Body Mass Research Articles

Effect of Dalbergiella welwitschi alkaloid-rich extracts on neuroprotective in streptozotocin-induced diabetic rats.

The neuroprotective ability of alkaloid-rich leaf extract of Dalbergiella welwitschii in streptozotocin-induced type 2 diabetic rats were investigated in this study. Dalbergiella welwitshii leaf alkaloid-rich extract was obtained using standard procedure. Streptozotocin was injected into the experimental animals intraperitoneally at a dose of 45mg/mg body weight. Prior to this, the animals were given 20% (w/v) fructose for one week. The animals were grouped into five (n = 8), comprising of normal control (NC), diabetic control (DC), diabetic rats treated with low (50mg/mg body weight) and high (100mg/kg body weight) doses of Dalbergiella welwitschii alkaloid-rich leaf extracts (i.e., DWL and DWH respectively) and 200mg/kg body weight of metformin (MET). The animals were sacrificed on the 21st day, blood and brain tissue were harvested and used for the determination of neurotransmitters, cholinesterase, some ATP activities, oxidative stress biomarkers and histological examination. The results show that diabetic rats placed on DWL, DWH and MET significantly (p < 0.05) reduced cholinergic, elevated some ATPase activities and ameliorated oxidative stress biomarkers. These were supported by the histological examination by improving neuroprotective effects in diabetic rats administered DWL, DWH and MET. Hence, it can be presumed that DWL and DWH could be beneficial in treating diabetic neurodegenerative diseases.

Intraperitoneal administration of α-melanocyte stimulating hormone (α-MSH) suppresses food intake and induces anxiety-like behavior via the brain MC4 receptor-signaling pathway in goldfish.

α-Melanocyte stimulating hormone (α-MSH) is a peptide hormone released from the intermediate lobe of the pituitary which regulates body pigmentation. In addition to the pituitary, α-MSH is also produced in the midbrain, and exerts both anorexigenic and an anxiogenic actions. Acyl ghrelin and cholecystokinin are peripheral hormones derived from the digestive tract which affect the brain to control food intake and feeding behavior in vertebrates. In the present study, hypothesizing that plasma α-MSH may also stimulate the brain and exert central effects, we examined whether peripherally administered α-MSH affects food intake and psychomotor activity using a goldfish model. Intraperitoneal (IP) administration of α-MSH at 100 pmol g-1 body weight (BW) reduced food consumption and enhanced thigmotaxis. These α-MSH-induced actions were blocked by intracerebroventricular administration of HS024, an antagonist of the melanocortin 4 receptor (MC4R), at 50 pmol g-1 BW, whereas these actions were not attenuated by pretreatment with an IP-injected excess amount of capsaicin, a neurotoxin that destroys primary sensory (vagal and splanchnic) afferents, at 160 nmol g-1 BW. Transcripts for the MC4R showed higher expression in the diencephalon in other regions of the brain. These results suggest that, in goldfish, IP administered α-MSH is taken up by the brain, and also acts as anorexigenic and anxiogenic factor via the MC4R signaling pathway.

Evaluationof feeding different forms of therapeutic diet on the feed intake, digestibility, feed efficiency, and growth of calves experimentally infected with foot-mouth disease virus.

Oral ulcers induce acute weight loss due to anorexia in foot-and-mouth disease virus (FMDV) infected cattle. We hypothesized that providing a palatable form of a therapeutic diet (TD) in different physical forms would increase the feed intake, digestibility and restoration of body weight. A TD was formulated with 19% CP and 2.9 Mcal ME/kg on dry matter basis. Bull calves of 10-12months with mean body weight of 123 ± 1.3kg were experimentally infected with FMDV (n = 18) and offered one of the following three forms of the TD (n = 6/group) for 6weeks post-FMDV infection (WPI): (i) TD in mash form (TDM) (ii) TD in cooked form (TDC) and (iii) TDC + customised nutrient supplement (TDCNS) such as Zn, Cu, Cr, Mn, and Se. The CNS was fed before the TDC. A group of uninfected control (n = 4) was fed TDM. Green fodder was offered in the afternoon. Dry matter intake (DMI) of TD and green fodder were recorded at 24h interval till WPI 6. Body weight (BW) was recorded at weekly interval. Digestibility trial was conducted at WPI 6. The palatability of the TD was scored from 1- 4 and healing of tongue ulcers was analyzed by Kaplan-Meier survival curve. The results indicated that the physical form of TD increased the total DMI by WPI 3, which was supported by the restoration of BW and higher palatability score. The digestibility of all the proximate principles except EE was significantly higher (P < 0.05) in the groups that were fed TDC. It was concluded that feeding TD irrespective of the physical form, restored the ADG and DMI in the calves by WPI 3. Further, feeding cooked form of TD increased the digestibility in the FMDV infected calves and supplementation of CNS hastened the healing of glossal ulcers.

