Design, Synthesis and Invitro Pharmacological Evaluation of Novel Resveratrol Surrogate Molecules against Alzheimer's disease.

A series of resveratrol surrogate molecules were designed, synthesized and biologically evaluated for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) along with anti-oxidant activity as potential novel multifunctional agents against Alzheimer's disease (AD). Six novel compounds were synthesized by reacting (E)-4-(3,5-Dimethoxystyryl) aniline with benzaldehyde and some selected derivatives of benzaldehyde in the presence of ethanol and a few drops of glacial acetic acid which followed the general scheme involved in the formation of Schiff bases. The spectral analysis data including FT-IR, 1H-NMR, 13C-NMR, and Mass spectroscopy results were found to be in good agreement with the newly synthesized compounds (Resveratrol Surrogate Molecules 1-6). The synthesized compounds were evaluated for their dual cholinesterase inhibitory activities, cytotoxic effect, and anti-oxidant potential. The results showed that compound RSM-5 showed potent inhibitory activity against AChE and BChE. In, addition the cytotoxicity of the compound RSM5 is less and found to be within the desirable limit indicating the potential safety of RSM5. Also, it possesses substantial anti-oxidant activity which qualifies RSM5 as an anti-AD agent. Taken together, these findings demonstrate that the molecule RSM5 had the most multifunctional properties and could be a promising lead molecule for the future development of drugs for Alzheimer's treatments.

Film Coating of Phosphorylated Mandua Starch on Matrix Tablets for pH-Sensitive Release of Mesalamine.

Chemically modified mandua starch was successfully synthesized and applied to coat mesalamine-loaded matrix tablets. The coating material was an aqueous dispersion of mandua starch modified by sodium trimetaphosphate and sodium tripolyphosphate. To investigate the colon-targeting release competence, chemically modified mandua starch film-coated mesalamine tablets were produced using the wet granulation method followed by dip coating. The effect of the coating on the colon-targeted release of the resultant delivery system was inspected in healthy human volunteers and rabbits using roentgenography. The results show that drug release was controlled when the coating level was 10% w/w. The release percentage in the upper gastric phase (pH 1.2, simulated gastric fluid) was less than 6% and reached up to 59.51% w/w after 14 h in simulated colonic fluid. In addition to in vivo roentgenographic studies in healthy rabbits, human volunteer studies proved the colon targeting efficiency of the formulation. These results clearly demonstrated that chemically modified mandua starch has high effectiveness as a novel aqueous coating material for controlled release or colon targeting.

Blastocystis sp. reduces the efficacy of 5-fluorouracil as a colorectal cancer chemotherapeutic treatment.

Blastocystis is an enteric protozoan parasite with extensive genetic variation and unclear pathogenicity. It is commonly associated with gastrointestinal symptoms such as nausea, diarrhea, vomiting and abdominal pain in immunocompromised individuals. In this study, we explored the in vitro and in vivo effects of Blastocystis on the activity of a commonly used CRC chemotherapeutic agent, 5-FU. The cellular and molecular effects of solubilized antigen of Blastocystis in the presence of 5-FU were investigated using HCT116, human CRC cell line and CCD 18-Co, normal human colon fibroblast cells. For the in vivo study, 30 male Wistar rats were divided into six groups, as follows; Control Group: oral administration of 0.3 ml Jones' medium, Group A: rats injected with azoxymethane (AOM), Group A-30FU: Rats injected with AOM and administered 30 mg/kg 5-FU, Group B-A-30FU: rats inoculated with Blastocystis cysts, injected with AOM and administered 30 mg/kg 5-FU, Group A-60FU: rats injected with AOM and administered 60 mg/kg 5-FU and Group B-A-60FU: rats inoculated with Blastocystis cysts, injected with AOM and administered 60 mg/kg 5-FU. The in vitro study revealed that the inhibitory potency of 5-FU at 8 µM and 10 µM was reduced from 57.7% to 31.6% (p < 0.001) and 69.0% to 36.7% (p < 0.001) respectively when co-incubated with Blastocystis antigen for 24 h. However, the inhibitory potency of 5-FU in CCD-18Co cells was not significantly affected in the presence of Blastocystis antigen. The reduced inhibitory potency of 5-FU against cancer cell proliferation due to the presence of Blastocystis is consistent with the upregulation of expression of type 2 cytokines, transforming growth factor (TGF-ß) and nuclear factor E2-related factor 2 (Nrf2) gene expression. Increased inflammation and abnormal histopathological findings along with a significant cancer multiplicity and adenoma incidence were evident in the intestine of the B-A-30FU and B-A-60FU groups when compared with the A-30FU and A-60FU groups respectively. Our in vitro and in vivo findings indicate that Blastocystis infection could potentially interfere with chemotherapy regimens such as 5-FU in CRC patients undergoing chemotherapy.

The association between mental health and obesity in postmenopausal women: A systematic review.

Postmenopausal women are at great risk of mental health deterioration, which may lead to morbidity and mortality. The decrement of mental health with aging is attributed to hormonal changes, lowered physical activity, sleep disturbances, economic factors, as well as modifiable variables such as smoking and obesity. Studies have shown controversial results on the association between obesity and mental health in postmenopausal women. This study is a systematic review of the evidence available on the association between obesity and mental health in postmenopausal women with the aim to identify the most reliable obesity measure that has been shown in association with mental health as well as the effective measures that have been practiced for improving mental health in postmenopausal obese women. CINAHL, Scopus, Science Direct and PubMed including Medline databases were searched. Out of 3,766 articles, 23 studies of average to good quality were included, out of which 17 were cross-sectional and 6 interventional. Out of the 17 studies, 12 showed a positive association between obesity and deterioration of mental health, 3 showed a negative association and two showed no association. From the interventional studies, 4 showed positive and two not significant impact of the intervention used on obesity and mental health. In conclusion, more studies showed a positive association between obesity, especially visceral obesity, and mental health issues particularly depression, anxiety, and sleep disorders. Combination of caloric restriction and exercise seems to have a better impact on the mental health of the postmenopausal in comparison with other interventions.

Chemistry, Biosynthesis and Pharmacology of Viniferin: Potential Resveratrol-Derived Molecules for New Drug Discovery, Development and Therapy.

Viniferin is a resveratrol derivative. Resveratrol is the most prominent stilbenoid synthesized by plants as a defense mechanism in response to microbial attack, toxins, infections or UV radiation. Different forms of viniferin exist, including alpha-viniferin (α-viniferin), beta-viniferin (ß-viniferin), delta-viniferin (δ-viniferin), epsilon-viniferin (ε-viniferin), gamma-viniferin (γ-viniferin), R-viniferin (vitisin A), and R2-viniferin (vitisin B). All of these forms exhibit a range of important biological activities and, therefore, have several possible applications in clinical research and future drug development. In this review, we present a comprehensive literature search on the chemistry and biosynthesis of and the diverse studies conducted on viniferin, especially with regards to its anti-inflammatory, antipsoriasis, antidiabetic, antiplasmodic, anticancer, anti-angiogenic, antioxidant, anti-melanogenic, neurodegenerative effects, antiviral, antimicrobial, antifungal, antidiarrhea, anti-obesity and anthelminthic activities. In addition to highlighting its important chemical and biological activities, coherent and environmentally acceptable methods for establishing vinferin on a large scale are highlighted to allow the development of further research that can help to exploit its properties and develop new phyto-pharmaceuticals. Overall, viniferin and its derivatives have the potential to be the most effective nutritional supplement and supplementary medication, especially as a therapeutic approach. More researchers will be aware of viniferin as a pharmaceutical drug as a consequence of this review, and they will be encouraged to investigate viniferin and its derivatives as pharmaceutical drugs to prevent future health catastrophes caused by a variety of serious illnesses.

