Search Results (1,571)

High-density lipoprotein (HDL) is a multifunctional lipoprotein involved in lipid transport, immune regulation, and redox homeostasis. Chronic inflammation and oxidative stress alter HDL composition and function, promoting the formation of dysfunctional HDL particles, impairing cholesterol efflux, and contributing to cardiovascular disease progression. To investigate the regulatory mechanisms underlying these changes, we developed a Petri net-based model of HDL metabolism and extended it to represent inflammatory conditions and selected therapeutic interventions. As a literature-derived qualitative model, it provides a simplified systems-level representation of HDL metabolism and its interactions with inflammation and oxidative stress. Nevertheless, the model captures the essential processes governing these pathways. Using in silico knock-out analysis, we evaluated the impact of disabling individual processes on global network dynamics and identified key regulatory bottlenecks. Network control was highly uneven and concentrated within a limited set of transitions. Under inflammatory conditions, the dominant bottlenecks included reduced LCAT-mediated cholesterol esterification, adiponectin-dependent regulation, and oxidized HDL-associated activity, indicating that HDL dysfunction arises from a tightly interconnected immunometabolic network linking lipid metabolism, inflammation, and oxidative stress. Therapeutic interventions reorganized network control toward the inhibition of inflammation, the restoration of redox balance, and the reconstitution of HDL-mediated cholesterol export. Inhibition of inflammation and oxidation-reduction remained dominant regulatory nodes across pathological and therapeutic states, suggesting a core regulatory backbone of HDL metabolism. These findings demonstrate that inflammation and oxidative stress fundamentally reshape HDL network control and identify a limited set of regulatory bottlenecks that may represent promising targets for therapeutic intervention in cardiovascular and chronic inflammatory diseases. However, because the model represents a simplified qualitative abstraction of HDL biology, the identified bottlenecks should be interpreted as systems-level hypotheses requiring further experimental validation. Full article

The cardiovascular actions of testosterone remain controversial, particularly regarding the safety of testosterone replacement therapy (TTh) in hypogonadal men. We investigated the effects of sustained supraphysiological testosterone exposure on aortic atherogenesis and cardiac remodelling in the testicular feminised (Tfm) mouse, a model of functional androgen receptor (AR) deficiency. Male Tfm mice and AR-intact XY littermate controls were fed a cholesterol-enriched diet for 28 weeks and received fortnightly intramuscular injections of saline or supraphysiological testosterone, alone or in combination with fulvestrant (oestrogen receptor antagonist) or anastrozole (aromatase inhibitor). Aortic lipid deposition was quantified by Oil Red O staining, while cardiac remodelling was assessed by heart weight, cardiomyocyte cross-sectional area and myocardial gene expression. Supraphysiological testosterone significantly reduced aortic fatty streak formation in Tfm mice compared with saline-treated controls (1.25 ± 0.36% vs. 2.85 ± 0.37%, p < 0.01), an effect preserved following fulvestrant or anastrozole treatment, consistent with mechanisms that do not require classical AR or oestrogen receptor signalling. No additional reduction in aortic lipid deposition was observed in AR-intact XY littermates. In contrast, supraphysiological testosterone increased heart weight, cardiomyocyte size and expression of hypertrophic markers exclusively in XY mice, with no evidence of cardiac remodelling in Tfm mice. Collectively, these findings demonstrate divergent tissue-specific cardiovascular actions of testosterone, whereby supraphysiological exposure promotes AR-dependent cardiac remodelling without conferring additional vascular benefit, supporting maintenance of physiological testosterone concentrations during TTh. Full article

Stress-induced sebaceous hyperactivity is a key driver of acne and seborrheic dermatitis; however, research investigating the pathway-specific mechanisms through which stress exerts its effects and the suppression of sebum production via targeting stress signaling remains relatively limited. In this study, we investigated whether Camellia nitidissima flower extract (CNF) could counteract stress-induced sebaceous dysfunction and its underlying mechanisms. Using a cortisone-stimulated SZ95 human sebocyte model, we evaluated lipid accumulation, cortisol production, signaling pathway activation, and apoptotic markers. CNF treatment dose-dependently suppressed cortisone-induced lipid production, reducing triglyceride, cholesterol, and free fatty acid levels by up to 35.44%, 38.02%, and 46.39%. Mechanistically, CNF inhibited 11β-HSD1 expression (17.17% reduction) and cortisol secretion (32.84% decrease), thereby blocking local cortisol reactivation. This upstream interception subsequently attenuated PI3K/Akt/mTOR hyperphosphorylation, downregulated lipogenic transcription factors (SREBP-1, PPARγ, LXRα, C/EBP-α) and their target enzymes (FAS, ACC, DGAT). Beyond lipid synthesis inhibition, CNF reversed cortisone-induced apoptosis resistance by reducing the Bcl-2/Bax ratio and suppressing PCNA-mediated hyperproliferation, thereby decreasing sebocyte number. These findings demonstrate that CNF exerts dual oil-control effects: reducing lipid production per cell and reducing lipid-producing cell abundance. Collectively, CNF represents a promising multi-target botanical agent for managing stress-related sebaceous disorders and cosmetic sebum regulation. Full article

The mitochondrial DNA copy number (mtDNA-CN) is considered an indirect indicator of the number of mitochondria and of mitochondrial dysfunction; its decrease may indirectly reflect mitochondrial DNA (mtDNA) alterations. A reduction in mtDNA-CN is associated with the development of cardiovascular diseases, including coronary artery disease (CAD). The study evaluates the association of relative blood mtDNA-CN with premature CAD (pCAD) and cardiometabolic factors among Mexican individuals from the GEA (Genetics of Atherosclerotic Disease) Mexican cohort. Relative blood mtDNA-CN was quantified by real-time PCR in 835 patients with pCAD and 896 control subjects (defined as a coronary artery calcium score of zero, assessed by computed tomography). Associations were evaluated using logistic regression (odds ratio [95% confidence interval]) adjusted for potential confounders. Compared with controls, patients with pCAD exhibited significantly lower relative blood mtDNA-CN (5.6 [3.5–9.8] vs. 9.1 [5.1–13.2]. p < 0.001). Similar results were observed in the sex-stratified analysis. Specifically, relative blood mtDNA-CN in women (6.2 [3.8–9.9]) and men (5.5 [3.4–9.7]) with pCAD was lower than that in women (9.5 [6.3–13.7]) and men (8.2 [5.5–12.5]) from the control group (p < 0.001). After adjusting for age, sex, body mass index, smoking status, LDL-cholesterol, type 2 diabetes mellitus, hypertension and physical activity, higher relative blood mtDNA-CN showed a negative association with pCAD (0.903 [0.881–0.927], p = 4.96 × 10⁻¹⁵). This association remained significant in men (0.894 [0.866–0.922], p = 2.90 × 10⁻¹²) and women (0.917 [0.876–0.960], p = 2.1 × 10⁻⁴). Among patients with pCAD, an inverse correlation was observed between relative blood mtDNA-CN and total abdominal fat (p = 0.001), visceral fat (p = 0.015), and subcutaneous fat (p = 0.004). Overall, our results show that reduced relative blood mtDNA-CN is associated with pCAD, which could be indicative of mitochondrial alterations. Furthermore, the inverse correlation between relative blood mtDNA-CN and total, visceral, and subcutaneous abdominal fat suggests a link between mitochondrial dysfunction and abdominal adiposity in patients with pCAD. These findings support that decreased relative blood mtDNA-CN may serve as a marker associated with the presence of pCAD and for adipose tissue alterations in Mexican women and men. Full article

Background: Malnutrition and metabolic dysregulation are common in motor neuron disease (MND) and contribute to accelerated functional decline and reduced survival. Routine serum biochemical analytes can be used to assess nutritional status; however, their interpretation in MND is confounded by systemic inflammation and disease-related metabolic changes. This study investigated the relationship between serum biochemical analytes, inflammatory status, disease severity, progression, and body composition in people living with MND. Methods: In this single-centre, longitudinal prospective cohort study, 19 participants with confirmed MND were assessed at enrolment and at three-month intervals up to nine months. Serum concentrations of albumin, prealbumin, creatinine, transferrin, ferritin, retinol-binding protein, and lipid fractions were measured alongside routine inflammatory markers. Disease severity and progression were assessed using the revised ALS functional rating scale and King’s College Staging System. Anthropometry included percentage weight change, body mass index, mid-upper arm circumference, triceps skinfold thickness, arm muscle area, and calf circumference. Participants with evidence of baseline inflammation were excluded from nutritional analyses. Results: Low-grade systemic inflammation was present in 9/19 (47%) of participants at enrolment, most commonly reflected by elevated fibrinogen. In the non-inflammatory sub-cohort (n/N = 10/19), serum creatinine was positively correlated with muscle-related functional subscores (p = 0.007) and declined between enrolment and three months (p = 0.02), showing predominantly negative trajectories by nine months. HDL cholesterol also declined over the nine-month follow-up (p = 0.03) and lipid fractions correlated positively with disease stage (p <0.001–0.02), suggesting evolving metabolic stress. Elevated serum retinol-binding protein was observed in 90% (n/N = 9/10) of participants without inflammation. Biochemical evidence of malnutrition (low transferrin and/or creatinine) was detected in one-third of participants, accompanied by weight loss and reductions in limb anthropometric parameters. Malnutrition risk was identified in 1/10 (10%) of the non-inflammatory sub-cohort using a modified ESPEN-based framework, and in 2/10 (20%) participants using GLIM criteria. Conclusions: Routine serum biochemical analytes provide complementary information on nutritional and metabolic status in MND when interpreted alongside inflammatory markers and anthropometry. Serum creatinine emerged as a longitudinal marker of muscle wasting, reflective of denervation and nutritional depletion, while lipid and retinol-binding protein alterations highlight non-nutritional disease mechanisms that may confound standard biomarker interpretation, informing more targeted nutritional assessments. These findings support a multimodal approach to nutritional monitoring in MND and emphasise the importance of accounting for inflammatory status in biomarker interpretation. Given the small sample size and the limited representation of non-ALS phenotypes, these findings should be regarded as hypothesis-generating and require confirmation in larger, multicentre cohorts with balanced phenotypic representation. Full article

Policosanol (sugarcane wax alcohol), phosphatidylserine, and Ginkgo biloba leaf extract are Ministry of Food and Drug Safety (MFDS), Republic of Korea-listed functional foods for health-promoting effects. Herein, a combination of policosanol, phosphatidylserine, and G. biloba leaf extract (hereafter PPG) was investigated against metabolic stress induced by a high-cholesterol, high-galactose (HCHG) diet in hyperlipidemic and hyperglycemic zebrafish. After 9 weeks of feeding, the zebrafish following the HCHG diet co-supplemented with PPG exhibited a significant 14.1% (p < 0.02) reduction in body weight and higher zebrafish survivability compared to the HCHG-supplemented group. Significantly reduced total cholesterol (TC, 1.2-fold), triglycerides (TG, 1.4-fold), low-density lipoprotein cholesterol (LDL-C, 1.3-fold), and glucose levels (1.2-fold), along with a 1.5-fold (p = 0.003) elevated high-density lipoprotein cholesterol (HDL-C), were observed in the PPG co-supplemented group relative to the HCHG group. In addition, the HCHG-elevated plasma malondialdehyde (MDA), diminished ferric ion reduction activity (FRA), and paraoxonase (PON)-like activity significantly (p < 0.001) reverted by 1.6-fold, 1.4-fold, and 1.6-fold, respectively, by co-supplementation with PPG. Consistently, the plasma from the PPG-supplemented group showed greater ability to prevent carboxymethyllysine (CML)-induced apoptotic death, altered heart rate, and developmental deformities in zebrafish embryos. Moreover, PPG exerted significant protective effects against HCHG-induced hepatomegaly and fatty liver, accompanied by marked inhibition of hepatic interleukin (IL)-6 and reactive oxygen species (ROS) generation. Consistently, PPG supplementation inhibits ROS generation and senescence in the liver, intestine, brain, kidney, testis and ovary and protects the organ damage caused by exposure to HCHG. Similarly, in intestinal tissue, HCHG-induced fibrosis and oxidative stress were mitigated by the co-supplementation of PPG. The findings indicate that PPG is an effective combination for preventing dyslipidemia, oxidative stress, inflammation, and multi-organ damage associated with HCHG-mediated metabolic stress in zebrafish. Full article

Background: The clinical course and mortality risk of COVID-19 in patients with type 2 diabetes (T2D) remain elevated. Understanding its pathogenesis is essential for prognostic and therapeutic strategies. Viral infections can disrupt host glucose and lipid metabolism. This study evaluated changes in glycemic and lipid parameters following COVID-19 infection in T2D patients. Methods: A retrospective analysis was conducted on T2D patients who tested positive for COVID-19 between April 2020 and December 2021. Laboratory results before and after infection were compared to assess changes in glycemic and lipid markers. Results: The study included 969 patients with T2D; 56.7% were female, and the median age was 58 years (IQR: 49–67). Hypertension, asthma, and chronic kidney disease were present in 51.5%, 14.2%, and 7.2% of patients, respectively. Fasting blood glucose did not change significantly from before to after COVID-19 infection [7.9 mmol/L (IQR: 6.2–10.6) vs. 7.8 mmol/L (IQR: 6.2–10.2)], nor did HbA1c [7.6% (IQR: 6.7–9.1) vs. 7.6% (IQR: 6.5–9.2)]. In contrast, modest but statistically significant reductions were observed in triglycerides [1.47 mmol/L (IQR: 1.13–2.00) vs. 1.44 mmol/L (IQR: 1.08–1.94)], total cholesterol [4.3 mmol/L (IQR: 3.67–5.03) vs. 4.1 mmol/L (IQR: 3.55–4.93)], and LDL cholesterol [2.7 mmol/L (IQR: 2.11–3.45) vs. 2.5 mmol/L (IQR: 1.98–3.23)]. HDL cholesterol remained unchanged [1.0 mmol/L (IQR: 0.90–1.21) vs. 1.0 mmol/L (IQR: 0.89–1.22)]. Conclusions: COVID-19 infection was not associated with significant long-term changes in glycemic control among patients with T2D, as fasting blood glucose and HbA1c levels remained broadly stable after infection. In contrast, significant reductions were observed in total cholesterol, LDL cholesterol, and triglyceride levels, while HDL cholesterol remained unchanged. These findings indicate that changes following COVID-19 infection were more apparent in lipid parameters than in glycemic markers. Full article

This study aims to evaluate the feasibility of substituting soybean meal with single-cell protein derived from Ralstonia eutropha H16 (SCP-H16) in broiler diets, with a specific emphasis on its impact on growth performance, meat quality, biochemical parameters, antioxidant capacity, and intestinal health. A total of 540 one-day-old Arbor Acres (AA) male broiler chicks were randomly allocated to five treatment groups, each comprising six replicates of 18 chicks. The control group (CON) was provided with a corn-soybean meal basal diet, whereas the experimental groups received the basal diet supplemented with 2%, 4%, 6%, and 8% SCP-H16, respectively, replacing soybean meal on an isonitrogenous basis. Specifically, dietary inclusion of 2%, 4%, 6%, and 8% SCP-H16 replaced approximately 9%, 18%, 27%, and 36% of the soybean meal in the starter diet and 10%, 21%, 31%, and 41% in the grower diet, respectively. The feeding period lasted 42 days. The findings demonstrated that dietary supplementation with SCP-H16 significantly reduced the average daily feed intake and feed conversion ratio of broilers (p < 0.05), without adversely affecting the final body weight and breast meat quality at 42 d. Compared to the CON group, the groups receiving 2% and 4% SCP-H16 exhibited significantly lower serum level of total cholesterol (T-CHO) (p < 0.05). Moreover, the serum activity of total superoxide dismutase (T-SOD) was significantly enhanced in the 2%, 4%, and 6% SCP-H16 groups, and the total antioxidant capacity (T-AOC) was significantly increased in the 2% and 4% SCP-H16 groups (p < 0.05), relative to the CON group. In the liver, glutathione peroxidase (GSH-Px) activity was significantly elevated in the 2% SCP-H16 group compared to the CON group (p < 0.05). Additionally, serum levels of IgG and IgM were significantly elevated in the 2%, 4%, and 6% SCP-H16 groups, while serum IgA level was increased across all SCP-H16-containing groups (p < 0.05). In the liver, both IgG and IgA levels were significantly elevated across all groups receiving SCP-H16 supplementation (p < 0.05). In the duodenum, the 2% SCP-H16 group exhibited a significantly greater villus height compared to the CON group (p < 0.05). Furthermore, in both the duodenum and ileum, the groups receiving 2% and 4% SCP-H16 demonstrated a significant reduction in crypt depth and an increased villus height-to-crypt depth ratio relative to the CON group (p < 0.05). The 2% SCP-H16 group also showed significantly elevated mRNA expression levels of Occludin and zonula occludens-1 (ZO-1) in the duodenum compared to the CON group (p < 0.05). In the ileum, the 2% and 4% SCP-H16 groups exhibited significantly increased Occludin mRNA expression relative to the CON group (p < 0.05), with the 2% SCP-H16 group also showing a significant increase in zonula occludens-1 (ZO-1) mRNA expression (p < 0.05). In conclusion, dietary supplementation with 2% to 4% SCP-H16 is associated with enhanced antioxidant capacity, elevated humoral immunity, and improved intestinal morphology and barrier-related gene expression, suggesting that SCP-H16 can serve as a promising alternative protein source to soybean meal. Full article

Extreme ultramarathon running provides a unique human model for examining physiological responses under sustained metabolic stress. This study compared acute endocrine and lipid responses across 100, 308, and 622 km ultramarathon events, with particular attention to whether these responses were uniformly amplified with increasing race distance or differed according to event characteristics. Forty-four experienced male ultramarathon runners participated in the study (100 km group: n = 17; 308 km group: n = 18; 622 km group: n = 9). Venous blood samples were collected within 2 h before race start and generally within 5 min after race completion, and post-race biochemical concentrations were corrected for participant-specific plasma volume changes. Insulin and triglycerides decreased significantly across all three events, whereas T3 and HDL-C increased across all events. FSH and C-peptide decreased significantly in the 100 and 308 km groups, and FT4 increased significantly in these two groups. LH showed a significant time × event group interaction, with a significant reduction in the 100 km group and no significant within-group change in the 308 or 622 km groups. Because LH secretion is pulsatile and only one venous sample was obtained at each pre- and post-race time point, these findings should be interpreted as acute differences in circulating LH concentrations rather than evidence of altered gonadotropin regulation or hypothalamic–pituitary–gonadal axis suppression. Total cholesterol decreased significantly only after the 622 km event, whereas LDL-C decreased after the 308 and 622 km events. The observed endocrine and lipid response patterns differed across ultramarathon events characterized by distinct cumulative durations, pacing characteristics, nutritional exposure, hydration conditions, and recovery opportunities. Extreme ultramarathon running may therefore serve as a useful physiological model for investigating context-dependent endocrine and lipid responses to prolonged endurance stress. Full article

Background/Objectives: Maternal obesity is associated with an increased risk of adverse maternal and neonatal outcomes. This study evaluated whether participation in a multidisciplinary antenatal care pathway improved pregnancy outcomes compared with routine clinical practice in women with pre-pregnancy obesity. Methods: 711 women of reproductive age with preconception body mass index (BMI) ≥ 30 kg/m² were identified from medical records collected between 2010 and 2023: 233 women were managed according to the multidisciplinary clinical pathway (pathway group), and 478 served as historical controls, followed at the same unit before pathway implementation. Age, BMI, gestational diabetes frequency, weight gain during pregnancy, gestational hypertension, preeclampsia/eclampsia, time and mode of delivery, birthweight, macrosomia, large for gestational age, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress, fetal morbidity, and congenital anomalies were collected. Fasting plasma glucose, glycated hemoglobin, plasma glucose values under oral glucose tolerance test, plasma cholesterol and triglyceride levels were also evaluated. Results: The first evaluation occurred significantly earlier in the pathway group than in controls. Only about half of the women in the pathway group developed gestational diabetes mellitus (GDM) during pregnancy compared with 84% of controls (47% vs. 84%, p < 0.001), a difference partly explained by a referral bias in the control group, where women were referred after GDM screening rather than on the basis of obesity alone. As for maternal complications, the frequency of hypertension, eclampsia, and preeclampsia was similar in the two groups. As for fetal outcomes, pathway group women with respect to control showed a significantly lower frequency of preterm birth (5% vs. 11%, p = 0.0275), fetal morbidity (2% vs. 6%, p = 0.0377) and a tendency to lower frequency of macrosomia (7% vs. 12%, p = 0.0677), large for gestational age (19% vs. 26%, p = 0.116) and small for gestational age babies (5% vs. 7%, p = 0.50). Conclusions: This study shows that a multidisciplinary antenatal clinical approach was associated with a reduction in some adverse maternal–fetal outcomes related to pregnancy complicated by obesity, despite a less favorable baseline risk profile in the pathway group. Preconception counseling starting before pregnancy may represent an even more effective strategy, and efforts must be made in this direction. Full article

Cardiometabolic multimorbidity is highly prevalent among postmenopausal women and is associated with adverse metabolic outcomes and a greater burden of climacteric symptoms. This secondary analysis of a quasi-experimental controlled clinical trial investigated the effects of a 12-week aerobic training program on climacteric symptoms, menopause-related quality of life, body composition, and cardiometabolic biomarkers in postmenopausal women with and without cardiometabolic multimorbidity. Forty-one postmenopausal women (50–70 years) were allocated to a single-cardiometabolic-condition group (SINGLE, n = 18) or a multimorbidity group (MULTI, n = 23) and completed supervised walking/jogging aerobic exercise three times per week at 65–75% of heart rate reserve. Climacteric symptoms, quality of life, anthropometric measures, body composition, and biochemical markers were assessed before and after the intervention. Generalized Estimating Equations (GEEs) with Bonferroni post hoc adjustment were used to compare group, time and group*time interactions with alpha of 5%. Significant group-by-time interactions were observed for the Menopause Rating Scale total score and psychological symptoms, as well as for the Cervantes Scale total score, indicating greater improvements among women with multimorbidity. The MULTI group demonstrated significant reductions in overall menopausal symptoms, psychological symptoms, and menopause-related quality of life scores following training. Body weight, triglycerides, and very-low-density lipoprotein cholesterol also decreased significantly only in the MULTI group, whereas several body composition parameters improved over time regardless of cardiometabolic burden. These findings indicate that aerobic training may be associated with improvements in menopausal symptoms, quality of life, body composition, and selected cardiometabolic markers in postmenopausal women, with some outcomes showing greater changes among women with cardiometabolic multimorbidity. Full article

Lipoprotein(a) [Lp(a)] is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS), with plasma levels largely genetically determined and minimally influenced by lifestyle. Contemporary dyslipidemia guidelines now recommend at least one lifetime measurement and increasingly incorporate Lp(a) into personalized cardiovascular risk evaluation. Recent guideline updates integrate traditional risk estimation with risk-enhancing factors and coronary artery calcium (CAC) imaging. The 2026 U.S. multi-society guideline classifies Lp(a) ≥ 125 nmol/L as a risk-enhancing factor and ≥250 nmol/L as a major risk enhancer. The PREVENT equations provide baseline risk estimation, personalized by Lp(a) and refined through CAC-based reclassification when treatment decisions remain uncertain. Despite its established role in risk assessment, current management remains indirect and emphasizes aggressive control of modifiable risk factors, particularly low-density lipoprotein cholesterol (LDL-C). Emerging Lp(a)-targeted therapies, including antisense oligonucleotides, small interfering RNA agents, and oral small-molecule inhibitors, have shown substantial and sustained reductions in Lp(a) levels, although definitive evidence of cardiovascular benefit is still pending. This review provides a practical, evidence-based synthesis of Lp(a) biology, contemporary guideline recommendations, integrated risk stratification using PREVENT and CAC, current management, and emerging Lp(a)-targeted therapies for use across primary care and cardiology practice. Full article

Background: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive option for weight reduction, but its effect on metabolic syndrome (MetS) and metabolic dysfunction-associated steatotic liver disease (MASLD) is less well characterized. Methods: Following PRISMA, we searched five databases to November 2025 (PROSPERO CRD420261283041) for adults with obesity undergoing ESG with ≥6-month follow-up. Continuous outcomes were pooled as mean differences (MDs) using DerSimonian–Laird random-effects models with Hartung–Knapp–Sidik–Jonkman sensitivity analysis. As MetS resolution was inconsistently defined, the primary outcome was post hoc operationalised as change in individual MetS components. Results: Of 858 records, 12 studies (4452 patients; two randomised) were included. At 12 months, ESG was associated with lower glycated haemoglobin (MD −0.33%), HOMA-IR (MD −3.52), triglycerides (MD −25.56 mg/dL), low-density lipoprotein cholesterol (MD −6.94 mg/dL), alanine aminotransferase, and non-invasive steatosis/fibrosis indices; aspartate aminotransferase did not change significantly. Total body weight loss was 16.54% at 12 months and 14.21% at 36 months. Liver stiffness (two studies, differing windows) is described narratively, not pooled. Heterogeneity was often substantial; certainty was low to very low. Conclusions: ESG was associated with metabolic and hepatic improvements alongside substantial weight loss; a weight-independent hepatic effect cannot be established, and randomised trials with histological endpoints are needed. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatic steatosis, inflammation, fibrosis, and metabolic dysfunction, with limited therapeutic options currently available. This study investigated whether pharmacological inhibition of Galectin-3 (Gal-3), a β-galactoside-binding lectin implicated in inflammation and fibrosis, using modified citrus pectin (MCP), attenuates established MASH in ApoE-deficient mice. Mice were assigned to four groups: standard chow (CTL), standard chow plus MCP (CTL + MCP), Western diet with fructose-enriched drinking water (WD), and WD plus MCP (WD + MCP). MCP (1% in drinking water) was administered during the final four weeks of the 11-week experimental protocol, after the establishment of metabolic dysfunction and hepatic steatosis. Compared with untreated WD mice, WD + MCP mice exhibited improved glucose tolerance, as evidenced by a 22.9% reduction in glucose area under the curve (p = 0.01), and enhanced hepatic insulin signaling, reflected by a 254.1% increase in insulin-stimulated AKT2 phosphorylation (p = 0.0002). MCP treatment also reduced hepatic lipid accumulation (39.8%, p = 0.0055) and hepatic triglyceride content (26.1%, p = 0.0003), accompanied by reductions in circulating triglyceride and cholesterol concentrations. Furthermore, WD + MCP mice exhibited reduced hepatic Gal-3 expression (25.8%, p = 0.0199), decreased F4/80 immunoreactivity (49.2%, p = 0.0061), attenuated JNK phosphorylation (46.6%, p = 0.0118), reduced collagen deposition (47.0%, p = 0.0002), and lower plasma ALT (52.9%, p = 0.0009) and AST (48.8%, p = 0.04) activities. Collectively, these findings demonstrate that MCP attenuates multiple metabolic, inflammatory, fibrotic, and hepatic injury features of established Western diet-induced MASH, supporting Gal-3 as a promising therapeutic target and MCP as a potential pharmacological strategy for MASH. Full article

Background and Clinical Significance: People with HIV (PWH) experience an elevated risk of atherosclerotic cardiovascular disease (ASCVD), driven by chronic immune activation, metabolic toxicities of antiretroviral therapy (ART), and traditional risk factors. Achieving target low-density lipoprotein cholesterol (LDL-C) levels is frequently impeded by adherence barriers, pharmacokinetic drug interactions, or muscle-related symptoms. Inclisiran is a hepatocyte-targeted small interfering RNA that halts proprotein convertase subtilisin/kexin type 9 synthesis, providing a long-acting therapeutic alternative. Case Presentation: We present two PWH with severe hypercholesterolemia and elevated cardiovascular risk on stable ART. Case 1 describes a 54-year-old male with a history of myocardial infarction presenting with persistent, refractory hypercholesterolemia on rosuvastatin and ezetimibe (baseline LDL-C 142 mg/dL). Case 2 describes a 58-year-old male with verified statin intolerance and inadequate response to ezetimibe (baseline LDL-C 194 mg/dL). Following subcutaneous inclisiran administration at Day 1 and Day 90, Case 1 achieved an 80.2% LDL-C reduction to 28 mg/dL at Month 6, and Case 2 achieved a 54.6% reduction to 88 mg/dL at Month 6 as monotherapy. Both patients tolerated therapy well, with stable CD4+ counts and sustained virological suppression. Conclusions: These cases illustrate that inclisiran can effectively lower LDL-C levels across primary and secondary prevention settings in PWH facing oral therapy limitations or statin intolerance. Provider-administered dosing every 6 months overcomes adherence challenges, supporting the inclusion of PWH in broader clinical pathways pending ongoing cardiovascular outcome trials. Full article