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14 pages, 4197 KB  
Article
The Effect of Renal Artery Stent Implantation on Clinical Outcomes in Patients with Early-Stage (Non-Atrophic Kidney) and Clinically Overt Severe Atherosclerotic Renal Artery Stenosis (ARAS-TR)
by Mehmet Kış, Fatih Levent, Mehmet Altunova, Sadık Volkan Emren, Mustafa Doğduş, Beytullah Çakal, Oktay Şenöz, Tuncay Güzel, Çisem Oktay, Ömer Faruk Kahraman, Sezgin Atmaca, Yunus Emre Erata, Tumarzat Ulanbekova and Mehmet Birhan Yılmaz
J. Clin. Med. 2026, 15(10), 3825; https://doi.org/10.3390/jcm15103825 - 15 May 2026
Abstract
Objective: Atherosclerotic renal artery stenosis (ARAS) is increasingly prevalent among aging populations and in patients with diabetes, hyperlipidemia, aortoiliac obstructive disease, coronary artery disease, and/or hypertension. Patients with severe ARAS are at a substantially elevated risk of cardiovascular disease, recurrent congestive heart failure, [...] Read more.
Objective: Atherosclerotic renal artery stenosis (ARAS) is increasingly prevalent among aging populations and in patients with diabetes, hyperlipidemia, aortoiliac obstructive disease, coronary artery disease, and/or hypertension. Patients with severe ARAS are at a substantially elevated risk of cardiovascular disease, recurrent congestive heart failure, stroke, ischemic nephropathy, and chronic kidney disease. Therefore, the ARAS-TR study aims to evaluate the effect of renal artery stenting on the clinical outcomes in patients with severe ARAS and renovascular hypertension. Materials: This study was conducted as a multicenter, prospective study between July 2024 and September 2025. It encompassed 278 patients with angiographically confirmed severe ARAS who underwent renal artery stent implantation. Patients were subsequently monitored for 6 months. A paired-samples t-test was used to compare continuous variables pre- and post-intervention, while categorical variables were analyzed using the Pearson chi-square test and Fisher’s exact test. Results: The mean age of the patients was 63.6 [±13.4] years, and the male gender ratio was 52.5%. After renal artery stenting, systolic and diastolic blood pressures decreased significantly at the 6-month follow-up compared with the pre-procedure levels (SBP 166.99 [21.24] vs. 135.40 [15.69], p < 0.001; DBP 96.28 [13.03] vs. 80.39 [11.03], p < 0.001, respectively). GFR (61.23 [28.33] vs. 63.35 [26.36], p = 0.029) and creatinine (1.40 [0.93] vs. 1.29 [0.66], p = 0.004) levels improved compared to baseline. The mean number of antihypertensive drugs required for patients to remain normotensive decreased significantly (3.19 [1.04] vs. 2.48 [1.13], p < 0.001) during the follow-up period. Conclusions: Percutaneous renal artery intervention appears to be a promising and safe strategy for carefully selected high-risk patients presenting with severe ARAS, renovascular hypertension, and non-atrophic kidneys. In this specific clinical context, restoring renal artery patency through percutaneous stenting was associated with improved renal function and observed reduction in the burden of antihypertensive drugs required to sustain normotension. Full article
(This article belongs to the Section Cardiovascular Medicine)
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17 pages, 998 KB  
Article
Self-Reported Habitual Daily Physical Activity as an Independent Predictor of Coronary Artery Disease Extension in Patients with Myocardial Infarction: A Prospective Observational Study
by Corina Cinezan and Maria Luiza Hiceag
J. Clin. Med. 2026, 15(10), 3814; https://doi.org/10.3390/jcm15103814 - 15 May 2026
Abstract
Background: The extent of coronary artery disease (CAD) is a major determinant of prognosis in patients with myocardial infarction (MI). While structured exercise is known to be cardioprotective, the association between habitual daily physical activity and angiographic CAD extension remains insufficiently characterized. [...] Read more.
