.9 million deaths as of today, with a mortality rate of 2.1%. ...Diabetes mellitus (DM) and its secondary complications are the major serious global health concerns today due to its growth rate, and it is the fastest-growing non-communicable disease. According to International Diabetes Federation (IDF) data, one out of 11 adults is diabetic, and the projection says that the figure will reach 642 million by 2040 globally. The occurrence of DM and its secondary complications is also associated with the severity of COVID-19 and high mortality. People with DM have a weakened immune system owing to innate immunity defects affecting phagocytosis, neutrophil chemotaxis, and cellmediated immunity; however, the high prevalence of diabetes in serious cases of COVID-19 may reflect the higher prevalence of type 2 DM (T2DM) in older people. Moreover, DM is linked to cardiovascular illness in older people, which could underlie the correlation between COVID-19 and fatal outcomes. SARS-CoV-2 infects via the angiotensin-converting enzyme 2 (ACE2), which is found in pancreatic islets, and infection with SARS-CoV-1 has been linked to hyperglycemia in individuals who do not have DM. And hence diabetic patients need to take more precautions and maintain their blood glucose levels. Many pieces of research say that COVID-19 and DM, especially its secondary complications are interlinked. But it also needs more elaborative evidence on whether the anti-diabetic drugs can manage only blood glucose or SARS-CoV-2.
Aims: To investigate the potential protective role of montelukast (Mont) in the pre-eclampsia rat model induced by L-NG-Nitro arginine methyl ester (L-NAME). Methods and materials: Thirty-two ...pregnant female albino Wistar rats were assigned to four groups: the control group: pregnant rats received vehicles; the Mont group: pregnant rats received Mont (10 mg/kg/day, p.o.) from the 6th to the 18th day of gestation; the L-NAME group: pregnant rats received L-NAME (50 mg/kg/day, i.p.) from the 9th to the 18th day of gestation; the Mont/L-NAME group: pregnant rats received Mont (10 mg/kg/day, p.o.) from the 6th to the 18th day of gestation and L-NAME (50 mg/kg/day, i.p.) from the 9th to the 18th day of gestation. Placental, hepatic, and renal malondialdehyde (MDA), total nitrites (NOx), interleukin 6 (IL-6), and tumor necrosis factor (TNF)-α were determined. Serum alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, 24-h urinary protein, and the placental growth factor (PGF) were measured. Histopathological examinations of the placental, hepatic, and renal tissues were also performed. In addition, placental, hepatic, and renal Janus kinase 2 (Jak2) and signal transducer and activator of transcription 3 (STAT3) immunoblotting were performed. Key findings: Mont improves oxidative stress, IL-6, TNF-α, ALT, AST, creatinine, urea, 24-h urinary protein, PGF, Jak2, and STAT3 which were all affected by L-NAME. Moreover, the histopathological assessment indicated that Mont restored the normal architecture that was markedly disturbed by L-NAME. Significance: Mont exerted the biochemical and histopathological amelioration of L-NAME-caused pre-eclampsia through its anti-inflammatory, anti-oxidant function and suppression of the IL-6/Jak2/STAT3 signaling pathway.
HIF-1α is a key factor promoting the development of hepatocellular carcinoma (HCC). As well, AKT-AMPKα-mTOR signaling is a promising target for cancer therapy. Yet, the AKT-AMPKα-mTOR-dependent ...activation of HIF-1α has not been studied in livers with HCC. In addition, the mechanisms underlying the potential antineoplastic effects of sitagliptin (STGPT), an antidiabetic agent, have not yet been elucidated. For that purpose, the N-nitrosodiethylamine (NDEA)-induced HCC mouse model was used in the present study using a dose of 100 mg/kg/week, i.p., for 8 weeks. NDEA-induced HCC mice received STGPT 20, 40, or 80 mg/kg starting on day 61 up to day 120. The present study revealed that STGPT inhibited HIF-1α activation via the interference with the AKT-AMPKα-mTOR axis and the interruption of IKKβ, P38α, and ERK1/2 signals as well. Accordingly, STGPT prolonged the survival, restored the histological features and improved liver function. Additionally, STGPT inhibited angiogenesis, as revealed by a significant downregulation in the VEGF and mRNA expression of CD309 with concomitant inhibition of tissue invasion was evident by an increased ratio of TIMP-1/MMP-2. STGPT exhibited apoptotic stimulatory effect as indicated upon calculating the BCL-2/Bax ratio and by the gene expression of p53. The decrease in AFP and liver index calculation, gene expression of Ki-67 confirmed the antiproliferative activity of STGPT. The anti-inflammatory potential was revealed by the decreased TNF-α level and the downregulation of MCP-1 gene expression. Moreover, an antifibrotic potential was supported by lower levels of TGF-β. These effects appear to be GLP1R-independent. The present study provides a potential basis for repurposing STGPT for the inhibition of HCC progression. Since STGPT is unlikely to cause hypoglycemia, it may be promising as monotherapy or adjuvant therapy to treat diabetic or even normoglycemic patients with HCC.
