Menopausal symptom management: Fezolinetant's varied doses provide effective relief for vasomotor symptoms in women - A meta-analysis of 3291 participants.

Menopause represents the physiological transition when a woman's reproductive period ends associated with a variety of symptoms, including vasomotor symptoms, such as night sweats and hot flashes. This systematic review and meta-analysis aimed to assess the effectiveness and safety of oral Fezolinetant for treating vasomotor symptoms associated with menopause. Five electronic databases were searched from their inception until May 2023. Via the Cochrane risk of bias tool, two reviewers assessed the studies' quality. The primary outcomes were a decrease in VMSs frequency and severity and safety outcomes at 4 and 12 weeks. Data were extracted and then analyzed using RevMan software. This meta-analysis included six trials with a total of 3291 women that compared Fezolinetant to a placebo in the treatment of menopausal VMSs. After 4 and 12 weeks of therapy, fezolinetant at 30 mg QD or 45 mg QD substantially decreased the frequency and severity of VMSs per 24 hours compared to placebo. Fezolinetant at 90 mg BID, 30 mg QD, or 45 mg QD did not show a significant difference in the rate of treatment-emergent adverse events (TEAEs), headache, and TEAEs leading to permanent discontinuation compared to placebo. Fezolinetant proves to be a successful and well-tolerated remedy for menopausal women suffering from VMSs. Notably, the 45 mg daily dosage over 12 weeks exhibited significant efficacy. Nonetheless, extensive future trials are necessary to ascertain its long-term safety, effectiveness, and relative potency compared to alternative VMS treatments like hormone therapy.

La ménopause représente la transition physiologique lorsque la période de reproduction d'une femme se termine, associée à divers symptômes, notamment des symptômes vasomoteurs, tels que des sueurs nocturnes et des bouffées de chaleur. Cette revue systématique et méta-analyse visaient à évaluer l'efficacité et l'innocuité du Fezolinetant oral pour traiter les symptômes vasomoteurs associés à la ménopause. Cinq bases de données électroniques ont été consultées depuis leur création jusqu'en mai 2023. Via l'outil Cochrane sur le risque de biais, deux examinateurs ont évalué la qualité des études. Les principaux critères de jugement étaient une diminution de la fréquence et de la gravité des SVM ainsi que des critères de sécurité à 4 et 12 semaines. Les données ont été extraites puis analysées à l'aide du logiciel RevMan. Cette méta-analyse comprenait six essais portant sur un total de 3 291 femmes comparant Fezolinetant à un placebo dans le traitement des SVM ménopausiques. Après 4 et 12 semaines de traitement, le fézolinetant à la dose de 30 mg une fois par jour ou de 45 mg une fois par jour a considérablement réduit la fréquence et la gravité des SMV toutes les 24 heures par rapport au placebo. Le fézolinetant à la dose de 90 mg deux fois par jour, de 30 mg une fois par jour ou de 45 mg une fois par jour n'a pas montré de différence significative dans le taux d'événements indésirables survenus pendant le traitement (TEAE), de maux de tête et de TEAE conduisant à un arrêt définitif par rapport au placebo. Le fézolinetant s'avère être un remède efficace et bien toléré pour les femmes ménopausées souffrant de VMS. Notamment, la dose quotidienne de 45 mg sur 12 semaines a montré une efficacité significative. Néanmoins, de futurs essais approfondis sont nécessaires pour vérifier son innocuité, son efficacité et sa puissance relative à long terme par rapport aux traitements alternatifs du VMS comme l'hormonothérapie.

