Weight Reduction Research Articles

271 Effects of Bariatric Surgery on Metabolic and Hormonal Balance: A 10-Year Retrospective Study

Abstract Background The increasing demand on Gastric bypass and other weight-loss surgeries known collectively as bariatric surgery is well documented but the long-term effects on some parameters have not been satisfactorily analysed over the years. Surgeons are dealing with a level of uncertainty regarding the most likely reason behind this metabolic derangement following such procedures in the follow up clinics. Aim To study the long-term effects of bariatric surgery and weight reduction procedures on Parathyroid function, calcium levels, Vitamin D and determinants of bone health. Method 10-year retrospective study looking at patients underwent bariatric surgery between the years 2006 – 2008 within the Yorkshire area and their follow up data. Results We found that the median calcium levels have decreased significantly compared to its level prior to the operation, even though the absolute value of calcium remained within the normal reference range, it was lower than that of the baseline for each individual, resulting in an increased PTH and ALP levels to a low statistical significance and important clinical significance. Conclusions Calcium levels being lower than the baseline but still within the normal reference range is affecting both PTH and ALP leaving the patient at increased risk of bone weakness complications and other hormonal disturbances. Recommendation During the post-operative follow up plan, calcium levels should be adjusted to mimic the levels of the individuals’ pre-operative values, and the baseline should be the reference range rather than the actual lab reference assuming Calcium levels preoperatively were within the normal range.

960 Quality of Life Outcomes of Metabolic and Bariatric Surgery Tourism: A Single-Centre Survey-Based Study

Abstract Global obesity affects one in three adults, prompting increased demand for metabolic and bariatric surgery (MBS). Despite its effectiveness, limited access to MBS has led to more people seeking it through medical tourism for lower costs and shorter wait times. However, ethical concerns arise due to limited follow-up care and potential complications. This study compares the quality of life (QOL) of native MBS patients (n = 69) to those engaged in MBS tourism (n = 36) from 11 different countries, utilizing the Bariatric Quality of Life Index (BQLI). Conducted in Lahore, Pakistan, with 105 participants who had MBS in the last 3 years, the survey-based study aims to assess the impact of MBS tourism on QOL and the efficacy of bariatric surgery for weight loss. The study revealed no significant difference in the quality of life between MBS tourism participants and native patients (p > 0.05). Both cohorts experienced considerable weight reduction post-MBS (p = 0.00001). A higher total weight loss percentage (TWL%) correlated positively with increased BQLI scores (p = 0.01). Younger patients experienced significantly improved quality of life after MBS compared to their older counterparts (r = -0.3, p = 0.005). The TWL% exhibited a progressive increase as the months advanced post-MBS (r =0.3, p = 0.004). The type of bariatric surgery (SG, RYGB, OAGB, SADI) didn't significantly affect post-MBS quality of life (p > 0.05).

Obesity treatment-associated transfer of exercise-related self-regulation to eating-related self-regulation changes in women

ABSTRACT Obesity in the United States has risen to 42 percent of its adult population and is similarly problematic in many other countries. Although the U.S. government has provided education on healthy eating and the need to exercise regularly, behavioral obesity treatments have largely failed to sustain reductions in weight. Self-regulation, and the incorporation of exercise for its psychological impacts on eating, has sometimes been targeted. While there has been sporadic investigation into the carry-over of exercise-related self-regulation to eating-related self-regulation, the present aim is to further inquiry in that area to inform future treatment content for improved effects. Women enrolled in community-based obesity treatments with either a self-regulation (n = 106) or education (n = 54) focus were assessed on changes in exercise- and eating-related self-regulation, negative mood, completed exercise, and weight. Improvements were significantly greater in the self-regulation-focused group. After controlling for initial change in eating-related self-regulation, change in that measure from Month 3 to 6 was significantly predicted by change in exercise-related self-regulation during the initial 3 treatment months. This suggested a carry-over effect. A stronger predictive relationship was associated with the self-regulation-focused treatment. In further analyses, paths from changes in exercise→negative mood→self-regulation of both exercise and eating were significant. Increase in eating-related self-regulation was significantly associated with weight loss over 6, 12, and 24 months. The self-regulation-focused group had stronger relationships, again. Findings suggested utility in targeting exercise-related self-regulation to impact later change in eating-related self-regulation, and the use of exercise-associated mood improvement to bolster participants’ self-regulation capabilities.