In utero nicotine exposure affects murine palate development.

Despite data linking smoking to increased risk of fetal morbidity and mortality, 11% of pregnant women continue to smoke or use alternative nicotine products. Studies confirm that nicotine exposure during pregnancy increases the incidence of birth defects; however, little research has focused on specific anatomic areas based on timing of exposure. We aim to determine critical in utero and postnatal periods of nicotine exposure that affect craniofacial development, specifically palate growth. Malformation of the palatal structures can result in numerous complications including facial growth disturbance, or impeding airway function. We hypothesized that both in utero and postnatal nicotine exposure will alter palate development. We administered pregnant C57BL6 mice water supplemented with 100 μg/mL nicotine during early pregnancy, throughout pregnancy, during pregnancy and lactation, or lactation only. Postnatal day 15 pups underwent micro-computed tomography (μCT) analyses specific to the palate. Resultant pups revealed significant differences in body weight from lactation-only nicotine exposure, and μCT investigation revealed several dimensions affected by lactation-only nicotine exposure, including palate width, palate and cranial base lengths, and mid-palatal suture width. These results demonstrate the direct effects of nicotine on the developing palate beyond simple tobacco use. Nicotine exposure through tobacco alternatives, cessation methods, and electronic nicotine delivery systems (ENDS) may disrupt normal growth and development of the palate during development and the postnatal periods of breastfeeding. Due to the recent dramatic increase in the use of ENDS, future research will focus specifically on this nicotine delivery method.

Impact of low-to moderate-intensity exercise training on the mRNA expression of purine receptors across various vessels in SHR.

In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

Identifying optimal dosing strategies for meropenem in the paediatric intensive care unit through modelling and simulation.

Meropenem, a β-lactam antibiotic commonly prescribed for severe infections, poses dosing challenges in critically ill patients due to highly variable pharmacokinetics. We sought to develop a population pharmacokinetic model of meropenem for critically ill paediatric and young adult patients. Paediatric intensive care unit patients receiving meropenem 20-40 mg/kg every 8 h as a 30 min infusion were prospectively followed for clinical data collection and scavenged opportunistic plasma sampling. Nonlinear mixed effects modelling was conducted using Monolix®. Monte Carlo simulations were performed to provide dosing recommendations against susceptible pathogens (MIC ≤ 2 mg/L). Data from 48 patients, aged 1 month to 30 years, with 296 samples, were described using a two-compartment model with first-order elimination. Allometric body weight scaling accounted for body size differences. Creatinine clearance and percentage of fluid balance were identified as covariates on clearance and central volume of distribution, respectively. A maturation function for renal clearance was included. Monte Carlo simulations suggested that for a target of 40% fT > MIC, the most effective dosing regimen is 20 mg/kg every 8 h with a 3 h infusion. If higher PD targets are considered, only continuous infusion regimens ensure target attainment against susceptible pathogens, ranging from 60 mg/kg/day to 120 mg/kg/day. We successfully developed a population pharmacokinetic model of meropenem using real-world data from critically ill paediatric and young adult patients with an opportunistic sampling strategy and provided dosing recommendations based on the patients' renal function and fluid status.

Tranilast Inhibits TRPV2 and Suppresses Fibrosis Progression and Weight Gain in a NASH Model Mouse.