Background: The extent of coronary artery disease (CAD) is a major determinant of prognosis in patients with myocardial infarction (MI). While structured exercise is known to be cardioprotective, the association between habitual daily physical activity and angiographic CAD extension remains insufficiently characterized. Methods: In this prospective observational study, 269 patients were hospitalized with acute MI underwent coronary angiography. Habitual daily physical activity during the four weeks preceding admission was assessed using 10-point self-reported daily preadmission effort questions to help the patients to report a final effort score. CAD extension was classified as single-, double- or triple-vessel disease. Differences in daily effort across CAD categories were evaluated using the Kruskal–Wallis test. Independent predictors of CAD extension were identified using ordinal logistic regression adjusted for age, sex, smoking, hypertension, diabetes mellitus, hyperlipidemia and body mass index. Results: Daily preadmission effort decreased progressively with increasing CAD severity (mean scores: 7.44 in single-vessel, 4.93 in double-vessel and 3.69 in triple-vessel disease; p < 0.0001). In multivariable ordinal logistic regression analysis, older age, hypertension, diabetes mellitus and hyperlipidemia were independently associated with greater CAD extension. Higher daily preadmission effort was strongly and independently associated with lower CAD severity; each one-point increase in effort score was associated with a 46% reduction in the odds of more extensive CAD (odds ratio 0.54, 95% confidence interval 0.45–0.64; p < 0.0001). Conclusions: Greater habitual daily physical activity prior to myocardial infarction is independently associated with less extensive coronary artery disease. Assessment of daily preadmission effort may provide clinically useful information regarding coronary disease burden and highlights the potential importance of everyday physical activity in cardiovascular prevention. These findings should be interpreted with caution given the use of a non-validated, self-reported measure of physical activity and the observational study design. Full article
(This article belongs to the Special Issue Acute Myocardial Infarction: Diagnosis, Treatment, and Rehabilitation)
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18 pages, 794 KB  
Article
Incidence and Risk Factors of Diabetic Retinopathy in Patients with Type 1 Diabetes Mellitus: A Retrospective Study in NGHA, Riyadh, Saudi Arabia
by Inam Ul-Haq, Hassan S. Alqahtani, Naila A. Shaheen, Meshal S. Alghamdi, Sultan A. Aldosari, Abdulrahman S. Altowaim, Naif H. Alqadhy, Abdulaziz M. Alqahtani, Mohammed Bukhaytan, Muhammad Imran Khan and Maliha Rani
J. Clin. Med. 2026, 15(10), 3811; https://doi.org/10.3390/jcm15103811 - 15 May 2026
Abstract
Background/Objectives: Diabetic retinopathy (DR) is a major microvascular complication of type 1 diabetes mellitus (T1DM) and remains an important cause of preventable visual impairment. Region-specific data on the incidence and clinical predictors of DR among patients with T1DM in Saudi Arabia remain limited. [...] Read more.
Background/Objectives: Diabetic retinopathy (DR) is a major microvascular complication of type 1 diabetes mellitus (T1DM) and remains an important cause of preventable visual impairment. Region-specific data on the incidence and clinical predictors of DR among patients with T1DM in Saudi Arabia remain limited. This study aimed to determine the incidence of DR and identify associated demographic and systemic risk factors among patients with T1DM at a tertiary care center in Riyadh, Saudi Arabia. Methods: This retrospective cohort study included 449 patients with T1DM aged ≥9 years who were followed at King Abdulaziz Medical City, Riyadh, between 2015 and 2025. Patients were selected using a consecutive non-probability sampling technique. Data were extracted from the BESTCare 2.0A electronic medical record system and supplemented, when required, by phone-based interviews to verify selected clinical and demographic variables. Patients were classified as controls without DR or cases with DR, including non-vision-threatening DR and vision-threatening DR (VTDR), according to the International Clinical Diabetic Retinopathy Severity Scale. Multivariable logistic regression, Cox proportional hazards models, and temporal trend analysis were performed, with statistical significance set at p < 0.05. Results: The overall incidence rate of DR was 92.66 per 1000 person-years, with similar rates among males and females. In multivariable logistic regression, older age at T1DM diagnosis, longer diabetes duration, hypertension, hyperlipidemia, and albuminuria were independently associated with DR. Mean HbA1c and HbA1c variability were not independently associated with DR after adjustment. In Cox regression, older age at T1DM diagnosis was associated with higher hazards of both DR and VTDR, while hypertension was associated with VTDR. Among patients with DR, younger age at T1DM diagnosis was associated with higher odds of proliferative disease in exploratory severity analysis. Conclusions: DR was common among patients with T1DM in this tertiary-care cohort and was mainly associated with disease duration, age at diagnosis, and systemic vascular comorbidities. These findings support the importance of routine ophthalmologic screening and integrated management of systemic risk factors in patients with T1DM. Full article
(This article belongs to the Special Issue Diabetic Retinopathy Screening: Current Advances and Future Options)
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13 pages, 909 KB  
Article
Neurodegenerative and Glial Physiology in Diabetic Retinopathy: Dissociated Effects of Forskolin on Neuronal Survival and Glial Activation
by Hesham Saad Ata, Nessren M. Abd el-Rady, Asmaa M. S. Gomaa, Ahmed F. Omar, Ahmed Abdou, Maha Ali, Shimaa E. Soliman, Nada M. Fathy, Marwa H. Bakr, Dalia A. Elgamal, Manal M. Sayed, Eman Radwan and Amel Ahmed
Biomedicines 2026, 14(5), 1104; https://doi.org/10.3390/biomedicines14051104 - 13 May 2026
Abstract
Background/Objectives: Using a well-established model of streptozotocin-induced diabetic retinopathy (DR), this study sought to evaluate the neuroprotective effect of intravitreal Forskolin (FSK) on retinal ganglion cell survival and glial activation and explore the association of circulating miR-200b with metabolic and oxidative stress [...] Read more.