A topology optimization design of a crane hook

The goal of this research was to demonstrate the effectiveness of optimization techniques and test the possibility of using ABS plastic to optimize the existing crane hooks that use these techniques. Based on the optimization results, verification of the modified hook, and structural stability, this optimization reduces the weight of the crane hook while maintaining durability. This study utilized 3D modeling software to optimize the design of an existing hook, ensuring both sufficient strength and weight reduction. The research analyzes the results, concentrating on the stress that falls within the material strength limit. The research begins by utilizing a maximum of 1 kg of ABS plastic and a 5 kg liftable load. Using topology techniques, the study proposed five models that meet technical requirements. As a result, the proposed structure is highly economical and optimized in terms of materials and time, while still ensuring working performance. This work utilizes 3D modeling software for optimization design. It was effective to combine 3D printing manufacturing technology with size considerations. This article serves as a reference for future research and hook design.

Ramadan Fasting in Individuals with Metabolic Dysfunction-Associated Steatotic Liver Disease, Liver Transplant, and Bariatric Surgery: A Narrative Review.

Metabolic dysfunction-associated steatotic liver disease is a growing worldwide pandemic. A limited number of studies have investigated the potential effect of Ramadan fasting on metabolic dysfunction-associated steatotic liver disease (MASLD). There is no single medication for the treatment of MASLD. There is a growing interest in dietary intervention as potential treatment for metabolic diseases including MASLD. The aim of this study was to discuss the epidemiology, pathogenesis, and risk factors of MASLD and the potential effects of Ramadan fasting on MASLD, liver transplant, and bariatric surgery. We searched PubMed and SCOPUS databases using different search terms. The literature search was based on research studies published in English from the year 2000 to the 2024. Thirty-two studies were included in this review. Ramadan fasting reduced body weight and improved lipid profile, anthropometric indices, fasting plasma glucose, plasma insulin, and inflammatory cytokines. Ramadan fasting improved risk factors of nonalcoholic fatty liver disease and might improve MASLD through weight reduction. However, further studies are needed to assess the safety and effectiveness of Ramadan fasting in liver transplant recipients and bariatric surgery.

Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus

Background & AimsVery-low calorie diets (VLCD) and the glucagon-like peptide-1 receptor agonist (GLP1RA) Semaglutide induce significant weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D). This pilot study was conducted to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition and metabolic outcomes. MethodsThirty individuals with T2D (age 18-75 years, BMI 27-50kg.m-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks. Measurement of weight and glycated haemoglobin (HbA1c), dual energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and post-intervention. Diet diaries were utilised to assess compliance. Insulin first phase response during IVGTT provided a marker of pancreatic beta-cell function, and insulin sensitivity was estimated using HOMA-IR. ResultsSignificantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p<0.01 v both). VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively. HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only. Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p<0.01). ConclusionVLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater improvements in pancreatic beta-cell function. Thus, combination of Semaglutide and VLCD warrants further exploration as a novel approach to T2D management.

Shear study on the interface between ultra-high durability concrete and low-cement-lightweight concrete for precast composite walls

Precast wall system is one of the solutions with great potential, as it makes it possible to build structures in a simple and quick way, without using columns and beams. Considering the advantages of this system, an innovative composite structural precast wall has been developed, using a layer of ultra-high durability concrete (UHDC) on the outside and another layer of low cement lightweight concrete (LCLWAC) on the inside. This provides a triple benefit: (a) a reduction in dead weight, (b) an increase in durability and therefore a higher life of the structure, and (c) a reduction in cement dosage and consequently a reduction of the carbon footprint of the product. The main topic of this research is the study of the interface shear strength between a low cement lightweight aggregate concrete (LCLWAC) and an eco-efficient ultra-high durability concrete (UHDC). An experimental program was carried out to evaluate this shear strength, considering two parameters: i) the roughness interface and (ii) the transversal reinforcement crossing the interface; and using two types of tests, push-off and flexural tests. Results were compared with the predictions of Eurocode 2 and fib Model Code 2010, including the new versions of both codes, to assess how suitable are the models and coefficients for this situation. The shear strength between LCLWAC-UHDC is quite effective, and the predictions are conservative for this combination, at least 2 times lower than the experimental results and close to 7 times in some cases.

