Search Results (1,401)

Neural electrodes used for bidirectional communication between the nervous system and external devices like prosthetic limbs have advanced in neuroprosthetic applications. However, their effectiveness is hindered by the foreign body reaction, a natural immune response causing inflammation and fibrosis around the implanted device. This process involves protein adsorption, immune cell recruitment, cytokine release, and fibroblast activation, leading to a fibrous capsule formation and a decrease in electrode functionality. Anti-inflammatory and antifibrotic strategies have the potential to diminish the impact of the foreign body response. In this work, we have evaluated long-term metformin administration and short-term dexamethasone administration as a combined therapy to modulate the foreign body reaction induced by a polyimide intraneural implant in the sciatic nerve of rats. After a 12-week implant, the foreign body reaction was significantly reduced only in the group administered both drugs. Full article

Background: Prolactin levels have been shown to influence metabolic outcomes, including insulin resistance. Metformin is known to be beneficial in polycystic ovary syndrome (PCOS) patients. PCOS women might react differently to metformin treatment depending on their baseline prolactin levels. Methods: In this retrospective study, the homeostasis model assessment for insulin resistance (HOMA-IR), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, and total testosterone and sex hormone-binding globulin (SHBG) were measured in 75 obese/overweight women with PCOS and insulin resistance before initiation of metformin treatment and after 6–8 months. Results: At baseline, HOMA-IR was inversely correlated to SHBG (r = −0.408; p < 0.001) and prolactin (r = −0.402; p < 0.001). After 6–8 months of metformin treatment, the LH:FSH ratio and the HOMA-IR declined significantly (p < 0.05). A significant positive correlation could be shown between basal prolactin and the difference in the HOMA-IR (r = 0.233; p = 0.044). Women with lower baseline prolactin (≤14.9 ng/mL) revealed a sharper decline in HOMA-IR (−0.8, IQR −1.0; −0.5 vs. −0.6, IQR −0.8; −0.3; p = 0.049) as well as an increase in prolactin at follow-up (1.6 ng/mL, IQR −0.2;3.8 vs. −1.3, IQR −4.6;3.2; p = 0.003) compared to patients with a baseline prolactin > 14.9 ng/mL. Conclusions: In overweight/obese, insulin-resistant PCOS women, lower baseline prolactin levels are associated with higher baseline HOMA-IR levels as well as with a better response to metformin treatment. More data are necessary to prove these observations in larger populations. Full article

Oral potentially malignant disorders (OPMD) are a group of lesions carrying the risk of developing into cancer. The gold standard to predict which lesions are more likely to undergo malignant transformation is the presence of dysplasia histologically. However, not all dysplastic lesions progress, and non-dysplastic lesions may also undergo malignant transformation. Oral carcinogenesis is a complex molecular process that involves somatic alterations and the deregulation of transcriptions, protein expression, and metabolite levels. Metabolomics, which is the scientific study of metabolites, has emerged as a promising high-throughput approach to investigate the metabolic changes of small molecules in biological pathways. In this review, we summarize the data relating to the metabolomic profiling of OPMDs, which will help elucidate the complex process of oral carcinogenesis. Furthermore, we identify that among all metabolites, citrate, pyruvate, and glutamate may serve as potential biomarkers for oral leukoplakia (OLK). Notably, metformin and gluconate have been shown to target glutamate and citrate, respectively, in cancer cells. Based on these findings, we propose that targeting these metabolites in patients with OPMD could be a promising therapeutic strategy to mitigate OPMD progression and potentially reduce the risk of malignant transformation. We also discuss the limitations and future directions of metabolomics in OPMD. Understanding these important metabolites is crucial for early detection and monitoring of oral cancer progression. Full article