Alginate-Based Encapsulation Fabrication Technique for Drug Delivery: An Updated Review of Particle Type, Formulation Technique, Pharmaceutical Ingredient, and Targeted Delivery System.

Alginate is a natural biopolymer widely studied for pharmaceutical applications due to its biocompatibility, low toxicity, and mild gelation abilities. This review summarizes recent advances in alginate-based encapsulation systems for targeted drug delivery. Alginate formulations like microparticles, nanoparticles, microgels, and composites fabricated by methods including ionic gelation, emulsification, spray drying, and freeze drying enable tailored drug loading, enhanced stability, and sustained release kinetics. Alginate microspheres prepared by spray drying or ionic gelation provide gastric protection and colon-targeted release of orally delivered drugs. Alginate nanoparticles exhibit enhanced cellular uptake and tumor-targeting capabilities through the enhanced permeation and retention effect. Crosslinked alginate microgels allow high drug loading and controlled release profiles. Composite alginate gels with cellulose, chitosan, or inorganic nanomaterials display improved mechanical properties, mucoadhesion, and tunable release kinetics. Alginate-based wound dressings containing antimicrobial nanoparticles promote healing of burns and chronic wounds through sustained topical delivery. Although alginate is well-established as a pharmaceutical excipient, more extensive in vivo testing is needed to assess clinical safety and efficacy of emerging formulations prior to human trials. Future opportunities include engineered systems combining stimuli-responsiveness, active targeting, and diagnostic capabilities. In summary, this review discusses recent advances in alginate encapsulation techniques for oral, transdermal, and intravenous delivery, with an emphasis on approaches enabling targeted and sustained drug release for enhanced therapeutic outcomes.

Exploring KRas Protein Dynamics: An Integrated Molecular Dynamics Analysis of KRas Wild and Mutant Variants.

This study employs a comprehensive approach combining protein retrieval, sequence alignment, and molecular dynamics simulations to investigate the structural dynamics and stability of wild-type KRas and its mutated variants (G12C, G12D, G12V, and G13D). The selected protein structures were retrieved from the Protein Data Bank (PDB) and prepared by using visual molecular dynamics (VMD) software. Sequence alignment using Clustal Omega provided a detailed comparison of the amino acid sequences, focusing on key mutation sites. Molecular dynamics simulations, performed with Gromacs, revealed distinct conformational changes and stability patterns in the wild-type and mutated KRas proteins over 100 ns. Clustering analysis identified higher conformational changes in the second α-helix of the mutated variants. The root-mean-square deviation (RMSD) distribution analysis showed variant-specific conformational dynamics, with G12V and G12D exhibiting slightly higher average RMSD values. Furthermore, clustering and RMSD analyses of specific amino acid residues (12, 13, 51, and 118) highlighted their roles in maintaining overall stability and influencing structural dynamics. The results indicate that mutations at positions 12 and 13 disrupt normal cycling between wild and mutated variants, leading to the persistent activation of KRas. Additionally, principal component analysis (PCA) elucidated unique conformational dynamics in mutated variants. Free energy landscape (FEL) analysis revealed alterations in the thermodynamic stability of mutated variants compared with the wild type. Overall, this study provides a detailed understanding of the structural changes associated with oncogenic mutations in KRas, offering insights crucial for targeted therapeutic strategies in KRas-driven cancers.

Generative artificial intelligence in drug discovery: basic framework, recent advances, challenges, and opportunities.

There are two main ways to discover or design small drug molecules. The first involves fine-tuning existing molecules or commercially successful drugs through quantitative structure-activity relationships and virtual screening. The second approach involves generating new molecules through de novo drug design or inverse quantitative structure-activity relationship. Both methods aim to get a drug molecule with the best pharmacokinetic and pharmacodynamic profiles. However, bringing a new drug to market is an expensive and time-consuming endeavor, with the average cost being estimated at around $2.5 billion. One of the biggest challenges is screening the vast number of potential drug candidates to find one that is both safe and effective. The development of artificial intelligence in recent years has been phenomenal, ushering in a revolution in many fields. The field of pharmaceutical sciences has also significantly benefited from multiple applications of artificial intelligence, especially drug discovery projects. Artificial intelligence models are finding use in molecular property prediction, molecule generation, virtual screening, synthesis planning, repurposing, among others. Lately, generative artificial intelligence has gained popularity across domains for its ability to generate entirely new data, such as images, sentences, audios, videos, novel chemical molecules, etc. Generative artificial intelligence has also delivered promising results in drug discovery and development. This review article delves into the fundamentals and framework of various generative artificial intelligence models in the context of drug discovery via de novo drug design approach. Various basic and advanced models have been discussed, along with their recent applications. The review also explores recent examples and advances in the generative artificial intelligence approach, as well as the challenges and ongoing efforts to fully harness the potential of generative artificial intelligence in generating novel drug molecules in a faster and more affordable manner. Some clinical-level assets generated form generative artificial intelligence have also been discussed in this review to show the ever-increasing application of artificial intelligence in drug discovery through commercial partnerships.

A dataset of microstructure features of electro-hydrodynamic assisted 5-fluorouracil-grafted alginate microbeads and physicochemical properties for effective colon targeted carriers drug delivery.

5-Fluorouracil (5-FU) has been the primary drug used in chemotherapy for colorectal carcinoma, and localizing the drug would be effective in avoiding its side effects and improving therapeutic outcomes. One approach to achieve this is by encapsulating the drug in microbeads. Alginate microbeads, in particular, exhibit promising pH-sensitive properties, making them an attractive option for colon targeting. Thus, the main aim of this study is to formulate and characterize 5-FU-encapsulated alginate microbeads as a pH-sensitive drug delivery system for controlled release in the gastrointestinal tract. In this study, the alginate microbeads encapsulating 5-FU was manufactured using electrospray methods. This method offers the advantages of promoting the formulation of uniformly small-sized microbeads with improved performance in terms of swelling and diffusion rates. The size and shape of the 5-FU microbeads are 394.23 ± 3.077 µm and have a spherical factor of 0.026 ± 0.022, respectively, which are considered acceptable and indicative of a spherical shape. The microbeads' encapsulation efficiency was found to be 69.65 ± 0.18%, which is considered high in comparison to other literature. The attenuated total reflectance - Fourier transform infrared spectroscopy (ATR-FTIR) data confirmed the complexation of sodium alginate with calcium ions, along with the encapsulation of 5-FU in the microbeads matrix. The 5-FU microbeads displayed pH-dependent swelling, exhibiting less swelling in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). Additionally, the release of 5-FU from the microbeads is pH-dependent, with the cumulative percentage drug release being higher in simulated intestinal fluid than in SGF. The data indicate that the 5-FU microbeads can be utilized for the delivery of 5-FU in colon-targeted therapy, potentially leading to improved tumor treatment.

Magnetic nanosystem a tool for targeted delivery and diagnostic application: Current challenges and recent advancement.

Over the last two decades, researchers have paid more attention to magnetic nanosystems due to their wide application in diverse fields. The metal nanomaterials' antimicrobial and biocidal properties make them an essential nanosystem for biomedical applications. Moreover, the magnetic nanosystems could have also been used for diagnosis and treatment because of their magnetic, optical, and fluorescence properties. Superparamagnetic iron oxide nanoparticles (SPIONs) and quantum dots (QDs) are the most widely used magnetic nanosystems prepared by a simple process. By surface modification, researchers have recently been working on conjugating metals like silica, copper, and gold with magnetic nanosystems. This hybridization of the nanosystems modifies the structural characteristics of the nanomaterials and helps to improve their efficacy for targeted drug and gene delivery. The hybridization of metals with various nanomaterials like micelles, cubosomes, liposomes, and polymeric nanomaterials is gaining more interest due to their nanometer size range and nontoxic, biocompatible nature. Moreover, they have good injectability and higher targeting ability by accumulation at the target site by application of an external magnetic field. The present article discussed the magnetic nanosystem in more detail regarding their structure, properties, interaction with the biological system, and diagnostic applications.

Enhancing drought tolerance in cauliflower (Brassica oleracea var. botrytis) by targeting LFY transcription factor modulation via the ethylene precursor, ACCA: an innovative computational approach.

Background: Brassica oleracea var. botrytis is an annual or biennial herbaceous vegetable plant in the Brassicaceae family notable for its edible blossom head. A lot of effort has gone into finding defense-associated proteins in order to better understand how cauliflower and pathogens interact. Endophytes are organisms that live within the host plant and reproduce. Endophytes are bacteria and fungi that reside in plant tissues and can either help or harm the plant. Several species have aided molecular biologists and plant biotechnologists in various ways. Water is essential for a healthy cauliflower bloom. When the weather is hot, this plant dries up, and nitrogen scarcity can be detrimental to cauliflower growth. Objective: The study sought to discern plant growth promoting (PGP) compounds that can amplify drought resilience and boost productivity in cauliflower. Methods: Investigations were centered on endophytes, microorganisms existing within plant tissues. The dual role of beneficial and detrimental Agrobacterium was scrutinized, particularly emphasizing the ethylene precursor compound, 1-amino-cyclopropane-1-carboxylic acid (ACCA). Results: ACCA possessed salient PGP traits, particularly demonstrating a pronounced enhancement of drought resistance in cauliflower plants. Specifically, during the pivotal marketable curd maturity phase, which necessitates defense against various threats, ACCA showcased a binding energy of -8.74 kcal/mol. Conclusion: ACCA holds a significant promise in agricultural productivity, with its potential to boost drought resistance and cauliflower yield. This could be particularly impactful for regions grappling with high temperatures and possible nitrogen shortages. Future research should explore ACCA's performance under diverse environmental settings and its applicability in other crops.

The Fabrication of Polymer-Based Curcumin-Loaded Formulation as a Drug Delivery System: An Updated Review from 2017 to the Present.

Turmeric contains curcumin, a naturally occurring compound with noted anti-inflammatory and antioxidant properties that may help fight cancer. Curcumin is readily available, nontoxic, and inexpensive. At high doses, it has minimal side effects, suggesting it is safe for human use. However, curcumin has extremely poor bioavailability and biodistribution, which further hamper its clinical applications. It is commonly administered through oral and transdermal routes in different forms, where the particle size is one of the most common barriers that decreases its absorption through biological membranes on the targeted sites and limits its clinical effectiveness. There are many studies ongoing to overcome this problem. All of this motivated us to conduct this review that discusses the fabrication of polymer-based curcumin-loaded formulation as an advanced drug delivery system and addresses different approaches to overcoming the existing barriers and improving its bioavailability and biodistribution to enhance the therapeutic effects against cancer and other diseases.

Identification of new potent NLRP3 inhibitors by multi-level in-silico approaches.

Nod-like receptor protein 3 (NLRP-3), is an intracellular sensor that is involved in inflammasome activation, and the aberrant expression of NLRP3 is responsible for diabetes mellitus, its complications, and many other inflammatory diseases. NLRP3 is considered a promising drug target for novel drug design. Here, a pharmacophore model was generated from the most potent inhibitor, and its validation was performed by the Gunner-Henry scoring method. The validated pharmacophore was used to screen selected compounds databases. As a result, 646 compounds were mapped on the pharmacophore model. After applying Lipinski's rule of five, 391 hits were obtained. All the hits were docked into the binding pocket of target protein. Based on docking scores and interactions with binding site residues, six compounds were selected potential hits. To check the stability of these compounds, 100 ns molecular dynamic (MD) simulations were performed. The RMSD, RMSF, DCCM and hydrogen bond analysis showed that all the six compounds formed stable complex with NLRP3. The binding free energy with the MM-PBSA approach suggested that electrostatic force, and van der Waals interactions, played a significant role in the binding pattern of these compounds. Thus, the outcomes of the current study could provide insights into the identification of new potential NLRP3 inflammasome inhibitors against diabetes and its related disorders.

A novel front in sustainable microbial management: computational analysis of curcumin and mangiferin's synergistic action against Bacillus anthracis.

Background: Microorganisms are crucial in our ecosystem, offering diverse functions and adaptability. The UNGA Science Summit has underscored the importance of understanding microbes in alignment with the UN Sustainable Development Goals. Bacillus anthracis poses significant challenges among various microorganisms due to its harmful effects on both soil and public health. Our study employed computational techniques to investigate the inhibitory effects of curcumin and mangiferin on Bacillus anthracis, with the aim of presenting a novel bio-based approach to microbial management. Methods: Employing high-throughput screening, we identified potential binding sites on B. anthracis. Molecular docking revealed that curcumin and mangiferin, when synergistically combined, exhibited strong binding affinities at different sites on the bacterium. Our findings demonstrated a significant drop in binding free energy, indicating a stronger interaction when these compounds were used together. Findings: Results of Molecular docking indicated binding energies of -8.45 kcal/mol for mangiferin, -7.68 kcal/mol for curcumin, and a notably higher binding energy of -19.47 kcal/mol for the combination of mangiferin and curcumin with CapD protein. Molecular dynamics simulations further validated these interactions, demonstrating increased stability and structural changes in the bacterium. Conclusion: This study highlights the effectiveness of natural compounds like curcumin and mangiferin in microbial management, especially against challenging pathogens like B. anthracis. It emphasizes the potential of sustainable, nature-based solutions and calls for further empirical research to expand upon these findings.

Nanomaterials-assisted photothermal therapy for breast cancer: State-of-the-art advances and future perspectives.

Breast cancer (BC) remains an enigmatic fatal modality ubiquitously prevalent in different parts of the world. Contemporary medicines face severe challenges in remediating and healing breast cancer. Due to its spatial specificity and nominal invasive therapeutic regime, photothermal therapy (PTT) has attracted much scientific attention down the lane. PTT utilizes a near-infrared (NIR) light source to irradiate the tumor target intravenously or non-invasively, which is converted into heat energy over an optical fibre. Dynamic progress in nanomaterial synthesis was achieved with specialized visual, physicochemical, biological, and pharmacological features to make up for the inadequacies and expand the horizon of PTT. Numerous nanomaterials have substantial NIR absorption and can function as efficient photothermal transducers. It is achievable to limit the wavelength range of an absorbance peak for specific nanomaterials by manipulating their synthesis, enhancing the precision and quality of PTT. Along the same lines, various nanomaterials are conjugated with a wide range of surface-modifying chemicals, including polymers and antibodies, which may modify the persistence of the nanomaterial and diminish toxicity concerns. In this article, we tend to put forth specific insights and fundamental conceptualizations on pre-existing PTT and its advances upon conjugation with different biocompatible nanomaterials working in synergy to combat breast cancer, encompassing several strategies like immunotherapy, chemotherapy, photodynamic therapy, and radiotherapy coupled with PTT. Additionally, the role or mechanisms of nanoparticles, as well as possible alternatives to PTT, are summarized as a distinctive integral aspect in this article.

Harnessing Nanovaccines for Effective Immunization─A Special Concern on COVID-19: Facts, Fidelity, and Future Prospective.