Biodegradable glycine betaine encapsulated chitosan nanoparticles induce the expression of antioxidant enzyme genes to improve drought tolerance in maize

Drought is one of the main abiotic stresses that affect the growth and development of maize crop, thus causing food crises across the world. Nanoparticles are considered an effective tool for improving crop yield by upgrading the plant tolerance mechanism under abiotic stress. In this study, we investigated the role of foliar application of glycine betaine-encapsulated chitosan loaded nanoparticles (LNPs) and unloaded chitosan nanoparticles (NPs) in improving morphological, physiological, biochemical and molecular attributes in two maize varieties, HNG and CZP, grown under drought stress. Petri plates experiment was performed to screen different levels of drought (5 % and 20 %) and nanoparticle concentrations (10, 20 and 40 μg NPs). In the pot experiment, 20 % drought stress along with 20 μg LNPs and 20 μg NPs were used to examine the morphological, physiological and biochemical attributes of maize plants. Drought stress led to a significant reduction in fresh and dry weight, relative water content, root and shoot lengths, photosynthetic pigments, and antioxidant enzyme activities, including catalase, superoxide dismutase, ascorbate peroxidase, and proline content compared to control plants. However, foliar application of LNPs resulted in increased photosynthetic pigments, enhanced antioxidant enzyme activity, and elevated proline content under both control and drought-stressed conditions. Conversely, malondialdehyde (MDA) content decreased significantly with the application of LNPs and NPs alone under stress conditions. Moreover, nanoparticles also enhanced the relative expression levels of antioxidant genes, ZmAPX, ZmCAT, and ZmSOD. These findings highlight the potential of LNPs as an ecofriendly which helps in ameliorating drought stress in maize, and other plants.

Genetically engineered long-acting Esculentin-2CHa(1−30) fusion protein with potential applicability for the treatment of NAFLD

Esculentin-2CHa(1–30) (‟ESC”) has been reported as a potent anti-diabetic peptide with little toxicity. However, its very short plasma residence time severely limits the therapeutic efficacy. To address this issue, we genetically engineered a fusion protein of tandem trimeric ESC with an albumin binding domain (ABD) and a fusion partner, SUMO (named ‟SUMO-3×ESC-ABD”). The SUMO-3×ESC-ABD, successfully produced from E. coli, showed low cellular and hemolytic toxicity while displaying potent activities for the amelioration of hyperglycemia as well as non-alcoholic fatty liver disease (NAFLD) in vitro. In animal studies, the estimated plasma half-life of SUMO-3×ESC-ABD was markedly longer (427-fold) than that of the ESC peptide. In virtue of the extended plasma residence, the SUMO-3×ESC-ABD could produce significant anti-hyperglycemic effects that lasted for >2 days, while both the ESC or ESC-ABD peptides elicited little effects. Further, twice-weekly treatment for 10 weeks, the SUMO-3×ESC-ABD displayed significant improvement in blood glucose control with a reduction in body weight. Most importantly, a significant improvement in the conditions of NAFLD was observed in the SUMO-3×ESC-ABD-treated mice. Along the systemic effects (by improved glucose tolerance and body weight reduction), direct inhibition of the hepatocyte lipid uptake was suggested as the major mechanism of the anti-NAFLD effects. Overall, this study demonstrated the utility of the long-acting SUMO-3×ESC-ABD as a potent drug candidate for the treatment of NAFLD.

