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Abstract Sleep quality and its effects have become a public concern over the last few years. While the prevalence of sleep disorders was increasing, several studies have linked diet and physical activity as a cause of it. Indeed, many people complain about their sleeping problems without considering their lifestyle as a cause. This leads the efforts to focus on these principal factors and find their specific effect. The study aims to map out the research on the effect of nutrition and physical activity on sleep quality. The literature search was conducted in electronic libraries and databases related to nutrition and medical literature – Google Scholar, PubMed, and ScienceDirect– using relevant selected keywords. Article inclusion and selection were made by excluding duplicates, analyzing titles and abstracts, and reviewing the articles’ full text. This review included 61 articles. This literature study reinforces the importance of researching sleep and the lifestyle contributors to poor sleep, such as physical activity and nutrition. more...

Abstract Background The protein kinase C (PKC) family of serine/threonine kinases contains more than ten isozymes that are involved in multiple signaling pathways, including cell cycle regulation and carcinogenesis. The PKCε isozyme is an oncogene known to be upregulated in various signaling pathways involved in hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC). However, there is no known association of missense SNPs in PKCε with this disease, which can be a potential biomarker for early diagnosis and treatment. This research reveals a novel missense SNP in PKCε that is associated with HCV-induced HCC in the Pakistani population. Methods The PKCε SNP with amino acid substitution of E14K was chosen for wet lab analysis. Tetra ARMS-PCR was employed for the identification of high-risk SNP in PKCε of HCV-induced HCC patients. Liver function testing was also performed for comparison between the liver condition of the HCC patient and control group, and the viral load of HCC patient samples was evaluated to determine any alteration in the viral infectivity between different genotypes of the selected high-risk PKCε variant SNP. Results Frequency distribution of the homozygous GG genotype was found to be highest among HCV-induced HCC patients and was also found to be significantly associated with disease development and progression. The p values of comparative data obtained for the other two genotypes, heterozygous AG and homozygous AA, of the SNP also showed the significance of the data for these alleles. Still, their odds ratio and relative risk analysis did not indicate their association with HCV-induced HCC. Conclusion The distribution of a genotype GG of PKCε has been found in HCV- induced HCC patients. Therefore, these PKCε SNP have the potential to be biomarkers for HCV-induced HCC. Further investigation using a larger sample size would provide additional insight into these initial data and open a new avenue for a better prognosis of this disease. more...

Abstract Acacia hydaspica possesses varied pharmacological attributes. We aimed to examine the antimicrobial potential and isolate the active antimicrobial metabolites. The plant extract was fractionated and the antimicrobial activity of the crude extract, fractions and compounds was tested by agar well diffusion and agar tube dilution and broth dilution methods. Bacterial strains selected for bioactivity testing were Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii while selected strains from kingdom fungi were Candida albicans, Cryptococcus neoformans, Fusarium solani and Aspergillus. The active compounds were isolated from Acacia hydaspica by bioassay-guided fractionation and identified by nuclear magnetic resonance and spectroscopic techniques. S. aureus cell surface proteins, Autolysins (Atl), Clumping factor A (ClfA), and Fibronectin Binding Proteins (FnBP), were molecularly docked with Catechin 3-O-gallate (CG) and Methyl gallate (MG) and binding energy and molecular interactions between the proteins and compounds were analyzed. Ethyl acetate (AHE) and Butanol (AHB) fractions of A. hydaspica were the most active fractions against tested microbial strains. Therefore, both were subjected to bioassay-directed fractionation which led to the isolation of one pure active antimicrobial AHE and one active pure compound from AHB fraction besides active enriched isolates. Methyl-gallate (MG) and catechin-3-gallate (CG) are active compounds extracted from AHE and AHB fractions respectively. In antibacterial testing MG significantly inhibited the growth of E. coli (MIC50 = 21.5 µg/ml), B. subtilus (MIC50 = 23 µg/ml) and S. aureus (MIC50 = 39.1 µg/ml) while moderate to low activity was noticed against other tested bacterial strains. Antifungal testing reveals that MG showed potent antifungal activity against F. solani (MIC50 = 33.9 µg/ml) and A. niger (MIC50 = 41.5 µg/ml) while lower antifungal activity was seen in other tested strains. AHB fractions and pure compound (CG) showed specific antibacterial activity against S. aureus only (MIC50 = 10.1 µg/ml) while compound and enriched fractions showed moderate to no activity against other bacterial and fungal strains respectively. Molecular docking analysis revealed that CG interacted more strongly with the cell surface proteins than MG. Among these proteins, CG made a stronger complex with ClfA (binding affinity − 9.7) with nine hydrophobic interactions and five hydrogen bonds. Methyl gallate (MG) and catechin 3-O-gallate (CG) are the major antimicrobial compound from A. hydaspica that inhibit the growth of specific microbes. The occurrence of MG and CG endorse the traditional antimicrobial applicability of A. hydaspica, and it can be a legitimate alternative to control specific microbial infections. more...

The ketogenic diet (KD) is a low-carbohydrate, high-fat diet that is primarily used to treat childhood epilepsy. The processes through which the ketogenic diet works, on the other hand, have been proposed as a preventative method for oxidative stress and as adjuvant therapy for various disorders, including cancer. The current review aim is to assess the effect of the ketogenic diet on oxidative stress and cancer. A review of the scientific literature on the effects of the ketogenic diet on oxidative stress, cancer, and the mitochondrial metabolism is provided. Furthermore, the review depicts the human research that evaluated the anti-tumour benefits of ketogenic diets on patients with cancer, with a total of 154 subjects. Although preclinical research indicates that KD has anticancer benefits, prolongs longevity, and inhibits cancer growth, human clinical trials are inconclusive. The effects of KD on cancer and as an adjuvant treatment are mostly unclear due to a paucity of high-quality clinical research. We suggest a series of research recommendations for clinical trials exploring the impact of KD on cancer growth and progression. more...

Abstract Background Low and middle-income countries are facing a rapid increase in obesity and overweight burden, particularly in urban settings. Being overweight in men is associated with infertility and a higher risk to have a low sperm count or no sperm in their ejaculate. Despite potential limitations, this is one of few studies conducted to determine the potential risk of paternal overweight on sperm standard parameters, sperm chromatin integrity and assisted conception outcome including fertilization, embryo quality, cleavage rate, reduce blastocyst development, implantation, and cumulative live birth rate (CLBR). Methods A cross-sectional study of 750 infertile couples undergoing assisted reproduction technique at a single reproductive medicine center of Salma Kafeel Medical Centre Islamabad. Sperm from men undergoing ART were analyzed for chromatin integrity using sperm chromatin dispersion assay (SCD), Chromomycin A3 staining (CMA3), and toluidine blue (TB) staining, while other semen parameters were assessed on same day includes; standard semen parameters, reactive oxygen species (ROS), sperm deformity index (SDI), teratozoospermic index (TZI), and hypo-osmatic swelling test (HOST). Paternal body mass index (BMI) 24.5-30 kg/m2 were considered to be overweight. Results In the analysis of the percentage of spermatozoa with chromatin maturity (CMA3) and chromatin integrity (TB) was reduced significantly in overweight men (p more...

Abstract Background Vitamin D can influence more than 200 genes in various tissues showing its credibility among the fat-soluble vitamins. Vitamin D deficiency is directly proportional to major clinical conditions such as cardiovascular diseases, diabetes, malignancy, and multiple sclerosis. This study was conducted to determine the vitamin D level of individuals and its association with depression. Methods Vitamin D levels of 100 healthy and 100 depressed subjects were determined. The isolated subjects were screened on the Beck Depression Inventory (BDI) scale and divided into three groups according to their age. Group-I comprised subjects of age 20 years and below, Group-II included subjects of age 21 to 60, and Group-III comprised subjects of ≥ 61 years of age. A sufficient level of vitamin D in normal subjects was noted, while mild deficiency of vitamin D status was observed in depressed subjects. Results Our study has reported a higher percentage of vitamin D deficiency in the Peshawar region. The results of our study indicated that depression was common in individuals having vitamin D deficiency. Conclusions The study showed a very high frequency of vitamin D deficiency in subjects with depression in Peshawar, Pakistan. The deficiency of vitamin D was observed more in females as compared to males. Further studies should explicate whether the highly widespread vitamin D deficiency could be cost-effectively treated as part of preventive or treatment interventions for depression. more...

Abstract This study aimed to explore the mechanisms of action of a sulindac acetohydrazide derivative, N'-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide, against anticancer drug cisplatin induced organ damage. Using a rodent model, various markers of organ function and signaling pathways were examined and validated by molecular docking studies. The study involves five groups of animals: control, DMSO, CDDP, CDDP + DMFM, and DMFM. Biochemical enzyme activity, histopathology, tissue antioxidant, and oxidative stress markers were examined. RT-PCR and western blot analyses were conducted for the expression of inducible cyclooxygenase enzyme (COX-2), nuclear factor kappa beta (NF-κB), p65, IL-1, TNF-α, and inducible nitric oxide synthase (iNOS). Flow cytometry analysis of CD4 + TNF-α, CD4 + COX-2, and CD4 + STAT-3 cells in whole blood was performed. Structural and dynamic behavior of DMFM upon binding with receptor molecule molecular docking and dynamic simulations were performed using bioinformatics tools and software. Treatment with DMFM reversed cisplatin-induced malondialdehyde (MDA) and nitric oxide (NO) induction, whereas the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD) in the kidney, heart, liver, and brain tissues were increased. DMFM administration normalized plasma levels of biochemical enzymes. We observed a marked decline in CD4 + STAT3, TNF-α, and COX2 cell populations in whole blood after treatment with DMFM. DMFM downregulated the expression factors related to inflammation at the mRNA and protein levels, i.e., IL-1, TNF-α, iNOS, NF-κB, STAT-3, and COX-2. Dynamic simulations and in silico docking data supports the experimental findings. Our experimental and in silico results illustrated that DMFM may affect protective action against cisplatin-induced brain, heart, liver, and kidney damage via reduction of inflammation and ROS. more...

Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer and is responsible for close to one million annual deaths globally. In Pakistan, HCC accounts for 10.7% of cancer incidence. Prior studies indicated an association between interleukin 4 (IL-4) and cytotoxic T lymphocyte protein 4 (CTLA-4) gene polymorphisms in many types of cancers, including HCC that are either hepatitis B virus (HBV)- or hepatitis C Virus (HCV)-induced. The association of IL-4 and CTLA-4 genetic polymorphisms with HCV-induced HCC is not yet determined in the Pakistani population. Therefore, this research is designed to investigate the implication of IL-4 and CTLA-4 gene polymorphisms by determining the association of IL-4 -590 C/T (rs2243250) and CTLA-4 + 49 A/G (rs231775) with HCC in Pakistan. Methods Different bioinformatics tools were employed to determine the pathogenicity of these polymorphisms. Samples were collected from HCV-induced HCC patients, followed by DNA extraction and ARMS-PCR analysis. Results The SNP analysis results indicated a positive association of IL-4 -590C/T and CTLA-4 + 49A/G gene polymorphisms with HCV-induced HCC in Pakistan. The CTLA-4 polymorphism might enhance therapeutic efficiency of HCC chemotherapy medicines. The IL-4 polymorphism might introduce new transcription factor binding site in IL-4 promoter region. Conclusion This study delineated risk factor alleles in CTLA-4 and IL-4 genes associated with HCV-mediated HCC among Pakistani patients that may have application to serve as genetic markers for pre- and early diagnosis and prognosis of HCC in HCV patients. more...

Abstract The present study aims to assess the effect of a heavy metal burden on general health, biochemical parameters, an antioxidant enzyme, and reproductive hormone parameters in adult male brick kiln workers from Pakistan. The study participants (n = 546) provided demographic data including general health as well as body mass index. Blood was collected to quantitatively assess hematological, biochemical, and reproductive hormone parameters as well as heavy metal concentrations using both atomic absorption spectroscopy (AAS) and particle-induced X-ray emission (PIXE). The data showed that 10% of the brick kiln workers were underweight and 10% obese (P = 0.059), with workers also reporting multiple health issues. Heavy metal concentrations utilizing AAS revealed significantly (p = 0.000) higher levels of cadmium, chromium, and nickel, while PIXE detected more than permissible levels of Si, P, S, Cl, K, Ca, Zn, Ti (p = 0.052), Mn (p = 0.017), Fe (p = 0.055), Co (p = 0.011), Ni (p = 0.045), and Cu (p = 0.003), in the blood of kiln workers. Moreover, a significant increase in platelet count (P = 0.010), a decrease in sodium dismutase levels (p = 0.006), a major increase in reactive oxygen species (p = 0.001), and a reduction in protein content (p = 0.013) were evident. A significant increase in cortisol levels (p = 0.000) among the workers group was also observed. The concentration of LH and FSH increased significantly (p = 0.000), while that of testosterone decreased (p = 0.000) in the worker group compared with controls. A significant inverse relationship was found between cortisol, LH (r = − 0.380), and FSH (r = − 0.946), while a positive correlation between cortisol and testosterone was also evident (r = 0.164). The study concludes that increased heavy metal burden in the blood of brick kiln workers exposes them to the development of general and reproductive health problems due to compromised antioxidant enzyme levels, increased oxidative stress conditions, and a disturbing reproductive axis. more...

Abstract Expression analysis of new protein targets may play a crucial role in the early detection and diagnosis of brain tumor progression. The study aimed to investigate the possible relation of KLF14, TPD52, miR-124, and PKCε in the development and progression of brain cancer and space occupying lesion (SOL) of the brain. One hundred human blood samples comprising varying diagnostic groups (SOL brain, grade I, II, III, IV) were analyzed by real-time quantitative PCR to determine the expression level of KLF14, TPD52, miR-124, and PKCε. TPD52 and PKCε were upregulated in brain cancer by 2.5- and 1.6-fold, respectively, whereas, KLF14 and miR-124 were downregulated in brain cancer. In metastatic and high-grade brain cancer, TPD52 and PKCε expression were up-regulated and KLF14 and miR-124 expression were down-regulated. Further, these genes were found to be differentially expressed in the blood of patients with SOL. Upregulation of TPD52 and PKCε, however, reduced expression of KLF14 and miR-124 in SOL of the brain as compared to healthy controls. Expression analysis of TPD52, KLF14, miR-124, and PKCε provided useful information on the differences existing between the normal brain and SOL, in addition to gliomas; thus, might prove to be useful having diagnostic or prognostic value. more...

Nonylphenol (NP) is an environmental pollutant that is recognized for its hazardous effects on humans and animals. NP has potential to induce oxidative stress that leads to hepatic toxicity. Diosmetin (DIOS) is a naturally occurring bioflavonoid that possesses several biological properties. The current study was designed to ascertain the curative effects of DIOS against NP prompted hepatotoxicity in rats. 32 male albino rats were randomly categorized in 4 groups i.e., control (0.1 % DMSO), NP (50 mg/kg), NP + DIOS (50 mg/kg + 100 mg/kg) and DIOS (100 mg/kg) group. Our results revealed that NP instigated substantial reduction in the antioxidant enzymes activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), glutathione peroxidase (GPx), glutathione S-transferases (GST) and glutathione (GSH). NP administration raised the levels of reactive oxygen species (ROS) as well as the levels of malondialdehyde (MDA). Treatment with DIOS significantly (p more...

This study investigates the possible effect of exogenous melatonin on appetite control by investigating plasma leptin and subjective appetite parameters. Nine healthy male participants [26 ± 1.3 years, body mass index (BMI) 24.8 ± 0.8 kg/m2] (mean ± SD) were recruited. The study was designed as a randomized three-way cross-over design; light (>500 lux) (LS), dark (500 lux) + exogenous melatonin (LSC), with an interval of at least 7 days between each session. Each session started at 18:00 h and ended at 06:00 h the following day. Participants were awake and in a semi-recumbent position during each clinical session. The meal times were individualized according to melatonin onset from 48 h sequential urine collection, whereas melatonin intake was given 90 min before the evening meal. Subjective appetite parameters were collected at 30 min intervals during each session. Plasma leptin was collected at specific time points to analyze pre-prandial and postprandial leptin. Subjective hunger and desire to eat were reported higher in LS than DSC and LSC (P = 0.03, and P = 0.001). Plasma leptin showed a significant increase in LSC and DSC (p = 0.007). This study suggested a positive impact of exogenous melatonin on subjective appetite and plasma leptin. more...

Nonylphenol (NP) is a ubiquitous environmental toxicant that is known to cause hepatotoxicity via generation of reactive oxygen species (ROS). Aucubin (AUC), an iridoid glucoside, is a potential phytochemical possessing antioxidant and anti-inflammatory features. The current study was intended to ascertain the hepatoprotective role of AUC against NP-generated liver toxicity in rats. 48 male rats were distributed into four groups. viz. Control, NP-intoxicated group (50 mg/kg), NP + AUC-treated group (50 mg/kg + 40 mg/kg) and AUC-treated group (40 mg/kg). All the doses were administered orally. Our findings indicated that the NP intoxication upregulated the alanine aminotransferase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) level. Moreover, it brought down the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GSR) and glutathione-S-transferase (GST), as well as the glutathione (GSH) content. Conversely, the levels of malondialdehyde (MDA) and ROS were escalated. Besides, the levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 as well as the cyclooxygenase-2 (COX-2) activity were elevated due to the NP administration. In addition to it, histopathological assessment displayed the prominent morphological alterations in hepatic tissues of rats. Nevertheless, treating the rats with AUC significantly (p more...

Warfarin has been widely used as an oral anticoagulant agent. In past, efforts have been done to study the contribution of genetic variation on warfarin dose requirements. The possible therapeutic dose determination of warfarin is very challenging, i.e., extremely low dose leading to unusable antithrombotic therapy or high dose causes particularly bleeding complications. Our study aimed to investigate these observations in more detail, we determined the correlation of interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) among VKORC1 and CYP2C9 genetic variants in patients with heart valve replacement who were treated with a range of warfarin doses and compared with levels in healthy controls. A total of 107 human subjects were recruited with low < 5 mg, medium 5–10 mg/day, and high > 10 mg/day warfarin doses. The genetic study of VKORC1–1639G/A, C1173T, 3730G > A, CYP2C9*2, and CYP2C9*3 was performed using TaqMan genotyping and DNA sequencing. The gene expression of IL-6, TNF-α, and COX-2 mRNA was analyzed. IL-6, TNF-α, and COX-2 protein expressions were determined by ELISA and Western blot analysis to evaluate the pro- and anti-inflammatory effects of warfarin. A statistically significant difference was found among the haplotypes of VKORC1 rs9934438 (C1173T), rs9923231 (−1639G > A), rs7294 (3730G > A) and CYP2C9 *2 p. Arg144 Cys (rs28371674), CYP2C9 *3 p. Ile359Leu (rs1057910) genotypes with warfarin dose requirements (p = 0.001). The increased levels of COX-2, IL-6, and TNF-α proteins were observed when a high dose of warfarin (>10 mg/ml) was administered. However, a lower concentration (1.0 mg/ml) was observed with decreased warfarin dose ( more...