Background/Objectives: Using a well-established model of streptozotocin-induced diabetic retinopathy (DR), this study sought to evaluate the neuroprotective effect of intravitreal Forskolin (FSK) on retinal ganglion cell survival and glial activation and explore the association of circulating miR-200b with metabolic and oxidative stress in DR. Methods: A total of 18 male Wistar rats were divided into a control group (n = 6) and a streptozotocin-induced diabetic group (n = 12), which were further divided into diabetic control and FSK-treated groups (n = 6 each). Total antioxidant capacity (TAC), total peroxide (TP), triglycerides (TGs), total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured. qRT-PCR analysis for miRNA-200b and immunohistochemistry were performed. Results: Diabetic rats showed oxidative stress and hyperlipidemia associated with increased circulating miR-200b levels. The retina showed reduced neuron numbers (Caspase-3), altered glial and astrocyte staining (IBA1, GFAP), and changes in microglia/macrophage morphology and distribution. Intravitreal FSK improved retinal ganglion cell survival and reduced glial activation, while systemic lipid profile and oxidative stress markers remained largely unchanged. Circulating miR-200b levels showed a positive correlation with oxidative stress markers across groups. Conclusions: Intravitreal FSK was able to limit the disease exacerbation via improved neuronal survival through inhibition of apoptosis. FSK did not produce observable qualitative changes in GFAP expression or IBA1+ cell morphology under the conditions tested. Full article
(This article belongs to the Section Cell Biology and Pathology)
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16 pages, 2472 KB  
Article
Evaluating the Impact of Social and Environmental Factors on the Use of HHH Medications Using Wastewater-Based Epidemiology in 30 Cities in China
by Ruyue Zhang, Lingrong Zhang, Peng Du, Qiuda Zheng, Kim Anh Dang, Yuyao Zhang, Ke Ma, Ziqi Fang, Xiqing Li and Phong K. Thai
Water 2026, 18(10), 1175; https://doi.org/10.3390/w18101175 - 13 May 2026
Abstract
(1) Background: Metabolic disorders, including hypertension, hyperlipidemia, and hyperglycemia (HHH), rank at the top of the disease burden in China. However, population-level assessment of pharmacological treatment remains limited by the lack of scalable metrics for monitoring medication use and outcomes. (2) Methods: We [...] Read more.
(1) Background: Metabolic disorders, including hypertension, hyperlipidemia, and hyperglycemia (HHH), rank at the top of the disease burden in China. However, population-level assessment of pharmacological treatment remains limited by the lack of scalable metrics for monitoring medication use and outcomes. (2) Methods: We pioneered the use of standardized combined “HHH” medication usage—encompassing antihypertensive, antidiabetic, and lipid-lowering agents—as an integrated proxy for evaluating interventions for cardiovascular diseases and diabetes. Leveraging wastewater-based epidemiology (WBE), we quantified HHH medication loads (mg/d/1000 persons) across 30 prefectures covering all regions in China, and mapped the associated geographical disparities using independent t-tests. Associations with environmental, socioeconomic, demographic, social service, and health-related behavioral and lifestyle factors were further examined via correlation analysis. (3) Results: Our findings confirmed a pronounced north–south gradient in HHH medication uses (the mean standardized loads in the north were approximately twice as high as those in the south, p < 0.05). Furthermore, aging, sex ratio, nicotine consumption, obesity rate, the comprehensive Air Quality Index (AQI), precipitation and the Urban Wellness and Healthcare Index were identified as the top seven influencing factors (|r| values ranging from 0.37 to 0.71, all p < 0.05). (4) Conclusions: As a comprehensive national-scale analysis of multi-drug use for HHH via WBE, this study provides valuable insights into national multi-disease pharmacological treatment, offering evidence-based support for refining clinical prescribing guidelines and rationalizing the allocation of healthcare resources. Full article
(This article belongs to the Special Issue Water Safety, Ecological Risk and Public Health)
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17 pages, 567 KB  
Article
Prevalence, Awareness, and Sociodemographic Determinants of Disc Herniation Among Adults in Saudi Arabia
by Yahya H. Khormi, Mohammad A. Jareebi, Afrah M. Humadi, Saja A. Almraysi, Ali Y. Madkhali, Saja S. Alqahtani, Eyad M. Albarrati, Abdulaziz M. Alibrahim, Saud N. Alwadani, Ahlam A. Harthi, Weam S. Alqattan, Roaa A. Bajafar, Najla A. Alhazmi, Ibrahim A. Hakami and Farjah H. Algahtani
Healthcare 2026, 14(10), 1309; https://doi.org/10.3390/healthcare14101309 - 12 May 2026
Viewed by 81
Abstract
Background/Objectives: Disc herniation, also termed herniated nucleus pulposus (HNP), is a common spinal disorder affecting approximately 10% of the global population, associated with pain, neurological complications, and diminished quality of life. Despite its global burden, regional variations in public awareness and sociodemographic [...] Read more.