Exploring Determinants of Successful Weight Loss with the Use of a Smartphone Healthcare Application: Secondary Analysis of a Randomized Clinical Trial.

Dietary and physical activity interventions through smartphone healthcare applications (apps) have recently surged in popularity as effective methods for weight loss. However, the specific factors contributing to successful weight loss remain uncertain. We conducted an analysis of baseline characteristics and app usage frequencies over three months among 68 Japanese adults with overweight and obesity who were assigned to the intervention group in a previous randomized controlled trial. Logistic regression analysis revealed a negative association (OR: 0.248; p = 0.018) between having a walking habit at baseline and successful weight loss, defined as a 3% reduction in initial weight. Additionally, slower walking speeds and family medical history were identified as potential predictors of successful weight loss. These findings offer insights into the profile of individuals who achieve success in weight loss through our smartphone app, providing valuable guidance for the development of future healthcare apps.

Toxicological Effects of Colloidal Silver Nanoparticles on Rat Health: Assessing Physiological, Hematological, Biochemical, and Behavioral Parameters

Introduction: Nanotechnology, a rapidly evolving field, has introduced silver nanoparticles (AgNPs) as promising materials with diverse applications. Their unique properties have revolutionized industries, raising concerns about potential health implications. This study aims to comprehensively evaluate the toxicological effects of AgNPs on rat health through a multidimensional approach, encompassing physiological, hematological, biochemical, and behavioral assessments. Methodology: Colloidal AgNPs with a minimum purity of 99.98% were synthesized using an inductive coupled plasma (ICP) method. Sixty male specific-pathogen-free (SPF) Wistar rats were exposed to low (10 μg/kg/day) and high (100 μg/kg/day) doses of AgNPs, alongside a control group. Throughout the exposure period, comprehensive assessments, including body weight changes, food intake, water consumption, hematological and biochemical parameters, and behavioral evaluations, were systematically conducted. The statistical analysis employed a combination of one-way ANOVA and Kruskal-Wallis tests for robust data interpretation. Results: Rats exposed to low (10 μg/kg/day) and high (100 μg/kg/day) doses of AgNPs displayed no significant changes in food intake, water consumption, or blood parameters compared to the control group. However, a notable reduction in body weight was observed in the high-dose group, suggesting a potential dose-dependent impact. Biochemical analyses indicated no significant differences in liver and kidney function parameters for the low-dose group, but the high-dose group exhibited potential elevation in liver enzymes, necessitating further scrutiny. Behavioral assessments revealed no significant alterations in open-field behavior or cognitive function, indicating minimal impact on exploratory and cognitive abilities within the tested doses. Conclusion: AgNPs demonstrated minimal impact on certain parameters, the high-dose group exhibited notable body weight reduction and potential liver enzyme alterations, warranting further investigation. Behavioral assessments indicated no significant cognitive effects. These findings emphasize the importance of continued research for informed regulatory decisions and the safe utilization of AgNPs in consumer products.

Exposure to Crime and Racial Birth Outcome Disparities.

Urban communities in the United States were transformed at the end of the twentieth century by a rapid decline in neighborhood crime and violence. We leverage that sharp decline in violence to estimate the relationship between violent crime rates and racial disparities in birth outcomes. Combining birth certificate data from US counties with the FBI's Uniform Crime Reporting statistics from 1992 to 2002, we show that lower crime rates are associated with substantially smaller Black-White disparities in birth weight, low birth weight, and small for gestational age. These associations are stronger in more segregated counties, suggesting that the impacts of the crime decline may have been concentrated in places with larger disparities in exposure to crime. We also estimate birth outcome disparities under the counterfactual that the crime decline did not occur and show that reductions in crime statistically explain between one-fifth and one-half of the overall reduction in Black-White birth weight, LBW, and SGA disparities that occurred during the 1990s. Drawing on recent literature showing that exposure to violent crime has negative causal effects on birth outcomes, which in turn influence life-course outcomes, we argue that these results suggest that changes in national crime rates have implications for urban health inequality.

