Curcumin-loaded polymeric nanomaterials as a novel therapeutic strategy for Alzheimer's disease: A comprehensive review.

Alzheimer's disease (AD) stands as a formidable challenge in modern medicine, characterized by progressive neurodegeneration, cognitive decline, and memory impairment. Despite extensive research, effective therapeutic strategies remain elusive. The antioxidant, anti-inflammatory, and neuroprotective properties of curcumin, found in turmeric, have demonstrated promise. The poor bioavailability and rapid systemic clearance of this drug limit its clinical application. This comprehensive review explores the potential of curcumin-loaded polymeric nanomaterials as an innovative therapeutic avenue for AD. It delves into the preparation and characteristics of diverse polymeric nanomaterial platforms, including liposomes, micelles, dendrimers, and polymeric nanoparticles. Emphasis is placed on how these platforms enhance curcumin's bioavailability and enable targeted delivery to the brain, addressing critical challenges in AD treatment. Mechanistic insights reveal how these nanomaterials modulate key AD pathological processes, including amyloid-beta aggregation, tau phosphorylation, oxidative stress, and neuroinflammation. The review also highlighted the preclinical studies demonstrate reduced amyloid-beta plaques and neuroinflammation, alongside improved cognitive function, while clinical trials show promise in enhancing curcumin's bioavailability and efficacy in AD. Additionally, it addresses the challenges of clinical translation, such as regulatory issues, large-scale production, and long-term stability. By synthesizing recent advancements, this review underscores the potential of curcumin-loaded polymeric nanomaterials to offer a novel and effective therapeutic approach for AD, aiming to guide future research and development in this field.

Proteomics profiling of extracellular vesicle for identification of potential biomarkers in Alzheimer's disease: A comprehensive review.

The intricate origins and diverse symptoms of Alzheimer's disease (AD) pose significant challenges for both diagnosis and treatment. Exosomes and microvesicles, which carry disease-specific cargo from a variety of central nervous system cell types, have emerged as promising reservoirs of biomarkers for AD. Research on the screening of possible biomarkers in Alzheimer's disease using proteomic profiling of EVs is systematically reviewed in this comprehensive review. We highlight key methodologies employed in EV isolation, characterization, and proteomic analysis, elucidating their advantages and limitations. Furthermore, we summarize the evolving landscape of EV-associated biomarkers implicated in AD pathogenesis, including proteins involved in amyloid-beta metabolism, tau phosphorylation, neuroinflammation, synaptic dysfunction, and neuronal injury. The literature review highlights the necessity for robust validation strategies and standardized protocols to effectively transition EV-based biomarkers into clinical use. In the concluding section, this review delves into potential future avenues and technological advancements pivotal in crafting EV-derived biomarkers applicable to AD diagnostics and prognostics. This review contributes to our comprehension of AD pathology and the advancement of precision medicine in neurodegenerative diseases, hinting at a promising era in AD precision medicine.

A review on advancements in the application of starch-based nanomaterials in biomedicine: Precision drug delivery and cancer therapy.

The burgeoning field of starch-based nanomaterials in biomedical applications has perceived notable progressions, with a particular emphasis on their pivotal role in precision drug delivery and the inhibition of tumor growth. The complicated challenges in current biomedical research require innovative approaches for improved therapeutic outcomes, prompting an exploration into the possible of starch-based nanomaterials. The conceptualization of this review emerged from recognizing the need for a comprehensive examination of the structural attributes, versatile properties, and mechanisms underlying the efficiency of starch-based nanomaterials in inhibiting tumor growth and enabling targeted drug delivery. This review delineates the substantial growth in utilizing starch-based nanomaterials, elucidating their small size, high surface-volume ratio, and biocompatibility, predominantly emphasizing their possible to actively recognize cancer cells, deliver anticancer drugs, and combat tumors efficiently. The investigation of these nanomaterials encompasses to improving biocompatibility and targeting specific tissues, thereby contributing to the evolving landscape of precision medicine. The review accomplishes by highlighting the auspicious strategies and modern developments in the field, envisioning a future where starch-based nanomaterials play a transformative role in molecular nanomaterials, evolving biomedical sciences. The translation of these advancements into clinical applications holds the potential to revolutionize targeted drug delivery and expand therapeutic outcomes in the realm of precision medicine.

New strategies of neurodegenerative disease treatment with extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs).

Neurodegenerative diseases are characterized by the progressive loss of neurons and intricate interactions between different cell types within the affected regions. Reliable biomarkers that can accurately reflect disease activity, diagnose, and monitor the progression of neurodegenerative diseases are crucial for the development of effective therapies. However, identifying suitable biomarkers has been challenging due to the heterogeneous nature of these diseases, affecting specific subsets of neurons in different brain regions. One promising approach for promoting brain regeneration and recovery involves the transplantation of mesenchymal stem cells (MSCs). MSCs have demonstrated the ability to modulate the immune system, promote neurite outgrowth, stimulate angiogenesis, and repair damaged tissues, partially through the release of their extracellular vesicles (EVs). MSC-derived EVs retain some of the therapeutic characteristics of their parent MSCs, including their ability to regulate neurite outgrowth, promote angiogenesis, and facilitate tissue repair. This review aims to explore the potential of MSC-derived EVs as an emerging therapeutic strategy for neurodegenerative diseases, highlighting their role in modulating disease progression and promoting neuronal recovery. By elucidating the mechanisms by which MSC-derived EVs exert their therapeutic effects, we can advance our understanding and leverage their potential for the development of novel treatment approaches in the field of neurodegenerative diseases.