This study aimed to investigate the role of transient receptor potential vanilloid 2 (TRPV2) in a mouse model with non-alcoholic steatohepatitis (NASH) and to examine the effects of tranilast on TRPV2 and fibrosis-related cytokines. C57BL/6N mice were fed a Gubra-Amylin NASH (GAN) diet for 20 weeks to induce NASH. The tranilast groups received oral administration of tranilast at doses of 300, 400 and 500 mg/kg/day, five days per week for 20 weeks, in addition to the GAN diet. The effects of tranilast were assessed based on the dosage of food intake, changes in body weight, liver weight, blood biochemical parameters, histopathological examination, and expression of TRPV2 and inflammatory cytokines. Hepatic expression of TRPV2 was observed in the GAN-fed NASH mouse model. The tranilast groups showed significantly suppressed increases in body and liver weights. The development of intrahepatic fat deposition and liver fibrosis, assessed histopathologically, was inhibited. Tranilast administration improved the expression of TRPV2 and inflammatory cytokines in the liver. Additionally, blood tests indicated a reduction in elevated liver enzyme levels. In GAN diet NASH models, TRPV2 was up-regulated in the liver and tranilast inhibited TRPV2 and suppressed fibrosis. Therefore, it might prevent the incidence of hepatocellular carcinoma associated with NASH.

Therapeutic effects of Artocarpus communis J.R.Forst. & G.Forst. Seeds on Letrozole-induced Polycystic Ovary Syndrome Wistar rats

BackgroundHerbal extracts are an effective treatment for polycystic ovarian syndrome (PCOS) and have been shown to improve insulin resistance, hyperandrogenism, sex hormones, ovulation, and PCOS symptoms. Artocarpus communis seed's potential effects on polycystic ovary syndrome (PCOS) have not been studied. PurposeThis research aims to investigate the beneficial effects of Artocarpus communis seeds on PCOS induced by letrozole in Wistar rats. MethodsTo induce PCOS, female Wistar rats weighing between 160g to 250g were administered letrozole (1 mg/kg) for 21 days. Subsequently, for 12 days, the rats were given the Artocarpus communis seed methanol extract, and its hexane, DCM, ethyl acetate and aqueous fractions (100 mg/kg body weight) and Clomiphene citrate (1 mg/kg body weight), a standard medication. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels were assessed using ELISA, and the expression of P53, insulin receptor substrate (IRS), type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), and 11a-hydroxylase/17,20-desmolase (CYP11a) genes were investigated. The data were analyzed using one-way ANOVA, and a significance threshold of p<0.05 was set for Dunnett's Multiple Comparison Test. ResultsAdministration of the methanol extract of Artocarpus communis seed and its Hexane fraction led to a decrease in LH level and an increase in FSH and estradiol levels in the PCOS-induced animals. Furthermore, methanol extract, DCM, and ethyl acetate fraction normalize the expression of P53, insulin receptor substrate (IRS), type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), and 11a-hydroxylase/17,20-desmolase (CYP11a) genes in PCOS rats cervix. ConclusionArtocarpus communis seed exhibited ameliorative effects on polycystic ovary conditions in Wistar rats, suggesting its potential use in the management of PCOS.

Protective effects of 3, 4-dihydroxybenzoic acid on myocardial infarction induced by isoproterenol in rats.

Despite considerable advances in interventions and treatment, there is a high mortality rate in patients with myocardial infarction (MI). This is the first study to investigate the protective effects of 3, 4-dihydroxybenzoic acid against isoproterenol induced MI in rats. MI was induced by isoproterenol (100-mg/kg body weight) in rats. Then, rats were treated with 3, 4-dihydroxybenzoic acid (16-mg/kg body weight) for 2 weeks. Serum creatine kinase-MB, cardiac troponin-T, cardiac troponin-I, and heart thiobarbituric acid reactive substances were significantly (p < 0.05) increased and heart superoxide dismutase and catalase activities were significantly (p < 0.05) reduced in isoproterenol-induced myocardial infarcted rats. Isoproterenol induction significantly (p < 0.05) elevated the plasma homocysteine and serum high sensitivity-C-reactive protein levels. Furthermore, an enzyme-linked immunosorbent assay, reverse transcription polymerase chain study, and immunohistochemical (IHC) staining revealed significantly (p < 0.05) elevated levels and expression of serum/myocardial nuclear factor-κB, tumor necrosis factor-alpha, interleukin-1 beta, and Interleukin-6 and significantly (p < 0.05) reduced levels/expression of serum/myocardial interleukin-10 in myocardial infarcted rats. Nevertheless, isoproterenol-induced rats treated with 3, 4-dihydroxybenzoic acid considerably (p < 0.05) attenuated all the biochemical, molecular, and IHC parameters investigated and inhibited oxidative stress and inflammation and protected the heart, through its antioxidant and anti-inflammatory mechanisms.