Background/Objectives: Disc herniation, also termed herniated nucleus pulposus (HNP), is a common spinal disorder affecting approximately 10% of the global population, associated with pain, neurological complications, and diminished quality of life. Despite its global burden, regional variations in public awareness and sociodemographic determinants remain inadequately characterized, particularly in Middle Eastern populations. This study aimed to assess the prevalence, public awareness, and sociodemographic determinants of HNP among adults in Saudi Arabia at a nationwide level. Methods: An analytical cross-sectional study was conducted from December 2024 to July 2025. Using a convenience sampling approach via social media platforms, an online questionnaire was distributed nationwide across Saudi Arabia. Data from 1112 participants were analyzed using descriptive statistics and multiple logistic regression. The questionnaire comprised two sections: sociodemographic characteristics and knowledge and awareness of HNP. Results: The prevalence of disc herniation was 8.9%, consistent with global estimates. Overall awareness was relatively high at 67.6%, though knowledge of specific risk factors varied considerably. Most participants recognized obesity (88.0%), poor sitting posture (85.8%), history of lower back trauma (86.2%), and work requiring physical effort (88.8%) as risk factors, while fewer acknowledged smoking (46.4%), diabetes (51.2%), sleeping on a soft bed (36.9%), and increased height (35.9%). Multiple logistic regression, adjusted for all sociodemographic, lifestyle, and health-related covariates, identified significant independent predictors of HNP including marital status (married OR = 2.90), current smoking (OR = 2.91), hyperlipidemia (OR = 1.86), family history (OR = 8.95), and prior knowledge of the condition (OR = 2.28). Knowledge of HNP was significantly associated with university education (OR = 1.70), higher income levels (OR = 2.23 for ≥15,000 SAR; OR = 2.07 for 5000–9999 SAR), and family history (OR = 4.70), while those in low and medium workload jobs demonstrated lower knowledge. Conclusions: Although overall public awareness of HNP is relatively high in Saudi Arabia, substantial gaps persist in knowledge of modifiable risk factors, particularly smoking and diabetes mellitus. Targeted smoking cessation campaigns, diabetes awareness programs, and ergonomic education initiatives delivered through primary healthcare centers, workplaces, and schools are recommended. Full article
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20 pages, 5624 KB  
Article
Combined Effect of Bifidobacterium longum Postbiotics and Dietary Herbs on Ameliorating Metabolic Disturbances in Hyperlipidemic Mice
by Yi Sun, Yihong Zeng, Ziyi Yue, Hang Yang, Yunhui Zhang, Haoxin Cui, Haiwei Liu, Hua Xiao, Jin Wang, Dancai Fan, Bowei Zhang, Huan Lv and Shuo Wang
Foods 2026, 15(10), 1679; https://doi.org/10.3390/foods15101679 - 11 May 2026
Viewed by 233
Abstract
Hyperlipidemia-associated obesity is frequently accompanied by hepatic injury, bile acid dysregulation, gut microbial remodeling, and anxiety-like behavioral alterations. As emerging functional food ingredients, postbiotics and dietary herbs (DH) may provide practical dietary strategies for metabolic health management, but the most suitable postbiotic form [...] Read more.
Hyperlipidemia-associated obesity is frequently accompanied by hepatic injury, bile acid dysregulation, gut microbial remodeling, and anxiety-like behavioral alterations. As emerging functional food ingredients, postbiotics and dietary herbs (DH) may provide practical dietary strategies for metabolic health management, but the most suitable postbiotic form and its compatibility with DH remain unclear. In this study, FB 3-14-derived postbiotics were first screened in vitro for cholesterol micellar binding. Inactivated bacterial cells (Postcell) exhibited the strongest cholesterol-binding capacity and were therefore selected for in vivo validation, alone or in combination with DH, in a high-fat, high-cholesterol (HFHC) mouse model. Consistently, Postcell showed superior efficacy in attenuating body weight gain, jejunal triglyceride accumulation, and hepatic dysfunction compared with other postbiotic forms. Importantly, Postcell_DH exerted broader metabolic benefits, including reductions in weight gain, food efficiency, bile acid dysregulation, and neuroinflammation. Multi-omics analysis further indicated that these effects may be mediated through remodeling of the gut microbiota and metabolome, particularly pathways involved in bile acid and tryptophan metabolism. Notably, Clostridioides and taurochenodeoxycholate-7-sulfate were negatively associated with total cholesterol (TC) and leptin, whereas Clostridium_sensu_stricto_1 and 3-Hydroxyindolin-2-1-sulfate were negatively correlated with brain inflammatory level, lipid, and bile acid-related index. This study supports a practical postbiotic–herbal combination strategy relevant to functional food and dietary supplement development for hyperlipidemia-associated metabolic disturbances. Full article
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19 pages, 3240 KB  
Article
Effect of Selenium-Enriched Donkey Milk on Lipid Metabolism Disorders Induced by a High-Fat Diet
by Qizhen Zhong, Jie Cheng, Gengli Huang, Julei Zhan, Xue Chen, Meixuan Liu, Guangyuan Liu, Zhuoru Ren, Xuemei Chen, Xiaoshu Tang and Zhouping Wang
Foods 2026, 15(10), 1640; https://doi.org/10.3390/foods15101640 - 8 May 2026
Viewed by 193
Abstract
Selenium-enriched donkey milk (Se-DM) is characterized by low fat levels, low casein levels, high antioxidant activity, and high selenium content. To date, the regulatory role of Se-DM in the context of a high-fat diet (HFD) is unclear, prompting this present study to elucidate [...] Read more.
Selenium-enriched donkey milk (Se-DM) is characterized by low fat levels, low casein levels, high antioxidant activity, and high selenium content. To date, the regulatory role of Se-DM in the context of a high-fat diet (HFD) is unclear, prompting this present study to elucidate the potential mechanisms by which it affects the gut microbiota and hepatic lipid metabolism in rats fed a high-fat diet. The effects of Se-DM on fat accumulation and lipid peroxidation in HFD rats were investigated through non-targeted fecal metabolomics, short-chain fatty acid (SCFA) quantification, 16S microbial analysis, and pathological assessments. The results showed that Se-DM enhanced SCFA production by promoting Akkermansia muciniphila (A. muciniphila) proliferation, thereby regulating the AMP-activated protein kinase pathway and ferroptosis. Immunoblotting of hepatic tissues and qPCR analyses confirmed the engagement of the AMP-activated protein kinase cascade, suppression of ferroptosis, and reduction in fatty acid synthesis-related proteins (FASN, CD36, SCD1). Our findings revealed that Se-enriched donkey milk (Se-DM) ameliorated lipid metabolism in rats, providing theoretical support for developing functional foods to treat hyperlipidemia. Full article
(This article belongs to the Section Dairy)
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14 pages, 2508 KB  
Article
Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and Stroke in Young Adults
by Kunho Bae, Ju-Yeun Lee and Hyuk Jin Choi
Biomedicines 2026, 14(5), 1035; https://doi.org/10.3390/biomedicines14051035 - 2 May 2026
Viewed by 943
Abstract
Background: Routine fundus photography is widely accessible; however, its utility in stratifying systemic vascular risk in asymptomatic, general populations remains understudied. We utilized a large-scale health screening cohort in South Korea to evaluate the clinical validity of the retinal arteriosclerosis index (RAI) in [...] Read more.
Background: Routine fundus photography is widely accessible; however, its utility in stratifying systemic vascular risk in asymptomatic, general populations remains understudied. We utilized a large-scale health screening cohort in South Korea to evaluate the clinical validity of the retinal arteriosclerosis index (RAI) in a generally healthy population. Methods: We conducted a cross-sectional study of 74,608 adults who underwent routine health screening (2003–2010) at a tertiary center. Retinal arteriosclerosis was graded (0–4) by masked readers with a modified Scheie classification; a higher eye grade was defined as a person-level grade. High-grade RAI was prespecified as ≥2. Associations with systemic conditions (hypertension, type 2 diabetes, hyperlipidemia, metabolic syndrome, cardiovascular