Sustainable Synthesis of Guanidine Derivatives and Computational Assessment of their Antidiabetic Efficacy.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) represents a significant and pressing worldwide health concern, necessitating the quest for enhanced antidiabetic pharmaceuticals. Guanidine derivatives, notably metformin and buformin, have emerged as pivotal therapeutic agents for T2DM management. AIMS: The present study introduces an efficient one-pot synthesis method for the production of symmetrical guanidine compounds. METHODS: This synthesis involves the reaction of isothiocyanates with secondary amines, employing an environmentally friendly and recyclable reagent, tetrabutylphosphonium tribromide (TBPTB). RESULTS: A comprehensive assessment of the biological activity of the synthesized guanidine compounds, specifically in the context of T2DM, has been rigorously conducted. CONCLUSION: Additionally, computational analyses have unveiled their substantial potential as promising antidiabetic agents. Results highlight the relevance of these compounds in the ongoing pursuit of novel therapeutic solutions for T2DM.

A Comprehensive Approach to Parkinson's Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects.

Parkinson's disease (PD) is a gradually worsening neurodegenerative disorder affecting the nervous system, marked by a slow progression and varied symptoms. It is the second most common neurodegenerative disease, affecting over six million people in the world. Its multifactorial etiology includes environmental, genomic, and epigenetic factors. Clinical symptoms consist of non-motor and motor symptoms, with motor symptoms being the classic presentation. Therapeutic approaches encompass pharmacological, non-pharmacological, and surgical interventions. Traditional pharmacological treatment consists of administering drugs (MAOIs, DA, and levodopa), while emerging evidence explores the potential of antidiabetic agents for neuroprotection and gene therapy for attenuating parkinsonian symptoms. Non-pharmacological treatments, such as exercise, a calcium-rich diet, and adequate vitamin D supplementation, aim to slow disease progression and prevent complications. For those patients who have medically induced side effects and/or refractory symptoms, surgery is a therapeutic option. Deep brain stimulation is the primary surgical option, associated with motor symptom improvement. Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy and a portable infusion pump succeeded in reducing "off" time, where non-motor and motor symptoms occur, and increasing "on" time. This article aims to address the general aspects of PD and to provide a comparative comprehensive review of the conventional and the latest therapeutic advancements and emerging treatments for PD. Nevertheless, further studies are required to optimize treatment and provide suitable alternatives.

Non-Insulin Antidiabetic Agents and Lung Cancer Risk in Drug-Naive Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Assessment of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and other antidiabetic agents in Alzheimer's disease: A population-based study.

The lack of effective treatments for dementia has led to explore the potential of antidiabetic agents as a possible approach. This cross-sectional and population-based study aimed to investigate the relationship between each antidiabetic drug and their defined daily doses (DDDs) and the use of anti-Alzheimer's disease (AD) drugs in order to establish new possible hypotheses about the role of antidiabetic drugs in AD. For that purpose, a database containing information on medications prescribed to 233183 patients aged 50 years or older between 2018 and 2020 was used. DDDs were calculated according to the ATC/DDD index 2023. Statistical analyses, with logistic regression, were carried out to assess antidiabetic and anti-AD drugs consumption. A total of 91836 patients who were prescribed at least one antihypertensive, antidiabetic, or lipid-modifying agent were included in the study; specifically, 29260 patients were prescribed antidiabetic medication. Among the antidiabetic agents, glucagon-like peptide-1 analogs (GLP-1) DDDs were likely to have a positive association with anti-AD drugs in people aged between 70 and 80 years. Additionally, sodium-glucose cotransporter 2 inhibitors (SGLT2i) were prone to have a positive association with anti-AD drug usage across almost every age. However, insulin usage was associated with an increased usage of anti-AD agents. In conclusion, there is evidence suggesting a correlation between certain antidiabetic agents and dementia. Specifically, GLP-1 and SGLT2i might be associated with lower odds of anti-AD drugs usage, while insulins might be linked to higher odds of using anti-AD drugs.

Less common forms of diabetes in young population.