The effects of intermittent fasting on body composition and cardiometabolic health in adults with prediabetes or type 2 diabetes: A systematic review and meta-analysis.

To perform a meta-analysis to investigate the effects of intermittent fasting (IF), as compared with either a control diet (CON) and/or calorie restriction (CR), on body composition and cardiometabolic health in individuals with prediabetes and type 2 diabetes (T2D). PubMed, Web of Science, and Scopus were searched from their inception to March 2024 to identify original randomized trials with parallel or crossover designs that studied the effects of IF on body composition and cardiometabolic health. Weighted mean differences (WMDs) or standardized mean differences with 95% confidence intervals (CIs) were calculated using random-effects models. Overall, 14 studies involving 1101 adults with prediabetes or T2D were included in the meta-analysis. IF decreased body weight (WMD -4.56 kg [95% CI -6.23 to -2.83]; p = 0.001), body mass index (BMI; WMD -1.99 kg.m2 [95% CI -2.74 to -1.23]; p = 0.001), glycated haemoglobin (HbA1c; WMD -0.81% [95% CI -1.24 to -0.38]; p = 0.001), fasting glucose (WMD -0.36 mmol/L [95% CI -0.63 to -0.09]; p = 0.008), total cholesterol (WMD -0.31 mmol/L [95% CI -0.60 to -0.02]; p = 0.03) and triglycerides (WMD -0.14 mmol/L [95% CI -0.27 to -0.01]; p = 0.02), but did not significantly decrease fat mass, insulin, low-densitiy lipoprotein, high-density lipoprotein, or blood pressure as compared with CON. Furthermore, IF decreased body weight (WMD -1.14 kg [95% CI -1.69 to -0.60]; p = 0.001) and BMI (WMD -0.43 kg.m2 [95% CI -0.58 to -0.27]; p = 0.001), but did not significantly affect fat mass, lean body mass, visceral fat, insulin, HbA1c, lipid profiles or blood pressure. Intermittent fasting is effective for weight loss and specific cardiometabolic health markers in individuals with prediabetes or T2D. Additionally, IF is associated with a reduction in body weight and BMI compared to CR, without effects on glycaemic markers, lipid profiles or blood pressure.

Recommended Diet Therapy of Mediterranean Diet (MD) and Low Carbohydrate Diet (LCD)

To maintain health and achieve longevity, an adequate diet is crucial, such as the Mediterranean diet (MD) and the low-carbohydrate diet (LCD). The MD is characterized by whole grains, fruits, vegetables, less red meat, more fish, and four eggs per week. The MD may reduce the risk of heart disease, stroke, dementia, and depression. The LCD shows remarkable weight reduction in a short period, but there may be a probable rebound effect within six months. In Japanese cuisine, the intake of fermented soy foods such as natto and miso can lower the risk of death. As a recommendation, the LCD can be started first, followed by the MD for the long term.

Extreme Temperatures, Birth Outcomes, and Social Inequalities: Evidence from South China

Abstract The impacts of climate change on health are a critical public health issue, but the association between extreme temperatures and birth outcomes remains poorly understood. This paper links over 1 million birth records from Dongguan, China, between 2004 and 2013, to meteorological data. We investigate the relationship between extreme temperatures and birth outcomes and explore the heterogeneity among different demographic and socioeconomic factors, including maternal migrant status, education level, and mode of delivery. We find that one percentage increase in the number of days exposed to extreme heat during pregnancy is associated with a reduction in birth weight of 2.31 g and a 2% increase in odds of low birth weight (LBW), while exposure to extreme cold temperatures is associated with a reduction in birth weight (0.66 g) and an increase in the risk of LBW (1%). The association between extreme high temperatures and adverse birth outcomes is stronger for groups with disadvantaged social status. Specifically, the migrant group (for extreme heat exposure, local residents, −0.37 g; intraprovincial migrants, −2.75 g; out-of-province migrants, −2.49 g), the less-educated group (for extreme heat exposure, middle school or below, −2.47 g; high school or above, −1.66 g), and the group with vaginal birth [for extreme heat exposure, cesarean sections (C-sections), −1.56 g; vaginal birth, −2.62 g] are more sensitive to extreme weather conditions. Our study provides further evidence about the association of extreme temperatures with birth outcomes and for vulnerable groups of pregnant women.