The main aim of this study was to synthesize copper oxide- (CuO-) titanium oxide- (TiO2-) chitosan-amygdalin nanocomposites (CTCANc) and to characterize them physically and biologically ...(antimicrobial and anticancer activity using MOLT4 blood cancer cell line) to endorse their useful applications as potential drug candidates in anticancer avenues. CuO-TiO2-chitosan-amygdalin nanocomposites were synthesized according to standard, reported methods. Physical characterization of the nanocomposites was performed using methods like X-ray diffractometer (XRD), and morphological and ultrastructural analysis of nanocomposites were done using electron microscope scanning and transmission. FTIR was recorded using a Perkin-Elmer spectrometer, and photoluminescence (PL) spectra were done using the spectrometer. Further, antibacterial activities were assessed using standard bacterial cultures. To demonstrate the nanocomposite’s anticancer effects, MTT assay, morphological analysis, apoptosis studies using acridine orange/ethidium bromide (AO/EtBr) dual staining, reactive oxygen species (ROS) analysis, and levels of antioxidant enzymes were analyzed using the MOLT4 blood cancer cell line. Synthesized nanocomposites were characterized using XRD and showed various peaks, respectively, for CuO-TiO2, amygdalin, and chitosan. MTT assay indicated an IC50 value of 38.41 μg/ml concentration of CTCANc. Hence, 30 and 40 μg/ml were used for the subsequent experiments. Morphological analysis, staining for apoptosis using AO/EtBr, mitochondrial membrane potential (MMP or ΔΨm) analysis, ROS analysis, and determination of the SOD, CAT, MDA, and GSH levels were performed. Observations like a significant loss of morphology, induction of apoptosis, elevated ROS, and decreased MMP were significant in 30 and 40 μg/ml nanocomposite-treated cells when compared to control cells. The bimetallic nanocomposites exhibited typical nanocomposites characteristics and significant antibacterial and anticancer effects. The study results endorse the antibacterial, anticancer activity of CuO-TiO2-chitosan-amygdalin nanocomposites and strongly suggest that further in-depth research using CuO-TiO2-chitosan-amygdalin nanocomposites could reveal their efficacy in the clinical scenario.
Cyclosporine A (CsA) shows significant inter-individual variability in its pharmacokinetics, which may be due to polymorphisms in ABCB-1 genes coding for P-glycoprotein. The aim of this study was to ...explore the role of genetic polymorphisms of ABCB-1 in affecting the CsA blood concentrations in renal transplanted patients over the first 3 months after transplantation. Renal transplanted patients receiving CsA (n = 40) were genotyped for ABCB -1 C3435T (I1145I) and G1199A (S400N) polymorphisms. CsA blood concentrations were measured on Day 7, 30, and 90 after transplantation. G1199A variant showed higher CsA blood concentrations in stable patients, that was significant for trough levels (198 vs. 136 ng/mL on Day 7, P = .004, 196 vs. 125 ng/mL on Day 30, P = .007, 194 vs. 121 ng/mL on Day 90, P = .005 for stable vs. unstable groups). Polymorphisms of ABCB-1 have only a minor effect on CsA blood concentrations. The functional G1199A polymorphism can affect the drug levels more than non-functional C3435T. This polymorphism might be of a potential prognostic value in renal transplanted patients.
The management of diabetes over the years has involved the use of herbal plants, which are now attracting interest. We assessed the antidiabetic properties of aqueous extract of
shoots (AECPS) and ...the mechanism of action on pancreatic
-cell dysfunction.
This study was conducted using Thirty-six 36) male Wistar rats. The animals were divided into six equal groups (
= 6) and treatment was performed over 14 days. To induce diabetes in the rats, a single dose of 65 mg/kg body weight of alloxan was administered intraperitoneal along with 5% glucose. HPLC analysis was carried out to identified potential compounds in the extract.
tests α-amylase, and α-glucosidase were analyzed. Body weight and fasting blood glucose (FBG) were measured. Biochemical parameters, such as serum insulin, liver glycogen, hexokinase, glucose-6-phosphate (G6P), fructose-1,6-bisphosphatase (F-1,6-BP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-ĸB), were analyzed. Additionally, mRNA expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), B-cell lymphoma 2 (Bcl-2), and proliferating cell nuclear antigen (PCNA) were each evaluated.
This
study showed inhibitory potency of
extract (AECPS) as compared with the positive controls. AECPS showed a gradual decrease in alloxan-induced increases in FBG, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-c), G6P, F-1,6-BP, malondialdehyde (MDA), IL-6, TNF-α, and NF-ĸB and increased alloxan-induced decreases in liver glycogen, hexokinase, and high density lipoprotein (HDL-c). The diabetic control group exhibited pancreatic dysfunction as evidenced by the reduction in serum insulin, homeostasis model assessment of
-cell function (HOMA-
), expressions of PI3K/AKT, Bcl-2, and PCNA combined with an elevation in homeostatic model assessment of insulin resistance (HOMA-IR). High performance liquid chromatography (HPLC) revealed 3-O-rutinoside, ellagic acid, catechin, rutin, and kaempferol in AECPS.
AECPS showed efficient ameliorative actions against alloxan-induced pancreatic dysfunction, oxidative stress suppression as well as, inflammation, and apoptosis via the activation of PI3K/AKT signaling pathways.
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