Search Results (28,360)

Background: Peripheral artery disease (PAD) affects more than 100 million people globally. Most PAD studies have been performed among predominantly White populations—less is known about other ethnicities. The aim of this cross-sectional study was to determine the prevalence and risk factors of PAD in a high-risk Asian population with ischaemic stroke (IS), myocardial infarction, unstable angina (CVD), or diabetes mellitus (DM). Methods: Patients admitted for IS, CVD, or DM were recruited. Data were collected on age, sex, body mass index (BMI), index condition (CVD, IS, DM), history of hypertension, DM, hypercholesterolaemia, cigarette smoking, and claudication. The Edinburgh Claudication Questionnaire was administered, the ankle brachial index (ABI) was determined, and PAD was diagnosed if ABI was ≤0.9. Results: Of the 450 subjects recruited, 150 were placed in each index disease group, the mean age was 61.9 ± 10.32 years, 43.1% were female, and the mean BMI was 23.9 ± 4.3. Hypertension was reported in 59.3%, DM in 63.6%, hypercholesterolaemia in 39.6%, and smoking in 42.9% of patients. The prevalence of PAD was 27.1%, 22.0% in IS, 29.3% in CAD, and 30.0% in DM. PAD was associated with increasing age (adjusted odds ratio (aOR) 1.04/year, 95% confidence interval [CI] 1.01–1.06; p < 0.001), reduced BMI (aOR 0.94, 95%CI 0.89–0.99; p = 0.026), DM (aOR 1.59, 95%CI 1.20–3.18; p = 0.007), and hypercholesterolaemia (aOR 1.82, 95%CI 1.17–2.28; p = 0.007). It was more frequent in non-lacunar versus lacunar acute IS, non-ST segment elevation versus ST-segment elevation acute myocardial infarction, and insulin-treated versus non-insulin-treated DM. Conclusions: Our study showed a high prevalence of PAD among high-risk Asian patients. This was associated with increasing age, DM, and hypercholesterolaemia and inversely associated with BMI. Different rates were found in sub-groups of IS, CVD, and DM. Systematic approaches were used to identify these high-risk individuals and to improve their outcomes. Full article

The orchestration of cellular metabolism and redox balance is a complex, multifaceted process crucial for maintaining cellular homeostasis. Lipid droplets (LDs), once considered inert storage depots for neutral lipids, are now recognized as dynamic organelles critical in lipid metabolism and energy regulation. Mitochondria, the powerhouses of the cell, play a central role in energy production, metabolic pathways, and redox signaling. The physical and functional contacts between LDs and mitochondria facilitate a direct transfer of lipids, primarily fatty acids, which are crucial for mitochondrial β-oxidation, thus influencing energy homeostasis and cellular health. This review highlights recent advances in understanding the mechanisms governing LD–mitochondria interactions and their regulation, drawing attention to proteins and pathways that mediate these contacts. We discuss the physiological relevance of these interactions, emphasizing their role in maintaining energy and redox balance within cells, and how these processes are critical in response to metabolic demands and stress conditions. Furthermore, we explore the pathological implications of dysregulated LD–mitochondria interactions, particularly in the context of metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease, and their potential links to cardiovascular and neurodegenerative diseases. Conclusively, this review provides a comprehensive overview of the current understanding of LD–mitochondria interactions, underscoring their significance in cellular metabolism and suggesting future research directions that could unveil novel therapeutic targets for metabolic and degenerative diseases. Full article

CXCL10 (IP-10) plays a key role in leukocyte homing to the inflamed tissues and its increased levels are associated with the pathophysiology of various inflammatory diseases including obesity and type 2 diabetes. IL-1β is a key proinflammatory cytokine that is found upregulated in meta-inflammatory conditions and acts as a potent activator, inducing the expression of cytokines/chemokines by immune cells. However, it is unclear whether IL-1β induces the expression of CXCL10 in monocytic cells. We, therefore, determined the CXCL10 induction using IL-1β in THP1 monocytic cells and investigated the mechanisms involved. Monocytes (human monocytic THP-1 cells) were stimulated with IL-1β. CXCL10 gene expression was determined with real-time RT-PCR. CXCL10 protein was determined using ELISA. Signaling pathways were identified by using Western blotting, inhibitors, siRNA transfections, and kinase assay. Our data show that IL-1β induced the CXCL10 expression at both mRNA and protein levels in monocytic cells (p = 0.0001). Notably, only the JNK inhibitor (SP600125) significantly suppressed the IL-1β-induced CXCL10 expression, while the inhibitors of MEK1/2 (U0126), ERK1/2 (PD98059), and p38 MAPK (SB203580) had no significant effect. Furthermore, IL-1β-induced CXCL10 expression was decreased in monocytic cells deficient in JNK/c-Jun. Accordingly, inhibiting the JNK kinase activity markedly reduced the IL-1β-induced JNK/c-Jun phosphorylation in monocytic cells. NF-κB inhibition by Bay-117085 and resveratrol also suppressed the CXCL10 expression. Our findings provide preliminary evidence that IL-1β stimulation induces the expression of CXCL10 in monocytic cells which requires signaling via the JNK/c-Jun/NF-κB axis. Full article