Cenobamate: real-world data from a retrospective multicenter study.

To report the effects of adjunctive cenobamate and concomitant antiseizure medications (ASMs) on weight from two double-blind, placebo-controlled, phase 2 studies (YKP3089C013 [C013] and YKP3089C017 [C017]) and their open-label extensions (OLEs) and from a long-term, open-label phase 3 safety study, YKP3089C021 (C021). Cenobamate is an ASM approved in the US and EU for treatment of focal seizures in adults. Some ASMs are associated with weight gain (e.g., valproate, gabapentin, pregabalin), which can negatively affect patient health. Patients with uncontrolled focal seizures taking stable doses of 1-3 ASMs were enrolled in each study. In C013, cenobamate was titrated to a target dose of 200 mg/day (max OLE dose 400 mg/day). In C017, patients were randomized to cenobamate 100, 200, or 400 mg/day (max OLE dose 400 mg/day). In C021, cenobamate was titrated to a target dose of 200 mg/day (max dose 400 mg/day). Median weight changes at 1 and 2 years from baseline were analyzed post hoc. Analyses included 39, 206, and 1054 patients from C013, C017 (dose groups combined), and C021, respectively. Median weight changes from baseline ranged from -0.2 to -0.9 kg at 1 year and from -1.0 to +1.0 kg at 2 years. Some numerical reductions in weight were noted in patients who discontinued valproate by 1 (-13.0 kg, C013, n=1) or 2 years (-24.5 kg, C017, n=2) and in patients who discontinued gabapentin by 1 (-7.1 kg, C017, n=2) or 2 years (-7.0 kg, C017, n=2). Otherwise, median weight changes from baseline for patients receiving concomitant valproate, gabapentin, or pregabalin ranged from -3.1 to +2.6 kg at 1 year and from -1.6 to +2.7 kg at 2 years. Adjunctive cenobamate was not associated with clinically significant changes in weight from baseline in patients treated for 1 and 2 years, including those receiving concomitant valproate, gabapentin, or pregabalin.

Multifunctional sandwich composites with optimized phase change material content for simultaneous structural and thermal performance

This work aims at developing novel multifunctional sandwich composites with optimized thermal energy storage and structural load-bearing performance by incorporating microencapsulated phase change materials (PCMs) into polyurethane (PU) foam cores. The optimized foam containing 20 wt% PCM, balancing good latent heat storage (up to 29 J/g) with low thermal conductivity (up to 0.035 W/(m·K) at 50 °C), and, was used to produce sandwich panels with high-performance epoxy/carbon fiber laminate skins. Microstructural characterization confirmed excellent interfacial adhesion between the core and skins. The multifunctional panels exhibited comparable flexural strengths (150 kPa) and facing stresses (25 MPa) to neat PU sandwich controls. By integrating thermal regulation from PCM phase change with structural reinforcement from the sandwich architecture in a single multifunctional material system, this work contributes to the development of lightweight, energy-efficient composite materials suitable when weight reduction and thermal management are paramount, such as in aeronautics and cold chain logistics.

Efficacy and safety of the combination or monotherapy with GLP-1 receptor agonists and SGLT-2 inhibitors in Type 2 diabetes mellitus: An update systematic review and meta-analysis

