Non-communicable diseases (NCDs) have emerged as a leading global health concern, particularly in low- and middle-income countries This study aims to analyze the effect of demographic and metabolic risk factors, including body mass index (BMI), HbA1c, smoking, and high blood pressure, on the incidence and mortality of cardiovascular diseases (CVDs), metabolic disorders, and cancers.

A prospective cohort study was conducted using data from the Iran Cohort Study (ICS), which followed participants from the 2016 STEPs survey. The cohort included 24,818 individuals, with data collected over three years through structured interviews and healthcare records. Statistical analyses were performed to calculate incidence rates, death rates, and rate ratios (RR) for NCDs based on demographic and risk factors.

Males exhibited a higher incidence rate of CVDs (RR 1.22, 95% CI 1.05-1.44), while females showed a higher incidence of cancers (males: RR 0.61, 95% CI 0.41-0.89). Individuals with diabetes had a markedly increased incidence rate of CVDs (RR 4.92, 95% CI 3.88-6.24) and metabolic disorders (RR 28.59, 95% CI 13.52-60.43). Hypertension was associated with a heightened incidence rate across all investigated NCDs, while obesity significantly correlated with increased incidences of CVDs (RR 1.92, 95% CI 1.56-2.38) and cancers (RR 1.78, 95% CI 1.13-2.82). Notably, smoking was linked to increased mortality from CVDs (RR 1.63, 95% CI 1.23-2.17).

Modifiable risk factors like smoking, high blood pressure, and high BMI, and non-modifiable risk factors like age and sex have significant effect on the burden of NCDs in Iran.

Type 2 diabetes mellitus (T2 DM) is a global health issue linked to high morbidity and mortality due to complications such as cardiovascular disease and nephropathy. Conventional treatments often have side effects and limited glycemic control, leading to interest in alternative therapies. Plants from the Zingiberaceae and Berberidaceae families, traditionally used for their anti-diabetic properties, have emerged as potential adjuncts. This meta-analysis evaluates and compares their efficacy in improving glycemic control in individuals with T2 DM. A systematic literature search, following PRISMA guidelines, was conducted in PubMed, Web of Science, SCOPUS, and Cochrane, identifying 1269 studies, of which 58 met inclusion criteria. Only randomized controlled trials assessing effects on fasting blood glucose (FBS), HbA1c, fasting insulin, and HOMA-IR were included. Study quality and risk of bias were assessed using Cochrane's RoB 2.0 tool. The review is registered in PROS-PERO (CRD42024516261). The analysis showed significant reductions in FBS (-1.06; 95% CI: -1.42 to -0.71), HbA1c (-1.42; 95% CI: -2.64 to -0.19), and fasting insulin (-0.75; 95% CI: -1.13 to -0.38) among participants using plant extracts, with stronger effects observed for the Berberidaceae species. HOMA-IR also decreased, indicating enhanced insulin sensitivity. While Berberidaceae showed higher effect sizes, Zingiberaceae species provided more consistent outcomes. Further research with standardized protocols is needed to confirm these results.

The current global obesity epidemic is often associated with changes in dietary habits and lifestyle. Increasing evidence from both observational and experimental animal studies has highlighted the relationship between prenatal exposures and an increased predisposition to metabolic and cognitive disorders, as well as obesity in adulthood. In this study, we used a rodent model to investigate brain energy metabolism by assessing mitochondrial respiratory chain complexes I and II, along with oxidative stress markers (DCF) and antioxidant defenses (GSH and SOD), aiming to identify potential alterations in the central nervous system during offspring neurodevelopment. Our results demonstrated increased body weight and mesenteric fat accumulation in early life and adolescence, along with an imbalance in brain energy metabolism when maternal obesity and early-life stress (maternal deprivation) were combined. By exploring the complex interactions between gestational exposures and long-term behavioral and metabolic outcomes in an experimental model, our findings contribute to a better understanding of the developmental origins of health and disease.

Obesity, as a public health disease, is prevalent among college students and seriously affects their quality of life and academic performance. Timely intervention through an effective exercise program is of great significance in improving the physical health status of obese college students and preventing the emergence of obesity complications. Due to the lack of a systematic review of the effects of exercise intervention on the body shape of obese college students, this study aims to systematically evaluate the effects of exercise intervention on the body shape of obese college students, to provide a reference for the development of an effective exercise intervention program for the group of obese college students.

Five databases, Web of Science, PubMed, Embase, MEDLINE, and The Cochrane Library, were searched for randomized controlled trials (RCTs) on the effects of exercise interventions on obese college student populations from the date of establishment. The methodological quality of the included literature was assessed using the Rob 2.0 risk of bias tool, and then meta-analysis, subgroup analysis, and sensitivity analysis were performed using Review Manager software version 5.4.

A total of 12 original studies with a sample size of 961 individuals were included in this study. Meta-analysis showed that exercise intervention had a statistically significant effect on obese college students' BMI [SMD = -0.42, 95% CI (-0.80, -0.04), p = 0.03], waist circumference [SMD = -0.61, 95% CI (-1.04, -0.18), p = 0.005] and hip circumference [SMD = -0.72, 95% CI (-1.40, -0.04), p = 0.04], and may be limited by factors such as intervention period, intervention duration, number of interventions, and type of interventions, Exercise interventions had a statistically significant effect on obese college students' body fat percentage [SMD = -0.33, 95% CI (-0.79, 0.13), p = 0.16] and waist-to-hip ratio [SMD = -0.34, 95% CI (-0.89, 0.22), p = 0.23] did not have a significant intervention effect. Subgroup analyses showed that overall the intervention effect of ≥12 weeks was better than 8 weeks; the intervention effect of 30-60 min/revision was better than <30 min/revision and >60 min/revision; the intervention effect of exercise <5 times per week was better than ≥5 times per week; and the intervention effect of exercise in combination with aerobic combined with resistance training and integrative training was better than that of performing aerobic exercise alone.

Exercise interventions have a positive effect on weight loss and improved body shape in obese college students.

PROSPERO, CRD420251012259, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251012259.