disease, and stroke) were examined by using multivariable logistic regression adjusted for demographic, lifestyle, and laboratory covariates; moreover, analyses were stratified by age and sex. Results: High-grade RAI was present in 4.5% of the participants and increased with age. After adjustment, high-grade RAI was associated with hypertension (OR, 2.97; 95% CI, 2.73–3.23), diabetes mellitus (OR, 1.35; 95% CI, 1.22–1.50), cardiovascular disease (OR, 1.46; 95% CI, 1.25–1.71), metabolic syndrome (OR, 1.63; 95% CI, 1.49–1.78), and stroke (OR, 1.98; 95% CI, 1.41–2.79) but not with hyperlipidemia. Sex-stratified analyses revealed broadly similar patterns, although high-grade RAI was associated with stroke in women and cardiovascular disease in men. Age-stratified analyses demonstrated consistent associations with hypertension, metabolic syndrome, and stroke across all age groups, with stronger effect sizes being observed in younger individuals. With respect to lifestyle factors, frequent alcohol consumption was associated with higher odds of high-grade RAI. Laboratory correlates included higher uric acid levels and lower red blood cell, albumin, and bilirubin levels (all p < 0.001). Conclusions: Fundus-defined arteriosclerotic changes were independently associated with multiple systemic vascular and metabolic conditions. An association with stroke in adults younger than 40 years of age was also observed, although this finding should be interpreted with caution given the cross-sectional design and limited number of events. These findings support the potential role of retinal vascular changes as cross-sectional correlates of systemic vascular health. Longitudinal studies are needed to clarify temporal relationships and causality. Full article
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14 pages, 862 KB  
Article
Longitudinal Adherence Patterns of Oral Antidiabetics Among Older Adults with Diabetes and Concomitant Hypertension and Hyperlipidemia Using Group-Based Trajectory Modeling
by Isaiah Olumeko, Sai S. Cheruvu, Samuel C. Ofili and Susan Abughosh
Diabetology 2026, 7(5), 87; https://doi.org/10.3390/diabetology7050087 - 2 May 2026
Viewed by 343
Abstract
Background/Objectives: Diabetes is a prevalent chronic condition and a major contributor to morbidity, mortality, and healthcare costs in the U.S., particularly among older adults with comorbidities such as hypertension and dyslipidemia. Complex medication regimens increase the risk of nonadherence, which can worsen [...] Read more.
Background/Objectives: Diabetes is a prevalent chronic condition and a major contributor to morbidity, mortality, and healthcare costs in the U.S., particularly among older adults with comorbidities such as hypertension and dyslipidemia. Complex medication regimens increase the risk of nonadherence, which can worsen glycemic control, cardiovascular outcomes, and healthcare utilization. This study assessed longitudinal adherence patterns to oral antidiabetic medications among high-risk older adults and identified predictors using group-based trajectory modeling (GBTM). Methods: This retrospective cohort study used 2016–2017 Texas Medicare Advantage claims. Participants were older adults with diagnoses of diabetes, hypertension, and hyperlipidemia who had continuous plan coverage throughout the study period and at least one prescription fill for an oral antidiabetic, a statin, and a renin–angiotensin system (RAS) antagonist. Adherence was measured monthly over 12 months using the proportion of days covered (PDC). GBTM identified adherence trajectories, and multinomial logistic regression, based on the Andersen Behavioral Model, evaluated predictors using perfect adherence as the reference. Results: Among 7847 patients, three trajectories were observed: perfect adherence (59.50%), near-perfect adherence (29.21%), and rapid decline (11.29%). Female sex (OR, 1.38; 95% CI, 1.19–1.60) and absence of health plan subsidy (OR, 0.79; 95% CI, 0.68–0.92) were associated with rapid decline. Female sex (OR, 1.13; 95% CI, 1.02–1.25) and age ≥ 75 years (OR, 1.20; 95% CI, 1.00–1.43) were associated with near-perfect adherence. Conclusions: Older adults with diabetes and comorbidities exhibit distinct medication adherence patterns. Trajectory-based methods can identify those at risk for declining adherence and guide interventions to improve outcomes. Full article
(This article belongs to the Special Issue Efficacy, Safety and Real-World Evidence of Hypoglycemic Drugs)
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15 pages, 10771 KB  
Article
Exogenous Ganglioside GM3 Attenuates Atherosclerosis via Multi-Organ Modulation of Lipid Metabolism
by Jinhua Zhou, Hongda Zhuang, Qinghua Sheng, Zhitao Qiu and Yong Chen
Pharmaceutics 2026, 18(5), 547; https://doi.org/10.3390/pharmaceutics18050547 - 29 Apr 2026
Viewed by 440
Abstract
Background: Atherosclerosis (AS) remains a leading cause of cardiovascular mortality worldwide and is significantly driven by hyperlipidemia. While ganglioside GM3 is known to regulate cellular lipid metabolism, its systemic pharmacological effects on atherosclerosis remain unclear. This study aims to evaluate the anti-atherosclerotic efficacy [...] Read more.