Background/Objectives: The prevalence of type 2 diabetes and smoking is increasing in developing countries and is associated with deteriorated health outcomes. Also, addiction to smartphone use is an alarming behavior that can be associated with clinical factors. This study aimed to determine the prevalence and clinical correlates of smartphone addiction in smokers with T2DM in Jordan, with a particular focus on the role of medications. Methods: This cross-sectional study recruited patients from Prince Hamza Hospital, Jordan, according to pre-defined criteria. Besides demographics and clinical information, this study used the validated Arabic version of the Smartphone Addiction Scale to assess addiction to smartphones and a multivariable regression analysis to identify the correlates of smartphone addiction. Results: Data analyzed from 346 patients revealed that 117 (33.8%) of these participants reported addiction to smartphones. Patients who had been diagnosed with T2DM for less than five years (aOR = 3.30; 95% CI = 1.43–7.60), who were “employed” (aOR = 8.85; 95% CI = 2.20–35.64), and who were “retired” (aOR = 11.46; 95% CI = 2.72–48.23) all reported a significantly (p < 0.05) higher odds of smartphone addiction. In contrast, patients on “sulfonylurea” (aOR = 0.18; 95% CI = 0.06–0.53); “metformin” (aOR = 0.19; 95% CI = 0.06–0.66), and “gabapentin” (aOR = 0.16; 95% CI = 0.04–0.67) and those with “comorbid hypertension” (aOR = 0.15; 95% CI = 0.06–0.38) had a significantly (p < 0.05) lower odds of smartphone addiction. Conclusion: These alarming results require adequate action from the health authorities to raise awareness of adopting positive behaviors that could improve the well-being of this high-risk population. Full article

Background: Metformin, a commonly prescribed medication for managing diabetes, has garnered increasing interest as a potential therapeutic option for combating cancer and aging. Methods: The current study investigated the effects of metformin treatment on human meibomian gland epithelial cells (hMGECs) at morphological, molecular, and electron microscopy levels. HMGECs were stimulated in vitro with 1 mM, 5 mM, and 10 mM metformin for 24, 48, and 72 h. The assessed outcomes were cell proliferation assays, lipid production, ultrastructural changes, levels of IGF-1, Nrf2, HO-1, apoptosis-inducing factor 1 (AIF1) at the protein level, and the expression of oxidative stress factors (matrix metallopeptidase 9, activating transcription factor 3, CYBB, or NADPH oxidase 2, xanthine dehydrogenase). Results: Morphological studies showed increased lipid production, the differentiation of hMGECs after stimulation with metformin, and the differentiation effects of undifferentiated hMGECs. Proliferation tests showed a reduction in cell proliferation with increasing concentrations over time. AIF1 apoptosis levels were not significantly regulated, but morphologically, the dying cells at a higher concentration of 5-10 mM showed a rupture and permeabilization of the plasma membrane, a swelling of the cytoplasm, and vacuolization after more than 48 h. The IGF-1 ELISA showed an irregular expression, which mostly decreased over time. Only at 72 h and 10 mM did we have a significant increase. Mitochondrial metabolic markers such as Nrf2 significantly increased over time, while HO-1 decreased partially. The RT-PCR showed a significant increase in MMP9, CYBB, XDH, and ATF with increasing time and metformin concentrations, indicating cell stress. Conclusions: Our results using a cell line suggest that metformin affects the cellular physiology of meibomian gland epithelial cells and induces cell stress in a dose- and duration-dependent manner, causing changes in their morphology and ultrastructure. Full article

Metformin, a widely used antidiabetic medication, has emerged as a promising broad-spectrum antiviral agent due to its ability to modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes cellular energy reserves that viruses rely on, effectively limiting the replication of pathogens such as influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting the mTOR pathway, crucial for viral protein synthesis and reactivation, is particularly significant in managing infections caused by HIV, CMV, and EBV. Furthermore, metformin reduces oxidative stress and reactive oxygen species (ROS), which are critical for replicating arboviruses such as Zika and dengue. The drug also regulates immune responses, cellular differentiation, and inflammation, disrupting the life cycle of HPV and potentially other viruses. These diverse mechanisms suppress viral replication, enhance immune system functionality, and contribute to better clinical outcomes. This multifaceted approach highlights metformin’s potential as an adjunctive therapy in treating a wide range of viral infections. Full article

Background and Objectives: Insulin resistance (IR) is the most important factor involved in the pathogenesis of type 2 diabetes but may also develop in type 1 diabetes (T1DM). Developing IR in patients with T1DM may generate a burden in achieving glycemic targets and may deteriorate the overall prognosis. This review aims to describe the pathogenesis of IR in T1DM, summarize the common associations of IR with other conditions in patients with T1DM, describe the consequences of developing IR in these patients, and present the interventions that target IR in people with T1DM. Results: The occurrence of IR in T1DM is multifactorial; however, it is frequently linked to overweight or obesity and sedentary lifestyle. Besides impairments in glycemic control and increased insulin requirements, the presence of IR is associated with an increased cardiovascular risk in patients with T1DM. Considering that patients with T1DM are insulin-treated, IR may be evaluated only using surrogate biomarkers, the most frequently used being the estimated glucose disposal rate. The most important interventions that are shown to be feasible in improving insulin sensitivity in patients with T1DM are lifestyle optimizations, including nutrition therapy or physical activity and pharmacotherapy with metformin, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and thiazolidinediones. Conclusions: Targeting the improvement of IR in patients with T1DM is a key element in achieving optimal glycemic control, as well as improving the overall patient’s prognosis besides glycemic control. Full article

