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Thyroid dysfunction and diabetes mellitus are prevalent endocrine disorders that often coexist and influence each other. The role of spexin (SPX) in diabetes and obesity is well documented, but its connection to thyroid function is less understood. This study investigates the influence of exercise (EX) and SPX on thyroid hypofunction in obese type 2 diabetic rats. Rats were divided into normal control, obese diabetic sedentary, obese diabetic EX, and obese diabetic SPX groups, with subdivisions for M871 and HT-2157 treatment in the latter two groups. High-fat diet together with streptozotocin (STZ) injection induced obesity and diabetes. The EX group underwent swimming, and the SPX group received SPX injections for 8 wk. Results showed significant improvements in thyroid function and metabolic, oxidative, and inflammatory states with EX and SPX treatment. The study also explored the involvement of galanin receptor isoforms (GALR)2/3 in SPX effects on thyroid function. Blocking GALR2/3 receptors partially attenuated the beneficial effects, indicating their interaction. These findings underscore the importance of EX and SPX in modulating thyroid function in obesity and diabetes. Comprehending this interplay could enable the development of new treatment approaches for thyroid disorders associated with obese type 2 diabetes. Additional research is necessary to clarify the exact mechanisms connecting SPX, EX activity, and thyroid function. NEW & NOTEWORTHY: This study proves, for the first time, the beneficial effects of SPX on thyroid dysfunction in obese diabetic rats and suggests that SPX mediates the EX effect on thyroid gland and exerts its effect mainly via GALR2. [ABSTRACT FROM AUTHOR]

Growing evidence supports the role of gut microbiota in chronic inflammation, insulin resistance (IR) and sex hormone production in polycystic ovary syndrome (PCOS). Adropin plays a pivotal role in the regulation of glucose and lipid metabolism and is negatively correlated with IR, which affects intestinal microbiota and sex hormones. However, the effect of adropin administration in PCOS has yet to be investigated. The present study aimed to assess the effects of adropin on letrozole (LTZ)‐induced PCOS in rats and the potential underlying mechanisms. The experimental groups were normal, adropin, letrozole and LTZ + adropin. At the end of the experiment, adropin significantly ameliorated PCOS, as evidenced by restoring the normal ovarian structure, decreasing the theca cell thickness in antral follicles, as well as serum testosterone and luteinizing hormone levels and luteinizing hormone/follicle‐stimulating hormone ratios, at the same time as increasing granulosa cell thickness in antral follicles, oestradiol and follicle‐stimulating hormone levels. The ameliorating effect could be attributed to its effect on sex hormone‐binding globulin, key steroidogenic genes STAR and CYP11A1, IR, lipid profile, gut microbiota metabolites–brain–ovary axis components (short chain fatty acids, free fatty acid receptor 3 and peptide YY), intestinal permeability marker (zonulin and tight junction protein claudin‐1), lipopolysaccharides/Toll‐like receptor 4/nuclear factor kappa B inflammatory pathway and oxidative stress makers (malondialdehyde and total antioxidant capacity). In conclusion, adropin has a promising therapeutic effect on PCOS by regulating steroidogenesis, IR, lipid profile, the gut microbiota inflammatory axis and redox homeostasis. Key points: Adropin treatment reversed endocrine and ovarian morphology disorders in polycystic ovary syndrome (PCOS).Adropin regulated the ovarian steroidogenesis and sex hormone‐binding globulin in PCOS.Adropin improved lipid profile and decreased insulin resistance in PCOS.Adropin modulated the components of the gut–brain–ovary axis (short chain fatty acids, free fatty acid receptor 3 and peptide YY) in PCOS.Adropin improved intestinal barrier integrity, suppressed of lipopolysaccharides/Toll‐like receptor 4/nuclear factor kappa B signalling pathway and oxidative stress in PCOS. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon‐like peptide 1 receptor (GLP‐1R) agonist that act as a novel antidiabetic drug with broad‐spectrum anti‐inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA‐induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid‐treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT‐PCR technique. Hepatic NF‐κB and TNF‐α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA‐hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA‐induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis. Significance statement: Valproic acid (VPA) is a commonly used drug for the management of epilepsy. However, Prolonged VPA administration raises the risk of hepatotoxicity. Liraglutide is a novel antidiabetic drug with broad‐spectrum anti‐inflammatory and antioxidant effects. Thus, we aimed to investigate the protective effect of liraglutide against VPA‐induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