PurposeTo evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter2(SGLT-2) inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). MethodsTo construct an exhaustive database of randomized controlled trials (RCTs) concerning SGLT-2 inhibitors and GLP-1 agonists, a methodical search was undertaken across a range of databases, such as Embase, PubMed, and the Cochrane Central Register of Controlled Trials, from their inception to January 2023. Following this, a meta-analysis was executed to amalgamate the collected data, which allowed for the calculation of standardized mean differences (SMDs), odds ratios (ORs), and 95 % confidence intervals (CIs) for a spectrum of outcomes. This analytical approach was designed to yield a quantitative evaluation of the therapeutic efficacy and safety profile of SGLT-2 inhibitors and GLP-1 agonists for the treatment of diabetes mellitus. ResultsWhen compared to GLP-1 agonist therapy alone, the combination therapy did not significantly reduce fasting plasma glucose (FPG) levels (95 % confidence interval [CI]: -0.27, 0.10; p = 0.35), body weight (95 % CI: -0.18, 0.18; p = 1.00), Glycosylated Hemoglobin, Type A1C (HbA1c) (95 % CI: -0.29, 0.07; p = 0.22), or systolic blood pressure (SBP) values (95 % CI: -0.29, 0.06; p = 0.21). In contrast, when compared to SGLT-2 inhibitor therapy alone, combination therapy significantly decreased FPG by 0.24 mmol/L (95 % CI: -0.43, -0.05; p = 0.01), HbA1c by 0.45 % (95 % CI: -0.72, -0.18; p = 0.001), and SBP by 0.12 mmHg (95 % CI: -0.24, 0.00; p = 0.05). However, the combination therapy failed to demonstrate a significant reduction in body weight when compared with either SGLT-2 inhibitor therapy (95 % CI: -0.20, 0.05; p = 0.24) or GLP-1 agonist therapy (95 % CI: -0.18, 0.18; p = 1.00). Additionally, the combination therapy did not increase the incidence of hypoglycemia. It should be noted that data regarding mortality and cardiovascular outcomes were limited. ConclusionsThe combination treatment of SGLT-2 inhibitors and GLP-1 receptor agonists effectively reduces HbA1c, FPG, and SBP without elevating the risk of hypoglycemia when compared to monotherapy with SGLT-2 inhibitors. However, these beneficial effects were not observed when the combination therapy was compared with GLP-1 receptor agonist treatment alone.

Lebanese cannabis oil as a potential treatment for acute myeloid leukemia: In vitro and in vivo evaluations

The Cannabis sativa L. ssp. indica (Lam.) plant has been historically utilized as a natural herbal remedy for the treatment of several ailments. In Lebanon, cannabis extracts have long been traditionally used to treat arthritis, diabetes, and cancer. The current study aims to investigate the anti-cancer properties of Lebanese cannabis oil extract (COE) on acute myeloid leukemia using WEHI-3cells, and a WEHI-3-induced leukemia mouse model. WEHI-3cells were treated with increasing concentrations of COE to determine the IC50 after 24, 48 and 72-h post treatment. Flow cytometry was utilized to identify the mode of cell death. Western blot assay was performed to assess apoptotic marker proteins. In vivo model was established by inoculating WEHI-3cells in BALB/c mice, and treatment commencing 10 days post-inoculation and continued for a duration of 3 weeks. COE exhibited significant cytotoxicity with IC50 of 7.76, 3.82, and 3.34μg/mL at 24, 48, and 72h respectively post-treatment. COE treatment caused an induction of apoptosis through an inhibition of the MAPK/ERK pathway and triggering a caspase-dependent apoptosis via the extrinsic and intrinsic modes independent of ROS production. Animals treated with COE exhibited a significantly higher survival rate, reduction in spleen weight as well as white blood cells count. COE exhibited a potent anti-cancer activity against AML cells, both in vitro and in vivo. These findings emphasize the potential application of COE as a chemotherapeutic adjuvant in treatment of acute myeloid leukemia.

Establishment of an animal model of immune-related adverse events induced by immune checkpoint inhibitors.

Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune-related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice. Subcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death-1 (PD-1) and cytotoxic t-lymphocyte antigen 4 (CTLA-4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin-eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic-pyruvic transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid-derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry. Mice treated with PD-1 and CTLA-4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL-6, TNF-α, IFN-γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3+T cells, Treg cells, and macrophages in the liver and lung tissues of mice in the experimental group compared with the control group, and the change trend of MDSCs was opposite. The irAE-related animal model was successfully established in BALB/c mice using a combination of PD-1 and CTLA-4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation.