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Researchers have studied probiotic-containing dressings to tackle burn injury concerns like infection and microbial resistance. The current study looked into the effects of novel probiotic-loaded microparticles with in situ gelling properties on infectious burn wounds. Lactiplantibacillus plantarum was chosen as a strain with proven wound-healing properties. Then, a formulation was developed to stabilize and maintain probiotic growth potential. To avoid shedding from wounds, only polymers with rapid moisture absorption were employed. The spray-drying method stabilized the formulation by reducing its water content. The optimal formulation was determined by studying how spray-drying inlet temperature, polymer type, and concentration affected probiotic viability, process yield, swelling ratio, and rheological properties of the particles. The morphological analyses revealed particles with substantial exchangeable surface areas. The formulation's rheological characteristics indicated its thermal and mechanical resistance. Also, the FTIR and DCS spectra proved interlinking between polymers. A comparison of the growth curves of formulated and unformulated probiotics demonstrated an increase in lag time and a steady growth rate. Examination of the formula's efficacy against common wound pathogens confirmed its antibacterial properties. Animal experiments revealed that the optimal microparticles for all criteria outperformed the control groups and were more effective against Pseudomonas aeruginosa. Burn wound infection management would be enhanced by the proposed delivery system's simple administration and prohibition of normal flora transmission.

Considering the progressive prevalence and co-occurrence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), as well as the current evidence suggesting the elevated levels of basal metabolic rate (BMR) among these individuals, the present study aimed to identify factors determining hypermetabolism in such subjects. This cross sectional study was conducted in 30 to 53-year-old individuals with concurrent T2DM and NAFLD (controlled attenuation parameter score ≥ 260 dB/m). Resting energy expenditure (REE) was determined by an indirect calorimetry device. Hypermetabolism was defined as an elevated measured REE > 110% of the predicted REE. The multivariate logistic regression test was used for detecting factors associated with hypermetabolism. Between September, 2017, and March, 2018, a total of 95 eligible participants (64.40% male) with both T2DM and NAFLD were included, while 32.63% of them were classified as hypermetabolic. Overall, the mean recruitment age ± standard deviation and median (interquartile range) body mass index were 44.69 ± 5.47 years and 30.20 (27.80–33.30) kg/m2, respectively. Demographic, anthropometric and biochemical variables did not vary significantly across two groups except for total body water, low-density lipoprotein cholesterol and dipeptidyl peptidase 4 (DPP-4) inhibitors (p

Background: As a medical dilemma, gastric cancer will have 7.3 million new cases in 2040. Despite the disease’s high economic and global burden, conventional chemotherapy regimens containing cisplatin have insufficient effectiveness and act non-specifically, leading to several adverse drug reactions To address these issues, the biological efficacy of the cisplatin-resveratrol combination was tested.Methods: To find IC50, gastric adenocarcinoma cells (AGS) were exposed to different concentrations of resveratrol and cisplatin. Anti-cancer and anti-metastatic effects of 100 M resveratrol with concentrations of cisplatin (25, 50, and 100 g/ml) were studied by assessing ß-galactosidase and telomerase activities, senescence and migration gene expression, reactive oxygen species (ROS) level, and cell cycle arrest.Results: Co-administration of cisplatin and resveratrol increased ß-galactosidase activity, ROS level as a key marker of oxidative stress, p53, p38, p16, p21, and MMP-2 gene expression, and induced G0/G1 cell cycle arrest. Additionally, telomerase activity, pro-inflammatory gene expression, and cell invasion were suppressed. The best results were achieved with 100 g/ml cisplatin co-administered with resveratrol.Conclusion: The current study proved the synergistic effect of the cisplatin-resveratrol combination on suppressing metastasis and inducing apoptosis and cell senescence through targeting P38/P53 and P16/P21 pathways. Such promising results warrant translation to animal models and the clinic. This may lead to cost-effective, available, and accessible treatment regimens with targeted action and the fewest ADRs.

Difficulties in delivering antimicrobial agents to wound areas and emersion of multiple drug resistant organisms (MDROs) have converted managing burn infections into a complicated task in medicine. Probiotics emerged not only as a probable solution for burn infections but also as an accelerator in the healing process. The probability of in vitro-in vivo correlation (IVIVC) in probiotic activity leads to lower costs in finding new therapeutic options. Simulated wound fluid (SWF) was used to evaluate the antibacterial function of Lactiplantibacillus plantarum in wounds. The growth parameters in SWF were evaluated using a logistic model to predict growth behavior in the wound area. In addition, probiotic antimicrobial activity and secretion of antibacterial substances in SWF were also studied. Data were used to select the initial dose and apply frequency for in vivo study. The wound models were infected by two main pathogens (Pseudomonas aeruginosa or Staphylococcus aureus). In vitro results showed less lag time associated with considerable acid production in SWF. In the following, secretion of antimicrobial substances and co-aggregation with pathogens became more important. The susceptibility of pathogens to these factors was different, and culture medium affected the yield of each factor involved in eliminating pathogens. Histological analysis and macroscopic examination of wounds revealed probiotics as effective as positive control or more. There were some differences in the antibacterial functions of probiotics in simulated and real wound environments. The in vitro effect of probiotics on removal of pathogens was not the same as the trend seen in vivo.