This study evaluated possible mitigating effect of adropin on lung injury in diabetic rats, targeting role of Rho A/Rho‐associated kinase pathway. Rats were allocated into four groups: control, adropin, diabetic, and diabetic+adropin groups. At the termination of the experiment, serum fasting glucose, insulin and adropin levels and insulin resistance were calculated. Wet/dry ratio, histopathological, immunohistochemical analyses, and relative real time gene expression of lung tissue was determined. Interleukin‐6, tumor necrosis factor alpha, malondialdehyde, 8‐Oxo‐2′‐deoxyguanosine, reduced glutathione, superoxide dismutase, Bcl‐2, BAX, myeloperoxidase, intracellular adhesion molecule‐1, vascular cell adhesion molecule‐1, and transforming growth factor‐β were determined in lung tissue. Adropin treatment in diabetic rats notably attenuated hyperglycemia and insulin resistance. Also, it mitigated diabetic lung injury via suppressing effect on Rho A/ROCK pathway, apoptosis, inflammatory reactions, oxidative stress, and fibrosis of lung tissue. Adropin can be considered as a promising therapeutic agent for treating diabetic lung injury. [ABSTRACT FROM AUTHOR]

Corticosteroids are used to treat a variety of diseases like bronchial asthma. However, long-term corticosteroids have a gastric ulcerogenic potential. Montelukast (MTK) and Nigella sativa oil (NSO) are used in treatment of bronchial asthma. Previous studies showed that MTK and NSO had gastroprotective effects in other models of gastric ulcer. The present study assesses synergistic gastroprotective effects of both drugs in dexamethasone (DXM)-induced gastric damage. Fifty male rats were divided into 5 groups: normal control (I), DXM group (II), MTK + DXM group (III), NSO + DXM group (IV), MTK + NSO + DXM group (V). After 7 days, stomachs were removed for biochemical analysis and histological examinations. Significant increases in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity, and proliferating cell nuclear antigen (PCNA) positive cells, with significant decreases in mucus secretion were detected in DXM-treated group compared with group I. Meanwhile, significant decreases of MDA level, MPO activity, and PCNA positive cells and significant increases in mucus secretion were detected in treated groups compared with group II. SOD activity significantly decreased in group V compared with group II. We could conclude that administration of either MTK or NSO or both with DXM counteracts DXM-induced gastric lesions. Key words: montelukast, Nigella sativa, dexamethasone, gastric damage. Les corticosteroides sont utilises pour traiter une variete de maladies telles que l'asthme. Cependant, l'administration de corticosteroides a long terme peut avoir comme consequence la formation d'ulceres gastriques. Le montelukast (MTK) et l'huile de Nigella sativa (HNS) sont utilises dans le traitement de l'asthme. Des etudes anterieures menees avec d'autres modeles d'ulcere gastrique ont permis de montrer que le MTK et l'HNS ont des effets gastroprotecteurs. La presente etude vise a evaluer les effets gastroprotecteurs synergiques des deux substances contre les dommages gastriques induits par la dexamethasone (DXM). Nous avons reparti 50 rats males dans 5 groupes : temoin normal (I), DXM (II), MTK + DXM (III), HNS + DXM (IV) et MTK + HNS + DXM (V). Apres 7 jours, nous avons preleve les estomacs pour proceder a des analyses biochimiques et des examens histologiques. Nous avons decele une augmentation des taux de malondialdehyde (MDA), de l'activite de la superoxyde dismutase (SOD) et de la myeloperoxydase (MPO) ainsi que du nombre de cellules exprimant l'antigene PCNA (pour<>), avec une diminution de la secretion de mucus nettement plus marquees dans les groupes DXM que dans le groupe I. Concurremment, nous avons observe une diminution des taux de MDA, de l'activite de la MPO et du nombre de cellules exprimant l'antigene PCNA, avec une augmentation de la secretion de mucus nettement plus marquees avec l'administration des substances a l'etude que dans le groupe II. L'activite de la SOD diminuait de facon beaucoup plus marquee dans le groupe V que dans le groupe II. Nous pourrions en arriver a la conclusion que l'administration concomitante de MTK, d'HNS ou de ces deux substances avec de la DXM permettrait de contrecarrer la formation de lesions gastriques induites par la DXM. [Traduit par la Redaction] Mots-cles: montelukast, Nigella sativa, dexamethasone, dommages gastriques., Introduction Corticosteroids are used to treat a variety of health problems (Lu and Cidlowski 2004). Bronchial asthma is one of the diseases that needs long-term treatment with corticosteroids (Ukena et [...]