Obesity is a global health crisis characterised by excessive accumulation of adipose tissue (AT). Under obesogenic conditions, this metabolically active tissue undergoes fibrosis and inflammation, leading to obesity-linked comorbidities. Modelling AT is essential for understanding its pathophysiology and developing treatments to protect against metabolic complications. 3D in vitro AT models are promising tools that address the limitations of traditional 2D in vitro models and in vivo animal models, providing enhanced biomimetic and human-relevant platforms. 3D models facilitate the study of AT pathophysiology and therapeutic screening. This review discusses the crucial role of AT in obesity-linked comorbidities, its dynamicity and complexity, and recent advances in engineering 3D scaffold-based in vitro dysfunctional AT models, highlighting potential breakthroughs in metabolic research and beyond.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder associated with intermittent hypoxia, sleep fragmentation, and systemic inflammation, all of which may influence cancer development. Continuous positive airway pressure (CPAP) therapy is the primary treatment for OSA, yet its impact on cancer risk remains uncertain. We conducted a systematic review and meta-analysis to evaluate the association between CPAP therapy and the incidence of newly diagnosed cancer in patients with OSA.

From inception to March 2025, a comprehensive literature search of MEDLINE, EMBASE, Cochrane databases, and reference lists was conducted. Observational studies assessing the risk of new cancer diagnoses in OSA patients treated with CPAP compared to non-CPAP users were included. Data extraction and quality assessment followed PRISMA guidelines, and meta-analysis was performed using a random-effects model.

Three cohort studies from France, Spain, and Canada, including 72,498 participants, met the inclusion criteria. CPAP compliance varied, defined as > 4 h/night in two studies, while one study lacked specific usage criteria. Cancer diagnoses were ascertained via national registries, hospital databases, or electronic medical records. Meta-analysis revealed a pooled hazard ratio (HR) of 0.81 (95% CI: 0.60-1.09), suggesting a potential reduction in cancer risk among CPAP users. Sensitivity analysis reduced heterogeneity (I² = 0%) and revised the HR to 0.93 (95% CI: 0.81-1.08).

CPAP therapy does not appear to increase cancer risk in OSA patients, but the evidence is limited and inconclusive. Further research, including randomized controlled trials, is needed to confirm these observations and explore underlying mechanisms.

Bariatric surgery, while effective for severe obesity, is often challenged by postoperative weight regain (WR), affecting 20-30% of patients. This review analyzes the mechanisms, risk factors, and management strategies for WR, emphasizing surgical considerations. WR is influenced by hormonal adaptations, including ghrelin rebound and leptin resistance, as well as metabolic adaptation, leading to reduced resting energy expenditure. Surgical factors, such as suboptimal technique, gastro-gastric fistulas, and stomach/anastomosis dilation, significantly contribute to WR. Specifically, inaccurate sleeve or pouch sizing, poorly calibrated anastomoses, and complications with gastric banding necessitate careful surgical planning and potential revision. Management strategies encompass lifestyle interventions (diet, exercise, behavioral therapy), pharmacotherapy (GLP-1 receptor agonists like liraglutide, semaglutide, and tirzepatide), and revisional surgery. Revisional procedures, including sleeve-to-bypass, bypass revision, sleeve-to-duodenal switch/SADI, and band removal with conversion to sleeve or bypass, address anatomical failures and enhance weight loss. Distinguishing surgical failure from patient nonadherence is crucial for appropriate intervention. Ultimately, a collaborative, multidisciplinary approach integrating these strategies optimizes long-term weight management and improves patient outcomes after bariatric surgery.

This systematic review evaluates the impact of obesity on both male and female reproductive health, assisted reproductive technology (ART) outcomes, and pregnancy-related complications, providing a comprehensive synthesis of the evidence.

Obesity is a critical factor adversely affecting reproductive health, ART success rates, and pregnancy outcomes. Recent studies indicate hormonal disruptions, metabolic syndrome, and epigenetic modifications as central mechanisms linking obesity to infertility and adverse pregnancy results. A systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines included 35 studies, focusing on obesity-related reproductive outcomes. The review highlights that obesity disrupts hormonal balance, including reductions in sex hormone-binding globulin (SHBG) and testosterone levels, alongside increased insulin resistance and chronic inflammation. These mechanisms impair ovarian function, endometrial receptivity, and sperm quality, resulting in prolonged time-to-pregnancy (TTP), reduced ART success rates, and increased miscarriage risk. During pregnancy, maternal obesity elevates risks of gestational diabetes mellitus (GDM), preeclampsia, and cesarean delivery while contributing to neonatal complications, such as macrosomia and neonatal intensive care unit (NICU) admissions. The findings emphasize the dual impact of maternal and paternal obesity on offspring health, particularly through epigenetic modifications leading to intergenerational metabolic dysfunction. This review underscores the necessity of preconception weight management, individualized ART protocols, and tailored antenatal care to mitigate obesity's adverse effects on reproductive outcomes. Future research should focus on understanding male infertility mechanisms, optimizing ART interventions for individuals with obesity, and conducting longitudinal studies on the intergenerational impacts of obesity on reproductive health. This synthesis provides actionable insights to guide clinical practices and future investigations.

Urinary tract cancers (UTCs), including bladder cancer, remain a significant public health challenge, particularly among individuals aged 75 and older. Despite declining bladder cancer-specific mortality rates between 2015 and 2020, the broader trends in UTC mortality and associated demographic disparities remain underexplored.

We analyzed mortality data from 1999 to 2022 using the CDC WONDER database. UTC deaths were identified using ICD- 10 codes C64 to C68. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, stratified by sex, race/ethnicity, and census regions. Joinpoint regression identified annual percent changes (APCs) to assess temporal trends.

From 1999 to 2022, 477,157 UTC deaths were recorded, 66% of which occurred among individuals aged 75 and older. The AAMR increased from 97.1 in 1999 to 103.5 in 2022, with a rise between 1999 and 2007 (APC: 0.63%), a decline from 2007 to 2019 (APC: - 0.33%), and a resurgence from 2019 to 2022 (APC: 2.42%). Older males exhibited higher AAMRs than females (178.7 vs. 53.6 in 2022), and Whites had the highest AAMR (108.5) among racial groups. The Western region recorded the highest AAMR (84.3) during the study period.

The resurgence in UTC mortality post- 2019 highlights emerging challenges, particularly among older males, Whites, and residents of the Western region. Targeted interventions, including improved screening and equitable healthcare access, are essential to mitigate these disparities and improve outcomes.