Reductions in materials consumption through the use of high-strength materials is important in building construction. However, high-strength steel applications have possible challenges such as their effects on bond behaviour and structural ductility. The bond behaviour, total energy capacity and failure modes of headed and straight high-strength and normal-strength steel bars were investigated using pull-out tests. In the experimental programme, 48 concrete specimens with a compressive strength of 40 MPa, different ratios of steel fibres and embedded steel bars with different yield strengths were subject to pull-out tests. The results showed that the headed bars had far greater bond stress and total energy capacity than the straight bars. It was also found that the higher the yield strength of the bars, the higher the energy capacity and bond stress. Although increases in fibre ratios led to increases in energy capacity, they did not absolutely increase the bond stress. The specimens with both headed and straight bars failed by splitting.

In this study, a novel magnetic MCM-41-type mesoporous silica-supported Fe/Cu (Fe3O4@Fe–Cu/MCM-41) was prepared, characterized, and used as a heterogeneous catalyst for the synthesis of symmetric biaryls by Ullmann cross-coupling reaction. This nanocomposite was characterized using Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and nitrogen adsorption–desorption isotherm. The Fe3O4@Fe–Cu/MCM-41 was applied as an efficient catalyst in the synthesis of biaryls under optimum conditions. This nanocatalyst was recovered and reused several times without significant loss of activity.

As the worldwide average life expectancy has grown, the prevalence of age-related neurodegenerative diseases (NDDs) has risen dramatically. A progressive loss of neuronal function characterizes NDDs, usually followed by neuronal death. Inflammation, apoptosis, oxidative stress, and protein misfolding are critical dysregulated signaling pathways that mainly orchestrate neuronal damage from a mechanistic point. Furthermore, in afflicted families with genetic anomalies, mutations and multiplications of α-synuclein and amyloid-related genes produce some kinds of NDDs. Overproduction of such proteins, and their excessive aggregation, have been proven in various models of neuronal malfunction and death. In this line, providing multi-target therapies carried by novel delivery systems would pave the road to control NDDs through simultaneous modulation of such dysregulated pathways. Phytochemicals are multi-target therapeutic agents, which employ several mechanisms towards neuroprotection. Besides, the blood–brain barrier (BBB) is a critical issue in managing NDDs since it inhibits the accessibility of drugs to the brain in sufficient concentration. Besides, discovering novel delivery systems is vital to improving the efficacy, bioavailability, and pharmacokinetic of therapeutic agents. Such novel formulations are also employed to improve the drug’s biodistribution, allow for the co-delivery of several medicines, and offer targeted intracellular delivery against NDDs. The present review proposes nanoformulations of phytochemicals and synthetic agents to combat NDDs by modulating neuroinflammation, neuroapoptosis, neuronal oxidative stress pathways and protein misfolding.

Background: The combination of sofosbuvir (SOF) and daclatasvir (DCV) has shown preliminary efficacy for patients with COVID-19 in five open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir and daclatasvir to standard care improved clinical endpoints in hospitalized patients with moderate or severe COVID-19. Methods: This was a placebo-controlled, randomized clinical trial in adults with moderate or severe COVID-19 admitted to 19 hospitals in Iran. Patients were randomized to SOF/DCV 400/60mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O 2 saturation

Background Aluminum phosphide (AlP) toxicity is associated with a high risk of death due to heart, liver, and kidney failure as the target organs. Phosphine gas released due to the ingestion is the main factor involved in the multi-organ failure with various mechanisms. Levosimendan (LEV) is a calcium sensitizer with a pleiotropic effect on multiple organs. This study aimed to investigate whether LEV can alleviate AlP-induced nephrotoxicity in the rat model. Method Six groups included control group (almond oil only), sole LEV group (48 µg/kg), AlP group (LD50=10 µg/kg), and the poisoned groups treated with LEV at doses of 12, 24, and 48 µg/kg 30 min after AlP gavage. After 24 hours of treatment, serum and kidney samples were taken for biochemical and histopathological analyses. Result Biochemical analysis of the AlP group showed that the activity of complexes I, II, and IV was significantly reduced, while the levels of lipid peroxidation (LPO) and reactive oxygen species (ROS), lactate, and myeloperoxidase (MPO) activity significantly increased. Also, AlP reduced live renal cells and elevated necrosis. However, the levels of serum creatinine and blood urea nitrogen were not affected by the poisoning. LEV co-treatment could increase mitochondrial complex activity and reduce MPO activity, LPO, ROS, and lactate levels. Additionally, the histopathological analysis showed the detrimental effects of AlP on kidney tissue, which was mitigated by LEV administration. Conclusion Our findings showed that LEV can potentially improve oxidative stress, imbalance in the redox status, necrosis, and pathological injuries in kidney tissue following AlP-poisoning.