Irisin is a new myokine that is suspected to influence metabolic syndrome (MetS). However, there is a great controversy with respect to its level in cases of MetS and its correlation with different metabolic parameters. The present study assesses irisin levels in MetS patients and studies its relationship to metabolic and liver functions to evaluate the possible role of the liver in regulation of this level. Sixty subjects were included in this experiment, who were divided into 3 groups: group I (normal control), group II (MetS patients with normal liver enzymes), and group III (MetS with elevated liver enzymes and fatty liver disease). Serum irisin levels showed significant increases in groups II and III compared with group I, and significant increases in group III compared with group II. Also, irisin levels were positively correlated with body mass index, serum triglycerides, homeostatic model assessment of insulin resistance index (HOMA-IR), and liver enzymes. We concluded that serum irisin levels increased in patients with MetS, especially those with elevated liver enzymes, and had a positive correlation with parameters of lipid metabolism and glucose homeostasis with the possibility of hepatic clearance to irisin. Key words: irisin, metabolic syndrome, fatty liver. L'irisine est une nouvelle myokine que l'on soupconne influencer le syndrome metabolique (SM). Cependant, les niveaux d'irisine trouves dans les cas de SM et leur correlation avec differents parametres metaboliques sont l'objet de controverses. Le but de cette presente etude etait d'evaluer le niveau d'irisine chez des patients presentant le SM et d'etudier sa relation avec les fonctions metaboliques et hepatiques afin d'evaluer le role possible du foie dans la regulation de ce niveau. Soixante sujets ont ete inclus dans cette experience et ils ont ete repartis en trois groupes : groupe I (personnes controles normales), groupe II (patients avec SM dont les enzymes hepatiques sont normales) et le groupe III (patients avec SM dont les enzymes hepatiques sont elevees et qui presentent un foie gras). Les niveaux d'irisine serique etaient significativement accrus dans les groupes II et III comparativement au groupe I et significativement plus eleves dans le groupe III comparativement au groupe II. Les niveaux d'irisine etaient aussi en correlation positive avec l'indice de masse corporelle, les triglycerides seriques, l'indice de resistance a l'insuline HOMA et les enzymes hepatiques. Les auteurs concluent que le niveau d'irisine serique est eleve chez les patients avec SM, particulierement les patients dont les enzymes hepatiques sont elevees, et qu'il est positivement correle avec les parametres du metabolisme des lipides et de l'homeostasie du glucose, avec la possibilite d'une clairance hepatique de l'irisine. [Traduit par la Redaction] Mots-cles: irisine, syndrome metabolique, foie gras., Introduction Metabolic syndrome (MetS) is a combination of medical disorders, which includes obesity, insulin resistance, hypertension, hypertriglyceridemia, and low high-density lipoprotein cholesterol (HDL- C), and it may be associated with [...]