Synergistic Differential DNA Demethylation Activity of Danshensu (Salvia miltiorrhiza) Associated with Different Probiotics in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a major hepatic disorder occurring in non-alcohol-drinking individuals. Salvianic acid A or Danshensu (DSS, 3-(3, 4-dihydroxyphenyl)-(2R)-lactic acid), derived from the root of Danshen (Salvia miltiorrhiza), has demonstrated heart and liver protective properties. In this work, we investigated the antioxidant activity and hepatoprotective activity of Danshensu alone and in combination with different agents, such as probiotic bacteria (Lactobacillus casei and Lactobacillus acidophilus), against several assays. The inhibition mechanism of the methylation gene biomarkers, such as DNMT-1, MS, STAT-3, and TET-1, against DSS was evaluated by molecular docking and RT-PCR techniques. The physicochemical and pharmacokinetic ADMET properties of DSS were determined by SwissADME and pkCSM. The results indicated that all lipid blood test profiles, including cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were reduced after the oral administration of Danshensu combined with probiotics (L. casei and L. acidophilus) that demonstrated good, efficient free radical scavenging activity, measured using anti-oxidant assays. ADMET and drug-likeness properties certify that the DSS could be utilized as a feasible drug since DSS showed satisfactory physicochemical and pharmacokinetic ADMET properties.

Symbiotic Antidiabetic Effect of Lactobacillus casei and the Bioactive Extract of Cleome droserifolia (Forssk.) Del. on Mice with Type 2 Diabetes Induced by Alloxan.

The consumption of probiotics protects pancreatic ß-cells from oxidative damage, delaying the onset of type 2 diabetes mellitus (T2DM) and preventing microvascular and macrovascular complications. This study aimed to evaluate the antidiabetic activity of CDE fermented by Lactobacillus casei (ATCC 39539) (LC) in alloxan-induced diabetic rats. The oxidative stress identified by catalase (CAT), serum AST, ALT, ALP, creatinine, urea, and uric acid were measured. The chemical profiles of the plant extract and the fermented extract were studied using HPLC/MS. The potential of the compounds towards the binding pockets of aldose reductase and PPAR was discovered by molecular docking. A significant reduction in fasting blood glucose in alloxan-treated rats. The CAT showed a significant decrease in diabetic rats. Also, serum AST, ALT, ALP, creatinine, urea, and uric acid were significantly decreased in the mixture group. Mild histological changes of pancreatic and kidney tissues suggested that the mixture of probiotics and cleome possesses a marked anti-diabetic effect. Overall, the study suggests that the combination of Cleome droserifolia fermented by Lactobacillus casei exhibits significant antidiabetic activity (p-value=0.05), reduces oxidative stress, improves lipid profiles, and shows potential for the treatment of diabetes.

AI-driven Discovery of Celecoxib and Dexamethasone for Exploring their Mode of Action as Human Interleukin (IL-6) Inhibitors to Treat COVID-19-induced Cytokine Storm in Humans.

BACKGROUND: In the case of COVID-19 patients, it has been observed that the immune system of the infected person exhibits an extreme inflammatory response known as cytokine release syndrome (CRS) where the inflammatory cytokines are swiftly produced in quite large amounts in response to infective stimuli. Numerous case studies of COVID-19 patients with severe symptoms have documented the presence of higher plasma concentrations of human interleukin-6 (IL-6), which suggests that IL-6 is a crucial factor in the pathophysiology of the disease. In order to prevent CRS in COVID-19 patients, the drugs that can exhibit binding interactions with IL-6 and block the signaling pathways to decrease the IL-6 activity may be repurposed. METHODS: This research work focused on molecular docking-based screening of the drugs celecoxib (CXB) and dexamethasone (DME) to explore their potential to interact with the binding sites of IL-6 protein and reduce the hyper-activation of IL-6 in the infected personnel. RESULTS: Both of the drugs were observed to bind with the IL-6 (IL-6 receptor alpha chain) and IL-6Rα receptor with the respective affinities of -7.3 kcal/mol and -6.3 kcal/mol, respectively, for CXB and DME. Moreover, various types of binding interactions of the drugs with the target proteins were also observed in the docking studies. The dynamic behaviors of IL-6/IL-6Rα in complex with the drugs were also explored through molecular dynamics simulation analysis. The results indicated significant stabilities of the acquired drug-protein complexes up to 100 ns. CONCLUSION: The findings of this study have suggested the potential of the drugs studied to be utilized as antagonists for countering CRS in COVID-19 ailment. This study presents the studied drugs as promising candidates both for the clinical and pre-clinical treatment of COVID-19.

