Search Results (1,241)

Background/Objectives: Cervicodorsal lipodystrophy, commonly referred to as “buffalo hump,” has traditionally been associated with Human Immunodeficiency Virus (HIV)-related antiretroviral therapy. However, similar deformities may also occur independently of HIV treatment. This study aimed to investigate non HIV-associated buffalo hump as a potential clinical marker of underlying metabolic or endocrine disorders. Methods: We retrospectively reviewed 12 HIV-negative patients who presented with cervicodorsal lipodystrophy between 2012 and 2022. Patient demographics, laboratory values, and imaging findings were analyzed. All patients underwent surgical resection of a hypertrophic fat pad. Exploratory statistical analyses were performed using Mann–Whitney U and Fisher’s exact tests and Spearman’s correlation analysis. Results: These 12 patients had a mean age of 56.92 ± 16.69 years and a mean Body Mass Index (BMI) of 30.15 ± 4.59 kg/m². Hypertension and diabetes were each present in 66.7% of patients, and hyperlipidemia in 75%. Three patients were newly diagnosed with metabolic disease. No significant differences were found between newly diagnosed and previously diagnosed patients in age (45.67 ± 21.46 vs. 60.67 ± 14.31 years, p = 0.194) or BMI (32.44 ± 2.39 vs. 29.39 ± 4.99 kg/m², p = 0.145). Group differences in hypertension, diabetes, hyperlipidemia, or liver dysfunction were also not significant (all p > 0.49). No correlation was observed between age and BMI (ρ = −0.158, p = 0.624). Conclusions: Although the small sample size precludes definitive conclusions, the prevalence of obesity, hypertension, and diabetes in this cohort was notably higher than reported in Korean population-based surveys. These findings suggest that non HIV-associated buffalo hump may serve as an externally visible marker of systemic metabolic burden. Metabolic screening should be considered even in the absence of overt systemic disease. Full article

Nephrotic syndrome (NS) is a complex kidney disorder characterized by profound proteinuria, hypoalbuminemia, hyperlipidemia, and edema, significantly impacting patients’ quality of life. While corticosteroids and calcineurin inhibitors (CNIs) have traditionally been the primary treatments, B cell-targeted therapies, especially the anti-CD20 monoclonal antibody rituximab, have transformed the management of steroid-dependent and multidrug-resistant NS (MRNS). Rituximab has demonstrated efficacy in reducing relapse rates and steroid dependence by depleting CD20+ B cells, which play a pivotal role in autoantibody production and immune dysregulation. However, limitations such as incomplete B cell depletion, immunogenicity leading to anti-rituximab antibodies, and variable efficacy in refractory cases have led to the development of next-generation therapies. This review critically examines recent advances in B cell-targeted therapies for NS, with a particular focus on overcoming the limitations of conventional rituximab treatment. This review systematically analyzes next-generation anti-CD20 monoclonal antibodies, CD38-targeted therapies, and emerging CAR-T cell approaches, evaluating their distinct mechanisms of action and clinical trial outcomes. The analysis extends to innovative combination strategies and biomarker-guided treatment algorithms for refractory cases. By synthesizing preclinical data with clinical evidence, this work provides a framework for optimizing therapeutic decision-making in NS, while identifying key knowledge gaps that warrant future investigation. Collaborative research and translational studies are essential for advancing precision medicine in NS, ensuring that new therapies provide lasting clinical benefits for patients. The evolving field of anti-B cell therapies marks a new era in managing refractory NS, offering hope for better long-term prognoses. Full article