A mechanistic understanding of the dynamic interactions between the mitochondria and the gut microbiome is thought to offer innovative explanations for many diseases and thus provide innovative management approaches, especially in GIT-related autoimmune diseases, such as ulcerative colitis (UC). β-Glucans, important components of many nutritious diets, including oats and mushrooms, have been shown to exhibit a variety of biological anti-inflammatory and immune-modulating actions. Our research study sought to provide insight into the function of β-glucan and/or fidarestat in modifying the microbiome/mitochondrial gut axis in the treatment of UC. A total of 50 Wistar albino male rats were grouped into five groups: control, UC, β-Glucan, Fidarestat, and combined treatment groups. All the groups were tested for the presence of free fatty acid receptors 2 and 3 (FFAR-2 and -3) and mitochondrial transcription factor A (TFAM) mRNA gene expressions. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP content were found. The trimethylamine N-oxide (TMAO) and short-chain fatty acid (SCFA) levels were also examined. Nuclear factor kappa β (NF-kβ), nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity, and peroxisome proliferator-activated receptor gamma co-activator-1 (PGC-1) were identified using the ELISA method. We observed a substantial increase FFAR-2, -3, and TFAM mRNA expression after the therapy. Similar increases were seen in the ATP levels, MMP, SCFA, PGC-1, and Nrf2 DNA binding activity. The levels of ROS, TMAO, and NF-kβ, on the other hand, significantly decreased. Using β-glucan and fidarestat together had unique therapeutic benefits in treating UC by focusing on the microbiota/mitochondrial axis, opening up a new avenue for a potential treatment for such a complex, multidimensional illness. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the potential mitigating effect of fisetin on monosodium glutamate (MSG)-induced testicular toxicity and investigate the possible involvement of silent mating type information regulation 2 homolog 1 (SIRT1) in this effect. Forty male rats were divided into normal control, fisetin-treated, MSG-treated, and fisetin + MSG-treated groups. Testosterone, GnRH, FSH, and LH were measured in plasma, as well as SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) levels in testicular tissues using ELISA. Hydrogen peroxide (H2O2), nitric oxide (NO), and reduced glutathione (GSH) were measured colorimetrically, while Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression was relatively quantified using RT–PCR in testicular tissues. After 30 days, fisetin could ameliorate MSG-induced testicular toxicity by acting centrally on the hypothalamic-pituitary-gonadal axis, increasing plasma levels of GnRH, FSH, LH, and testosterone. Peripheral actions of fisetin on the testis were indicated as it increased testicular SIRT1 and pAMPK. Furthermore, it antagonized glutamate-induced oxidative stress by significantly lowering H2O2, NO, and relative NOX4 expression while significantly increasing reduced GSH levels. It also improved the architecture of the seminiferous tubules, reduced sperm abnormality, and increased sperm count. Fisetin ameliorates MSG-induced testicular toxicity via central and peripheral mechanisms making it a promising therapeutic target for male infertility. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is a drug used in treatment of various malignancies. Unfortunately, it leads to life-threatening complications including hepatorenal toxicity. Previous studies revealed the protective effects of metformin (MET) on hepatorenal toxicity in other models in addition to its anticancer effects. The current study investigates the effect of MET on MTX-induced hepatorenal toxicity and the possible mechanisms involved in this toxicity which can be overwhelmed by MET. Thirty male rats were divided into 3 groups: normal control, MTX treated and MET/MTX treated. After 7 days, MTX induced hepatorenal toxicity as proved by histological examinations and biochemical analysis of liver and kidney functions. Also, it led to significant increase in hepatic and renal malondialdehyde levels, significant decrease in hepatic and renal total antioxidant capacity levels and Na+/K+-ATPase activities and significant up regulation of mRNA expressions of nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2 and caspase 3 compared with the control group. While, MET could significantly reduce hepatorenal toxicity and counteract the effects of MTX on all measured parameters. In conclusion, MET can be an effective adjuvant to MTX chemotherapy that could ameliorate its hepatorenal toxicity through antioxidant, anti-inflammatory and anti-apoptotic mechanisms. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Treg) has been documented to be protective against myocardial ischemia-reperfusion injury (MIRI). The administration of drugs which recruit Treg cells may participate in the cardioprotection of MIRI. The purpose of the present study was to investigate whether the add-on vildagliptin (vild) to standard treatment of MIRI prior to reperfusion could increase Treg recruitment, anti-inflammatory, and antioxidant effects of the standard treatment or not. Sixty diabetic patients with ST-segment elevation myocardial infarction were randomly divided into two equal groups: control group was given the standard medical treatment and vild group was given the standard medical treatment plus vild. There were no statistical differences between the mean of percentage of changes in nitric oxide, ischemia modified albumin, highly sensitive C reactive protein, and interferon-gamma levels in the studied groups. While, the percentages of changes of myeloperoxidase level, CD4+CD25+ Treg cells count, and transforming growth factor-beta1 level were significantly higher in vild group compared with control group. We concluded that addition of vild to standard medical treatment of MIRI could increase its effectiveness through recruitment of CD4+CD25+ Treg cells. [ABSTRACT FROM AUTHOR]