Subjective cognitive complaints (SCCs) are a crucial modifiable risk factor for dementia. There is increasing interest in the association between SCC and sleep disturbance; however, the effects of sleep disturbance on SCC development among community-dwelling elderly individuals in Japan remain unclear. We aimed to cross-sectionally investigate the association between SCC and sleep disturbance, with adjustment for multiple factors related to cognitive decline, among 241 community-dwelling elderly persons without cognitive impairment. The measures were SCCs (Kihon Checklist-Cognitive Function, KCL-CF), sleep disturbance (Japanese version of the Athens Insomnia Scale, AIS-J), general cognitive function (Mini-Mental State Examination), and depressive symptoms (five-item version of the Geriatric Depression Scale [GDS-5]). The following data were collected: sex, age, educational history, whether the participants had visited a medical institution for diseases (hypertension, diabetes, hyperlipidemia, heart disease), and the presence/absence of established risk factors (hearing loss, history of head injury, drinking habits, smoking habits, social isolation, and physical inactivity and activity). Based on the KCL-CF, 96 and 145 participants were considered to have and lack SCCs, respectively. On logistic regression analysis, the AIS-J score and smoking history were significantly associated with SCCs. Our findings suggest that sleep disturbance is associated with SCC development among community-dwelling elderly people in Japan. Evaluating and managing sleep disturbances can be important in preventing SCCs and dementia. Full article

Background: Diabetic foot is a serious and often debilitating diabetes complication that poses a significant risk of morbidity and even mortality. However, ensuring good knowledge and good practice of appropriate foot care for patients with diabetes has been frequently neglected in diabetes management. Objectives: This study aimed to assess foot care knowledge and practice in patients with diabetes. Methods: We conducted a cross-sectional study on 400 patients with diabetes at Madinah Diabetes Center, Madinah City, Saudi Arabia, in 2023. Sociodemographic, knowledge score, practice of foot care, and diabetes-related data were collected using a valid interview structured questionnaire. The prevalence of good knowledge and practice level was calculated and compared using the studied patients’ characteristics using appropriate statistical tests. Results: The prevalence of good knowledge of foot care and its practice was 35% and 27%, respectively. The knowledge level showed statistically significant differences among patients based on their age and diabetes type and duration. Patients who were >50 years (70.1%), had type 2 diabetes (89.5%), and with diabetes duration >10 years (65%) showed significantly better knowledge. Female patients (65.7%) had a higher good practice level compared with male patients (34.3%) (p < 0.001). Conclusions: This study highlights the insufficient knowledge and inadequate foot care practice among patients with diabetes in the studied population. Educational interventions and targeted strategies are necessary to improve knowledge about the importance of foot care and promote better foot care practices among patients with diabetes. Full article

Cardiovascular disease (CVD) and kidney disease are the main causes of morbidity and mortality in type 2 diabetes mellitus (T2DM). Globally, the incidence of T2DM continues to rise. A substantial increase in the burden of CVD and renal disease, alongside the socioeconomic implications, would be anticipated. Adopting a purely glucose-centric approach focusing only on glycemic targets is no longer adequate to mitigate the cardiovascular risks in T2DM. In the past decade, significant advancement has been achieved in expanding the pharmaceutical options for T2DM, with novel agents such as the sodium-glucose cotransporter type 2 (SGLT2) inhibitors and glucagon-like peptide receptor agonists (GLP-1 RAs) demonstrating robust evidence in cardiorenal protection. Combinatorial approaches comprising multiple pharmacotherapies combined in a single agent are an emerging and promising way to not only enhance patient adherence and improve glycemic control but also to achieve the potential synergistic effects for greater cardiorenal protection. In this review, we provide an update on the novel antidiabetic agents in the past decade, with an appraisal of the mechanisms contributing to cardiorenal protection. Additionally, we offer a glimpse into the landscape of T2DM management in the near future by providing a comprehensive summary of upcoming agents in early-phase trials. Full article

Nonmydriatic retinal fundus images often suffer from quality issues and artifacts due to ocular or systemic comorbidities, leading to potential inaccuracies in clinical diagnoses. In recent times, deep learning methods have been widely employed to improve retinal image quality. However, these methods often require large datasets and lack robustness in clinical settings. Conversely, the inherent stability and adaptability of traditional unsupervised learning methods, coupled with their reduced reliance on extensive data, render them more suitable for real-world clinical applications, particularly in the limited data context of high noise levels or a significant presence of artifacts. However, existing unsupervised learning methods encounter challenges such as sensitivity to noise and outliers, reliance on assumptions like cluster shapes, and difficulties with scalability and interpretability, particularly when utilized for retinal image enhancement. To tackle these challenges, we propose a novel robust PCA (RPCA) method with low-rank sparse decomposition that also integrates affine transformations ${\tau }_i$, weighted nuclear norm, and the $L_{2,1}$ norms, aiming to overcome existing method limitations and to achieve image quality improvement unseen by these methods. We employ the weighted nuclear norm $\left(L_{w,*}\right)$ to assign weights to singular values to each retinal images and utilize the $L_{2,1}$ norm to eliminate correlated samples and outliers in the retinal images. Moreover, ${\tau }_i$ is employed to enhance retinal image alignment, making the new method more robust to variations, outliers, noise, and image blurring. The Alternating Direction Method of Multipliers (ADMM) method is used to optimally determine parameters, including ${\tau }_i$, by solving an optimization problem. Each parameter is addressed separately, harnessing the benefits of ADMM. Our method introduces a novel parameter update approach and significantly improves retinal image quality, detecting cataracts, and diabetic retinopathy. Simulation results confirm our method’s superiority over existing state-of-the-art methods across various datasets. Full article

The enhancement of seed germination by using nanoparticles (NPs) holds the potential to elicit the synthesis of more desired compounds with important biomedical applications, such as preventing protein glycation, which occurs in diabetes. Here, we used 7 nm and 100 nm ZnO and 4.5 nm and 16.7 nm Fe₂O₃ NPs to treat sunflower seeds. We evaluated the effects on germination, total phenolic content, and the anti-glycation potential of extracted polyphenols. Sunflower seeds were allowed to germinate in vitro after soaking in NP solutions of different concentrations. Polyphenols were extracted, dosed, and used in serum albumin glycation experiments. The germination speed of seeds was significantly increased by the 100 nm ZnO NPs and significantly decreased by the 4.5 nm Fe₂O₃ NPs. The total phenolic content (TPC) of seeds was influenced by the type of NP, as ZnO NPs enhanced TPC, and the size of the NPs, as smaller NPs led to improved parameters. The polyphenols extracted from seeds inhibited protein glycation, especially those extracted from seeds treated with 7 nm ZnO. The usage of NPs impacted the germination speed and total polyphenol content of sunflower seeds, highlighting the importance of NP type and size in the germination process. Full article

The Asian region of earth has a rich agriculture system that provides extensive opportunities to boost pharmaceutical and nutritional research to address the use of food crops for health benefits and potential clinical applications. The traditionally cropped green leaf vegetable indigenously known as Bathu and botanically known as Chenopodium album (C. album) is traditionally used as a sedative, blood purifier, hepatoprotectant, diuretic, and antiscorbutic laxative. In this study, we investigated the anti-infection potential, anti-diabetic potential, and mineral composition of indigenously cultivated C. album plant extracts. Methanol and n-hexane solvents were used to extract phytochemicals at different extraction conditions. The maximum yield of 12.72 ± 0.36 g/100 g extract was obtained in methanol with 200 rpm shaking, 200 mL solvent, and an 8 h extraction period. Under the same conditions, n-hexane gave 2.09 ± 0.29 g/100 g extract. Good alpha-amylase inhibition efficiency was shown by the n-hexane extracts, while the methanol extracts showed good urease inhibition potential. The H6 extract had the lowest IC₅₀ (8.16 ± 0.2 ug/mL) as compared to the standard acarbose (9.27 ± 0.6 ug/mL). Similarly, the M6 extract revealed a significant urease inhibitory potential, i.e., IC₅₀ of 18.77 ± 0.6 ug/mL, which was close to the standard thiourea (IC₅₀: 19.09 ± 0.7 ug/mL). Regarding the antibacterial study, the M6 extract showed 16.55 ± 0.57 mm ZOI against E. coli and 15.54 ± 0.55 mm in the case of S. aureus, as compared to the standard ciprofloxacin, which showed 26.08 ± 0.73 mm, and penicillin, which showed 21.12 ± 0.81 mm ZOI. Mineral profiling was investigated by ICP-OES, which showed significant amounts of Mg and Fe in all extracts. Our findings tend to show that systematic harvesting and utilization of this vegetable crop could be recommended as an alternative nutritional therapy in the management of internal infections and diabetes. Full article

Background and Objectives: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may cause acute respiratory failure, but also remains responsible for many other pathologies, including electrolyte disorders. SARS-CoV-2 infection causes disorders in many systems and can disrupt water homeostasis with thirst and appetite abnormalities. Dysnatremia affects prognosis, and may be associated with mortality in patients admitted to an intensive care unit (ICU) diagnosed with SARS-CoV-2. Materials and Methods: The study included 209 patients admitted to the ICU between 12 April 2021 and 1 March 2022 who were over 18 years old and diagnosed with SARS-CoV-2 infection by clinical and thoracic tomography findings or with a positive reverse transcription polymerase chain reaction (RT-PCR) test result. The laboratory markers, treatment modalities, nutritional, and respiratory support also for outcome evaluation, length of stay in the ICU, total hospitalization duration, and mortality in the ICU were recorded. The laboratory marker comparison was made using admission with the final assessment performed before the time of mortality in the ICU or after discharge. Results: Inotropic requirements among patients were high, which reflected mortality in the ICU. Hypernatremia presence was associated with an increase in enteral support, the inotropic support requirement, and mortality. Hypernatremia was correlated with diabetes mellitus, chronic renal failure, and a longer duration under mechanical ventilation. Conclusions: Hypernatremia was an important risk factor in ICU patients hospitalized for SARS-CoV-2 infection, which was also affected by the treatment regimens given themselves. This complex relationship underlies the importance of proper electrolyte management, especially in patients who were under severe stress and organ failure. Full article

With around one billion of the world’s population affected, the era of the metabolic-associated fatty liver disease (MAFLD) pandemic has entered the global stage. MAFLD is a chronic progressive liver disease with accompanying metabolic disorders such as type 2 diabetes mellitus and obesity which can progress asymptomatically to liver cirrhosis and subsequently to hepatocellular carcinoma (HCC), and for which to date there are almost no approved pharmacologic options. Because MAFLD has a very complex etiology and it also affects extrahepatic organs, a multidisciplinary approach is required when it comes to finding an effective and safe active substance for MAFLD treatment. The optimal drug for MAFLD should diminish steatosis, fibrosis and inflammation in the liver, and the winner for MAFLD drug authorisation seems to be the one that significantly improves liver histology. Saroglitazar (Lipaglyn^®) was approved for metabolic-dysfunction-associated steatohepatitis (MASH) in India in 2020; however, the drug is still being investigated in other countries. Although the pharmaceutical industry is still lagging behind in developing an approved pharmacologic therapy for MAFLD, research has recently intensified and many molecules which are in the final stages of clinical trials are expected to be approved in the coming few years. Already this year, the first drug (Rezdiffra™) in the United States was approved via accelerated procedure for treatment of MAFLD, i.e., of MASH in adults. This review underscores the most recent information related to the development of drugs for MAFLD treatment, focusing on the molecules that have come furthest towards approval. Full article

Optical coherence tomography (OCT) is an indispensable instrument in ophthalmology; however, some facilities lack permanent OCT devices. ACT100, a portable SD-OCT system, allows for medical examinations at hospitals that do not have OCT and house calls. We investigated the usefulness of ACT100 by examining the reproducibility of retinal thickness measurements in 35 healthy participants with normal eyes using ACT100 and Cirrus. Using two OCTs, the OCT imaging of both eyes of each subject was performed. Macular retinal thickness was evaluated using the average value in nine lesions of the Early Treatment Diabetic Retinopathy Study (ETDRS) circle. Both models captured images in all cases. In the right eye, mean retinal thickness was significantly lower than in the ACT100 group in all regions; however, the measured values correlated well. The intraclass correlation coefficients showed the same high reliability as the Cirrus. The coefficients of variation (CVs) of both models showed little variation and high stability; however, the CV of ACT100 was significantly higher. The left eye was almost identical. Macular retinal thickness measured using ACT100 showed slightly greater variability than that by Cirrus; the reproducibility was good and correlated well with that of Cirrus. This technique is a suitable alternative to conventional OCT. Full article

Type 2 diabetes mellitus (T2DM) is a burgeoning public health challenge worldwide. Individuals with T2DM are at increased risk for skeletal muscle atrophy, a serious complication that significantly compromises quality of life and for which effective prevention measures are currently inadequate. Emerging evidence indicates that systemic and local inflammation stemming from the compromised intestinal barrier is one of the crucial mechanisms contributing to skeletal muscle atrophy in T2DM patients. Notably, natural plant polysaccharides were found to be capable of enhancing intestinal barrier function and mitigating secondary inflammation in some diseases. Herein, we hypothesized that Grifola frondosa polysaccharide (GFP), one of the major plant polysaccharides, could prevent skeletal muscle atrophy in T2DM via regulating intestinal barrier function and inhibiting systemic and local inflammation. Using a well-established T2DM rat model, we demonstrated that GFP was able to not only prevent hyperglycemia and insulin resistance but also repair intestinal mucosal barrier damage and subsequent inflammation, thereby alleviating the skeletal muscle atrophy in the T2DM rat model. Additionally, the binding free energy analysis and molecular docking of monosaccharides constituting GFP were further expanded for related targets to uncover more potential mechanisms. These results provide a novel preventative and therapeutic strategy for T2DM patients. Full article

In this study, we present in vitro actions of pure commercial preparations of oxidized and/or dehydrated metabolites of cholesterol (OS) identified in the lipid fraction of Fraction B (FB) prepared from a catfish skin preparation on calcium transients and on the formation of human neutrophil extracellular traps (NETs). These investigations are part of an ongoing effort to understand the important roles these compounds play as components of FB when FB is applied to accelerate the healing of wounds and the healing of highly infected non-healing diabetic foot ulcers, without the use of antibiotics. Our aim was to determine potential therapeutic interventions for various disease states. Our results reveal interesting findings, demonstrating specific actions of the individual compounds. Compounds 7α-hydroxy-cholesterol (S3), Cholestane-3,5,6-triol (S5), 5-cholesten-3β-ol-7-one (S8) and Cholesta-3,5 dien-7-one (S10) are inhibitory, while Cholesterol 5β,6β-epoxide (S4) and 5α-cholestane-3,6-dione (S11) activate the response for calcium influx in human neutrophils. A somewhat similar response is observed in dHL60 cell lines, where S3, S5, S7, S8, and cholesta-2,4-diene (S14) inhibit the calcium influx, although S4, S10, and S11 activate the response in this cell line. Furthermore, we observed a relationship between actions against NETosis and calcium transients. Interestingly, relative to the vehicle control, S3, Cholesta-3,5 diene (S9), and S14 appeared to significantly stimulate DNA release (NETosis), while S2, 7α-hydroxy-cholesterol (S6) and cholesta-3,5 dien-7-one (S10) caused lesser stimulation. We provide the IC50 activities for each compound tested in each assay. Calcium influx and NETs formation (NETosis) correlate with diseases exacerbation. These findings offer valuable insights into the potential therapeutic applications of individual OS for various diseases, highlighting their importance in future interventions. Full article

Intermittent fasting (IF) has been indicated as a valuable alternative to the classical caloric restriction dietary regimen for lowering body weight and preventing obesity-related complications, such as metabolic syndrome and type II diabetes. However, is it effective? In this review article, we analyzed over 50 clinical studies in which IF, conducted by alternate day fasting (ADF) or time-restricted feeding (TRF), was compared with the caloric restriction approach. We evaluated the different roles of IF in treating and preventing human disorders such as metabolic syndrome, type II diabetes, and some types of cancer, as well as the usefulness of IF in reducing body weight and cardiovascular risk factors such as hypertension. Furthermore, we explored the cellular pathways targeted by IF to exert their beneficial effects by activating effector proteins that modulate cell functions and resistance to oxidative stress. In contrast, we investigated concerns regarding human health related to the adoption of IF dietary regimens, highlighting the profound debate surrounding weight loss regimens. We examined and compared several clinical trials to formulate an updated concept regarding IF and its therapeutic potential. Full article