The option of transosseous distal suture placement during minimally invasive Achilles tendon repair for high-risk patients can improve outcomes, however does not prevent re-rupture

PurposeAchilles tendon ruptures (ATRs) close to the insertion, in high-level athletes, and in patients at high risk of re-rupture, may be better suited to operative repair. Minimally Invasive Repair (MIR) of the Achilles tendon has excellent outcome and low complication rates. Traditionally MIR has showed lower repair strength, failing due to suture pull-out from the distal tendon stump. The aim of this study was to describe the outcome of ATR patients who received transosseous distal suture placement using a standard technique as a reference.MethodsFollowing ATR, patients were evaluated for pre-injury activity level, body weight, location of the tear and size of the distal Achilles tendon stump. Patients considered to be at high-risk of re-rupture: Tegner level ≥ 8, body weight ≥ 105Kg and distal ATR, received transosseous (TO) distal suture placement (n = 20) rather than the usual transtendinous (TT) technique (n = 55). Patient reported outcome measures and functional evaluation was performed at 12 months following repair.ResultsAt 12 months follow up both methods resulted in good median (IQR) Achilles tendon Total Rupture Score TO 83.8 (74-88.3) vs. TT 90 (79–94), low increased relative Achilles Tendon Resting Angle TO -3.5˚ (3.6) vs. TT -3.5˚ (3.3) and mean (SD) Single leg Heel-Rise Height Index TO 88.2% (9.9) vs. TT 85.6% (9.9) (n.s.). There were 4 re-ruptures in the high-risk group and 2 in the group receiving TT distal suture placement. All but one of these were traumatic in nature. The mode of failure following TO distal suture placement was proximal suture pull out.ConclusionsTo distal suture placement during minimally-invasive Achilles tendon repair for higher-risk patients can lead to results equivalent to those in lower-risk patients treated with a standard TT MIR technique, except for the re-rupture rate which remained higher. There may be factors that have greater influence on outcome other than suture placement following ATR.

Oral Mucositis and Nutritional Status in Children Who Underwent Hematopoietic Cell Transplantation: AComparison Between Nonmalignant and Malignant Primary Diseases.

There is a lack of studies analyzing the association between oral mucositis (OM) and nutritional imbalance in children during hematopoietic stem cell transplantation (HSCT). The aim of this study was to compare the risk factors for OM and nutritional imbalance during HSCT in pediatric patients with nonmalignant diseases (NMD) and malignant diseases (MD). Data on age, sex, primary disease, transplantation type, conditioning regimen, GVHD prophylaxis, gastrointestinal toxicity, OM, percent body weight loss or gain, nutritional repositioning, and overall survival (OS) were retrospectively collected from the 132 medical records. The data were then compared between patients with NMD (n = 70) and MD (n = 62). OM had a similar severity between the groups. The primary risk factor for OM in the NMD group was the conditioning regimen with busulfan, while in the MD group it was GVHD prophylaxis with cyclosporin and methotrexate. OM did not have an impact on body weight loss or gain in any of the groups. In the NMD, body weight gain due to fluid overload was more pronounced and associated with a lower age range. OS was similar between the groups and was not affected by OM. OM pattern was similar in pediatric patients with or without MD, but the factors that determined these oral lesions were different. There were disparities in body weight changes between the two groups, and these changes were not associated to OM.