Types diabetes other than type 1 are generally considered rare in children and adolescents. The incidence of type 2 diabetes has increased dramatically over the past decade in some ethnic groups. The increased incidence of this type of diabetes mellitus has corresponded tem-porally to unprecedented increases in body weight and obesity prevalence in adolescents in various ethnic populations. Early treatment of insulin resistance is important to prevent the development of diabetes. In therapy, lifestyle modification is essential for weight loss, and if this is not enough, pharmacotherapy is required. Maturity-onset diabetes of the young (MODY), another type of insulin-dependent diabetes, is characterised by early onset and autosomal dominant inheritance. MODY is mainly caused by ß-cell defects, resulting in insufficient insulin secretion for a given blood glucose level. Unlike non-insulin-dependent diabetes in youth (NIDDM-Y), there is no significant increase in insulin resistance. The purpose of this article is to characterise and present types of diabetes other than type 1 found in the young population.

Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives.

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.

Antidiabetic potency and molecular insights of natural products bearing indole moiety: A systematic bioinformatics investigation targeting AKT1.

Diabetic mellitus (DM) is a chronic disorder, and type 2 DM (T2DM) is the most prevalent among all categories (nearly 90%) across the globe every year. With the availability of potential drugs, the prevalence rate has remained uncontrollable, while natural resources showed a promising potency, and exploring such potential candidates at the preclinical stage is essential. An extensive literature search selected 89 marine and plant-derived indole derivatives with anti-inflammatory, antioxidant, lipid-lowering, etc., activities. However, as we know, drugs have not been able to convert from 'lead' to 'mainstream' due to inadequate drug-ability profiles, as our systematic investigation proved and selected herdmanine_A (HERD_A) and penerpene_D (PENE_D) as the most potential antidiabetic candidates from the library of indole derivatives. Based on our previous network pharmacology study, we selected three new target enzymes: Acetyl-CoA carboxylase 2 (ACACB; PDB ID: 3JRX), cyclin-dependent kinase 4 (CDK4; PDB ID: 3G33), and alpha serine/threonine-protein kinase 1 (AKT1; PDB ID: 3O96) to assess the antidiabetic potency of selected indole derivatives through binding energy or docking score. To conduct molecular docking studies with these enzymes, we used the PyRx-AutoDock platform. Furthermore, molecular dynamic simulation at 100 ns, physicochemical analysis, pharmacokinetics, toxicity assessment, and drug-likeness evaluation suggested that HERD_A and penerpene PENE_D were the most potent inhibitors against AKT1 compared to koenimbine (most potential based on the recorded IC50 value) and murrayakonine_A (most potential based on the docking score). In summary, HERD_A and/or PENE_D have the potential to be used as alternative therapeutic agent for the treatment of diabetes after some pharmacological investigation.

The amelioration effect of antidiabetic agents on cytokine expression in patients with type 2 diabetes mellitus.

Inflammation is a condition that is closely linked to diabetes mellitus type 2 (T2DM), short for T2DM several different antidiabetic medications have been produced to regulate hyperglycemia, with indications that these therapies may have anti-inflammatory effects along with their glucose-lowering efficacy. Thus, this research was planned to explore the impact of antidiabetic agents on the cytokine expression levels -interleukin (IL)-1ß, IL-6, IL-17, and IL-37 when patients have T2DM. In this study, 168 eligible subject matter was split into two groups: 50 healthy individuals and 118 cases with T2DM, who were classified into two subgroups: 30 untreated patients and 88 patients treated with metformin-based therapy. The outcome exhibited a significant increase within HbA1c% and proinflammatory cytokines (i.e., IL-1ß, IL- 6, and IL-17), whereas IL-37 decreased considerably in untreated cases with T2DM compared to those in subjects who are healthy. Furthermore, the results showed increased levels Regarding waist size, body mass index and assessment using that homeostasis model, cholesterol, triglycerides, low-density lipoprotein levels, and heart danger elements in untreated cases with T2DM in comparison with hygienic subjects. Notably, treated patients with T2DM revealed an ameliorative impact on HbA1c, IL-6, IL-17, IL-37, IL-1ß levels and lipid profile compared with untreated patients with T2DM. Antidiabetic agents may have a beneficial activity on the inflammatory status by reducing blood glucose levels, hyperlipidemia, and proinflammatory cytokines. The anti-inflammatory activity of IL-37 can apply a potentially effective therapeutic goal in treating T2DM and its complications.