Background: Lipid disturbance is a hallmark of cardiometabolic abnormalities and a primary contributor to cardiovascular disease risk. Immunometabolic markers show promise for better risk classification. This study evaluated the uric acid to Platelet ratio (UAPR) as lipid abnormality marker in a broad cohort of Saudi adults. Methods: Data from 7781 adults in the Elta Medical Laboratory database were analysed. Subjects were stratified by lipid status, and UAPR levels were analyzed. Additionally, lipid abnormality distribution across UAPR tertiles and risk profiles, including ROC analysis, were evaluated. Results: UAPR were markedly increased in patients with abnormal lipid profiles while high UAPR (H-UAPR) subjects showed multiple dyslipidemic patterns including elevated levels of triglycerides (TG), low-density lipoprotein (LDL-C), non-high-density lipoprotein (non-HDL-C), and remnant cholesterol (RC), alongside reduced HDL-C levels. Notably, UAPR correlated with all lipid parameters, most strongly and inversely with HDL-C (r = −0.314) and remained independently associated with TG and HDL-C in multivariable regression. Consistently, H-UAPR was common across all dyslipidemic forms, especially low HDL-C, nearly twice as frequent as in N-UAPR (52.4% vs. 35.0%). The odds were specifically increased for low HDL-C (OR = 2.02, p < 0.0001) and a high TC/HDL-C ratio (OR = 2.94, p < 0.0001) in H-UAPR patients. ROC analysis demonstrated that UAPR had moderate yet significant diagnostic performance, particularly for identifying high TC/HDL-C (AUC = 0.671, p < 0.001) and HDL-C (AUC = 0.618, p < 0.001). Conclusions: UAPR shows considerable promise as an immunometabolic marker linked to various dyslipidemic forms with potential for hyperlipidemia screening and stratification, warranting further validation. Full article

Aortic stenosis (AS) and atherosclerosis are progressive cardiovascular conditions that frequently coexist and share multiple clinical and molecular features. Medical therapies have shown effectiveness in preventing and treating atherosclerosis and its consequences. For AS, effective pharmacological therapies remain limited. Understanding the shared risk factors and mechanisms between the two conditions may provide opportunities for therapeutic repositioning in AS. We performed a narrative review focusing on studies published from 2005 to 2025. Inclusion criteria encompassed clinical trials, experimental models, and molecular studies addressing overlapping risk factors, pathological pathways, and treatment approaches for AS and atherosclerosis. AS and atherosclerosis share key risk factors, including age, hypertension, hyperlipidemia, and diabetes. Molecular mechanisms, such as chronic inflammation, endothelial dysfunction, oxidative stress, lipid accumulation, and calcific remodeling, are common to both. Pathways involving the renin-angiotensin system, Notch signaling, and osteogenic mediators contribute to disease progression. Several drug classes, notably proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipoprotein(a) (Lp(a)) lowering therapies, anti-inflammatory agents, and immunomodulators, show potential for repositioning in AS management. The substantial overlap in risk factors and molecular mechanisms between AS and atherosclerosis supports a rationale for therapeutic repositioning. Targeting shared pathways could lead to innovative strategies for slowing AS progression and improving patient outcomes. Full article

Background and Clinical Significance: Ischemic optic neuropathies (IONs) are significant causes of vision loss resulting from compromised blood flow to the optic nerve. Diabetes mellitus (DM) exacerbates the risk of IONs through chronic hyperglycemia and associated vascular dysfunction. Recently, semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been linked to ocular complications, including non-arteritic anterior ischemic optic neuropathy (NAION), potentially due to the rapid glycemic changes or vascular effects. Case Presentation: A 55-year-old female with type 2 DM, hypertension, and hyperlipidemia presented with blurred vision and optic disc edema after four months of semaglutide therapy (Ozempic^®, Sydney, Australia). Initially diagnosed with diabetic papillopathy (DP), her condition progressed to NAION, leading to partial visual recovery with corticosteroid treatment and improved glycemic management. Diagnostic evaluations, including visual field testing, optical coherence tomography, and fluorescein angiography, supported the diagnosis. Conclusions: This case report describes the clinical course of a diabetic patient treated with a semaglutide who developed an ischemic optic event. The timing of symptom onset in relation to the initiation of semaglutide therapy raises the possibility of a causal association between the drug and this rare ocular complication. Close monitoring of ocular health is crucial for patients on GLP-1 receptor agonists, particularly those with pre-existing vascular risk factors. Further research is needed to elucidate the underlying mechanisms and guide clinical practice. Full article

Background/Objectives: Overnutrition increases comorbidities such as gestational diabetes during pregnancy that can have detrimental consequences for both parent and progeny. We previously reported that high-fat (HF) diet and late-gestation diabetes (DM) incite mitochondrial dysfunction, oxidative stress, and cardiometabolic disease in first generation (F1) rat offspring, partially through epigenomic and transcriptomic programming. Primordial germ cells, which become the second generation (F2), are also exposed, which could incite generational risk. This study aimed to determine whether the F2 transcriptome already has genomic variation at the preimplantation embryo stage, and whether variations normalize, persist or compound in the third generation (F3). Methods: F0 female rats were fed a control or HF diet, then DM was induced in HF-fed dams on gestational day (GD)14, exposing F1 offspring and F2 primordial germ cells to hyperlipidemia, hyperglycemia and fetal hyperinsulinemia during the last third of pregnancy. F1 pups were reared by healthy dams and bred to produce F2 embryos (F2e) and F2 pups. F2 offspring were bred to produce F3 embryos (F3e). Embryos were assessed by a novel grading method, live cell imaging, and single-cell RNA sequencing. Results: Embryo grades were not different, but HF+DM F2e had more cells while F3e had fewer cells and overall fewer embryos. HF+DM F2e had similar mitochondria quantity but a downregulation of genes involved in lipid metabolism and more oxidative stress, consistent with mitochondrial dysfunction. They also had an upregulation of chromatin-remodeling genes. The predicted developmental effect is accelerated embryo aging and epigenetic drift. In contrast, HF+DM F3e had an adaptive stress response leading to increased mitochondria quantity and an upregulation of genes involved in mitochondrial respiration, metabolism, and genomic repair that led to a predicted developmental effect of delayed embryo maturation. Conclusions: Although pathways vary, both generations have metabolically linked differentially expressed genes that influence cell fate and developmental pathways. In conclusion, HF+DM pregnancy can program the early embryonic transcriptome for three generations, despite an intergenerational healthy diet. Full article

Background: The aim of this study was to explore the intention of Jordanian patients diagnosed with hyperlipidemia to engage in physical activity. This objective was achieved via an in-depth analysis of how patient attitudes, subjective norms, and perceived behavioral control can influence patient intentions to exercise. Additionally, this research examined how sociodemographic factors and perceived barriers can impact patient participation in physical activity. Methodology: This study employed a cross-sectional approach on a convenience sample of Jordanian patients diagnosed with hyperlipidemia. To gain the required data, a 15-item questionnaire (derived from the Theory of Planned Behavior) was presented to the participants in the form of an online survey (via several platforms, including WhatsApp, Facebook, and email). Results: The results indicate that perceived behavioral control had a significant correlation with the participants’ intentions to participate in physical activity. Additionally, the findings revealed that there were no significant correlations between demographic features (age, marital status, level of education, and monthly income) and intention to engage in physical activity. However, the results ascertained the existence of several facilitators to exercise (such as financial resource availability, self-interest, beneficial weather conditions, and supportive friends or exercise partners). The most commonly reported barriers to physical activity included time constraints, work commitments, and limitations imposed by existing health conditions. Conclusions: These findings provide valuable insights that can be employed to develop physical activity programs that address the cultural needs of Jordanian patients diagnosed with hyperlipidemia and enhance their levels of physical activity. Full article

This paper reports the first case in which a hyperlipidemic retriever (due to hypothyroidism) with a nasal tumor was successfully treated—achieving partial remission—and managed using a metronomic combination of chlorambucil (3.74 mg/m², SID) and prednisolone (0.28 mg/kg, SID) orally for 9 months at a general practice. A 35 kg spayed female golden retriever aged 8 years and 8 months with nosebleeds visited the Bundang New York Animal Hospital in July 2023 after being diagnosed with nasal carcinoma. A protocol of 4 weeks of chemotherapy followed by 1 week of rest was repeated in two cycles and continued metronomically for 9 months without pause after the two cycles. The nasal exudate was significantly reduced. The size of the nasal tumor was monitored using computed tomography (CT) imaging at a referral hospital. Since the first occurrence of epistaxis, 18 months have passed (as of January 2025) and the nasal exudate is barely visible, and the vital signs and weight of the dog remain stable. The size of the nasal tumor significantly decreased after 9 months of chemotherapy completion without moderate side effects, and all the blood work was normalized, including hypercholesteremia. This study demonstrates that, in hyperlipidemic cancer patients, a prednisolone/chlorambucil metronomic combination which is cost-effective can be an alternative to tyrosine kinase inhibitors such as sorafenib, even when excluding the price. Through a literature review, the author also investigates the effect of the hyperlipidemic state on cancer, focusing on carcinoma and vascular endothelial growth factor (VEGF), as well as the RAS-RAF-MEK pathway, which is a target for tyrosine kinase inhibitors, in order to reveal the molecular mechanism of chlorambucil metronomic chemotherapy. Also, the author investigates the molecular pathway of carcinoma development in human hyperlipidemia patients through single-cell RNA sequence analysis using open public data, and discusses the molecular action of chlorambucil. Full article

Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate the effects of cumin and fennel EO nanocapsules in a mouse model of depression caused by a high-fat diet (HFD) and chronic mild stress (CMS) using both in silico and in vivo studies. The cumin and fennel EOs were extracted, analyzed by GC-MS, and encapsulated in nano-form using gum Arabic and maltodextrin as wall materials. The freeze-dried nanocapsules were evaluated in HFD/CMS-treated mice. Molecular docking was used to examine the significance of the oils’ compounds in blocking the active sites of hydroxymethylglutaryl-CoA (HMG-CoA) and indoleamine 2,3-dioxygenase (IDO). According to the molecular docking results, the interactions between EO components and HMG-CoA or IDO indicate that these EOs may have hypercholesterolemic and antidepressive effects. Cumin and fennel EO nanocapsules showed hypolipidemic, antioxidant, and anti-inflammatory effects in vivo. This was demonstrated by the down-regulation of oxidants (ROS, MDA, and NO) and inflammatory markers (TLR4, TNF-α, and IL-6) in the brain, changes in lipid profile parameters, and the up-regulation of antioxidant enzymes (SOD, CAT, and GSH). The in silico and in vivo outputs revealed the potential preventive impact of cumin and fennel EO nanocapsules against depression-like states in the mouse model through the prevention of dyslipidemia, neuroxidation, and neuroinflammation. More human studies are needed to fully understand the antidepressive effects of cumin and fennel EO nanocapsules. Full article

Background: Nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia is a prevalent metabolic disorder, often triggered by high-fat diets (HFDs) in animal models. Amaranthus graecizans L. (AGs), rich in bioactive compounds, offers potential antioxidant and lipid-lowering benefits, making it a candidate for natural liver protection. This study evaluated the protective role of Amaranthus graecizans L. against hyperlipidemia-induced NAFLD in rats. Methods: Thirty male Wistar rats (150 ± 20 g, 10 weeks old) were split into five groups (n = 6 each). A control group received 0.25 mL 0.1% DMSO orally. Four HFD-fed groups included one with only DMSO (0.25 mL) and three supplemented with AG solution (0.25 mL) at 100, 200, or 500 mg/kg body weight. Treatments were given daily via gavage for two months. AGs’ nutritional profile, serum lipids, liver function, and liver histology were analyzed. Results: AGs contain 21.3% protein, 1.1% fat, 15% fiber, moderate vitamins (ascorbic acid, B-complex), and minerals (high potassium, calcium; low magnesium, phosphorus, sodium). AG-treated rats weighed less than the HFD controls. Unlike the control group (normal lipids, liver function, no steatosis), the HFD rats showed severe hyperlipidemia, liver dysfunction, and steatosis with fat changes. The AG groups exhibited dose-dependent improvements in lipids and liver function; the 200 mg/kg group had reduced fatty changes, and the 500 mg/kg group showed minimal hepatocyte fat. Conclusions: Amaranthus graecizans L. reduces hyperlipidemia and NAFLD progression in HFD-fed rats, which suggests its potential as a natural liver-protective agent. Full article

Background: Premature atherosclerosis (PreAS) is generally defined as a disease affecting those under the age of 50 and has an outsized impact on quality-adjusted life years. We sought to better understand what individuals are at the highest risk for PreAS by examining differences in demographics and comorbidities compared to traditional atherosclerosis (TradAS). Study Design: An Institutional Review Board (IRB) approved retrospective study was conducted using retrospective data from a large regional health system. Patients who received a diagnosis of cerebrovascular disease (CeVD), coronary artery disease (CAD) or peripheral arterial disease (PAD) between 2012 and 2023 were included. Results: The review identified 136,328 patients in which 17,008 or 13% presented with PreAS (diagnosed from age 18 up to, and including, age 50). Rates of comorbidities were as follows (PreAs/TradAS): hypertension 63%/86%, diabetes 29%/35%. hyperlipidemia 45%/67%, chronic kidney disease 15%/26%, tobacco use 52%/60% and substance use 25%/9%. Differences in race, ethnicity and gender were as follows (PreAS/TradAS): White 59%/80%, Black 22%/10% and Latinx 17%/6%; male 51%/55%, and female 49%/45%. Conclusions: Patients with PreAS had lower rates of diseases that typically progress with aging, including hypertension, hyperlipidemia, chronic kidney disease, and diabetes. Tobacco use was less prevalent in the PreAS group and there was a significantly higher rate of illicit substance use in the PreAS population. Race and ethnicity were notably different with Black and Hispanic patients representing a significantly larger proportion of those with PreAS relative to TradAS. Our findings suggest risk factors beyond those classically described may play key roles in causing patients to develop PreAS. Full article

Metabolic diseases such as high blood lipids, high blood sugar, and disrupted gut microbiota pose a serious threat to people’s physical health. The occurrence of these diseases is closely related to the lack of nutrients in daily rice staple foods, but there is a lack of comprehensive analysis of the underlying mechanisms. This study used fully nutritious brown rice as raw material, and after germination under various stress conditions, it significantly increased the levels of gamma aminobutyric acid (GABA, four carbon non protein amino acid), resistant starch, flavonoids, and other components that regulate metabolic diseases. Using rats as experimental subjects, a model of hyperlipidemia and hyperglycemia was constructed, with rice consumption as the control. The experimental period was 8 weeks. Research has found that feeding sprouted brown rice can significantly improve the accumulation of white fat in the liver caused by a high-fat diet, significantly reduce TC, TG, LDL-C, apoB, HL, LPL, and LCAT, significantly increase HDL-C and apoA1, and significantly reduce the levels of inflammatory factors IL-6 and TNF-α. Therefore, consuming sprouted brown rice can reduce the risk of hyperlipidemia, inflammation, and tumor occurrence by promoting fat breakdown, and can also increase the abundance of metabolic-promoting microorganisms (especially Euryarchaeota and Lactobacillus) in the intestine, improving the entire metabolic ecological network of rats. Full article

Dementia with Lewy bodies (DLB), the second common primary degenerative neurocognitive disorder after Alzheimer disease (AD), frequently presents concurrent co-pathologies that impact clinical presentation and progression. Neuropathological studies have demonstrated a high prevalence of coexistent AD-related neuropathological changes (ADNC), TAR DNA-binding protein 43 (TDP-43) proteinopathies, and cardiac and aging-related disorders, while frontotemporal lobar degeneration (FTLD) and tau-related syndromes play a minor role as DLB-related co-pathologies. Cerebrovascular lesions, including cerebral amyloid angiopathy, are the most prevalent non-neurodegenerative co-pathologies. Cardiovascular disorders, hypertension, and hyperlipidemia are also frequent comorbidities. Due to their high prevalence and clinical impact on DLB patients, clinical trials should account for these and other co-pathologies in their design and selection. Evaluation of these co-pathologies using and interpreting biomarkers may allow greater clinical diagnostic accuracy and the opportunity to better predict clinical progression. Therefore, there is an increasing need for biomarkers in dementia research. This review discusses the kind and frequency of the different co-pathologies in DLB and their clinical impact. It evaluates the possible value of disease-specific biomarkers and how they are helpful in the assessment and prevention of DLB and its co-pathologies. Full article

Triple-negative breast cancer (TNBC) is a highly aggressive and therapeutically challenging subtype of breast cancer due to its lack of estrogen receptors, progesterone receptors, and HER2 (Human epidermal growth factor receptor 2) expression, which severely limits available treatment options. Recently, Simvastatin—a widely used HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor for hyperlipidemia—has garnered interest for its potential anticancer effects. This study investigates the therapeutic potential of Simvastatin in triple-negative breast cancer (TNBC). The results demonstrate that Simvastatin significantly inhibits the proliferation of TNBC cells, particularly MDA-MB-231, in a dose- and time-dependent manner. Mechanistically, Simvastatin primarily induces G1 phase cell cycle arrest to exert its antiproliferative effects, with no significant evidence of apoptosis or necrosis. These findings support the potential repositioning of Simvastatin as a therapeutic agent to suppress TNBC cell growth. Further analysis shows that Simvastatin downregulates cyclin-dependent kinase 4 (CDK4), a key regulator of the G1/S cell cycle transition and a known marker of poor prognosis in breast cancer. These findings highlight a novel, apoptosis-independent mechanism of Simvastatin’s anticancer action in TNBC. Importantly, given that many breast cancer patients also suffer from hyperlipidemia, Simvastatin offers dual therapeutic benefits—managing both lipid metabolism and tumor cell proliferation. Thus, Simvastatin holds promise as an adjunctive therapy in the treatment of TNBC and warrants further clinical investigation. Full article

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article