Linggui Zhugan Decoction: A Potential Weight Reduction Solution via Gut Microbiota and Cinnamic Acid Metabolites

Linggui Zhugan Decoction (LGZGD) has demonstrated promising potential in the treatment of obesity, prompting further investigation. In a study involving sixty-nine obese patients who received LGZGD for two months, changes in body composition, gut microbiota, and plasma metabolomics were assessed. An animal experiment with ob/ob mice assessed LGZGD and antibiotics’ effects on body weight, fat mass, gut microbiota, and metabolomics. Clinical results showed LGZGD reduced body weight, fat, and waist-to-hip ratio, improved gut microbiota diversity favoring beneficial strains, and revealed Cinnamic acid presence in non-targeted plasma metabolomics. In obese mice, LGZGD effectively reduced body weight and fat mass, with this effect attenuated in microbiota-depletedmice. The treatment also influenced gut microbiome composition, aligning it more closely with that of normal mice. Non-targeted metabolomics analysis identified various metabolites in stool and plasma, including Cinnamic acid. In vitro experiments demonstrated that Cinnamic acid, devoid of toxicity, inhibited lipid synthesis and improved lipid metabolism in adipocytes. The immunofluorescence demonstrated Cinnamic acid activated the expression of Uncoupling protein 1 in differentiated adipocytes in a dose-dependent way. This study suggests that LGZGD’s weight-reduction effects are mediated through interactions with gut microbiota and its metabolites. Activating the browning of white adipocytes maybe the underlying mechanism.

Preclinical Appraisal of the Aphrodisiac Effects of Emblica officinalis Seed Extract on Stress-induced Sexual Behavior in Albino Rats

Background: The king of herbs, Emblica officinalis, is one of the most important herbs in Ayurveda. It contains significant amounts of Vitamin C and has been reported to have antioxidant, anticancer, antiretroviral, antidepressant, antiulcerogenic, wound healing, and many other medicinal properties. Objective: The current study is designed to investigate the aphrodisiac effects of E. officinalis seed extract on albino Wistar rats as well as its effects on stress-related sexual behaviour. Materials and Methods: The aphrodisiac effect of E. officinalis was evaluated by mating the pretreated male rats with female rats. For 30 days, test group rats (n=6) were given methanolic extracts (95%) from E. officinalis seeds (500 and 1000 mg/kg). Control rats received saline. Standard group rats received testosterone (0.5 mg/ kg, i.m). The sexual behavior study tracked Mount Latency (ML), Intromission Latency (IL), Mounting Frequency (MF), Intromission Frequency (IF), sniffing, and licking on days 0 through 30. After 30 days, rats were sacrificed, and the anabolic effect was assessed using body weight, reproductive organ weight, sperm concentration, and histopathology of the testes. The stress was induced by immobilization stress in the stress-affected alteration in the sexual behavior model, and the above procedure was repeated for evaluation. Results: The 95% methanolic extract (1000 mg/kg) of E. officinalis significantly reduced ML and IL while significantly increasing MF, IF, sniffing, licking, body weight, reproductive organ weight, and sperm concentration. Methanolic extract of E. officinalis increased sexual activities in the stress-free group and restored the stress-affected group's altered sexual behaviour. Conclusion: The current study's findings indicate that 95% methanolic extract of E. officinalis has dose-dependent aphrodisiac activity and restores sexual behavior in a stress-induced group.

Replacing Inorganic Source of Zinc with Zinc Hydroxy Chloride: Effects on Health Status, Hemato-biochemical Attributes, Antioxidant Status, and Immune Responses in Pre-ruminant Crossbred Calves.

The current research aimed to assess the feasibility of using Zn hydroxy chloride (ZnOHCl) as an alternative to ZnSO4 in pre-ruminant crossbred calves. Twenty-four male crossbred calves (Tharparkar × Holstein Friesian) were categorized into four groups according to body weight and age (body weight 31kg; age 10days). Experimental calves were kept on a similar feeding regimen except that different groups were supplemented with either 0mg Zn/kg DMI (Zn-0), 80mg Zn/kg DMI as ZnSO4 (ZnS-80), 40mg Zn/kg DMI as ZnOHCl (ZnH-40), or 80mg Zn/kg DMI as ZnOHCl (ZnH-80). All the calves were fed for 90days as per ICAR (2013) feeding standard to fulfill their nutrient requirements for growth rate of500g/day. The study observed the influence of different sources and varying levels of Zn supplementation over a 90-day experimental period on health status, hemato-biochemical attributes, antioxidant status, immune responses, and plasma minerals and erythrocyte Zn concentrations. The data was examined using a randomized complete block design (RCBD) with fixed effects of treatment, period, and their interaction. The results indicated that irrespective of the sources and levels of Zn, supplementation did not lead to significant changes in health status as assessed by fecal score, nasal score, ear score, and eye score. Hematological parameters remained unchanged following supplementation with different sources and levels of Zn. Zn-supplemented groups showed higher levels of total protein, globulin, and alkaline phosphates (ALP) compared to the non-supplemented group. However, no significant variations were detected within the Zn-supplemented groups. Zinc supplementation significantly increased total antioxidant capacity (TAC), antioxidant enzyme activity, total immunoglobulin (Ig), immunoglobulin G (IgG), cell-mediated immunity (CMI), and humoral immunity (HI); however, no significant variations were detected among Zn-supplemented groups. Zn supplementation enhanced plasma and RBC Zn concentration without affecting the plasma concentration of other minerals. However, among the Zn-supplemented groups, 80mg Zn/kg DMI as ZnOHCl resulted in the highest RBC Zn concentration. The study results demonstrate that Zn supplementation enhanced biomarkers of zinc status, antioxidant levels, and immune responses in pre-ruminant crossbred calves. Nevertheless, no significant variations were observed between the different Zn sources (ZnSO4 and ZnOHCl) utilized in this study. Research suggests that ZnOHCl could be a feasible alternative to ZnSO4 in the diet of pre-ruminant crossbred calves.

Safety and Efficacy of Injection Tenecteplase in 4.5 to 24 Hours Imaging Eligible Window Patients with Acute Ischemic Stroke (EAST-AIS) - Study Protocol

Abstract Background and Aims: Tenecteplase is used as the standard of care treatment for thrombolysis in acute ischemic stroke (AIS) patients within 4.5 h of symptom onset. Documented reports were less certain to claim the benefits of it in an extended window period. EAST-AIS (CTRI/2022/03/040718) trial is designed to determine the success rate of thrombolysis in an extended window period for good clinical outcomes. Study Design: It is a randomized, placebo-controlled trial of tenecteplase administered within 4.5–24 h of stroke onset (with or without large vessel occlusion) based on evidence of salvageable tissue through baseline computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) scan. Criteria of patient inclusion are as follows: patients of both genders (male and female), age &gt;18 years, pre-stroke modified Ranking Scale (mRS) &lt;2, baseline NIHSS &gt;5, CTP showing penumbra–ischemic core ratio &gt;1.8, absolute difference in volume &gt;10 ml, and ischemic core volume &lt;70 ml. The sample size for the study is 100 patients: 50 in the tenecteplase arm (0.25 mg/kg body weight; maximum- 25 mg) and 50 in the placebo arm (controls). Study Outcomes: The study’s primary objective is safety endpoints along with the efficacy of tenecteplase assessed using the mRS score at 90 days of stroke onset. Conclusion: The result obtained from EAST-AIS will determine the safety and efficacy of tenecteplase injection administered 4.5–24 h following the symptom onset for AIS patients within the territory of Internal Carotid Artery (ICA), Middle Cerebral Artery (MCA), or Anterior Cerebral Artery (ACA) occlusion.