Background: Diabetes is a growing global health crisis that requires effective therapeutic strategies to optimize treatment outcomes. This study aims to address this challenge by developing and characterizing extended-release polymeric matrix tablets containing metformin hydrochloride (M-HCl), a first-line treatment for type 2 diabetes, and honokiol (HNK), a bioactive compound with potential therapeutic benefits. The objective is to enhance glycemic control and overall therapeutic outcomes through an innovative dual-drug delivery system. Methods: The tablets were formulated using hydrophilic polymers, such as Carbopol^® 71G NF and Noveon^® AA-1. The release kinetics of M-HCl and HNK were investigated through advanced mathematical models, including fractal and multifractal dynamics, to capture the non-linear and time-dependent release processes. Traditional kinetic models (zero-order, first-order, Higuchi equations) were also evaluated for comparison. In vitro dissolution studies were conducted to determine the release profiles of the active ingredients under varying polymer concentrations. Results: The study revealed distinct release profiles for the two active ingredients. M-HCl exhibited a rapid release phase, with 80% of the drug released within 4–7 h depending on polymer concentration. In contrast, HNK demonstrated a slower release profile, achieving 80% release after 9–10 h, indicating a greater sensitivity to polymer concentration. At shorter intervals, drug release followed classical kinetic models, while multifractal dynamics dominated at longer intervals. Higher polymer concentrations resulted in slower drug release rates due to the formation of a gel-like structure upon hydration, which hindered drug diffusion. The mechanical properties and stability of the matrix tablets confirmed their suitability for extended-release applications. Mathematical modeling validated the experimental findings and provided insights into the structural and time-dependent factors influencing drug release. Conclusions: This study successfully developed dual-drug extended-release matrix tablets containing metformin hydrochloride and honokiol, highlighting the potential of hydrophilic polymers to regulate drug release. The findings emphasize the utility of advanced mathematical models for predicting release kinetics and underscore the potential of these formulations to improve patient compliance and therapeutic outcomes in diabetes management. Full article

Background: This study explored the potential of MCM-48 mesoporous silica matrices as a drug delivery system for metformin hydrochloride, aimed at improving the therapeutic management of type 2 diabetes mellitus. The objectives included the synthesis and characterization of MCM-48, assessment of its drug loading capacity, analysis of drug release profiles under simulated physiological conditions, and the development of a multifractal dynamics-based theoretical framework to model and interpret the release kinetics. Methods: MCM-48 was synthesized using a sol–gel method and characterized by SEM-EDX, TEM, and nitrogen adsorption techniques. Drug loading was performed via adsorption at pH 12 using metformin hydrochloride solutions of 1 mg/mL (P-1) and 3 mg/mL (P-2). In vitro dissolution studies were conducted to evaluate the release profiles in simulated gastric and intestinal fluids. A multifractal dynamics model was developed to interpret the release kinetics. Results: SEM-EDX confirmed the uniform distribution of silicon and oxygen, while TEM images revealed a highly ordered cubic mesoporous structure. Nitrogen adsorption analyses showed a high specific surface area of 1325.96 m²/g for unloaded MCM-48, which decreased with drug loading, confirming efficient incorporation of metformin hydrochloride. The loading capacities were 59.788 mg/g (P-1) and 160.978 mg/g (P-2), with efficiencies of 99.65% and 89.43%, respectively. In vitro dissolution studies showed a biphasic release profile: an initial rapid release in gastric conditions followed by sustained release in intestinal fluids, achieving cumulative releases of 92.63% (P-1) and 82.64% (P-2) after 14 hours. The multifractal dynamics-based theoretical release curves closely matched the experimental data. Conclusions: MCM-48 mesoporous silica effectively enhanced metformin delivery, offering a controlled release profile well-suited for type 2 diabetes management. The multifractal theoretical framework provided valuable insights into drug release dynamics, contributing to the advancement of innovative drug delivery systems. Full article

Objectives: Traditional Chinese Medicine (TCM) is recognized for its complex composition and multiple therapeutic targets. However, current pharmacological research often concentrates on extracts or individual components. The former approach faces numerous challenges, whereas the latter oversimplifies and disregards the synergistic effects among TCM components. This study aims to investigate the scientific validity of focusing on the active constituent in TCM efficacy research, using Pueraria lobata (P. lobata) as a case study. Methods: Through spectrum-effect correlation analysis, network pharmacology, and molecular docking, five active ingredients of P. lobata were identified: puerarin, formononetin, tuberosin, 4′,7-dihdroxy-3′-methoxyisoflavone, and Daidzein-4,7-diglucoside. These ingredients were combined to form an active constituent, which was subsequently tested in vitro and in vivo. Results: In in vitro, the active constituent exhibited superior effects in enhancing glucose consumption and glycogen synthesis compared to both the P. lobata extract and individual components. In vivo experiments demonstrated that medium and high doses of the active constituent were significantly more effective than P. lobata extract, with effects comparable to those of metformin in reducing blood sugar levels. Conclusions: The active constituent effectively improves T2DM by lowering blood glucose levels, promoting glycogen synthesis, and modulating glycolipid metabolism. Both in vitro and in vivo studies indicate that it outperformed the P. lobata extract and individual components. This study establishes the scientific validity and feasibility of utilizing the active constituent as the focus for investigating the efficacy of TCM, thereby offering novel insights and a new research paradigm for future TCM investigations. Full article

Neuropsychiatric disorders are a public health concern, in which diagnosis and prognosis may be based on clinical symptoms that might often diverge across individuals. Schizophrenia is a major neuropsychiatric disorder, which may affect millions worldwide. However, the biochemical alterations of this disorder have not been comprehensively distinguished. In addition, there is less confidence in finding specific biomarkers for neuropsychiatric disorders, including schizophrenia, but rather a specific characteristic behavioral pattern. In general, maternal immune activation is considered to be one of the important factors in the development of neuropsychiatric disorders. Here, a mouse model of neuropsychiatric disorders was created, in which poly I:C, sodium dextran sulfate (DSS), and κ-carrageenan (CGN) were utilized for maternal immune activation during the pregnancies of mother mice. Subsequently, we examined the link between biochemical changes in p62 and/or glutamate aspartate transporter (GLAST) in the brains of offspring mice and the alteration in their experimental behavior scores. Furthermore, a therapeutic study was conducted on these neuropsychiatric disorder model mice using butyric acid, piceid, and metformin. It was found that some molecules could effectively improve the behavioral scores of neuropsychiatric model mice. Importantly, significant correlations between certain behavioral scores and p62 protein expression, as well as between the scores and GLAST expression, were recognized. This is the first report of a significant correlation between pathological behaviors and biochemical alterations in neuropsychiatric disorder model animals. This concept could contribute to the development of innovative treatments to at least ameliorate the symptoms of several psychiatric disorders. Full article

Nervous system diseases represent a significant global burden, affecting approximately 16% of the world’s population and leading to disability and mortality. These conditions, encompassing both central nervous system (CNS) and peripheral nervous system (PNS) disorders, have substantial social and economic impacts. Metformin, a guanidine derivative derived from a plant source, exhibits therapeutic properties in various health conditions such as cancer, aging, immune-related disorders, polycystic ovary syndrome, cardiovascular ailments, and more. Recent studies highlight metformin’s ability to cross the blood–brain barrier, stimulate neurogenesis, and provide beneficial effects in specific neurological disorders through diverse mechanisms. This review discusses the advancements in research on metformin’s role and mechanisms in treating neurological disorders within both the central and peripheral nervous systems, aiming to facilitate further investigation, utilization, and clinical application of metformin in neurology. Full article

Background: SGLT-2 inhibitors (SGLT-2i) and GLP-1 receptor agonists (GLP-1RA) have demonstrated nephro- and cardioprotective effects, but their neuroprotective properties, especially concerning stroke severity, and mechanisms are not unambiguous. We aimed to study the influence of SGLT-2i with different selectivity and GLP-1RA on brain damage volume and neurological status in non-diabetic and diabetic rats and to investigate the underlying mechanisms. Methods: Non-diabetic Wistar rats were divided into five groups (n = 10 each) and received empagliflozin, canagliflozin, or dulaglutide as study drugs and metformin as comparison drug. Control animals were administered 0.9% NaCl for 7 days before stroke. At 48 h after stroke, we assessed neurological deficit, neuronal and astroglial damage markers, and brain damage volume. We also modeled type 2 DM in Wistar rats using the high-fat diet+nicotinamide/streptozotocin method and established similar treatment groups. After 8 weeks, rats were subjected to stroke with further neurological deficit, neuroglial damage markers, and brain necrosis volume measurement. Results: In non-diabetic rats, all the drugs showed an infarct-limiting effect; SGLT-2i and dulaglutide were more effective than metformin. DULA improved neurological status compared with MET and SGLT-2i treatment. All the drugs decreased neurofilament light chains (NLCs) level and neuronal damage markers, but none of them decreased the glial damage marker S100BB. In DM, similarly, all the drugs had infarct-limiting effects. Neurological deficit was most pronounced in the untreated diabetic rats and was reduced by all study drugs. All the drugs reduced NLC level; dulaglutide and empagliflozin, but not canagliflozin, also decreased S100BB. None of the drugs affected neuron-specific enolase. Conclusions: SGLT-2i and GLP-1RA are neuroprotective in experimental stroke. GLP-1RA might be more effective than SGLT-2i as in non-diabetic conditions it influences both brain damage volume and neurological status. All study drugs decrease neuronal damage, while GLP-1RA and highly selective SGLT-2i EMPA, but not low-selective CANA, also have an impact on neuroglia in diabetic conditions. Full article

Background: The association between diabetic nephropathy and arterial elasticity and endothelial function is well established. In this study, we compared the effect of the combination of dulaglutide and dapagliflozin versus DPP-4 inhibitors on the endothelial glycocalyx, arterial stiffness, myocardial function, and albuminuria. Methods: Overall, 60 patients were randomized to combined dulaglutide and dapagliflozin treatment (n = 30) or DPP-4 inhibitors (DPP-4i, n = 30) (ClinicalTrials.gov: NCT06611904). We measured at baseline and 4 and 12 months post-treatment: (i) the perfused boundary region of the sublingual arterial microvessels, (ii) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (iii) global left ventricular longitudinal strain (GLS), and (iv) urine albumin-to-creatinine ratio (UACR). Results: After twelve months, dual therapy showed greater improvements vs. DPP-4i in PBR (2.10 ± 0.31 to 1.93 ± 0.23 μm vs. 2.11 ± 0.31 to 2.08 ± 0.28 μm, p < 0.001), UACR (326 ± 61 to 142 ± 47 mg/g vs. 345 ± 48 to 306 ± 60 mg/g, p < 0.01), and PWV (11.77 ± 2.37 to 10.7 ± 2.29 m/s vs. 10.64 ± 2.44 to 10.54 ± 2.84 m/s, p < 0.001), while only dual therapy showed improvement in cSBP (130.21 ± 17.23 to 123.36 ± 18.42 mmHg). These effects were independent of glycemic control. Both treatments improved GLS, but the effect of dual therapy was significantly higher compared to DPP-4i (18.19% vs. 6.01%, respectively). Conclusions: Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in arterial stiffness, endothelial function, myocardial function, and albuminuria than DPP-4is. Early initiation of combined therapy as an add-on to metformin should be considered in these patients. Full article

Fibromyalgia (FM) is a chronic and debilitating condition characterized by diffuse pain, often associated with symptoms such as fatigue, cognitive disturbances, and mood disorders. Metformin, an oral hypoglycemic agent, has recently gained attention for its potential benefits beyond glucose regulation. It has shown promise in alleviating neuropathic and inflammatory pain, suggesting that it could offer a novel approach to managing chronic pain conditions like FM. This study aimed to further explore metformin’s analgesic potential by evaluating its effects in an experimental FM model induced by reserpine in both male and female mice. After the administration of 200 mg/kg metformin to male and female mice, the FM-related symptoms were assessed, including mechanical allodynia, thermal hyperalgesia, and depressive-like behaviors. A histological examination of the thalamus, hippocampus, and spinal cord was conducted using haematoxylin and eosin staining. The neurotransmitter and proinflammatory cytokines levels were measured in the brains and spinal cords. Our results have shown that metformin treatment for seven days significantly reversed these FM-like symptoms, reducing pain sensitivity and improving mood-related behaviors in both the male and female mice. Additionally, metformin exhibited neuroprotective effects, mitigating reserpine-induced damage in the hippocampus, thalamus, and spinal cord. It also significantly lowered the levels of the proinflammatory cytokine interleukin 1-beta (IL-1β) in the brain and spinal cord. Notably, metformin modulated the neurotransmitter levels differently between the sexes, decreasing glutamate and increasing serotonin and norepinephrine in the male mice, but not in the females. These findings underscore metformin’s potential as an alternative therapy for FM, with sex-specific differences suggesting distinct mechanisms of action. Full article