Hypoglycemic Potential of Carica papaya in Liver Is Mediated through IRS-2/PI3K/SREBP-1c/GLUT2 Signaling in High-Fat-Diet-Induced Type-2 Diabetic Male Rats.

Regardless of socioeconomic or demographic background, the prevalence of type 2 diabetes mellitus, which affects more than half a billion people worldwide, has been steadily increasing over time. The health, emotional, sociological, and economic well-being of people would suffer if this number is not successfully handled. The liver is one of the key organs accountable for sustaining metabolic balance. Elevated levels of reactive oxygen species inhibit the recruitment and activation of IRS-1, IRS-2, and PI3K-Akt downstream signaling cascade. These signaling mechanisms reduce hepatic glucose absorption and glycogenesis while increasing hepatic glucose output and glycogenolysis. In our work, an analysis of the molecular mechanism of Carica papaya in mitigating hepatic insulin resistance in vivo and in silico was carried out. The gluconeogenic enzymes, glycolytic enzymes, hepatic glycogen tissue concentration, oxidative stress markers, enzymatic antioxidants, protein expression of IRS-2, PI3K, SREBP-1C, and GLUT-2 were evaluated in the liver tissues of high-fat-diet streptozotocin-induced type 2 diabetic rats using q-RT-PCR as well as immunohistochemistry and histopathology. Upon treatment, C. papaya restored the protein and gene expression in the liver. In the docking analysis, quercetin, kaempferol, caffeic acid, and p-coumaric acid present in the extract were found to have high binding affinities against IRS-2, PI3K, SREBP-1c, and GLUT-2, which may have contributed much to the antidiabetic property of C. papaya. Thus, C. papaya was capable of restoring the altered levels in the hepatic tissues of T2DM rats, reversing hepatic insulin resistance.

Effect of Carica papaya on IRS-1/Akt Signaling Mechanisms in High-Fat-Diet-Streptozotocin-Induced Type 2 Diabetic Experimental Rats: A Mechanistic Approach.

Despite rigorous endeavors, existing attempts to handle type 2 diabetes (T2DM) are still a long way off, as a substantial number of patients do not meet therapeutic targets. Insulin resistance in skeletal muscle is discerned as a forerunner in the pathogenesis of T2DM and can be detected years before its progress. Studies have revealed the antidiabetic properties of Carica papaya (C. papaya), but its molecular mechanism on insulin receptor substrate-1 (IRS-1)/Akt signaling mechanisms is not yet known. The present study aimed to evaluate the role of C. papaya on IRS1 and Akt in high-fat-diet-streptozotocin-induced type 2 diabetic rats and also to analyze the bioactive compounds of C. papaya against IRS-1 and Akt via in silico analysis. Ethanolic extract of the leaves of C. papaya (600 mg/kg of body weight) was given daily for 45 days postinduction of T2DM up to the end of the study. Gluconeogenic enzymes, glycolytic enzymes, gene expression, and immunohistochemical analysis of IRS-1 and Akt in skeletal muscle were evaluated. C. papaya treatment regulated the levels of gluconeogenic and glycolytic enzymes and the levels of IRS-1 and Akt in skeletal muscle of type 2 diabetic animals. In silico studies showed that trans-ferulic acid had the greatest hit rate against the protein targets IRS-1 and Akt. C. papaya restored the normoglycemic effect in diabetic skeletal muscle by accelerating the expression of IRS-1 and Akt.

Carica papaya Reduces Muscle Insulin Resistance via IR/GLUT4 Mediated Signaling Mechanisms in High Fat Diet and Streptozotocin-Induced Type-2 Diabetic Rats.

In the management of type 2 diabetes, oral antidiabetic drugs have several side effects, which in turn have led the pharmaceutical industry to search for good therapeutic, non-toxic and reliable drugs. Carica papaya (C. papaya) is one of several plants in nature that have been found to possess anti-diabetic properties. Despite studies being focused on the antidiabetic activity of C. papaya, the molecular mechanism against high fat diet induced insulin resistance is yet to be identified. The role of C. papaya was evaluated on insulin signaling molecules, such as the insulin receptor (IR) and glucose transporter-4 (GLUT4) in high fat, diet-streptozotocin induced type 2 diabetic rats, and analyzed the bioactive compounds of C. papaya against IR and GLUT4 via molecular docking and dynamics. The ethanolic extract of C. papaya leaves (600 mg/kg of body weight) was given daily to male wistar rats for 45 days and we observed the various biochemical parameters, gene expression analysis and histopathology of skeletal muscle. Molecular docking and dynamics were undertaken to understand the bioactive compounds with the greatest hit rate. C. papaya treatment was able to control blood glucose levels, the lipid profile and serum insulin, but it facilitated tissue antioxidant enzymes and IR and GLUT4 levels. The in-silico study showed that kaempferol, quercitin and transferulic acid were the top three ligands with the greatest hit rate against the protein targets. Our preliminary findings, for the first time, showed that C. papaya reinstates the glycemic effect in the diabetic skeletal muscle by accelerating the expression of IR and GLUT4.