Prior authorization for diabetes medications: Clinical outcomes and health disparities.

BACKGROUND: Prior authorization (PA) is a utilization management strategy used by health plans to ensure affordable, cost-effective care; however, PA may lead to therapy delay/abandonment and exacerbate health disparities. The purpose of this observational study was to assess the clinical outcomes and any health disparities associated with PA for diabetes mellitus (DM) medications. MATERIALS AND METHODS: This was a cohort study of US adult patients from health plans with integrated and non-integrated system providers who were prescribed a DM medication that required a PA. Patients were categorized into three groups: received the requested DM medication (PA Med) or a new, alternative DM medication (DM Med), or did not receive the requested or new DM medication (No Med). The primary outcome was change in hemoglobin A1c (HbA1c). Adjusted and unadjusted analyses were performed. Patient characteristics associated with the No Med group were identified, also, with multivariable logistic regression modeling. RESULTS: 6305 patients were included: 2434, 1323, and 2548 in the PA Med, DM Med, and No Med groups, respectively. Patients in the PA Med (-0.9 %) and DM Med (-1.0 %) groups had statistically significantly greater reductions in HbA1c compared to the No Med group (-0.4 %) in both unadjusted and adjusted analyses (all p < 0.05). Patients who were Hispanic/Latino, had a non-integrated system prescriber, and had a higher burden of chronic disease were statistically significantly associated with the No Med group. CONCLUSIONS: Receiving a new DM medication following PA was associated with better clinical outcomes but health disparities were present in the PA process.

Identification of dual-target isoxazolidine-isatin hybrids with antidiabetic potential: Design, synthesis, in vitro and multiscale molecular modeling approaches.

In the development of novel antidiabetic agents, a novel series of isoxazolidine-isatin hybrids were designed, synthesized, and evaluated as dual α-amylase and α-glucosidase inhibitors. The precise structures of the synthesized scaffolds were characterized using different spectroscopic techniques and elemental analysis. The obtained results were compared to those of the reference drug, acarbose (IC50 = 296.6 ± 0.825 µM for α-amylase & IC50 = 780.4 ± 0.346 µM for α-glucosidase). Among the title compounds, 5d exhibited impressive α-amylase and α-glucosidase inhibitory activity with IC50 values of 30.39 ± 1.52 µM and 65.1 ± 3.11 µM, respectively, followed by 5h (IC50 = 46.65 ± 2.3 µM; IC50 = 85.16 ± 4.25 µM) and 5f (IC50 = 55.71 ± 2.78 µM; IC50 = 106.77 ± 5.31 µM). Mechanistic studies revealed that the most potent derivative 5d bearing the chloro substituent attached to the oxoindolin-3-ylidene core, and acarbose, are a competitive inhibitors of α-amylase and α-glucosidase, respectively. Structure activity relationship (SAR) was examined to guide further structural optimization of the most appropriate substituent(s). Moreover, drug-likeness qualities and ADMET prediction of the most active analogue, 5d was also performed. Subsequently, 5d was subjected to molecular docking and dynamic simulation during the progression of 120 ns analysis to check the essential ligand-receptor patterns, and to estimate its stability. In silico studies were found in good agreement with the in vitro enzymatic inhibitions results. In conclusion, we demonstrated that most potent compound 5d could be exploited as dual potential inhibitor of α-amylase and α-glucosidase for possible management of diabetes.

Novel molecular hybrids of EGCG and quinoxaline: Potent multi-targeting antidiabetic agents that inhibit α-glucosidase, α-amylase, and oxidative stress.

Diabetes mellitus is a multifactorial disease and its effective therapy often demands several drugs with different modes of action. Herein, we report a rational design and synthesis of multi-targeting novel molecular hybrids comprised of EGCG and quinoxaline derivatives that can effectively inhibit α-glucosidase, α-amylase as well as control oxidative stress by scavenging ROS. The hybrids showed superior inhibition of α-glucosidase along with similar α-amylase inhibition as compared to standard drug, acarbose. Most potent compound, 15c showed an IC50 of 0.50 µM (IC50 of acarbose 190 µM) against α-glucosidase. Kinetics studies with 15c revealed a competitive inhibition against α-glucosidase. Binding affinity of 15c (-9.5 kcal/mol) towards α-glucosidase was significantly higher than acarbose (-7.7 kcal/mol). 15c exhibited remarkably high antioxidant activity (IC50 = 18.84 µM), much better than vitamin C (IC50 = 33.04 µM). Of note, acarbose shows no antioxidant activity. Furthermore, α-amylase activity was effectively inhibited by 15c with an IC50 value of 16.35 µM. No cytotoxicity was observed for 15c (up to 40 µM) in MCF-7 cells. Taken together, we report a series of multi-targeting molecular hybrids capable of inhibiting carbohydrate hydrolysing enzymes as well as reducing oxidative stress, thus representing an advancement towards effective and novel therapeutic approaches for diabetes.

Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: A post-hoc study of the CONFIDENCE trial.

Background: Adipokines and inflammatory cytokines (ADICs) play important roles in type 2 diabetes mellitus (T2DM). This study aimed to compare the changes of ADIC levels (ΔADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, ß-cell function and insulin resistance (IR). Methods: Four hundred and sixteen patients with newly diagnosed T2DM from 25 centers in China randomly received 48-week intervention with exenatide, insulin or pioglitazone. Anthropometric and laboratory data, indices of ß-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1ß), interferon-gamma (IFN-γ), leptin, and fibroblast growth factor 21 (FGF21) were detected at baseline and the end of the study. Results: In total, 281 participants (68 % male, age: 50.3 ± 9.4 years) completed the study. After 48- week treatment, IL-1ß and IFN-γ were significantly decreased with exenatide treatment (P < 0.001 and P = 0.001, respectively), but increased with insulin (P = 0.009 and P = 0.026, respectively). However, pioglitazone treatment had no impact on ADICs. No significant change in leptin or FGF21 was detected with any of the treatments. After adjustment for baseline values and changes of body weight, waist and HbA1c, the between-group differences were found in ΔIL-1ß (exenatide vs. insulin: P = 0.048; and exenatide vs. pioglitazone: P = 0.003, respectively) and ΔIFN-γ (exenatide vs. insulin: P = 0.049; and exenatide vs. pioglitazone: P < 0.001, respectively). Multiple linear regression analysis indicated that Δweight was associated with ΔIL-1ß (ß = 0.753; 95 % CI, 0.137-1.369; P = 0.017). After adjusting for treatment effects, Δweight was also be correlated with ΔFGF21 (ß = 1.097; 95%CI, 0.250-1.944; P = 0.012); furthermore, ΔHOMA-IR was correlated with Δleptin (ß = 0.078; 95%CI, 0.008-0.147; P = 0.029) as well. However, ΔHOMA-IR was not significantly associated with ΔIL-1ß after adjusting for treatment effects (P = 0.513). Conclusion: Exenatide treatment led to significant changes of inflammatory cytokines levels (IL-1ß and IFN-γ), but not adipokines (leptin and FGF21), in newly diagnosed T2DM patients. The exenatide-mediated improvement in weight and IR may be associated with a decrease in inflammatory cytokine levels.

Discovery and biological evaluation of novel dual PTP1B and ACP1 inhibitors for the treatment of insulin resistance.

In this study, a virtual screening pipeline comprising ligand-based and structure-based approaches was established and applied for the identification of dual PTP1B and ACP1 inhibitors. As a result, a series of benzoic acid derivatives was discovered, and compound H3 and S6 demonstrated PTP1B and ACP1 inhibitory activity, with IC50 values of 3.5 and 8.2 µM for PTP1B, and 2.5 and 5.2 µM for ACP1, respectively. Molecular dynamics simulations illustrated that H3 interacted with critical residues in the active site, such as Cys215 and Arg221 for PTP1B, and Cys17 and Arg18 for ACP1. Enzymatic kinetic research indicated that identified inhibitors competitively inhibited PTP1B and ACP1. Additionally, cellular assays demonstrated that H3 and S6 effectively increased glucose uptake in insulin-resistant HepG2 cells while displaying very limited cytotoxicity at their effective concentrations. In summary, H3 and S6 represent novel dual-target inhibitors for PTP1B and ACP1, warranting further investigation as potential agents for the treatment of diabetes.

An Insight into the Development of Potential Antidiabetic Agents along with their Therapeutic Targets.

Diabetes is a metabolic disorder that has been reported to increase the mortality rate worldwide. About 40 million people across the globe suffer from diabetes, with people living in developing countries being affected the most due to this deadly disease. Although the therapeutic management of hyperglycaemia can treat diabetes, metabolic disorders associated with this disease are a greater challenge in its treatment. Hence, potential strategies to treat hyperglycaemia and its side effects are needed. In this review, we have summarized several therapeutic targets, like dipeptidyl peptidase-4 (DPP-4), glucagon receptor antagonists, glycogen phosphorylase or fructose-1,6- biphosphatase inhibitors, SGLT inhibitors, 11beta-HSD-1 inhibitors, glucocorticoids receptor antagonists, glucose-6-phosphatase and glycogen phosphorylase inhibitors. These targets can help in designing and developing novel antidiabetic agents.

Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents.

Tetrazole heterocycle is a promising scaffold in drug design, and it is incorporated into active pharmaceutical ingredients of medications of various actions: hypotensives, diuretics, antihistamines, antibiotics, analgesics, and others. This heterocyclic system is metabolically stable and easily participates in various intermolecular interactions with different biological targets through hydrogen bonding, conjugation, or van der Waals forces. In the present review, a systematic analysis of the activity of tetrazole derivatives against type 2 diabetes mellitus (T2DM) has been performed. As it was shown, the tetrazolyl moiety is a key fragment of many antidiabetic agents with different activities, including the following: peroxisome proliferator-activated receptors (PPARs) agonists, protein tyrosine phosphatase 1B (PTP1B) inhibitors, aldose reductase (AR) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, G protein-coupled receptor (GPCRs) agonists, glycogen phosphorylases (GP) Inhibitors, α-glycosidase (AG) Inhibitors, sodium glucose co-transporter (SGLT) inhibitors, fructose-1,6-bisphosphatase (FBPase) inhibitors, IkB kinase ε (IKKε) and TANK binding kinase 1 (TBK1) inhibitors, and 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). In many cases, the tetrazole-containing leader compounds markedly exceed the activity of medications already known and used in T2DM therapy, and some of them are undergoing clinical trials. In addition, tetrazole derivatives are very often used to act on diabetes-related targets or to treat post-diabetic disorders.

An age-stratified cross-sectional study of antidiabetic and non-antidiabetic drugs prescribed to Japanese outpatients with diabetes.

Polypharmacy, common in patients with diabetes, may cause adverse drug reactions. The number of antidiabetic and non-antidiabetic drugs prescribed to patients in different age groups remains unclear. The aim of this study was to examine the number and class of antidiabetics and non-antidiabetics prescribed to Japanese patients with diabetes, stratified by age for reducing polypharmacy. This cross-sectional study examined all prescriptions of patients prescribed antidiabetics at 257 pharmacies of Matsumotokiyoshi Holdings in Japan from May 2018 to March 2019. Total prescription numbers including antidiabetic drugs were 263,915 in this study. Mean numbers of antidiabetic drugs per prescription were 1.71, 2.17, and 1.52 in the patient age groups of 10-19, 50-59, and 90-99 years, respectively. Count of antidiabetics was not related to age. However, the mean total number of drugs prescribed increased with age, which was 2.22 and 7.99 in the age groups of 10-19 and 90-99 years, respectively. The linear regression coefficient (b) according to age was 0.07 (p < 0.001) for 10-99 years. The mean non-antidiabetic number of agents prescribed increased with age among 10-99 years (b = 0.07, p < 0.001). Among outpatients treated for diabetes, dipeptidyl peptidase-4 inhibitors (29%) and antihypertensive, ß-blocking and renin-angiotensin system blocking drugs (32%) were the most prescribed antidiabetics and non-antidiabetics in all ages, respectively. The number of prescribed antidiabetic agents did not increase with age, whereas the total and non-antidiabetic numbers of medications prescribed increased linearly. For reduction of polypharmacy in older people with diabetes, we need to focus on non-antidiabetics.