An efficient multilevel image thresholding method based on improved heap-based optimizer.

Image segmentation is the process of separating pixels of an image into multiple classes, enabling the analysis of objects in the image. Multilevel thresholding (MTH) is a method used to perform this task, and the problem is to obtain an optimal threshold that properly segments each image. Methods such as the Kapur entropy or the Otsu method, which can be used as objective functions to determine the optimal threshold, are efficient in determining the best threshold for bi-level thresholding; however, they are not effective for MTH due to their high computational cost. This paper integrates an efficient method for MTH image segmentation called the heap-based optimizer (HBO) with opposition-based learning termed improved heap-based optimizer (IHBO) to solve the problem of high computational cost for MTH and overcome the weaknesses of the original HBO. The IHBO was proposed to improve the convergence rate and local search efficiency of search agents of the basic HBO, the IHBO is applied to solve the problem of MTH using the Otsu and Kapur methods as objective functions. The performance of the IHBO-based method was evaluated on the CEC'2020 test suite and compared against seven well-known metaheuristic algorithms including the basic HBO, salp swarm algorithm, moth flame optimization, gray wolf optimization, sine cosine algorithm, harmony search optimization, and electromagnetism optimization. The experimental results revealed that the proposed IHBO algorithm outperformed the counterparts in terms of the fitness values as well as other performance indicators, such as the structural similarity index (SSIM), feature similarity index (FSIM), peak signal-to-noise ratio. Therefore, the IHBO algorithm was found to be superior to other segmentation methods for MTH image segmentation.

An Improved Search and Rescue Algorithm for Global Optimization and Blood Cell Image Segmentation.

Image segmentation has been one of the most active research areas in the last decade. The traditional multi-level thresholding techniques are effective for bi-level thresholding because of their resilience, simplicity, accuracy, and low convergence time, but these traditional techniques are not effective in determining the optimal multi-level thresholding for image segmentation. Therefore, an efficient version of the search and rescue optimization algorithm (SAR) based on opposition-based learning (OBL) is proposed in this paper to segment blood-cell images and solve problems of multi-level thresholding. The SAR algorithm is one of the most popular meta-heuristic algorithms (MHs) that mimics humans' exploration behavior during search and rescue operations. The SAR algorithm, which utilizes the OBL technique to enhance the algorithm's ability to jump out of the local optimum and enhance its search efficiency, is termed mSAR. A set of experiments is applied to evaluate the performance of mSAR, solve the problem of multi-level thresholding for image segmentation, and demonstrate the impact of combining the OBL technique with the original SAR for improving solution quality and accelerating convergence speed. The effectiveness of the proposed mSAR is evaluated against other competing algorithms, including the L'evy flight distribution (LFD), Harris hawks optimization (HHO), sine cosine algorithm (SCA), equilibrium optimizer (EO), gravitational search algorithm (GSA), arithmetic optimization algorithm (AOA), and the original SAR. Furthermore, a set of experiments for multi-level thresholding image segmentation is performed to prove the superiority of the proposed mSAR using fuzzy entropy and the Otsu method as two objective functions over a set of benchmark images with different numbers of thresholds based on a set of evaluation matrices. Finally, analysis of the experiments' outcomes indicates that the mSAR algorithm is highly efficient in terms of the quality of the segmented image and feature conservation, compared with the other competing algorithms.

Amelioration effect of 18ß-Glycyrrhetinic acid on methylation inhibitors in hepatocarcinogenesis -induced by diethylnitrosamine.

Aim: suppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid. Method: In the current work, we investigated the effect of sole GA combined with different agents such as doxorubicin (DOX) or probiotic bacteria (Lactobacillus rhamanosus) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats' liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats' liver tissue. Results: Our results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively. Conclusion: GA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes.

Peri-anal infiltration versus caudal block for multimodal analgesia in paediatric patients with Hirschsprung's disease undergoing transanal endorectal pull-through procedure: A randomised trial.

Background and Aims: Transanal endorectal pull-through (TERPT) is a standard procedure for managing paediatric patients with Hirschsprung's disease (HD). This study aimed to evaluate peri-anal infiltration versus caudal block as a part of multimodal analgesia for paediatric patients with HD undergoing the TERPT procedure. Methods: This randomised trial included 60 patients of both genders, aged 6 to 18 months who underwent the TERPT procedure under general anaesthesia. The patients were randomly assigned into two groups to receive either peri-anal infiltration or caudal block with 1 ml/kg bupivacaine 0.25% and dexmedetomidine 1 µg/kg in 0.5 ml normal saline. The primary outcome was the time to the first rescue analgesia. The secondary outcomes were the total consumption, the frequency of nalbuphine administration as rescue analgesia within 24 hours and the level of postoperative sedation. Results: The time to first rescue analgesia was significantly shorter in the peri-anal infiltration group versus the caudal block group (median [interquartile range] 10 [7.5-12.5] h versus 16 [13.5-18.5] h, respectively, P = 0.008). The frequency of administration and the total dose of nalbuphine was significantly higher in the peri-anal infiltration group (P = 0.003 and 0.013, respectively). The sedation score was significantly higher in the caudal block group postoperatively. Conclusion: For paediatric patients undergoing the TERPT procedure, peri-anal infiltration was less effective than caudal block in terms of the duration of postoperative analgesia. However, both techniques were comparable during the first 6 hours postoperatively.

Factors Affecting the Psychological Well-Being of Health Care Workers During the COVID-19 Crisis.

Background: Health care workers (HCWs) are a group that especially suffered during the COVID-19 pandemic. In addition to facing the stress of dealing with patients and social isolation, they had to worry about being infected themselves and transmitting the infection to their families. This study evaluated the fear, anxiety, and depression experienced by HCWs during the COVID-19 crisis. Subjects and Methods: The sample size was 541 HCWs. Data collection was done using an online validated questionnaire through Google Docs, sent to HCWs by email and WhatsApp groups. We assessed depression and anxiety with the 4-item Patient Health Questionnaire-4 (PHQ-4), while evaluating fear with the Fear of COVID-19 Scale (FCV-19S). Results: A statistically significant difference was found in the perception of fear between married and unmarried people, and between those with colleagues who had died from COVID-19 infection and those without. There was a significant relation between HCWs' anxiety and a history of death from COVID-19 infection, either of friends or of close relatives. The prevalence of depression was 18.48% in the tested sample of HCWs. Participants who had close relatives or friends infected with COVID-19 showed a significantly higher degree of depression. The age group <30 and those working 20 to 30 hours weekly showed higher degrees of anxiety and depression. Conclusion: Sociodemographic variables such as age, marital status, and working area had a significant impact on the mental and psychological health of HCWs during the COVID-19 crisis. HCWs who lost patients due to COVID-19 had a significantly higher prevalence of fear, depression, and anxiety.

Impact of Plant Spacing and Nitrogen Rates on Growth Characteristics and Yield Attributes of Egyptian Cotton (Gossypium barbadense L.).