Abstract: Lactoferrin (LF) was previously suggested to have a protective effect against liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was designed to investigate LF effect on HSP47 as a potential target for management of liver fibrosis and comparing it with silymarin (SM) in a thioacetamide (TAA)‐induced liver fibrosis model. Rats were divided into four groups; normal control, TAA (TAA‐treated), LF (LF + TAA‐treated), and SM (SM + TAA‐treated). After 6 weeks, both LF and SM improved the grade of cirrhosis, reduced collagen fibers deposition, inactivated HSCs, significantly decreased elevated liver enzymes, HSP47, hydroxyproline content, transforming growth factor‐beta 1, matrix metalloproteinase‐2, 8‐hydroxydeoxyguanosine, malondialdehyde, nitric oxide levels and the percentage of alpha smooth muscle actin positive HSCs compared with TAA group. Moreover, LF significantly increased the total antioxidant capacity compared with TAA group. It could be concluded that LF is a promising antifibrotic drug and could be considered as one of the HSP47 inhibitors but SM is still more potent. © 2018 IUBMB Life, 70(8):795–805, 2018 [ABSTRACT FROM AUTHOR]

Objectives. We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. Methods. A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia), time needed for complete recovery, and time needed for discharge. Results. There was no statistical significant difference between the studied groups regarding age, sex, weight, Child–Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (P=0.001). Conclusion. The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with ClinicalTrials.gov Identifier: NCT03063866. [ABSTRACT FROM AUTHOR]

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with poor social interaction, communication issues, aberrant motor movements, and limited repetitive interests and behaviour. Spirulina platensis (SP) contains several multi-nutrients and has a wide range of neuroprotective properties.Aim: The target of the current experiment is to detect the protective effects of S. platensis on valproic-induced autism in adult female albino rats’ siblings for the first time.Materials and Methods: Twelve Pregnant rats were separated into four main groups; Group I (control); Group II (S. platensis); Group III (autistic group); and Group IV (autistic SP-treated group). Fifteen offspring pups from each group were sacrificed, brain was divided for biochemical analysis as superoxide dismutase and malondialdehyde were evaluated spectrophotometrically while interleukin-6, interleukin-12, Bcl-2-associated X protein, B-cell lymphoma-2, Beclin-1, brain-derived neurotrophic factor were assessed by ELISA, other division of brain were used for gene expression of PI3k, Akt and mTOR pathway, last division of brain were stained using (H&E) and Giemsa stains. Tumour necrosis factor alpha (TNF-$\alpha \rpar$α) and Synaptophysin (SYN) markers were used for immunohistochemical staining.Results: Autistic Group (III) showed an increment in levels of MDA, IL-6, IL12 and BAX while showing a decrement in SOD, Bcl-2 and Beclin-1 as well as increased PI3k, Akt and mTOR gene expression. Autistic Group (III) also exhibited hypocellularity and disorganization of hippocampal and prefrontal cortex cells. The autistic SP-treated group (IV) showed improvement in these biochemical markers and pathological changes. Our findings suggest that Spirulina platensis will be significant in managing autism. [ABSTRACT FROM AUTHOR]

Background and Aims: Treatment of hepatitis C virus (HCV) infection has significantly changed during the last few years. The combination of ledipasvir and sofosbuvir has been shown to treat high proportions of patients with HCV genotype 1 with remarkable tolerability. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ledipasvir in treating treatment-naïve Egyptian patients with genotype 4 HCV infection., Patients and Methods: In this open-label randomized study, 200 treatment-naive patients who were HCV antibody positive and HCV RNA positive by polymerase chain reaction, aged >18 years, were enrolled. The patients were classified into two groups: group I included 100 patients who received single therapy with sofosbuvir plus ledipasvir for 12 weeks and group II included 100 patients who received sofosbuvir plus oral weight-based ribavirin for 24 weeks. The primary end point was a sustained virological response at 12 weeks (SVR12) after the end of treatment, determined by quantitative polymerase chain reaction for HCV RNA., Results: Group I patients showed statistically significant ( p <0.05) higher SVR12 compared with group II patients (99% vs. 80%). There was no statistical difference ( p >0.05%) between the studied groups regarding the frequencies of the side effects (26% vs. 29%). The most common adverse effects were headache, fatigue, myalgia, and cough., Conclusion: Sofosbuvir and ledipasvir treatment for 12 weeks was well tolerated by patients with HCV genotype 4 and resulted in 99% SVR for all patients who received 12 weeks of the study drugs. ClinicalTrials.gov Identifier: NCT02992457., Competing Interests: Disclosure The authors report no conflicts of interest in this work.