Background: Atherosclerosis (AS) remains a leading cause of cardiovascular mortality worldwide and is significantly driven by hyperlipidemia. While ganglioside GM3 is known to regulate cellular lipid metabolism, its systemic pharmacological effects on atherosclerosis remain unclear. This study aims to evaluate the anti-atherosclerotic efficacy of exogenous GM3 and elucidate its underlying systemic mechanisms. Methods: C57BL/6N ApoE−/− mice fed a high-fat diet were intravenously treated with exogenous GM3 (1 or 4 mg/kg) every three days for 12 weeks. Atherosclerotic progression and lipid profiles were evaluated through histological analyses of the aortic arch and aortic sinus, alongside biochemical and molecular assessments of plasma, hepatic, and intestinal tissues. Results: GM3 treatment significantly reduced plaque formation in the aortic arch and aortic sinus, along with decreased plasma levels of triglycerides, total cholesterol, and LDL-C. Mechanistically, GM3 suppressed hepatic VLDL secretion by downregulating ApoB100 and MTTP expression. Concurrently, hepatic lipid clearance was enhanced via the upregulation of Ldlr, Scarb1, and Lrp1. GM3 also lowered circulating PCSK9 levels and reduced intestinal cholesterol absorption by decreasing NPC1L1 expression. Although GM3 promoted lipid accumulation in the liver, no evidence of liver dysfunction or systemic toxicity was observed. Conclusions: Exogenous GM3 acts as a potent multi-target modulator that attenuates atherosclerosis by coordinating hepatic lipoprotein metabolism and restricting intestinal cholesterol uptake. This multi-organ metabolic partitioning strategy highlights the potential of GM3-based therapeutics for managing complex dyslipidemia. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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19 pages, 8211 KB  
Article
Hawthorn Polysaccharides Relieve High-Fat Blood Disease in Mice by Improving Intestinal Flora and Promoting Lipid Metabolism
by Jingxuan Ke, Xinyu Li, Xiaoyu Yin, Yabin Wang, Xin Wang, Qingshan Shen and Yanli Ma
Foods 2026, 15(9), 1525; https://doi.org/10.3390/foods15091525 - 28 Apr 2026
Viewed by 345
Abstract
In this research, the anti-hyperlipidemic effects of hawthorn polysaccharides in experimental mice fed a high-fat diet were thoroughly investigated. The findings indicated that the body and organ weights of the high-fat group (HC) mice increased significantly, fat accumulation was evident, and serum indicators [...] Read more.
In this research, the anti-hyperlipidemic effects of hawthorn polysaccharides in experimental mice fed a high-fat diet were thoroughly investigated. The findings indicated that the body and organ weights of the high-fat group (HC) mice increased significantly, fat accumulation was evident, and serum indicators showed elevated lipid levels. After 8 weeks of the intragastric administration of hawthorn polysaccharides, the data showed that the body weight of the hawthorn polysaccharide (HA) group was notably lower than that of the HC group and close to that of the NC group. In addition, the hawthorn polysaccharide intervention improved the symptoms of the mice. In particular, the hawthorn polysaccharide intervention significantly increased HDL-C levels and decreased LDL-C levels in the HA group mice. Furthermore, gut microbiota analysis demonstrated that a high-fat diet altered its structure. The intervention with hawthorn polysaccharides modulated the intestinal flora structure, lowered the F/B ratio, and increased the abundance of beneficial bacterial strains associated with lower blood lipid levels. Full article
(This article belongs to the Section Food Nutrition)
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16 pages, 1184 KB  
Review
Advances in the Role of the CD40–CD154 Pathway in the Pathogenesis of Diabetic Retinopathy
by Carlos S. Subauste
Int. J. Mol. Sci. 2026, 27(9), 3862; https://doi.org/10.3390/ijms27093862 - 27 Apr 2026
Viewed by 300
Abstract
Diabetic retinopathy is one of the most important complications of diabetes. It is a leading cause of visual loss in the world. While adequate control of hyperglycemia, hypertension and hyperlipidemia can decrease the prevalence of diabetic retinopathy, 60% of patients with type 2 [...] Read more.
Diabetic retinopathy is one of the most important complications of diabetes. It is a leading cause of visual loss in the world. While adequate control of hyperglycemia, hypertension and hyperlipidemia can decrease the prevalence of diabetic retinopathy, 60% of patients with type 2 diabetes develop this complication whereas it is estimated that most patients with type 1 diabetes will develop diabetic retinopathy. Upregulation of various pro-inflammatory molecules and vascular endothelial growth factor (VEGF) play a central role in the pathogenesis of the disease. Here we review the role of CD40 as an upstream inducer of these abnormalities and the development of diabetic retinopathy. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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17 pages, 934 KB  
Article
Association Between Cardiovascular Risk Factors and the Progression of Motor and Non-Motor Symptoms in Parkinson’s Disease: A Five-Year Cohort Study
by Junyi Chen, Jing Chen, Zhe Zhao, Danhua Zhao, Baoyu Chen, Qi Wang, Yuan Li, Chaobo Bai, Xintong Guo, Jinjin Wang and Junliang Yuan
J. Clin. Med. 2026, 15(9), 3217; https://doi.org/10.3390/jcm15093217 - 23 Apr 2026
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Abstract
Objective: To investigate the relationship between cardiovascular risk factors and the progression of motor and non-motor symptoms in Parkinson’s disease (PD). Methods: We used data from the Parkinson’s Progression Markers Initiative (PPMI) cohort with a follow-up duration of >5 years. Baseline [...] Read more.