Probiotics intervention by Lactobacillus acidophilus has potential effect on alleviating obesity and insulin resistance. However, the limited knowledge of functional substances and potential regulatory mechanisms hinder their widespread application. Herein, L. acidophilus YL01 was firstly isolated from Chinese traditional yogurt, demonstrating inhibitory activities on amylase and glucosidase that are comparable to those of L. rhamnosus LGG. Besides, the oral administration of L. acidophilus YL01 and its EPS significantly reduced body weight in high-fat mice (p < 0.05), as well as fat accumulation in liver and adipocytes. Moreover, they not only reduced fasting blood glucose and glucose/insulin resistance, but also improved dyslipidemia, liver function and inflammation. Further high-performance liquid chromatography analysis and Fourier transform infrared spectroscopy indicated that EPS is an acidic polysaccharide, characterized by a molecular weight of 952 kDa and predominantly composed of glucose. Additionally, the mechanism investigation revealed that the L. acidophilus YL01 and EPS demonstrated limited efficacy in restoring the composition of gut microbiota, but rather exerted an influence on the abundance of specific bacterial groups. The enrichment of the bacterial groups resulted in the increase of acetic acid and butyric acid, which further mediates the gut-liver crosstalk in regulating lipid metabolism by the activation of AMPK/ACC pathway.

Cancer and cardiovascular disease remain the leading causes of morbidity and mortality worldwide, and the two separate disease entities share several similarities and possible interactions. Patients with cancer may have underlying cardiovascular disease, which is often exacerbated by the stress of tumor growth or treatment. At the same time, cardiotoxicity induced by anti-cancer therapies or the malignant process itself can lead to new cardiovascular diseases. Efforts have been made to find a rational explanation for this phenomenon. As a classical tumor-promoting factor, we notice that SNAI2 simultaneously plays an important pathogenic role in cardiovascular diseases. Moreover, there are several striking parallels in the mechanisms of cancer and CVD, such as shared risk factors (e.g., smoking and diabetes), cellular phenotypic switching, and metabolic remodeling, all of which are mediated by SNAI2. This review aims to summarize SNAI2's role in the core mechanisms linking cancer and CVD, as well as explore therapeutic approaches targeting SNAI2 and also seeks to provide insights into the common mechanisms underlying both cancer and CVD.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, but their association with cancer remains unclear. The aim of this study was to compare the effect of combined treatment (SGLT2i and GLP1ra) and monotherapy (SGLT2i or GLP1ra) on hospitalization and/or death from cancer in a general population and a subgroup of patients with cardiovascular disease (CVD).

We conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome.

We included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P<.001; and HR, 0.1928; 95%CI, 0.071-0.5219; P=.001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P<.049; and HR, 0.1329; 95%CI, 0.024-0.6768; P=.014, respectively).

Initiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, but their association with cancer remains unclear. The aim of this study was to compare the effect of combined treatment (SGLT2i and GLP1ra) and monotherapy (SGLT2i or GLP1ra) on hospitalization and/or death from cancer in a general population and a subgroup of patients with cardiovascular disease (CVD).

We conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome.

We included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P<.001; and HR, 0.1928; 95%CI, 0.071-0.5219; P=.001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P<.049; and HR, 0.1329; 95%CI, 0.024-0.6768; P=.014, respectively).

Initiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis.

The worldwide health emergency of obesity is closely connected to how dietary fats are metabolized, whereas the process is significantly influenced by pancreatic lipase (PL), an enzyme critical for lipid hydrolysis into fatty acids. This narrative review employs a methodological approach utilizing literature searches of PubMed data up to March 2024. The search term criteria encompasses keywords related to the role, mechanism, challenges, and current and future treatments of pancreatic lipase in obesity with an overall references is 106. This paper offers a comprehensive explanation of the role of PL, underlining its significance in the digestive process and lipid imbalances that contribute to obesity and by extension, its impact on obesity development and progression. Additionally, it delves into the dual functionality of the pancreas, emphasizing its impact on metabolism and energy utilization which, when dysregulated, promotes obesity. A focal point of this review is the investigation into the efficacy, challenges, and adverse effects of current pancreatic lipase inhibitors, with orlistat being highlighted as a primary current drug delivery. By discussing advanced obesity treatments, including the exploration of novel anti-obesity medications that target specific biological pathways, this review underscores the complexity of obesity treatment and the necessity for a multifaceted approach. In conclusion, this paper emphasizing the importance of understanding the role of enzymes like pancreatic lipase mechanistic and adopting a multidisciplinary approach to treatment and side effects of current obesity drugs and explore new emerging therapeutic strategies for more effective obesity management.

The nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a critical modulator in inflammatory disease. Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome, Muckle-Wells syndrome, and familial cold autoinflammatory syndrome 1. To date, a great effort has been made to decode the underlying mechanisms of NLRP3 activation. The priming and activation of NLRP3 drive the maturation and release of active interleukin (IL)-18 and IL-1β to cause inflammation and pyroptosis, which can significantly trigger many diseases including inflammatory diseases, immune disorders, metabolic diseases, and neurodegenerative diseases. The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials. Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields. In this minireview, we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways. We then reviewed the molecular and cellular pathways of NLRP3 in many diseases, including obesity, diabetes, and other metabolic diseases. In addition, we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy. Finally, clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.

This cross-sectional study examines sociodemographic, nutritional, and lifestyle factors affecting Body Mass Index (BMI) in the Spanish population, with a particular emphasis on obesity.

A sample of 22,181 Spanish residents aged 18 years and older was recruited through digital and physical channels from August 2020 to November 2021. Data were collected using the validated NutSo-HH questionnaire, which includes sections on sociodemographic information, health perceptions, eating habits, and lifestyle factors.