This current study was performed to determine the influences of plant spacing, Nitrogen (N) fertilization rate and their effect, on growth traits, yield, and yield components of cotton (Gossypium barbadense L.) cv. Giza 97 during the 2019 and 2020 seasons. A split plot experiment in three replicates was utilized whereas the cotton seeds were planted at 20, 30, and 40 cm, as main plots and nitrogen at 75, 100, and 125%, was in subplots. The results revealed that the planting spacing at 40 cm significantly (p ≤ 0.01) increased plant height, number of fruiting branches per plant, number of bolls per plant, boll weight (BW), lint percentage (L%), seed cotton yield (SCY), lint cotton yield (LCY), seed index and lint index by 165.68 cm, 20.92, 23.93, 3.75 g, 42.01%, 4.24 ton/ha, 5.16 ton/ha, 12.05, 7.86, respectively, as average in both seasons. The application of N fertilizer rate at 125% caused a maximum increase in growth and yield parameters i.e., plant height (169.08 cm), number of vegetative branches (2.67), number of fruiting branches per plant (20.82), number bolls per fruiting branch (1.39), number of bolls per plant (23.73), boll weight (4.1 g), lint percent (41.9%), seed index (11.8 g), and lint index (8.2), while the plants treated with 100% N rates exhibited highest seed cotton yield (4.3 ton/ha) and lint cotton yield (5.6 ton/ha), as average in both seasons. Combining plant spacing at 40 cm between plants with a 100% N fertilizer rate recorded the highest lint cotton yield (5.67 ton/ha), while the highest seed cotton yield (4.43 and 4.50 ton/ha) was obtained from 125% N fertilizer rate under planting spacing 20 and 40 cm, respectively. Conclusively, a wide density (40 cm) with 125% N is a promising option for improved biomass, cotton growth, yield, physiological traits, and fiber quality.

Chlorella vulgaris or Spirulina platensis mitigate lead acetate-induced testicular oxidative stress and apoptosis with regard to androgen receptor expression in rats.

The current research was constructed to throw the light on the protective possibility of Chlorella vulgaris (C. vulgaris) and Spirulina platensis (S. platensis) against lead acetate-promoted testicular dysfunction in male rats. Forty rats were classified into four groups: (i) control, (ii) rats received lead acetate (30 mg/kg bw), (iii) rats concomitantly received lead acetate and C. vulgaris (300 mg/kg bw), (vi) rats were simultaneously treated with lead acetate and S. platensis (300 mg/kg bw) via oral gavage for 8 weeks. Lead acetate promoted testicular injury as expressed with fall in reproductive organ weights and gonadosomatic index (GSI). Lead acetate disrupted spermatogenesis as indicated by sperm cell count reduction and increased sperm malformation percentage. Lead acetate-deteriorated steroidogenesis is evoked by minimized serum testosterone along with maximized follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Testicular oxidative, inflammatory, and apoptotic cascades are revealed by elevated acid phosphatase (ACP) and sorbitol dehydrogenase (SDH) serum leakage, declined testicular total antioxidative capacity (TAC) with elevated total oxidative capacity (TOC), tumor necrosis factor alpha (TNF-α), caspase-3 levels, lessened androgen receptor (AR) expression, and histopathological lesions against control. Our research highlights that C. vulgaris or S. platensis therapy can modulate lead acetate-promoted testicular dysfunction via their antioxidant activity as expressed by elevated TAC and reduced TOC, immunomodulatory effect as indicated by lessened TNF-α level, and anti-apoptotic potential that was revealed by minimized caspase-3 levels. As well as restoration of testicular histoarchitecture, androgen receptor, steroidogenesis, and spermatogenesis were detected with better impacts to S. platensis comparing with C. vulgaris. Therefore, further clinical trials are needed to test S. platensis and C. vulgaris as a promising candidate in treating male infertility.

The Significance of Buffer Solutions on Corrosion Processes of Cobalt Ferrite CoFe2O4 Thin Film on Different Substrates.

BACKGROUND: The spinel ferrite nanoparticles, such as zinc, nickel, and cobalt ferrites have exceptional electronic and magnetic properties. Cobalt ferrite nanomaterial (CoFe2O4) is a hard material that reveals high magnetic, mechanical, and chemical stability. AIM AND OBJECTIVE: The objective of this research is to predict the corrosion behavior of cobalt ferrite (CoFe2O4) thin films deposited on different substrates (platinum Pt, stainless steel S.S, and copper Cu) in acidic, neutral, and alkaline medium. MATERIALS AND METHODS: Cobalt ferrite thin films were deposited on platinum, stainless steel, and copper via electrodeposition-anodization process. After that, corrosion resistance of the prepared nanocrystalline cobalt ferrite on different substrates was investigated in acidic, neutral, and alkaline medium using open circuit potential and potentiodynamic polarization measurements. The crystal structure, crystallite size, microstructure, and magnetic properties of the ferrite films were investigated using a combination of XRD, SEM and VSM. RESULTS: The results of XRD revealed a cubic spinel for the prepared cobalt ferrite CoFe2O4. The average size of crystallites was found to be about 43, 77, and 102 nm precipitated on platinum, stainless steel, and copper respectively. The magnetic properties of which were enhanced by rising the temperature. The sample annealed at 800oC is suitable for practical application as it showed high magnetization saturation and low coercivity. The corrosion resistance of these films depends on the pH of the medium as well as the presence of oxidizing agent. CONCLUSION: Depending on the obtained corrosion rate, we can recommend that, CoFe2O4 thin film can be used safely in aqueous media in neutral and alkaline atmospheres for Pt and Cu substrates, but it can be used in all pH values for S.S. substrate.

Surface functionalized folate targeted oleuropein nano-liposomes for prostate tumor targeting: Invitro and invivo activity.

AIMS: This study aims to develop and evaluate oleuropein loaded surface functionalized folate-targeted - PEG liposomes for the effective management of prostate cancer in an animal model. MATERIALS AND METHODS: Film hydration-cum-extrusion technique was used to produce liposomes. Particle size, entrapment efficiency, drug loading, electron microscopy, and drug release study were performed for the characterization. Cell viability and various in vitro studies (phosphatidylserine internalization, TUNEL assay, measurement of mitochondrial membrane potential and caspase-3 assay) were performed to compare the anticancer and apoptotic effects of developed liposomes against the plain oleuropein. Comparative pharmacokinetic profiling and anticancer efficacy studies including a change in tumor volume, body weight, and survival analysis were performed in mice model. KEY FINDINGS: The developed liposomes (OL-FML) showed the particle size of 184.2 ±â€¯9.16 nm, the zeta potential of 1.41 ±â€¯0.24 mV, entrapment efficiency of 63.52 ±â€¯4.15% and drug loading of 21.31 ±â€¯2.37%. OL-FML showed higher in vitro anti-proliferative effect and apoptosis on 22Rv1 cells. In vivo pharmacokinetic study revealed a nearly 6 fold increase in the bioavailability of OL-FML (AUC0→∞ = 641.78 ±â€¯103.764 µg/mL·hr) as compared to OL solution (AUC0→∞ = 104.11 ±â€¯18.374 µg/mL·hr) in mice. Increased tumor suppression, weight loss resistance, and survival probability were observed in 22Rv1 induced tumor-bearing mice with OL-FML treatment as compared to OL. SIGNIFICANCE: The study provides conclusive evidence for the utilization of combining passive and active targeting strategy to enhance the anticancer effect of OL.

Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells.

Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of 15.6 ±â€¯1.49 and 41.1 ±â€¯2.19 µM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200 µM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.

Response Surface Methodology for Optimization of Genistein Content in Soy Flour and its Effect on the Antioxidant Activity.

Biotransformation of isoflavones glycosides into the aglycone form is essential to attain the maximum bioavailability. The factors affecting deglycosylation of genistin in soy flour using commercial ß-glucosidase enzyme were evaluated. The presence of genistin in soy flour was confirmed by isolation through chromatographic fractionation and identification by spectral method. Two-levels Plackett-Burman design was applied and effective variables for genistein production were determined. Agitation rate, enzyme concentration, and reaction time, owing to their significant positive effect, and pH, owing to its significant negative effect, were further evaluated using Box-Behnken model. Accordingly the optimal combination of the major reaction affecting factors was "enzyme concentration, 1 IU; agitation speed, 250 rpm; reaction time, 5 h and pH 4. The concentration of genistein can be increased by 9.91 folds (from 0.8 mg/g in the non biotransformed soy flour to 7.93 mg/g in the biotransformed one) using the determined optimal combination of major reaction affecting factors. The antioxidant activity of the non biotransformed and biotransformed soy flour extracts was determined by DPPH method. It was found that biotransformation increase the antioxidant activity by two folds. The concentration causing a 50% reduction of DPPH absorbance (EC50) were 10 and 5 mg/mL for the non biotransformed and biotransformed soy flour extracts, respectively.

Renal protective effect of SGLT2 inhibitor dapagliflozin alone and in combination with irbesartan in a rat model of diabetic nephropathy.

Considering the complementary mechanisms of SGLT2 inhibitors and angiotensin inhibitors on kidney, it is postulated that combination of both agents could afford greater protection against diabetic renal injury. So, we investigated renal protective effects of SGLT2 inhibitor, dapagliflozin, alone and in combination with irbesartan in a rat model of diabetic nephropathy. Diabetic rats, injected with nicotinamide-streptozotocin, were treated orally for 12 weeks with either vehicle, dapagliflozin 2 mg/kg/day, irbesartan 30 mg/kg/day, or combination of both drugs; respectively. Biochemical analysis included blood glucose, HbA1c, urinary albumin excretion, creatinine clearance, TGF-ß1, sRAGE, oxidative markers, and histopathological examination of kidneys. Treatment with dapagliflozin, irbesartan, and especially their combination, produced significant reduction in albuminuria, improved renal function parameters, increased sRAGE level and improved inflammatory and oxidative markers, together with amelioration of renal histopathological changes. Beside glycemic control, dapagliflozin produced higher sRAGE levels than irbesartan, suggesting that inhibition of AGE-RAGE axis is important in its renoprotective action. Combination of dapagliflozin and irbesartan produced more remarkable protective effects on renal function and structure, than use of either agent alone. It is concluded that, combination of SGLT2 inhibitor, dapagliflozin and ARB, irbesartan could offer more effective renal protection and represent a promising therapeutic option for management of diabetic nephropathy.

Biotransformation of soy flour isoflavones by Aspergillus niger NRRL 3122 ß-glucosidase enzyme.

ß-glucosidase enzyme produced from Aspergillus niger NRRL 3122 has been partially purified and characterised. Its molecular weight was 180 KDa. The optimal pH and temperature were 3.98 and 55 °C, respectively. It promoted the hydrolysis of soy flour isoflavone glycosides to their aglycone. Two-level Plackett-Burman design was applied and effective variables for genistein production were determined. Reaction time had a significant positive effect, and pH had a significant negative effect. They were further evaluated using Box-Behnken model. Accordingly, the optimal combination of the major reaction affecting factors was reaction time, 5 h and pH, 4. The concentration of genistein increased by 11.73 folds using this optimal combination. The antioxidant activity of the non-biotransformed and biotransformed soy flour extracts was determined by DPPH method. It was found that biotransformation increased the antioxidant activity by four folds.

Neuroprotective effects of vitamin D alone or in combination with lamotrigine against lithium-pilocarpine model of status epilepticus in rats.

Status epilepticus (SE) is considered one of the major serious forms of epilepsy with high mortality rate. Since the currently available antiepileptic drugs have low efficacy and high adverse effects, new more efficient and safe therapies are critically needed. There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Recent studies have shown significant prophylactic and therapeutic potential of vitamin D (vit-D) use in many neurological disorders. Therefore, in the present study, the neuroprotective effects and mechanisms of vit-D alone or in combination with lamotrigine have been evaluated in the lithium-pilocarpine model of SE in rats. Rats were divided into five groups: normal group, SE group, lamotrigine (25 mg/kg/day) pretreated group, vit-D (1.5 mcg/kg/day) pretreated group, and group pretreated with vit-D and lamotrigine for 2 weeks. At the end of treatment, SE was induced by single intraperitoneal injection of LiCl (127 mg/kg), followed 24 h later by pilocarpine (30 mg/kg). Seizures' latency, cognitive performance in Morris water maze, brain oxidative stress biomarkers (glutathione, lipid peroxides, and nitric oxide), brain neurochemistry (γ-aminobutyric acid and glutamate), and brain histopathology have been evaluated. Vit-D prevented pilocarpine-induced behavioral impairments and oxidative stress in the brain; these results were improved in combination with lamotrigine. Vit-D has a promising antiepileptic, neuroprotective, and antioxidant effects. It can be provided to patients as a supportive treatment besides antiepileptic drugs. However, clinical trials are needed to establish its efficacy and safety.

No Association between 25 (OH) Vitamin D Level And Hypothyroidism among Females.

AIM: The aim was to investigate serum vitamin D (25-OH) level among females with hypothyroidism. MATERIALS AND METHODS: A case-control study (58 in each arm) was conducted in Arar Central Hospital, Kingdom Saudi Arabia. The cases were females with hypothyroidism, and healthy females were controls. TSH, thyroid hormones: Free T3 (FT3) and Free T4 (FT4) and haemoglobin levels were measured in all participants. Serum vitamin D (25-OH) level was measured using the spectrophotometry. RESULTS: While there was no significant difference in the age and haemoglobin level, body mass index (BMI) was significantly higher in the cases. Compared with the controls, cases had significantly higher TSH, had significantly lower T4, and there was no significant difference in FT3 and 25 (OH) vitamin D, [16.1 (8.8-26.7) vs. 14.0 (9.5-20.3 ng/ml; P = 0.577]. Linear regression showed no association between, age, BMI, haemoglobin, TSH, FT3, FT4 and the log of 25 (OH) vitamin D levels. CONCLUSION: There was no significant difference in vitamin D level among females with hypothyroidism and healthy controls.

The effect of some immunomodulatory and anti-inflammatory drugs on Li-pilocarpine-induced epileptic disorders in Wistar rats.

Evidence shows that inflammatory and immune processes within the brain might account for the pathophysiology of epilepsy. Therefore, developing new antiepileptic drugs that can modulate seizures through mechanisms other than traditional drugs is required for the treatment of refractory epilepsy. This study aims to determine the relationship between brain inflammation and epilepsy, to examine the contribution of some biochemical parameters involved in brain inflammation, and to address the effect of pharmacological interventions using some anti-inflammatory and immunomodulatory drugs in an experimental epilepsy model. Adult male rats were divided into seven groups of 20. G1 was the normal, non-treated control. G2 was the epileptic, non-treated group. G3-G7 were treated with celecoxib, methotrexate, azathioprine, dexamethasone, and valproate, respectively, for a period of three weeks. Induction of status epilepticus (SE) by Li-pilocarpine was performed on groups G2-G7. EEG tracing was conducted, and inflammatory mediators (brain and serum IL-1ß, IL 6, PGE2, HSP70, TGF-ß2, and IFNγ) were measured. The induction of SE increased the amplitude and frequency of EEG tracing and inflammatory mediators more than in the normal control group. Treatments of epileptic rats reduced the frequency and amplitude of EEG tracing and significantly decreased the levels of inflammatory mediators in some treated rats compared to G2. These findings demonstrate that some anti-inflammatory and immunomodulatory drugs can lower the frequency and amplitude of seizures and reduce some inflammatory mediators in epilepsy treatments, strengthening the possibility that targeting these immunological and inflammatory pathways may represent another effective therapeutic approach to preventing epileptic seizures.