Objective: To investigate the relationship between cardiovascular risk factors and the progression of motor and non-motor symptoms in Parkinson’s disease (PD). Methods: We used data from the Parkinson’s Progression Markers Initiative (PPMI) cohort with a follow-up duration of >5 years. Baseline assessments included genetic analysis, brain MRI, cardiovascular risk factors, and overall cardiovascular disease (CVD) risk. Motor symptoms and non-motor symptoms of PD were evaluated using the Movement Disorders Society revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and sub-scores, Hoehn–Yahr stage, and Montreal Cognitive Assessment (MoCA). Statistical analyses comprised univariate and multivariate linear regression and stratified analysis. Results: A total of 169 newly diagnosed PD patients and 78 healthy controls (HCs) were included. At baseline, no significant differences in cardiovascular risk factors or overall CVD risk were observed between PD patients and HCs. Hypertension (β = 6.748, p = 0.040) and hyperlipidemia (β = 8.316, p = 0.005) were associated with faster motor progression. ApoE genotype was correlated with motor progression (β = 7.593, p = 0.007). PD patients with a moderate-to-low CVD risk (<20%) had milder axial motor symptoms (3.0 [IQR, 4.0] vs. 4.0 [IQR, 5.0], p = 0.048) and lower MDS-UPDRS Part I total scores (7.0 [IQR, 6.25] vs. 9.0 [IQR, 7.0], p = 0.039) at last follow-up compared to high-CVD-risk (≥20%) patients. Overall CVD risk was negatively correlated with total MoCA score at last follow-up (β = −0.208, p< 0.001). Conclusions: Cardiovascular risk factors accelerate the progression of motor and non-motor symptoms in PD, suggesting that management of modifiable CVD risk factors may represent a promising target to delay the progression of PD. Full article
(This article belongs to the Section Clinical Neurology)
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27 pages, 1638 KB  
Review
Altered Lipid Profile and Oxidative Stress During Pregnancy: Impact on the Fetus and Risk of Metabolic Disorders in Adulthood
by Kristina Jovanovic, Miljana Z. Jovandaric, Darko Jovanovic, Milos Milincic, Mirjana Krstic, Bojan Cegar and Dimitrije M. Nikolic
Int. J. Mol. Sci. 2026, 27(9), 3744; https://doi.org/10.3390/ijms27093744 - 23 Apr 2026
Viewed by 340
Abstract
Pregnancy is characterized by progressive maternal hyperlipidemia, including increased triglycerides, total cholesterol, and low-density lipoprotein, with dynamic fluctuations in high-density lipoprotein. Excess maternal free fatty acids induce oxidative stress through reactive oxygen species, causing mitochondrial dysfunction, lipid peroxidation, activation of inflammatory pathways, and [...] Read more.
Pregnancy is characterized by progressive maternal hyperlipidemia, including increased triglycerides, total cholesterol, and low-density lipoprotein, with dynamic fluctuations in high-density lipoprotein. Excess maternal free fatty acids induce oxidative stress through reactive oxygen species, causing mitochondrial dysfunction, lipid peroxidation, activation of inflammatory pathways, and epigenetic remodeling in the placenta and fetal tissues. These molecular alterations impair placental lipid transport and nutrient sensing, leading to hypertrophy of fetal liver, myocardium, and adipose tissue, while disrupting neonatal glucose and lipid homeostasis and increasing susceptibility to perinatal complications and long-term metabolic disorders. This review aims to evaluate mechanistic pathways linking maternal lipid metabolism, oxidative stress, placental function, and fetal organ remodeling. Mechanistic and translational studies were identified through searches of PubMed, Scopus, the Cochrane Library, and Web of Science (2000–2025) using predefined keywords including lipid metabolism, free fatty acids, oxidative stress, placental lipid transport, epigenetics, DNA methylation, fetal programming, and perinatal outcomes. Evidence indicates that maternal lipid imbalance drives placental oxidative and epigenetic modifications, directly contributing to fetal organ hypertrophy and neonatal metabolic dysregulation. In conclusion, maternal dyslipidemia represents a modifiable determinant of fetal organ hypertrophy and long-term metabolic risk, supporting the clinical relevance of maternal lipid monitoring and targeted metabolic interventions during pregnancy. Full article
(This article belongs to the Special Issue Endocrinology of Pregnancy)
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