After the spread of Covid 19 worldwide, the use of cloth masks increased significantly due to a shortage of medical masks. Meanwhile, there were different opinions about the effectiveness of these masks and, so far, no study has been done to find the best fabric masks. This study reviews and summarizes all studies related to fabric masks' effectiveness and various fabrics against coronavirus. This systematic review is based on PRISMA rules. Two researchers separately examined three databases: PubMed, Scopus, and Web of Science. Laboratory and clinical studies were included. After extracting the articles, their quality was assessed with the Joanna Briggs Institute (JBI) tool. In addition to efficacy, other factors, including the penetration of masks, pressure drop, and quality factor, were examined to select the best fabrics. Of the 42 studies selected, 39 were laboratory studies, and 3 were clinical studies. Among the various fabrics examined, cotton quilt 120 thread per inch (TPI), copy paper (bonded), hybrid of cotton with chiffon/ silk, and flannel filtration were found to have over 90% effectiveness in the particle size range of Covid-19. The results and comparison of different factors (pressure drop, filtration efficacy, penetration, filtration quality, and fit factor have been evaluated) showed that among different fabrics, hybrid masks, 2-layered cotton quilt, 2-layered 100% cotton, cotton flannel, and hairy tea towel + fleece sweater had the best performance. Clinical studies have not explicitly examined cloth masks' effectiveness in Covid-19, so the effectiveness of these types of masks for Covid 19 is questionable, and more studies are needed.

BackgroundDiabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used to improve reproductive health in diabetic patients. Melatonin, mainly produced by the pineal gland, may improve diabetes-associated reproductive complications through various mechanisms and may be a preferred candidate to protect the reproductive system. The present review aims to elucidate the underlying mechanisms of melatonin’s effect on the reproductive system adversely affected by diabetes mellitus (DM).MethodsA comprehensive systematic literature electronic search was done using the PRISMA guidelines. Web of Science, PubMed, Embase, and Scopus were searched for publications up to June 2022. Search terms were selected based on the study purpose and were explored in titles and abstracts. After screening, out of a total of 169 articles, 14 pertinent articles were included based on our inclusion and exclusion criteria.ResultsThe results of studies using rats and mice suggest that DM adversely affects reproductive tissues, including testes and epididymis, prostate, corpus cavernosum, and ovary leading to alterations in histological and biochemical parameters compared to the normal groups. Treatment with melatonin improves oxidative stress, blocks apoptosis induced by endoplasmic reticulum stress and caspase activation, reduces pro-inflammation cytokines, and enhances steroidogenesis.ConclusionMelatonin exerted a protective action on the impaired reproductive system in in-vivo and in-vitro models of DM. The topic has to be followed up in human pregnancy cases that will need more time to be collected and approved.

Aluminum phosphide (AlP) poisoning can be highly fatal due to its severe toxicity to the heart. Based on the evidence, edaravone (EDA) has protective effects on various pathological conditions of the heart. This research aimed to examine the potential protective effects of EDA on AlP-induced cardiotoxicity in rats. The rats were divided into six groups, including almond oil (control), normal saline, AlP (LD50), and AlP + EDA (20, 30, and 45 mg/kg). Thirty minutes following AlP poisoning, the electrocardiographic (ECG), blood pressure (BP), and heart rate (HR) parameters were examined for 180 min. The EDA was injected 60 min following the AlP poisoning intraperitoneally. Also, 24 h after poisoning, echocardiography was carried out to evaluate the ejection fraction (EF), stroke volume (SV), and cardiac output (CO). The biochemical and molecular parameters, such as the activities of the mitochondrial complexes, reactive oxygen species (ROS), apoptosis and necrosis, and troponin I and lactate levels, were also examined after 12 and 24 h in the heart tissue. According to the results, AlP-induced ECG abnormalities, decrease in blood pressure, heart rate, SV, EF%, and CO were significantly improved with EDA at doses of 30 and 45 mg/kg. Likewise, EDA significantly improved complex I and IV activity, apoptosis and necrosis, ROS, troponin I, and lactate levels following AlP-poisoning (p < 0.05). Also, the mean survival time was increased following EDA treatment, which can be attributed to the EDA’s protective effects against diverse underlying mechanisms of phosphine-induced cardiac toxicity. These findings suggest that EDA, by ameliorating heart function and modulating mitochondrial activity, might relieve AlP-induced cardiotoxicity. Nonetheless, additional investigations are required to examine any potential clinical advantages of EDA in this toxicity.

INTRODUCTION Although the incidence and prevalence of duodenal and gastric ulcers have been declining, it remains challenging for health care systems. Based on the underlying cause, history, and characteristics of ulcers, management is generally provided by administering proton pump inhibitors (PPIs) or antibiotics. AREAS COVERED This article is based on global guidelines and English language literature from the past decade obtained through searches using PubMed, Clinicaltrials.gov, the US FDA, and the Cochrane library. Using a stepwise approach, dose and duration of treatment, drug interactions, warnings and contraindications, adverse effects, and administration points were specified. New drug candidates that may get American and European approvals were also introduced. EXPERT OPINION Despite the wide use of PPIs, their development lags behind the clinical need. There is an absolute requirement to develop third-generation PPIs with higher potency and improved pharmacokinetic and safety profiles. Regarding the antibiotic resistance crisis, including those used against H. pylori, conducting more clinical trials and investigating regional antibiotic resistance are warranted. Potassium competitive acid blockers, ilaprazole, and an H. pylori vaccine all show promise for the future.