Among respondents, 661 (3%) were underweight (BMI < 18.5 kg/m2), 14,562 (65.7%) were normal weight (18.5 kg/m2 ≤ BMI ≤ 25 kg/m2), 4825 respondents (21.8%) were overweight (25 kg/m2 < BMI ≤ 30 kg/m2), and 2133 (9.6%) were obese (BMI > 30 kg/m2), with significant differences across these groups in relation to diet and lifestyle behaviors. Principal Component Analysis (PCA) was employed to identify the primary variables influencing obesity, revealing that poor dietary habits (frequent consumption of fast food, fried foods, and ultra-processed items) were negatively correlated with healthy behaviors such as regular fish consumption and physical activity. The PCA plot indicated notable distinctions based on educational attainment and age, with individuals with lower educational levels displaying poorer nutritional patterns and younger participants exhibiting higher fast food consumption and poorer sleep quality. Statistical analyses confirmed that sociodemographic factors, including age, education, and income level, significantly influenced BMI. Some differences were also found according to the place of residence.

These findings underscore the need for targeted interventions that address both sociodemographic and lifestyle factors to mitigate obesity risk in Spain.

Body mass index (BMI) may misclassify obesity-related cancer (ORC) risk, as metabolic dysfunction can occur across BMI levels. We hypothesized that metabolic dysfunction at any BMI increases ORC risk compared with normal BMI without metabolic dysfunction. Postmenopausal women (n = 20,593) in the Women's Health Initiative with baseline metabolic dysfunction biomarkers [blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), and high-sensitive C-reactive protein (hs-CRP)] were included. Metabolic phenotype (metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy overweight/obese, and metabolically unhealthy overweight/obese) was classified using four definitions of metabolic dysfunction: (i) Wildman criteria, (ii) National Cholesterol Education Program Adult Treatment Panel III, (iii) HOMA-IR, and (iv) hs-CRP. Multivariable Cox proportional hazards regression, with death as a competing risk, was used to assess the association between metabolic phenotype and ORC risk. After a median (IQR) follow-up duration of 21 (IQR, 15-22) years, 2,367 women developed an ORC. The risk of any ORC was elevated among metabolically unhealthy normal weight (HR = 1.12, 95% CI, 0.90-1.39), metabolically healthy overweight/obese (HR = 1.15, 95% CI, 1.00-1.32), and metabolically unhealthy overweight/obese (HR = 1.35, 95% CI, 1.18-1.54) individuals compared with metabolically healthy normal weight individuals using Wildman criteria. The results were similar using Adult Treatment Panel III criteria, hs-CRP alone, or HOMA-IR alone to define metabolic phenotype. Individuals with overweight or obesity with or without metabolic dysfunction were at higher risk of ORCs compared with metabolically healthy normal weight individuals. The magnitude of risk was greater among those with metabolic dysfunction, although the CIs of each category overlapped. Prevention Relevance: Recognizing metabolic dysfunction as a significant risk factor for ORCs underscores the importance of preventive measures targeting metabolic health improvement across all BMI categories.

Humans are perhaps evolutionarily engineered to get deeply addicted to sugar, as it not only provides energy but also helps in storing fats, which helps in survival during starvation. Additionally, sugars (glucose and fructose) stimulate the feel-good factor, as they trigger the secretion of serotonin and dopamine in the brain, associated with the reward sensation, uplifting the mood in general. However, when consumed in excess, it contributes to energy imbalance, weight gain, and obesity, leading to the onset of a complex metabolic disorder, generally referred to as diabetes. Type 2 diabetes mellitus (T2DM) is one of the most prevalent forms of diabetes, nearly affecting all age groups. T2DM is clinically diagnosed with a cardinal sign of chronic hyperglycemia (excessive sugar in the blood). Chronic hyperglycemia, coupled with dysfunctions of pancreatic β-cells, insulin resistance, and immune inflammation, further exacerbate the pathology of T2DM. Uncontrolled T2DM, a major public health concern, also contributes significantly toward the onset and progression of several micro- and macrovascular diseases, such as diabetic retinopathy, nephropathy, neuropathy, atherosclerosis, and cardiovascular diseases, including cancer. The current review discusses the epidemiology, causative factors, pathophysiology, and associated comorbidities, including the existing and emerging therapies related to T2DM. It also provides a future roadmap for alternative drug discovery for the management of T2DM.

Obesity has become a worldwide health problem. Seeking natural products with anti-obesity activity from lots of fungi has drawn the attention of pharmacologists. In our study, dipenipenoids A and B (1 and 2), the first dimeric indole-diterpenoids with a rare C-20-C-22' linkage, and their monomers (3 and 4), were isolated from a marine-derived Penicillium sp. CF-06 fungus from Suaeda salsa. The absolute configurations of 1-3 were assigned by the calculated TDDFT ECD method. The structure of 4 was verified by a single-crystal X-ray diffraction method for the first time. Interestingly, 1 and 2 displayed significant effects on the differentiation of 3T3-L1 adipocytes by down-regulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα) proteins, while monomers 3 and 4 exhibited no activity. Molecular docking results explained the mechanism that the interaction between dimer 1 and PPARγ was stronger than that between monomer 3 and PPARγ. Our research could provide new insight for the discovery of anti-obesity drugs.

The online version contains supplementary material available at 10.1007/s42995-024-00253-x.

Lagopsis supina, a traditional Chinese medicine valued for its diuretic properties, has limited research on its antioxidant, adipogenic, and anti-inflammatory effects. This study aimed to investigate the chemical composition and biological activities of Lagopsis supina extract (LSE).

LSE was prepared and evaluated for antioxidant activity, effects on adipocyte differentiation in 3T3-L1 preadipocytes, and anti-inflammatory properties in RAW 264.7 macrophages. Ultra-high-performance liquid chromatography-electrospray ionization Orbitrap tandem mass spectrometry (UHPLC-ESI-Orbitrap-MS/MS)-based molecular networking was used to characterize its secondary metabolites.

LSE exhibited antioxidant activity in DPPH and ABTS assays. It significantly enhanced the differentiation of 3T3-L1 preadipocytes into mature adipocytes during early and intermediate stages by upregulating adipogenic transcription factors such as PPARγ, C/EBPα, and C/EBPβ, along with promoting cyclin E expression. LSE also increased PPARγ activity and the expression of its target genes, such as Glut 4, PEPCK, FABP4, and Plin2. Moreover, LSE inhibited lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages by downregulating pro-inflammatory mediators (iNOS, COX-2, TNF-α, IL-6) and inhibiting extracellular signal-regulated kinase (ERK) phosphorylation. Chemical profiling revealed eight major compound groups: glycosides, organic acids, terpenoids, flavonoids, phenylglycosides, phenolics, fatty acids, and others characterized by their mass fragmentation patterns, precursors, and UV absorption spectra. In silico analysis confirmed these compounds' bioactivities, demonstrating strong interactions and binding affinities with antioxidant, adipogenic, and anti-inflammatory protein targets.

These findings highlight LSE's triple therapeutic potential: antioxidant activity, adipogenesis promotion, and inflammation attenuation. LSE emerges as a promising therapeutic candidate for managing obesity and related inflammatory complications.

Today, accumulating evidence highlights the impact of oxidative stress (OS) on semen quality. It is considered to be a key factor contributing to the decline in male fertility. OS is detected in 30-80% of men with infertility, highlighting its strong association with impaired reproductive function and with clinical outcomes following the use of assisted reproductive technologies. Spermatozoa are particularly vulnerable to oxidative damage due to their high content of polyunsaturated fatty acids (PUFAs) and limited antioxidant defense abilities. OS arises from an imbalance between the production of reactive oxygen species and the capacity to neutralize or repair their adverse effects. Evidence indicates that OS leads to lipid peroxidation, protein oxidation, mitochondrial dysfunction, and genomic instability. Micronutrient-antioxidant therapies can play a key role in infertility improvement by neutralizing free radicals and preventing cellular damage. Many different micronutrients, including L-carnitine, L-glutathione, coenzyme Q10, selenium, and zinc, as well as vitamins complexes, are proposed to improve sperm parameters and male fertility potential. This study aims to review the impact of antioxidant supplementation on semen parameters, including sperm volume, motility, concentration, morphology, genome integrity (maturity and fragmentation), and in vitro fertilization (IVF) outcomes. Antioxidant intake and a balanced lifestyle reduce oxidative stress and mitochondrial dysfunction, enhancing the spermatogenesis and spermiogenesis processes, improving sperm quality, and protecting DNA integrity.

Cell culture plays a crucial role in addressing fundamental research questions, particularly in studying insulin resistance (IR) mechanisms. Multiple in vitro models are utilized for this purpose, but their technical distinctions and relevance to in vivo conditions remain unclear. This study aims to assess the effectiveness of existing in vitro models in inducing IR and their ability to replicate in vivo IR conditions.

Insulin resistance (IR) is a cellular condition linked to metabolic disorders. Despite the utility of cell culture in IR research, questions persist regarding the suitability of various models. This study seeks to evaluate these models' efficiency in inducing IR and their ability to mimic in vivo conditions. Insights gained from this research could enhance our understanding of model strengths and limitations, potentially advancing strategies to combat IR and related disorders.

1- Investigate the technical differences between existing cell culture models used to study molecular mediators of insulin resistance (IR). 2- Compare the effectiveness of present in vitro models in inducing insulin resistance (IR). 3- Assess the relevance of the existing cell culture models in simulating the in vivo conditions and environment that provoke the induction of insulin resistance (IR).

In vitro, eight sets of 3T3-L1 cells were cultured until they reached 90% confluence. Subsequently, adipogenic differentiation was induced using a differentiation cocktail (media). These cells were then divided into four groups, with four subjected to normal conditions and the other four to hypoxic conditions. Throughout the differentiation process, each cell group was exposed to specific factors known to induce insulin resistance (IR). These factors included 2.5 nM tumor necrosis factor-alpha (TNFα), 20 ng/ml interleukin-6 (IL-6), 10 micromole 4-hydroxynonenal (4HNE), and high insulin (HI) at a concentration of 100 nM. To assess cell proliferation, DAPI staining was employed, and the expression of genes associated with various metabolic pathways affected by insulin resistance was investigated using Real-Time PCR. Additionally, insulin signaling was examined using the Bio-plex Pro cell signaling Akt panel.

We induced insulin resistance in 3T3-L1 cells using IL-6, TNFα, 4HNE, and high insulin in both hypoxic and normoxic conditions. Hypoxia increased HIF1a gene expression by approximately 30% (P<0.01). TNFα reduced cell proliferation by 10-20%, and chronic TNFα treatment significantly decreased mature adipocytes due to its cytotoxicity. We assessed the impact of insulin resistance (IR) on metabolic pathways, focusing on genes linked to branched-chain amino acid metabolism, detoxification, and chemotaxis. Notably, ALDH6A1 and MCCC1 genes, related to amino acid metabolism, were significantly affected under hypoxic conditions. TNFα treatment notably influenced MCP-1 and MCP-2 genes linked to chemotaxis, with remarkable increases in MCP-1 levels and MCP-2 expression primarily under hypoxia. Detoxification-related genes showed minimal impact, except for a significant increase in MAOA expression under acute hypoxic conditions with TNFα treatment. Additional genes displayed varying effects, warranting further investigation. To investigate insulin signaling's influence in vitro by IRinducing factors, we assessed phospho-protein levels. Our results reveal a significant p-Akt induction with chronic high insulin (10%) and acute TNFα (12%) treatment under hypoxia (both P<0.05). Other insulin resistance-related phospho-proteins (GSK3B, mTOR, PTEN) increased with IL-6, 4HNE, TNFα, and high insulin under hypoxia, while p-IRS1 levels remained unaffected.

In summary, different in vitro models using inflammatory, oxidative stress, and high insulin conditions under hypoxic conditions can capture various aspects of in vivo adipose tissue insulin resistance (IR). Among these models, acute TNFα treatment may offer the most robust approach for inducing IR in 3T3-L1 cells.

In this study, we describe the anti-obesity effects of a novel combination of Lactobacillus mixture (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032) and leaf extract of Lagerstroemia speciosa (L. speciosa) in mice. The administration of the probiotic mixture of HY7601 and KY1032 in combination with the leaf extract of L. speciosa significantly attenuated fat tissue formation and body weight gain in mice fed a high-fat diet. The white adipose fat mass, comprising the inguinal and epididymal fat pads, was most effectively reduced when the probiotic mixture and L. speciosa leaf extract was orally administered to the mice in combination. This combination also reduced the mRNA expression of adipogenic genes (those encoding CCAAT/enhancer-binding protein alpha, peroxisome proliferator-activated receptor gamma, and fatty acid-binding protein 4) in inguinal and epididymal white adipose tissue depots and the liver. Finally, the combination of reduced blood glucose concentrations regulated the insulin resistance of high-fat diet-fed obese mice. These findings provide insight into the mechanisms underlying the effect of this combination and suggest that using Lactobacillus mixture (HY7601 and KY1032) is as safe as microbial monotherapy, but more effective at preventing obesity.

Compared to the general population of Hawai'i, Native Hawaiians and Other Pacific Islanders (NHPI) shoulder a disproportionately high risk for obesity-related cardiometabolic disorders, such as type 2 diabetes and cardiovascular disease. The gut microbiome is an area of rapid research interest for its role in regulating adjacent metabolic pathways, offering novel opportunities to better understand the etiology of these health disparities. Obesity and the gut microbiome are influenced by regional, racial-ethnic, and community-specific factors, limiting the generalizability of current literature for understudied populations. Additionally, anthropometric and directly measured obesity indices are variably predictive of adiposity and metabolic health risk in this diverse population. Thus, further NHPI-inclusive research is required to adequately characterize community-specific factors in the context of obesity-related disease etiology. Culturally responsible research ethics and scientific communication are crucial to conducting such research, especially among indigenous and understudied populations. In this review, we explore these limitations in current literature, emphasizing the urgent need for NHPI-inclusive research to assess community-specific factors accurately. Such accuracy in Indigenous health research may ensure that findings relevant to individual or public health recommendations and/or policies are meaningful to the communities such research aims to serve.

Background: Despite considerable literature supporting the benefit of dietary interventions in individuals with type 2 diabetes mellitus (T2DM) and overweight/obesity, which diet works best is currently unknown. We conducted a systematic review and network meta-analysis (NMA) to evaluate the comparative effectiveness of different dietary approaches in overweight or obese adults with T2DM. Methods: We searched EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed up till July 2023 for controlled studies using different dietary approaches. Next, we updated the literature search to September 2024 but found no new relevant studies. Glycated hemoglobin A1c (HbA1c) levels and body weight were used as primary outcomes. For each outcome, a pooled effect was determined for each intervention compared with other interventions. Mean differences (MDs) and 95% confidence intervals (95% CIs) were computed. The surface under the cumulative ranking curve (SUCRA) was used for ranking the dietary approaches. Moreover, confidence was assessed using the CINeMA (confidence in network meta-analysis) framework. Results: Overall, 31 trials that compared eight diet interventions (Mediterranean, moderate-carbohydrate, low-carbohydrate, vegetarian, low-glycaemic index/load, low-fat, high-protein and control diets) and involved 3096 people were included. In terms of glycemic control, the Mediterranean diet yielded the best ranking (SUCRA: 88.15%), followed by the moderate-carbohydrate diet (SUCRA: 83.3%) and low-carbohydrate (LC) diet (SUCRA: 55.7%). In terms of anthropometric measurements, the LC diet (SUCRA: 74.6%) ranked first, followed by the moderate-carbohydrate diet (SUCRA: 68.7%) and vegetarian diet (SUCRA: 57%). These results also showed that the differences in almost all dietary patterns regarding anthropometric measurements were mostly small and often trivial. Conclusions: In summary, the Mediterranean diet was the most efficient dietary intervention for the improvement of glycaemic control, and the LC diet obtained the highest score for anthropometric measurements in individuals with T2DM and concurrent overweight/obesity.

This study investigated the therapeutic potential of Lactobacillus plantarum NCHBL-004 (NCHBL-004) in the treatment of obesity and associated metabolic disorders.

Mice were fed either a normal diet (ND) or a high-fat diet (HFD) with oral administration of NCHBL-004. After euthanasia, blood, liver and adipose tissue were collected. Furthermore, the microbiome and short-chain fatty acids (SCFAs) were analyzed from feces.

Oral administration of live NCHBL-004 to mice fed a HFD resulted in notable reductions in weight gain, improvements in glucose metabolism, and maintenance of balanced lipid levels. A comparative analysis with other Lactobacillus strains highlighted the superior efficacy of NCHBL-004. Moreover, heat-killed NCHBL-004 demonstrated beneficial effects similar to those of live NCHBL-004. Additionally, administration of live NCHBL-004 induced glucagon-like peptide 1 (GLP-1) production and increased the levels of short-chain fatty acids (SCFAs), including acetate and propionate, in feces, positively influencing liver lipid metabolism and mitigating inflammation. Consistent with this, analysis of the gut microbiome following NCHBL-004 administration showed increases in SCFA-producing microbes with increased proportions of Lactobacillus spp. and a significant increase in the proportion of microbes capable of promoting GLP-1 secretion.

These findings underscore the potential of both live and inactivated NCHBL-004 as potential therapeutic approaches to managing obesity and metabolic disorders, suggesting avenues for further investigation and clinical applications.

Weight stigma, and more specifically, anti-fat attitudes, is associated with disordered eating. Furthermore, these anti-fat attitudes influence various appearance ideals. Muscle dysmorphia (MD) is characterized by preoccupation with the muscular ideal and is a potential form of disordered eating commonly experienced by men. Despite theory suggesting that anti-fat attitudes may contribute to MD, research has yet to examine associations between anti-fat attitudes and MD symptoms. Therefore, the current study investigated longitudinal relationships between anti-fat attitudes and MD symptoms. Participants were 269 U.S. men recruited from Prolific who completed three self-report surveys each separated by one month. Primary analyses examined longitudinal relationships between specific anti-fat attitudes and MD symptoms using an adapted three-wave cross-lagged panel model. Results demonstrated that believing that fat people do not have willpower was longitudinally associated with desires to increase muscle size at multiple time points. Furthermore, MD-specific functional impairment predicted fears of becoming fat longitudinally. Practically, men may desire to increase their muscularity to demonstrate their own willpower and distance themselves from anti-fat stereotypes. Thus, clinicians may consider targeting weight stigmatizing attitudes to reduce MD symptom severity among their male clients.

Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for obesity. However, the incidence and long-term risk of hypoglycemia after surgery in patients without diabetes remains unclear. This study aimed to investigate the prevalence of hypoglycemia following RYGB surgery in patients with obesity and without diabetes.

A retrospective cohort study was conducted using the TriNetX database. The study population included 15,085 patients with obesity (BMI ≥ 30 kg/m2) who underwent RYGB surgery and 3,200,074 non-surgical controls, all without a history of diabetes or GLP-1 receptor agonist use. Propensity score matching was performed to balance baseline characteristics. The primary outcome was the incidence of hypoglycemia, defined by ICD-10-CM codes or laboratory values (glucose ≤ 70 mg/dL). Cox regression analysis was employed to calculate hazard ratios (HR) and 95% confidence intervals (CI).

In the overall study population, the risk of hypoglycemia was significantly higher in the RYGB group (18.70%, n = 2,810) compared to the control group (3.80%, n = 120,923; HR 4.3, 95% CI 4.14-4.46, p < 0.001). After propensity score matching (n = 14,916 per group), RYGB patients maintained an elevated risk (18.70%, n = 2,795) compared to matched controls (5.0%, n = 749; HR 3.7, 95% CI 3.44-4.05, p < 0.001). Time-series analysis revealed consistently higher hypoglycemia risk in the RYGB group, with hazard ratios ranging from 5.37 (95% CI 4.09-7.03) at 1 week to 3.75 (95% CI 3.45-4.06) at 10 years post-surgery (all p < 0.001). Subgroup analysis of RYGB patients who developed hypoglycemia showed a 30-day hospitalization rate of 21.3% and a mortality rate of 0.71%.

RYGB surgery is associated with a significantly increased risk of hypoglycemia in patients with obesity and without diabetes, both in the short-term and long-term follow-up. These findings underscore the importance of monitoring and managing hypoglycemia in patients undergoing RYGB surgery, even in the absence of preexisting diabetes.

Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role of GLP-1R in type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, and facilitating insulin release. GLP-1R agonists have effectively managed obesity by reducing hunger, moderating food intake, and regulating body weight. Beyond diabetes and obesity, GLP-1R agonists exhibit a multifaceted impact on cancer progression across various malignancies. The mechanisms underlying these effects involve the modulation of signaling pathways associated with cell growth, survival, and metabolism. However, the current literature reveals a lack of in vivo studies on specific GLP-1R agonists such as semaglutide, necessitating further research to elucidate its precise mechanisms and effects, particularly in cancer. While other GLP-1R agonists have shown promising outcomes in mitigating cancer progression, the association between some GLP-1R agonists and an increased risk of cancer remains a topic requiring more profound investigation. This calls for more extensive research to unravel the intricate relationships between the GLP-1R agonist and different cancers, providing valuable insights for clinicians and researchers alike.

To ascertain the involvement of insulin receptors (IRs) in colorectal carcinogenesis, we investigated the association of height, body mass index (BMI), and physical activity with colorectal cancer (CRC) and two subtypes of CRC according to the expression level of IR. We utilized data from a large-scale, population-based prospective cohort study of 18,158 middle-aged and elderly subjects in Akita and Okinawa, Japan. In the statistical analysis, we used the Cox proportional hazards model and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subtypes as defined by immunohistochemistry of IRβ, a transmembrane subunit of IR. In the IRβ-defined subtypes, height showed no apparent association with the risk of IRβ-positive CRC. In contrast, a multivariable HR of IRβ-positive CRC was 1.77 (95% CI = 1.04-3.03) with a BMI of ≥30.0 kg/m2 (i.e., obesity), compared to a BMI of <25.0 kg/m2. Further, an increase in physical activity was significantly associated with decreased risk of IRβ-positive CRC (multivariable HR per 5 METs-hour/day = 0.93, 95% CI = 0.88-0.99). Meanwhile, we found no significant association between any exposure and IRβ-negative CRC. Likewise, heterogeneity between the two subtypes of CRC was not statistically significant. These findings imply that obesity and physical activity exert promoting and suppressing effects on the development of CRC expressing IRs, respectively.

An established hallmark of cancer cells is metabolic reprogramming, largely consisting in the exacerbated glucose uptake. Adipocytes in the tumor microenvironment contribute toward breast cancer (BC) progression and are highly responsive to metabolic fluctuations. Metabolic conditions characterizing obesity and/or diabetes associate with increased BC incidence and mortality. To explore BC-adipocytes interaction and define the impact of glucose in such dialogue, Mammary Adipose-derived Mesenchymal Stem Cells (MAd-MSCs) were differentiated into adipocytes and co-cultured with ER+ BC cells while exposed to glucose concentration resembling hyperglycemia or normoglycemia in humans (25mM or 5.5mM). The transcriptome of both cell types in co-culture as in mono-culture was profiled by RNA-Seq to define the impact of adipocytes on BC cells and viceversa (i), the action of glucose on BC cells, adipocytes (ii) and their crosstalk (iii). Noteworthy, we provided evidence that co-culture with adipocytes in a glucose-rich environment determined a re-program of BC cell transcriptome driving lipid accumulation, a hallmark of BC aggressiveness, promoting stem-like properties and reducing Tamoxifen responsiveness. Moreover, our data point out to a transcriptional effect through which BC cells induce adipocytes de-lipidation, paralleled by pluripotency gain, as source of lipids when glucose lowering occurs. Thus, modulating plasticity of peri-tumoral adipocytes may represent a key point for halting BC progression in metabolically unbalanced patients.

This study investigated the effects of ascochlorin (ASC), a natural compound derived from the fungus Ascochyta viciae, on adipogenesis and obesity. We determined the effects of ASC on 3T3-L1 preadipocytes and whether it ameliorated to mitigate high-fat diet (HFD)-induced obesity in C57BL/6J mice. We found that ASC significantly inhibited the differentiation of preadipocytes by modulating the Wnt/β-catenin signaling pathway, a key regulator of adipogenic processes. Treatment with ASC not only reduced the mRNA and protein expression of key adipogenic transcription factors such as C/EBPα and PPARγ, but also reduced lipid accumulation both in vitro and in vivo. In addition, treatment HFD-fed mice with ASC significantly reduced their weight gain and adiposity vs. control mice. These results suggest that ASC has considerable potential as a therapeutic agent for obesity, owing to its dual action of inhibiting adipocyte differentiation and reducing lipid accumulation. Thus, ASC represents a promising candidate as a natural anti-obesity agent.