Indole-pyridine carbonitriles: multicomponent reaction synthesis and bio-evaluation as potential hits against diabetes mellitus.

Background: Diabetes mellitus is a significant health disorder; therefore, researchers should focus on discovering new drug candidates. Methods: A series of indole-pyridine carbonitrile derivatives, 1-34, were synthesized through a one-pot multicomponent reaction and evaluated for antidiabetic and antioxidant potential. Results: In this library, 12 derivatives - 1, 2, 4, 5, 7, 8, 10-12, 14, 15 and 31 - exhibited potent inhibitory activities against α-glucosidase and α-amylase enzymes, in comparison to acarbose (IC50 = 14.50 ± 0.11 µM). Furthermore, kinetics, absorption, distribution, metabolism, excretion and toxicity and molecular docking studies were used to interpret the type of inhibition, binding energies and interactions of ligands with target enzymes. Conclusion: These results indicate that the compounds may be promising hits for controlling diabetes mellitus and its related complications.

Exploring the Potential of Antidiabetic Agents as Therapeutic Approaches for Alzheimer's and Parkinson's Diseases: A Comprehensive Review.

Alzheimer's and Parkinson's are two prevalent neurodegenerative disorders with significant societal and healthcare burdens. The search for effective therapeutic approaches to combat these diseases has led to growing interest in exploring the potential of antidiabetic agents. This comprehensive review aims to provide a detailed overview of the current literature on using antidiabetic agents as therapeutic interventions for Alzheimer's and Parkinson's diseases. We discuss the underlying pathological mechanisms of these neurodegenerative diseases, including protein misfolding, inflammation, oxidative stress, and mitochondrial dysfunction. We then delve into the potential mechanisms by which antidiabetic agents may exert neuroprotective effects, including regulation of glucose metabolism and insulin signaling, anti-inflammatory effects, modulation of oxidative stress, and improvement of mitochondrial function and bioenergetics. We highlight in vitro, animal, and clinical studies that support the potential benefits of antidiabetic agents in reducing disease pathology and improving clinical outcomes. However, we also acknowledge these agents' limitations, variability in treatment response, and potential side effects. Furthermore, we explore emerging therapeutic targets and novel approaches, such as glucagon-like peptide-1 receptor (GLP-1R) agonists, insulin sensitizer drugs, neuroinflammation-targeted therapies, and precision medicine approaches. The review concludes by emphasizing the need for further research, including large-scale clinical trials, to validate the efficacy and safety of antidiabetic agents in treating Alzheimer's and Parkinson's disease. The collaboration between researchers, clinicians, and pharmaceutical companies is essential in advancing the field and effectively treating patients affected by these debilitating neurodegenerative disorders.

Protein-modified nanomaterials: emerging trends in skin wound healing.

Prolonged inflammation can impede wound healing, which is regulated by several proteins and cytokines, including IL-4, IL-10, IL-13, and TGF-ß. Concentration-dependent effects of these molecules at the target site have been investigated by researchers to develop them as wound-healing agents by regulating signaling strength. Nanotechnology has provided a promising approach to achieve tissue-targeted delivery and increased effective concentration by developing protein-functionalized nanoparticles with growth factors (EGF, IGF, FGF, PDGF, TGF-ß, TNF-α, and VEGF), antidiabetic wound-healing agents (insulin), and extracellular proteins (keratin, heparin, and silk fibroin). These molecules play critical roles in promoting cell proliferation, migration, ECM production, angiogenesis, and inflammation regulation. Therefore, protein-functionalized nanoparticles have emerged as a potential strategy for improving wound healing in delayed or impaired healing cases. This review summarizes the preparation and applications of these nanoparticles for normal or diabetic wound healing and highlights their potential to enhance wound healing.