Mobile sensor networks consist of a set of mobile sensor nodes, which establish wireless communications within a specific area. In WSNs, mobile sensor nodes can sense the physical status of a given environment, process information and report them to the sink node or the base station. Due to nodes’ movements, these networks do not have a fixed infrastructure. There is no centralized controlling infrastructure for wireless sensor networks and different nodes are at relative liberty for joining and leaving network. Furthermore, due to the specific applications of these networks, it is highly probable that malicious nodes may exist in the network. The available malicious nodes in these networks do not follow the general principles, which dominate the execution of the routing protocols. They make hostile changes and abuse the rules, so as to disrupt the normal functioning of the routing protocols. In this way, malicious nodes aim to demolish the network or they refuse to cooperate fully with other available nodes in the network so that they can preserve their own limited energy. Consequently, they would like to destroy the possibility for providing services for some users. In order to ensure routing security in sensor networks and consider their fundamental challenge, i.e. nodes’ optimal power consumption, we proposed clustering-based secure routing protocol by capitalizing on willow butterfly algorithm. It has three phases, i.e. clustering, encryption and routing. The results of simulating the proposed method using OPNET showed its better performance in terms of power consumption, data transmission delay and access delay to media, data-packet loss rate by destructive nodes and productivity rate.

Oxidative stress induces cell senescence and aging. Cell senescence is an irreversible cell cycle arrest mechanism responsible for various pathological diseases and aging. Cerium oxide nanoparticles (CeO2 NPs) have been found to have anti-oxidant effects with a capacity to scavenge free radicals. With this background, we aimed to investigate the senolytic property of CeO2 NPs on mouse embryonic fibroblasts (NIH3T3). NIH3T3 cells were exposed to CeO2 NPs with or without hydrogen peroxide (H2O2). The senolytic effect of CeO2 NPs was evaluated by measuring reactive oxygen species (ROS) production, lipid peroxidation (LPO), β-galactosidase, cell cycle phase analysis, and expression of p21, p38, p53, and NF-кB genes. EC50 of CeO2 NPs significantly reduced the β-galactosidase activity in NIH3T3 cells without apparent cytotoxicity and generation of ROS. Also, it decreased LPO, and expression of IL-6. The number of cells increased significantly, indicating that CeO2 NPs can reverse cell senescence and cell cycle arrest in the S phase. Also, p21, p38, p53, and NF-кB gene expressions were significantly down-regulated. CeO2 NPs as a senolytic or inhibitor of senescence can attenuate the senescence-inducing signal transduction pathways, i.e., p38/ NF-кB and p53/p21. It reduced the production of ROS and LPO and the expression of IL-6.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) as multifactorial chronic liver disease and the lack of a specific treatment have begun a new era in its treatment using gene expression changes and microRNAs. This study aimed to investigate the potential therapeutic effects of natural compounds in NAFLD by regulating miRNA expression. MicroRNAs play essential roles in regulating the cell’s biological processes, such as apoptosis, migration, lipid metabolism, insulin resistance, and adipocyte differentiation, by controlling the posttranscriptional gene expression level. The impact of current NAFLD pharmacological management, including drug and biological therapies, is uncertain. In this context, various dietary fruits or medicinal herbal sources have received worldwide attention versus NAFLD development. Natural ingredients such as berberine, lychee pulp, grape seed, and rosemary possess protective and therapeutic effects against NAFLD by modifying the gene’s expression and noncoding RNAs, especially miRNAs.

In this study, the high versus low analysis method was applied to evaluate the association of maternal nitrate intake and risk of heart defect, limb deficiency, cleft lip, and preterm birth. Also, linear and non-linear dose-response associations between maternal intake of nitrate and risk of heart defects were investigated. In high versus low intake, the risk of heart defects in infants is directly associated with the level of nitrate exposure, but no significant relationship was found between the cleft lip, limb deficiency, and preterm birth. The linear dose-response meta-analysis was associated with risk of heart defects (RR: 1.03; 95% CI: 1.00 to 1.05, P = 0.400, I2= 0%, P heterogeneity= 0.602, n = 3) and nonlinear dose-response meta-analysis showed that maternal intake of nitrate higher than ∼4 mg/day is positively associated with heart defects risk (P non-linearity= 0.012).

Background: It has been found that there is a link between hypertension and elevated risk of Alzheimer’s Disease (AD). Herein, a meta-analysis based on Randomized Clinical Trials (RCTs) was used to assess the effect of antihypertensive drugs on cognition and behavioral symptoms of AD patients. Methods: The three databases, PubMed/Medline, Scopus, and Cochrane Library, were searched up to March 2020. The quality of the studies included in the meta-analysis was evaluated by the Jadad score. Clinical Global Impression of Change (CGIC) included in two studies, Mini-Mental State Examination (MMSE) included in three studies, and Neuropsychiatric Inventory (NPI) in three studies were the main outcomes in this systematic review. Results: Out of 1506 studies retrieved in the databases, 5 RCTs were included and analyzed in the meta-analysis. The pooled mean differences of CGIC, MMSE, and NPI in patients with AD receiving antihypertensive drugs compared to placebo were -1.76 with (95% CI = -2.66 to -0.86; P=0.0001), 0.74 (95% CI = 0.20 to 1.28; P= 0.007), and -9.49 (95% CI = -19.76 to 0.79; P = 0.07), respectively. Conclusion: The findings of the present meta-analysis show that antihypertensive drugs may improve cognition and behavioral symptoms of patients with AD. However, more well-designed RCTs with similar drugs are needed to achieve more conclusive results.