Our study aimed to identify the new blood-based biomarkers for the diagnosis and prognosis of cervical cancer. Moreover, the three-dimensional (3D) structure of Kruppel-like factor 9 (KLF9) was also determined in order to better understand its function, and a signaling pathway was constructed to identity its upstream and downstream targets. In the current study, the co-expressions of tumor protein D52 (TPD52), KLF9, microRNA 223 (miR-223), and protein kinase C epsilon (PKCϵ) were evaluated in cervical cancer patients and a possible relation with disease outcome was revealed. The expressions of TPD52, KLF9, miR-223, and PKCϵ were studied in the blood of 100 cervical cancer patients and 100 healthy controls using real-time PCR. The 3D structure of KLF9 was determined through homology modeling via the SWISS-MODEL and assessed using the Ramachandran plot. The predicted 3D structure of KLF9 had a similarity index of 62% with its template (KLF4) with no bad bonds in it. In order to construct a genetic pathway, depicting the crosstalk between understudied genes, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and DAVID software were used. The constructed genetic pathway showed that all the understudied genes are linked to each other and involved in the PI3K/Akt signaling pathway. There was a 23-fold increase in TPD52 expression, a 2-fold increase in miR-223 expression, a 0.14-fold decrease in KLF9 expression, and a 0.05-fold decrease of PKCϵ expression in cervical cancer. In the present study, we observed an association of the expressions of TPD52, KLF9, miR-223, and PKCϵ with tumor stage, metastasis, and treatment status of cervical cancer patients. Elevated expressions of TPD52 and miR-223 and reduced expressions of KLF9 and PKCϵ in peripheral blood of cervical cancer patients may serve as predictors of disease diagnosis and prognosis. Nevertheless, further in vitro and tissue-level studies are required to strengthen their role as potential diagnostic and prognostic biomarkers. more...

Arsenic exposure alters redox balance, induces DNA damage, and deregulates many genes. OGG1 gene involved in base repair mechanism, for excision of 8-oxoguanine (8-oxoG) from DNA formed as a result of accumulation of ROS in cell. HPRT gene encode transferase enzymes involved in purine recycling mechanism. The main focus of the study was to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage of industrial workers. Blood samples of 300 occupational workers were collected from welding, brick kiln, furniture, pesticide, and paint industry (n = 60/industry) to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage in blood cells by comet assay along with age and gender matched 300 control individuals. Blood arsenic content was higher (P25years of age as well as between workers with 10year exposure. Reduced expression (P more...

Based on the biologically active compounds of Pulicaria jaubertii studied so far, there are no studies on the use of this plant in broilers. Therefore, the present study aims is to investigate the effect of Pulicaria jaubertii on the performance, blood biochemistry, internal organs, gene expression related to immune response, and the cecal microbiota of broiler chickens. A total of two hundred and forty male broilers were used and divided into four diet groups (T1 = 0, T2 = 3, T3 = 6, and T4 = 9 g Pulicaria jaubertii powder/kg basal diet). The performance evaluation, serum biochemical parameters, internal organ indicators, cytokines’ gene expression, and microbiota colonization were determined. The study results showed that this plant was rich in nutrients, some fatty acids, and bioactive phenolic compounds. All growth performance indicators and relative liver weight were improved by Pulicaria jaubertii levels (T2 to T4) with no effect on feed intake. T3 and T4 showed higher total protein and lower triglycerides and total cholesterol. Birds fed Pulicaria jaubertii showed immune regulation through the modulation of pre-inflammatory cytokines and increased mucin-2 and secretory Immunoglobulin A compared with the control group. Diet groups (T2 to T4) had higher quantities of Lactobacillus spp. and lower levels of Salmonella spp. than the control group. We conclude that Pulicaria jaubertii could be used as a feed supplement for broilers due to its beneficial effects on overall performance, immune response, and microbiota. Further studies are recommended to investigate the potential mechanism of Pulicaria jaubertii in broilers. more...

Glucose-galactose malabsorption is a rare inherited autosomal recessive genetic defect. A mutation in the glucose sodium-dependent transporter-1 gene will alter the transportation and absorption of glucose and galactose in the intestine. The defect in the SGLT-1 leads to unabsorbed galactose, glucose, and sodium, which stay in the intestine, leading to dehydration and hyperosmotic diarrhea. Often, glucose-galactose malabsorption patients are highly dependent on fructose, their primary source of carbohydrates. This study aims to investigate all published studies on congenital glucose-galactose malabsorption and fructose malabsorption. One hundred published studies were assessed for eligibility in this study, and thirteen studies were identified and reviewed. Studies showed that high fructose consumption has many health effects and could generate life-threatening complications. None of the published studies included in this review discussed or specified the side effects of fructose consumption as a primary source of carbohydrates in congenital glucose-galactose malabsorption patients. more...