Liver biopsy is the gold standard to evaluate hepatic fibrosis; however, it has many drawbacks, especially in patients with severe obesity. Noninvasive testing such as the FIB-4 score is increasingly being used as the initial screening tool to identify patients at risk for advanced fibrosis. The broader applicability of FIB-4 and the precision of its cutoff values remain uncertain in metabolic dysfunction-associated steatotic liver disease and patients with severe obesity. Our study explored the correlation between FIB-4 scores and intraoperative liver biopsy in patients with severe obesity undergoing bariatric surgery.

A total of 632 patients with severe obesity underwent preoperative vibration-controlled transient elastography and intraoperative liver biopsy during bariatric surgery from January 2020 to August 2021. Variables collected included patient demographics, laboratory values, abdominal ultrasound, vibration-controlled transient elastography, and liver biopsy results. ANOVA 1-way test, χ 2 tests, and Fisher exact tests were used for quantitative and qualitative variables, respectively. The 95% CIs for the mean FIB-4 scores were used to generate surrogate cutoff values. The proposed FIB-4 cutoffs for F0-1, F2, F3, and F4 were 0.62 (CI: 0.59, 0.64), 0.88 (0.74, 1.01), 1.24 (0.94, 1.54), and 1.53 (0.82, 2.24), respectively. Area under the curve (AUC) methods were used to compare traditional to proposed cutoff values.

Applying the traditional FIB-4 cutoffs to approximate advanced fibrosis yielded an AUC of 0.5748. Use of the proposed FIB-4 cutoffs increased the AUC to 0.6899. The proposed FIB-4 cutoffs correctly identified 40 patients with biopsy-proven advanced fibrosis (F3-F4), all of which would have been missed using traditional cutoffs.

Our study revealed that the use of the currently accepted FIB-4 cutoffs as the screening modality for identifying patients with advanced fibrosis due to metabolic dysfunction-associated steatotic liver disease is insufficient and will result in missing patients with histologically confirmed advanced fibrosis. Use of the revised FIB-4 scores should be considered to diagnose patients with severe obesity at high risk of liver disease progression.

Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role in cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression of certain RTKs, are critical in creating environments conducive to tumor development. Following their discovery, extensive research has revealed how RTK dysregulation contributes to oncogenesis, with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation, survival and progression. These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer. As a result, RTKs have emerged as primary targets in anticancer therapeutic development. Over the past two decades, this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors (TKIs), now effectively utilized in treating various cancer types. In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer. We explored the various alterations and overexpression of specific receptors across different malignancies, with special attention dedicated to the examination of current RTK inhibitors, highlighting their role as potential targeted therapies. By integrating the latest research findings and clinical evidence, we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.

We aimed to characterize the anti-obesity and anti-atherosclerosis effects of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 using high-fat diet (HFD)-fed obese C57BL/6 mice. We divided the mice into control (CON), HFD, HFD with 108 CFU/kg/day probiotics (HFD + KL, HY7301:KY1032 = 1:1), and HFD with 109 CFU/kg/day probiotics (HFD + KH, HY7301:KY1032 = 1:1) groups and fed/treated them during 7 weeks. The body mass, brown adipose tissue (BAT), inguinal white adipose tissue (iWAT), and epididymal white adipose tissue (eWAT) masses and the total cholesterol and triglyceride concentrations were remarkably lower in probiotic-treated groups than in the HFD group in a dose-dependent manner. In addition, the expression of uncoupling protein 1 in the BAT, iWAT, and eWAT was significantly higher in probiotic-treated HFD mice than in the HFD mice, as demonstrated by immunofluorescence staining and Western blotting. We also measured the expression of cholesterol transport genes in the liver and jejunum and found that the expression of those encoding liver-X-receptor α, ATP-binding cassette transporters G5 and G8, and cholesterol 7α-hydroxylase were significantly higher in the HFD + KH mice than in the HFD mice. Thus, a Lactobacillus HY7601 and KY1032 mixture with 109 CFU/kg/day concentration can assist with body weight regulation through the management of lipid metabolism and thermogenesis.

Obesity and its associated comorbidities place a substantial burden on public health. Given the considerable potential of brown adipose tissue in addressing metabolic disorders that contribute to dysregulation of the body's energy balance, this area is an intriguing avenue for research. This study aimed to assess the impact of various polymers, including collagen type I, fibronectin, laminin, gelatin, gellan gum, and poly-l-lysine (PLL), on the in vitro brown adipogenic differentiation of dedifferentiated fat cells within a fibrin gel matrix. The findings, obtained through RT-qPCR, immunofluorescent imaging, ELISA assay, and mitochondria assessment, revealed that PLL exhibited a significant browning-inducing effect. Compared to fibrin-only brown-like drops after two weeks of incubation in brown adipogenic medium, PLL showed 6 (±3) times higher UCP1 gene expression, 5 (±2) times higher UCP1 concentration by ELISA assay, and 2 (±1) times higher mitochondrial content. This effect can be attributed to PLL's electrostatic properties, which potentially facilitate the cellular uptake of crucial brown adipogenic inducers such as the thyroid hormone, triiodothyronine (T3), and insulin from the induction medium.

Type 2 diabetes (T2D) is a risk factor for female breast cancer (FBC). Obesity has also been associated with FBC, also depending on menopausal status. This study aimed to evaluate the impact of obesity and T2D on the development, aggressiveness, and invasiveness of FBC.

Demographic, clinical, and histopathological data from 335 women with FBC were collected, and analyzed according to weight category (102 normal weight, 117 overweight, and 116 living with obesity) and the presence/absence of T2D.

Age at oncologic diagnosis was not statistically significantly different for body weight; women with overweight or obesity were more likely to have an oncologic diagnosis after menopause than normal weight (p < 0.001). The presence of overweight/obesity and T2D seemed to be associated with a higher incidence of metastasis, recurrence, and triple-negative breast cancer (TNBC) subtype (p < 0.001). Excess body weight was also associated with high histologic grade (G3) (p < 0.005).

These results confirm excess body weight and T2D as unfavorable prognostic factors in terms of the presence of the TNBC subtype, tumor metastasis, recurrence, and aggressiveness (G3 and Ki-67 > 20%). This study highlights the importance of prevention in all women, with early screening, and adequate nutritional programs.