Theaflavins Induce Autophagy in Ehrlich’s Ascites Carcinoma Cells both In vivo and In vitro

Aims: To investigate the efficacy of Theaflavins to induce autophagy and its tumoricidal activity towards Ehrlich’s Ascites Carcinoma cells. Background: The apoptosis-inducing role of Theaflavins against cancer is reported. Autophagy, a cellular mechanism under stress, occurs either as a survival process or Type-II programmed-cell death in the presence/absence of apoptosis. The report of Theaflavins inducing autophagy against cancer is poor. Objective: Here, for the first time, the investigation for the anti-tumor efficacy of Theaflavins via autophagy in EAC was attempted. Methods: EAC-bearing mice were treated orally with Theaflavins (10 mg/kg b.w.) every alternate day with a total of 27 doses. Body weight, tumor volume and survivability were recorded. Tumoricidal and cellular dehydrogenase activity, in vivo and in vitro, were studied using Trypan-blue exclusion and MTT assay respectively. Theaflavins-treated EAC cells were subjected to Monodansylcadaverine- staining. LC3II turnover and LC3I conversion were detected by western blotting. Apoptosis up to 12 h TF-treatment was estimated by AnnexinV binding. Results: This is the first report of Theaflavins inducing autophagy in EAC cells in vivo and in vitro. Oral Theaflavins treatment restricted excessive body-weight increase due to tumors, reduced tumor volume, and increased survivability of tumor-bearing mice. Theaflavins caused EAC cell death (~8% in vitro, ~30% in vivo), significantly reduced metabolic activity, and created conspicuous vacuolization in surviving cells. Resultant vacuoles (in vitro, 6 h) were marked as autophagosomes by Monodansylcadaverine-staining. Autophagy was confirmed by LC3II augmentation. No significant apoptosis was observed up to 12 h TF-treatment in vitro. Conclusion: Theaflavins were efficient inducing autophagy and Type-II PCD in EAC cells. Notably, Theaflavins induced autophagy prior to apoptosis in vitro.

Health behaviors predicting risk of obesity in US adults: What does a healthy lifestyle look like?

The purpose of this study was to examine the association between lifestyle factors and body weight in a nationally representative sample of US adults and to evaluate the association between a novel "Healthy Habits Composite Score (HHCS)" and risk of obesity. This cross-sectional study included data from 4870 adults who participated in the 2017-2018 National Health and Nutrition Examination Survey (NHANES). The HHCS was developed based on 4 factors: diet, physical activity, sedentary time, and sleep, all of which were measured during the NHANES. A "healthy lifestyle" was defined as meeting ≥3 of the 4 established criteria. Data analysis was conducted using SAS 9.4 and procedures to account for the complex survey design. All models were adjusted for age, sex, race, household income, and education. Adults with obesity had significantly lower dietary quality (48.8±0.6 vs. 53.2±0.9) and reported significantly more sedentary time (∼1h more; 356.3±7.0 vs. 301.4±8.3min) than lean adults, both p<0.001. Achieving a healthy lifestyle based on the HHCS was associated with nearly double the odds of having a healthy body weight (OR 1.9, p<0.001). Following a lifestyle focused on healthy habits (diet quality, physical activity, limited sedentary time, and sleep) was strongly associated with a decreased risk of obesity: an individual who achieved three or more healthy habits had nearly twice the odds of having a healthy body weight. Therefore, comprehensive interventions that address and promote a wide range of healthy habits may be most effective for lowering obesity risk.

Autologous Bone Marrow Aspiration Concentrate (BMAC) Therapy for Primary Knee Osteoarthritis-An Observational and Dose Escalation Study.

Anti-inflammatory and anti-fibrotic properties maximize the therapeutic potential of bone marrow aspiration concentrate (BMAC) in osteoarthritis (OA) knee. There is a lack of studies to standardize the treatment procedure to make the studies done across various centers comparable to understand the lacunae better and develop further the deficiency in our understanding of BMAC for OA knee. We aimed to assess the degree of pain relief, functional outcome, and cartilage thickness with different doses of BMAC in primary OA knee. A single-centered prospective observational study was conducted with 80 patients of OA knee who were divided into 4 groups where group A (n = 20), group B (n = 20), group C (n = 20), and group D (n = 20) received intra-articular 1, 2, 5million BMAC cells per kg body weight, and intra-articular saline, respectively. All patients were followed up with Visual Analog Scale (VAS), knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores both pre and post-procedurally at 1, 3, 6, and 12months follow-up. The study found no significant differences in demographics or co-morbidities across four participant groups (A, B, C, D). However, clinical outcomes varied markedly: Groups B and C showed significant improvements in pain perception (VAS scores), knee function, and quality of life (KOOS and WOMAC scores), while Group A showed marginal or non-significant changes, and Group D exhibited no significant improvements. These findings suggest that treatments in Groups B and C reached the Minimal Clinically Important Difference, significantly enhancing patient-reported outcomes. A dose of 2million BMAC cells per kg body weight for knee OA serves as the better regenerative modality of choice in cartilage regeneration. With our dose-escalation study, we would be able to standardize the treatment procedure and enable global comparison of the treatment method across various regions of the world.