Aluminum phosphide (AlP) causes serious poisoning in which severe cardiac suppression is the significant lethal consequence. According to evidence, levosimendan can exert outstanding cardiac support and protection in different pathological conditions. This study aimed to investigate the mechanisms by which levosimendan may alleviate cardiovascular toxicity due to AlP intoxication in the rat model. The groups included control group (normal saline only), sole levosimendan groups (12, 24, 48 μg/kg), AlP group (10 mg/kg), and AlP + levosimendan groups receiving 12, 24, 48 μg/kg levosimendan intraperitoneally 30 min after AlP administration. Electrocardiographic (ECG) parameters (QRS and PR duration and ST height), heart rate, and blood pressure were monitored for 180 minutes. Also, after 24 h of poisoning, echocardiography was applied to assess left ventricle function. Evaluation of the biochemical parameters in heart tissue, including mitochondrial complexes I, II, IV activity, ADP/ATP ratio, the rate of apoptosis, malondialdehyde (MDA), lactate, and troponin I levels, were done after 12 and 24 h. AlP-induced ECG abnormalities (PR duration and ST height), reduction in heart rate, blood pressure, cardiac output, ejection fraction, and stroke volume were improved by levosimendan administration. Besides, levosimendan significantly improved complex IV activity, the ADP/ATP ratio, apoptosis, MDA, lactate, and troponin I level following AlP-poisoning. Our results suggest that levosimendan might alleviate AlP-induced cardiotoxicity by modulating mitochondrial activity and improving cardiac function. However, the potential clinical use of levosimendan in this toxicity needs more investigations.

Graphical abstract, Highlights • Drosophila melanogaster can be used as a good model for investigating aging pathways. • Botulinum toxin type-A induced dose-dependent cytotoxicity and oxidative stress in larvae of D. melanogaster. • Botulinum toxin type-A induced DNA damage, activated caspase-3 and -9, and flies' body size reduction. • Senescence markers, including β-galactosidase, p16, p21, p38, and p53, were down-regulated by Botulinum toxin type-A., Botulinum toxin type-A (BoNT/A) application, especially neurological disorders, has been spread nowadays while it may cause side effects. The current study aimed to assess the BoNT/A dose-dependent effect on induction of aging in the Drosophila melanogaster model. The third instar larvae of Drosophila melanogaster were exposed to ¼ LC50, ½ LC50, and LC50 of BoNT/A in the Drosophila diet for 48 h while H2O2 1% was used as a positive control. After the exposure time, some larvae were collected for molecular study, including gene expression analysis, comet assay, oxidative stress markers, and the phenotype changes. BoNT/A induced dose-dependent cytotoxicity, elevated reactive oxygen species (ROS) levels, and superoxide dismutase (SOD) enzyme activity. In addition, it caused DNA damage and activated caspase-3 and -9, and reduced the body size of the fly, especially in high doses. In line with the purpose of the study, aging markers, including β-galactosidase (β-gal), p16, p21, p38, and p53, were up-regulated by BoNT/A low dose. BoNT/A activates the aging pathway in the low dose, and increasing the dose induces toxicity, including oxidative stress, DNA damage, and apoptosis.

The rapid-growing population of diabetic patients and the elderly are among the direst challenges that the science of medicine is facing today. Targeting these two challenges can shed light on new means to control and ideally reverse this trend. In this experiment, Vinpocetine's effect on aged pancreatic beta-cell functions in correlation with oxidative stress was studied.Islet cells were isolated from the pancreas of aged rats and exposed to Vinpocetine, dissolved in acetone and RPMI, for 48 h. Then, senescence-associated molecular parameters, includingExperimental results showed that Vinpocetine could significantly increase aged islets insulin secretion and also make a meaningful reduction in oxidative stress markers. This drug can also decrease expression levels ofThe current study showed that Vinpocetine, a derivative of the secondary plant metabolite called Vincamine, could break this vicious cycle of oxidative stress and aging by reducing oxidative stress and inflammation, thus inhibiting cellular aging.The rapid-growing population of diabetic patients and the elderly are among the direst challenges that the science of medicine is facing today. Targeting these two challenges can shed light on new means to control and ideally reverse this trend. In this experiment, Vinpocetine’s effect on aged pancreatic beta-cell functions in correlation with oxidative stress was studied.Islet cells were isolated from the pancreas of aged rats and exposed to Vinpocetine, dissolved in acetone and RPMI, for 48 h. Then, senescence-associated molecular parameters, includingExperimental results showed that Vinpocetine could significantly increase aged islets insulin secretion and also make a meaningful reduction in oxidative stress markers. This drug can also decrease expression levels ofThe current study showed that Vinpocetine, a derivative of the secondary plant metabolite called Vincamine, could break this vicious cycle of oxidative stress and aging by reducing oxidative stress and inflammation, thus inhibiting cellular aging.

Due to the high cost, low effectiveness, and adverse effects plus the life-long nature of inflammatory bowel disease (IBD), and misconception on safety, efficacy, and cost-effectiveness of compleme...

Oral targeted small molecules, including sphingosine 1 phosphate receptor (S1PR) modulators and tyrosine kinase inhibitors (TKIs), seem to revolutionize the management of inflammatory bowel disease (IBD). To select the most effective treatment, there is an unmet need to comparatively study their mechanism of action, efficacy, and toxicity in the preclinical stage and further translate it into clinical practice.Using 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced adult zebrafish colitis model, LC50 of fingolimod and tofacitinib were determined based on the acute toxicity test to compare aquatic toxicity potential. Subsequently, the efficacy of different concentrations of tofacitinib and fingolimod was compared using flow cytometry, qPCR, and histopathology analyses.TNBS significantly reduced the length of villi, and the number of goblet cells increased the level of TNF-α, MyD88, and NF-κB2, the thickness of villi and necrosis, and induced histopathological changes. All of these parameters were reversed almost dose-dependently with both medications, with the highest concentration of fingolimod being superior to other groups. Additionally, results from qPCR analysis suggested that these medications might suppress canonical and non-canonical NF-κB pathways by targeting toll-like receptors and MyD88. LC50 of tofacitinib and fingolimod was 0.9014 and 0.36 mg/L, respectively. Hence, both are in the cory 1 of the Global Harmonization System (GHS) aquatic toxicity and are toxic to adult zebrafish life.Given the better efficacy of fingolimod, it is worth translating the effectiveness and safety of S1PR modulators into IBD patients and comparing them with TKIs in head-to-head studies; albeit, their toxicity should not be overlooked.

Background: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods: For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0·603 (0·400-1·00) standard drinks per day, and the NDE varied between 0·002 (0-0) and 1·75 (0·698-4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0-0·403) to 1·87 (0·500-3·30) standard drinks per day and an NDE that ranged between 0·193 (0-0·900) and 6·94 (3·40-8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3-65·4) were aged 15-39 years and 76·9% (73·0-81·3) were male. Interpretation: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Research reported in this publication was supported by the Bill & Melinda Gates Foundation. S Afzal acknowledges the support for intellectual contributions to this manuscript by the Department of Community Medicine and Epidemiology at King Edward Medical University, Lahore, Pakistan. T Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. L Belo acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. D Bennett is supported by the UK Medical Research Council Population Health Research Unit at the University of Oxford (Oxford, UK). M Carvalho acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. L Castro-de-Araujo was funded by the Medical Research Council (UK), Grant no. MR/T03355X/1 and by the National Institute of Mental Health Grant no. R01MH128911. FJ Elgar is supported by the Canada Research Chairs program. F Greaves acknowledges support from the NIHR Applied Research Collaboration for NW London. V K Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. VB Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. C Herteliu is partially supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. C Herteliu is partially supported by a grant from the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. S Hussain was supported by the Operational Programme Research, Development and Education –Project, Postdoc2MUNI “(No. CZ.02.2.69/0.0/0.0/18_053/0016952). S M S Islam is funded by the National Health and Medical Research Council and received funding from the National Heart Foundation of Australia. The Serbian part of this GBD-related contribution has been co-financed through Grant OI 175 014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. M Kivimaki was supported by the Wellcome Trust (221854/Z/20/Z), the UK Medical Research Council (MR/S011676/1), the US National Institute on Aging (R01AG056477), and the Academy of Finland (350426). K Krishan is supported by the UGC Centre of Advanced Study (Phase II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. B Lacey acknowledges support from the UK Biobank, funded largely by the UK Medical Research Council and Wellcome. S Lorkowski acknowledges institutional support from the Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig (Germany; German Federal Ministry of Education and Research; grant agreement number 01EA1808A). G Lucchetti received a productivity scholarship from the Brazilian National Council for Scientific and Technological Development — CNPq (Level 1D). J McGrath was supported by the Danish National Research Foundation (Niels Bohr Professor). J McGrath is employed by the Queensland Centre for Mental Health Research (Australia), which receives support from the Queensland Health Department. C Parry acknowleges the South African Medical Research Council. A Peden is supported by a National Health and Medical Research Council Emerging Leadership Fellowship (Grant ID: APP2009306). M R Phillips was supported in part by the Global Alliance for Chronic Diseases - National Natural Science Foundation of China (NSFC. No. 81761128031). M Pinheiro acknowledges FCT for funding through program DL 57/2016 – Norma transitória. A Rahman acknowledges the support from the Data Science Research Unit in Charles Sturt University (Bathurst, NSW, Australia). U Saeed would like to acknowledge the International Center of Medical Sciences Research (ICMSR), Islamabad, Pakistan. A M Samy acknowledges support from Ain Shams University (Cairo, Egypt) and the Egyptian Fulbright Mission Program. N Senthil Kumar acknowledges the DBT, New Delhi sponsored Advanced State Level Biotech Hub (BT/NER/143/SP44475/2021), Mizoram University (Aizawl, Mizoram, India) for facilitating this work. F Sha is supported by the Shenzhen Science and Technology Program (Grant No. KQTD20190929172835662). A Shetty acknowledges Kasturba Medical College (Mangalore, India) and Manipal Academy of Higher Education (Manipal, India) for all the academic support. R Shrestha acknowledges a career development award from the National Institutes of Health (K01DA051346). D Silva was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES)-Finance Code 001 and is supported in part by CNPq - Brazil (309589/2021-5). D Sleet acknowledges partial support from Veritas Management Group, Inc and The Bizzell Group, LLC. S Trias-Llimós acknowledges research funding from the Juan de la Cierva-Formación program of the Spanish Ministry of Science and Innovation (FJC-2019-039314-I). Sí