Cis-diamminedichloroplatinum (II) (CDDP) is a widely used antineoplastic agent with numerous associated side effects. We investigated the mechanisms of action of the indole derivative N’-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide (MMINA) to protect against CDDP-induced testicular damage. Five groups of rats (n = 7) were treated with saline, DMSO, CDDP, CDDP + MMINA, or MMINA. Reproductive hormones, antioxidant enzyme activity, histopathology, daily sperm production, and oxidative stress markers were examined. Western blot analysis was performed to access the expression of steroidogenic acute regulatory protein (StAR) and inflammatory biomarker expression in testis, while expression of calcium-dependent cation channel of sperm (CatSper) in epididymis was examined. The structural and dynamic molecular docking behavior of MMINA was analyzed using bioinformatics tools. The construction of molecular interactions was performed through KEGG, DAVID, and STRING databases. MMINA treatment reversed CDDP-induced nitric oxide (NO) and malondialdehyde (MDA) augmentation, while boosting the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the epididymis and testicular tissues. CDDP treatment significantly lowered sperm count, sperm motility, and epididymis sperm count. Furthermore, CDDP reduced epithelial height and tubular diameter and increased luminal diameter with impaired spermatogenesis. MMINA rescued testicular damage caused by CDDP. MMINA rescued CDDP-induced reproductive dysfunctions by upregulating the expression of the CatSper protein, which plays an essential role in sperm motility, MMINA increased testosterone secretion and StAR protein expression. MMINA downregulated the expression of NF-κB, STAT-3, COX-2, and TNF-α. Hydrogen bonding and hydrophobic interactions were predicted between MMINA and 3β-HSD, CatSper, NF-κβ, and TNFα. Molecular interactome outcomes depicted the formation of one hydrogen bond and one hydrophobic interaction between 3β-HSD that contributed to its strong binding with MMINA. CatSper also made one hydrophobic interaction and one hydrogen bond with MMINA but with a lower binding affinity of -7.7 relative to 3β-HSD, whereas MMINA made one hydrogen bond with NF-κβ residue Lys37 and TNF-α reside His91 and two hydrogen bonds with Lys244 and Thr456 of STAT3. Our experimental and in silico results revealed that MMINA boosted the antioxidant defense mechanism, restored the levels of fertility hormones, and suppressed histomorphological alterations. more...

Several studies have found a correlation between inflammatory markers and sarcopenia; however, limited research has been conducted on the Arabic population. Therefore, this study aimed to investigate the value of inflammatory parameters in Saudi elderly women with sarcopenia. In this cross-sectional study, 76 elderly Saudi women (>65 years) were stratified according to the presence (n = 26) or absence (n = 50) of sarcopenia, using the operational definition of the Asian Working Group for Sarcopenia (AWGS). Demographics and clinical data were collected. Muscle mass, muscle strength, and physical performance were assessed using bioelectrical impedance, hand grip and timed-up-and-go (TUG) tests, respectively. Inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP) were assessed using commercially available assays. Muscle mass and strength indicators were lower in the sarcopenia group (p-value < 0.05). Moreover, interleukin 6 (IL-6) was positively correlated with TUG (r = 0.48, p-value < 0.05), while CRP showed an inverse correlation with the right leg muscle (R-Leg-M) and a positive correlation with triceps skinfold (TSF) (r = −0.41, r = 0.42, respectively, p-values < 0.05). Additionally, TSF and R-Leg-M were independent predictors of CRP variation (R2 = 0.35; p < 0.01). Lastly, participants with a TNF-α > 71.2 were five times more likely to have sarcopenia [(OR = 5.85), 95% CI: 1.07–32.08; p = 0.04]. In conclusion, elevated levels of TNF-α are significantly associated with the risk of sarcopenia, while variations perceived in circulating CRP can be explained by changes in the muscle mass indices only among individuals with sarcopenia. The present findings, while promising, need further investigations on a larger scale to determine whether inflammatory markers hold any diagnostic value in assessing sarcopenia among elderly Arab women. more...