Tenofovir alafenamide compared to tenofovir disoproxil fumarate, induces dysglycemia, and dyslipidemia in Wistar rats.

To determine the metabolic effects of tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) in vivo. Male Wistar rats (Rattus novergicus, 250-300 g body weight) were divided into 3 groups (n = 8) and orally treated daily with 1.0 ml distilled water (group 1), TAF (0.42 mg/kg) (group 2), or TDF (5.0 mg/kg) (group 3), respectively, for 56 days. Glucose tolerance tests were done before the animals were sacrificed by halothane overdose, and blood was collected by cardiac puncture for the analysis of plasma lipids, electrolytes, and insulin. The kidney and pancreatic tissues were excised and homogenized to measure oxidative stress. Compartmentation of TAF and TDF was determined in NRK-52 and Peripheral Blood Mononuclear Cells (PBMC). There were no significant differences in weight gain among controls, TAF- or TDF-treated rats. TAF-treated rats had significantly increased fasting blood glucose (FBG), fasting plasma insulin (FPI), insulin resistance, impaired glucose tolerance, and dyslipidemia compared to control or TDF-treated rats, respectively. There was increased lipid peroxidation in the pancreas of TAF-treated compared to TDF-treated or control animals, respectively. TDF- treated rats presented with symptoms of Fanconi syndrome compared to TAF-treated or control animals, respectively. Kidney homogenates from TDF-treated animals had significantly reduced antioxidant enzyme activity compared to TAF-treated animals or controls, respectively. Intracellular concentrations of TAF were significantly higher than TDF in both NRK-52E cells and PBMC, respectively. TAF treatment is weight-neutral and causes dysglycemia, and dyslipidemia but not Fanconi syndrome compared to TDF.

Testosterone with Silymarin Improves Diabetes-obesity Comorbidity Complications by Modulating Inflammatory Responses and CYP7A1/ACC Gene Expressions in Rats.

The co-morbidity of DMOB has become increasingly problematic among the world's population because of a high-calorie diet and sedentary lifestyle. DMOB is associated with lower testosterone (TN) levels, the male sex hormone. The phytochemical compound silymarin (SN) exerts antidiabetic activity by modifying β-cells and anti-obesity activity by inhibiting adipogenesis by methylxanthine. The goal of this study was to find out how well testosterone (TN) with silymarin (SN) protects against oxidative stress and inflammation in the liver of the experimental rats with type 2 diabetes (T2D) and obesity (DMOB). The present study evaluates the efficacy of TN and SN combination (TNSN) on the levels of the potential parameters, such as body mass, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profile, enzymatic and non-enzymatic antioxidants, proinflammatory cytokines, gene expression pathways, and histopathology in a DMOB comorbidity rat model. Male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 20 weeks with an administration of a single dose of streptozotocin (STZ) i.p. injection (30 mg/kg) on the 9th week of the study. The procedure was to develop the DMOB co-morbidity model in the experimental animals. Co-treatment of TN and SN administration were followed throughout the experiment. Rats were sacrificed after overnight fasting to collect serum and liver tissue samples. Samples were analyzed using a clinical chemistry automated analyzer, spectrophotometry, and quantitative real-time PCR (qPCR) methods and protocols. Analyses of body mass changes, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profiles, enzymatic and non-enzymatic antioxidants, TNF-α, IL-6, adiponectin, CYP7A1, ACC expression pathways, and histopathology showed significant abnormal levels (P ≤ 0.05) in the pathological group. These were efficiently treated to normal by the administration of TNSN. These results concluded that TNSN exerted protective efficacy against the liver abnormalities in the co-morbidity of the DMOB rat model.