Background: The delaying of absorption of glucose is one of the principal therapeutic approaches of type 2 diabetes. α-glucosidase inhibitors compete with the α-glucosidase enzyme activity, which helps to reduce the conversion of carbohydrates into glucose and thereby control the postprandial hyperglycemia incidence. Objective: The aim of this study was to synthesize a series of novel 1,5-diphenyl pyrrole derivatives and evaluate their in vitro α-glucosidase inhibitory activities. Methods: Compounds were synthesized through a multistep reaction and were evaluated for α- glucosidase inhibitory activities. Molecular docking and kinetic studies were carried out to predict the mode of binding and mechanism of inhibition for the most active compounds, 5g and 5b, against α-glucosidase. Results: Synthesized compounds showed good in vitro α-glucosidase inhibitory activity with IC50 values in the range of (117.5 ± 3.8 to 426.0 ± 10.2 μM) as compared to acarbose, the standard drug, (750 ± 8.7 μM). Compound 5g (117.5 ± 3.8 μM) ascertained as the most potent inhibitor of α-glucosidase in a competitive mode. The binding energies of compounds 5g and 5b (119.0 ± 7.5 μM), as observed from the best docking conformations, indicate that they have a lower free binding energy (-3.26 kcal/mol and -3.0 kcal/mol, respectively) than acarbose (2.47 kcal/mol). Conclusion: The results of our study revealed that the synthesized compounds are a potential candidate for α-glucosidase inhibitors for the management of postprandial hyperglycemia for further investigation.

Summary The acquired resistance of plants to root-knot nematodes (Meloidogyne spp.) can be achieved by applying chemical inducers, such as β-aminobutyric acid (BABA). Recently, the use of metal nanoparticles with multifunctional use against plant-parasitic nematodes has been presented. In this study, silver nanoparticles (AgNPs) were synthesised using the aqueous leaf extract of Malva sylvestris. The effect of different AgNPs concentrations on hatching and mortality of the second-stage juveniles (J2) of Meloidogyne javanica was investigated in vitro. The effects of AgNPs on eggplants infected with 0, 1, 2, 4 and 8 eggs (cm3 soil)−1 were investigated under glasshouse conditions. The combined effects of AgNPs and BABA on eggplants infected with 4 and 8 eggs (cm3 soil)−1 were investigated in another study. The results showed that increasing the concentration of AgNPs the hatching of M. javanica decreased and the mortality of J2 increased. The number of eggs, galls, egg masses and reproduction factor in plants treated with AgNPs infected with 4 eggs (cm3 soil)−1 decreased by 43.4, 24.7, 23.5 and 43.2%, and in plants infected with 8 eggs (cm3 soil)−1, decreased by 64.5, 25.5, 63.1 and 64.5%, respectively, compared to control plants. The reproduction factor in infected plants with 4 and 8 eggs (cm3 soil)−1 that were treated with BABA (1 mM) and AgNPs decreased by 51.6 and 55.9%, respectively, compared to control plants. The results of this study demonstrated the effects of BABA, AgNPs and the combination of these two substances in reducing the damage of different inoculum densities of M. javanica in eggplant.

Background and objectives: Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory disease of the gastrointestinal tract. In Iranian traditional medicine, the oleo-gum-resin of the genus Pistacia is recommended for treatment of various diseases including gastrointestinal disorders. The present study investigated the therapeutic action of a combination of Pistacia atlantica subspecies kurdica oleo-gum-resin and honey in acetic acid-induced colitis in rats. Methods: Pistacia atlantica oleo-gum-resin was mixed with honey. The mixture was suspended in distilled water. Following induction of colitis with 4% acetic acid in all animals, except in sham group,themixture was orally administered for two consecutive days at the concentrations of 100, 200, 400 mg/kg. Other groups included the control, sham and a standard group (dexamethasone). Microscopic and histopathologic examinations were conducted in inflamed colonic tissue. The inflammatory biomarkers of colitis including interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and myeloperoxidase (MPO) and the gene expression level of toll like receptor-4 (TLR-4) were assessed. Results: Pistacia atlantica oleo-gum-resin+ honey induced significant progress in macroscopic and microscopic scores. Colonic levels of MPO, IL-6, and TNF-α significantly declined in rats treated with the mixture; while significant decrease in mucosal gene expression of TLR-4 and significant improvement of colitis were observed. Pistacia atlantica oleo-gum-resin (400 mg/kg) + honey (400 mg/kg)reduced inflammation of the bowel and colonic ulcer severity shown by downregulation of inflammation cytokines, reduction of neutrophil infiltration, and suppression of TLR-4 expression. Conclusion: The combination might be a promising supplement for treatment of inflammatory disorders.

BACKGROUND: Controversial data on the effects of vitamins (V) and nutrients on the management of type 2 diabetes mellitus (T2DM) is available. Thus, it is aimed to clarify the role of vitamins and nutrients through an umbrella review regarding the available observational/ trials meta-analyses. METHODS: All meta-analyses of observational and clinical trials conducted on the impact of vitamins and nutrients in T2DM published until 5(th) June 2021 in PubMed or Web of Sciences were included in this review. Also, the meta-analysis on children, pregnant women, type 1 DM, or in vivo/in vitro studies was excluded. Search results were reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) flowchart. RESULTS: The overall of 93 papers (99 studies) consisting of 75 trials and 24 observational studies were included. Most studies were conducted on the effect of VD and alpha-lipoic acid (ALA) in both genders. Consumption of VD or its analogous; 20 IU/d to 450,000 IU/once for 3 weeks to 7 years showed to have a positive effect on the parameters of glucose hemostasis. Moreover, an inverse association was observed between VD level and T2DM risk. Daily consumption of 1200 mg VC for at least 12 weeks improved lipid profile and glucose hemostasis parameters. Furthermore, VB and medications for diabetic polyneuropathy (DPN) increased nerve conduction velocity. Vitamins K and E were showen to not have significant impact on T2DM. ALA had a beneficial effect on DPN symptoms after 2–4 weeks of intake of at least 300 mg/d. T2DM risk was reduced by doubling ALA intake. The effective daily doses of chromium, zinc and coenzyme Q10 on lipid profile and glucose hemostasis parameters were > 200 mg

Repaglinide (RPG) is an oral insulin secretagogue used in the treatment of diabetes. In this study, a new RPG analog was synthesized. Its antidiabetic and neuroprotective effects on dorsal root ganglions (DRG) in streptozotocin (STZ)-induced diabetic rats were examined compared to RPG. To assess the effects of 2-methoxy-4-(2-((3-methyl-1-(2-(piperidin-1-yl)phenyl)butyl)amino)-2-oxoethoxy)benzoic acid (OXR), the impact of OXR on oxidative stress biomarkers, motor function, and the expression of the glutamate dehydrogenase 1 (GLUD1), SLC2A2/glucose transporter 2 (GLUT2), and glucokinase (GCK) genes in STZ-induced diabetic rats were assessed. DRGs were examined histologically using hemotoxylin and eosin staining. Molecular docking was used to investigate the interactions between OXR and the binding site of RPG, the ATP-sensitive potassium (KATP) channel. Following 5 weeks of treatment, OXR significantly increased the level of total antioxidant power, decreased reactive oxygen species, and lipid peroxidation in the DRGs of diabetic rats. OXR restored STZ-induced pathophysiological damages in DRG tissues. Administration of OXR improved motor function of rats with diabetic neuropathy. Administration of 0.5 mg/kg OXR reduced blood glucose while promoting insulin, mainly through upregulation of messenger RNA expression of GLUD1, GLUT2, and GCK in the pancreas. Molecular docking revealed a favorable binding mode of OXR to the KATP channel. In conclusion, OXR has neuroprotective effects in diabetic rats by lowering oxidative stress, lowering blood glucose, and stimulating insulin secretion. We report that 0.5 mg/kg OXR administration was the most effective concentration of the compound in this study. OXR may be a promising target for further research on neuroprotective antidiabetic molecules.

Type 1 diabetes mellitus is an autoimmune disease characterized by the loss of pancreatic islet β cells. Insulin injections and pancreas transplants are currently available therapies. The former requires daily insulin injections, while the latter is constrained by donor organ availability. Islet transplantation is a promising alternative treatment for type 1 diabetes mellitus that may overcome the limitations of previous techniques. Two challenges, however, must be addressed: limited cell retention as a result of the immune response and limited function of the transplanted cells that survive. To address these problems, we developed a microfluidic technology for a one-step generation of islet-laden fibers to protect them from the immune response. This approach enables continuous generation of microfibers with a diameter suitable for islet encapsulation (275 µm). We, then, transplanted islet-laden fibers into diabetic Wistar rats. While islet-laden fibers alone were unable to restore normoglycemia in diabetic rats, adding mesenchymal stromal cells (MSCs) restored normoglycemia for an extended time. It increased the animals’ lifespan by up to 75 d. Additionally, it improved the glucose-stimulated response of islets to the point where there was no significant difference between the treatment group and the healthy animals. Additionally, the presence of MSCs suppressed the immune response, as seen by decreased levels of pro-inflammatory cytokines such as tumor necrosis factor-α. Taken together, these fibers including islet and MSCs provide a versatile platform for concurrently improving cell preservation and functioning following in vivo transplantation.

Chlorpyrifos (CPF) is an organophosphorus (OP) pesticide, resulting in various health complications as the result of ingestion, inhalation, or skin absorption, and leads to DNA damage and increased oxidative stress. Metformin, derived from Galegaofficinalis, is reported to have anti-inflammatory and anti-apoptotic properties; thus, this study aimed to investigate the beneficial role of metformin in neurotoxicity induced by sub-acute exposure to CPF in Wistar rats. In this study, animals were divided into nine groups and were treated with different combinations of metformin and CPF. Following the 28 days of CPF and metformin administration, brain tissues were separated. The levels of inflammatory biomarkers such as tumor necrosis factor alpha (TNFα) and interleukin 1β (IL-1β), as well as the expression of 5HT1 and 5HT2 genes, were analyzed. Moreover, the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and the ADP/ATP ratio, in addition to the activity of acetylcholinesterase (AChE) and superoxide dismutase (SOD), were tested through in vitro experiments. This study demonstrated the potential role of metformin in alleviating the mentioned biomarkers, which can be altered negatively as a result of CPF toxicity. Moreover, metformin showed protective potential in modulating inflammation, as well as oxidative stress, the expression of genes, and histological analysis, in a concentration-dependent manner.