Nanotechnology has emerged as a transformative pathway in vaccine research and delivery. Nanovaccines, encompassing lipid and nonlipid formulations, exhibit considerable advantages over traditional vaccine techniques, including enhanced antigen stability, heightened immunogenicity, targeted distribution, and the potential for codelivery with adjuvants or immune modulators. This review provides a comprehensive overview of the latest advancements and applications of lipid and non-lipid-based nanovaccines in current vaccination strategies for immunization. The review commences by outlining the fundamental concepts underlying lipid and nonlipid nanovaccine design before delving into the diverse components and production processes employed in their development. Subsequently, a comparative analysis of various nanocarriers is presented, elucidating their distinct physicochemical characteristics and impact on the immune response, along with preclinical and clinical studies. The discussion also highlights how nanotechnology enables the possibility of personalized and combined vaccination techniques, facilitating the creation of tailored nanovaccines to meet the individual patient needs. The ethical aspects concerning the use of nanovaccines, as well as potential safety concerns and public perception, are also addressed. The study underscores the gaps and challenges that must be overcome before adopting nanovaccines in clinical practice. This comprehensive analysis offers vital new insights into lipid and nonlipid nanovaccine status. It emphasizes the significance of continuous research, collaboration among interdisciplinary experts, and regulatory measures to fully unlock the potential of nanotechnology in enhancing immunization and ensuring a healthier, more resilient society.

CircRNAs: Pivotal modulators of TGF-ß signalling in cancer pathogenesis.

The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation of biological functions. The study investigates the elusive link between circRNAs and the Transforming Growth Factor-ß (TGF-ß) signalling pathway, exploring their collective influence on cancer progression and metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns in diverse cancer types, revealing a repertoire of circRNAs intricately linked to the TGF-ß pathway. Through integrated bioinformatics analyses and functional experiments, we elucidate the specific circRNA-mRNA interactions that modulate TGF-ß signalling, unveiling the regulatory controls governing this crucial pathway. Furthermore, we provide compelling evidence of the impact of circRNA-mediated TGF-ß modulation on key cellular processes, including epithelial-mesenchymal transition (EMT), migration, and cell proliferation. In addition to their mechanistic roles, circRNAs have shown promise as diagnostic and prognostic biomarkers, as well as potential molecular targets for cancer therapy. Their ability to modulate critical pathways, such as the TGF-ß signalling axis, underscores their significance in cancer biology and clinical applications. The intricate interplay between circRNAs and TGF-ß is dissected, uncovering novel regulatory circuits that contribute to the complexity of cancer biology. This review unravels a previously unexplored dimension of carcinogenesis, emphasizing the crucial role of circRNAs in shaping the TGF-ß signalling landscape.

Kaempferol: Paving the path for advanced treatments in aging-related diseases.

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the ß-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.

From nature to nanotechnology: The interplay of traditional medicine, green chemistry, and biogenic metallic phytonanoparticles in modern healthcare innovation and sustainability.

As we navigate the modern era, the intersection of time-honoured natural remedies and contemporary scientific approaches forms a burgeoning frontier in global healthcare. For generations, natural products have been foundational to health solutions, serving as the primary healthcare choice for 80% to 85% of the world's population. These herbal-based, nature-derived substances, significant across diverse geographies, necessitate a renewed emphasis on enhancing their quality, efficacy, and safety. In the current century, the advent of biogenic phytonanoparticles has emerged as an innovative therapeutic conduit, perfectly aligning with principles of environmental safety and scientific ingenuity. Utilizing green chemistry techniques, a spectrum of metallic nanoparticles including elements such as copper, silver, iron, zinc, and titanium oxide can be produced with attributes of non-toxicity, sustainability, and economic efficiency. Sophisticated herb-mediated processes yield an array of plant-originated nanomaterials, each demonstrating unique physical, chemical, and biological characteristics. These attributes herald new therapeutic potentials, encompassing antioxidants, anti-aging applications, and more. Modern technology further accelerates the synthesis of natural products within laboratory settings, providing an efficient alternative to conventional isolation methods. The collaboration between traditional wisdom and advanced methodologies now signals a new epoch in healthcare. Here, the augmentation of traditional medicine is realized through rigorous scientific examination. By intertwining ethical considerations, cutting-edge technology, and natural philosophy, the realms of biogenic phytonanoparticles and traditional medicine forge promising pathways for research, development, and healing. The narrative of this seamless integration marks an exciting evolution in healthcare, where the fusion of sustainability and innovation crafts a future filled with endless possibilities for human well-being. The research in the development of metallic nanoparticles is crucial for unlocking their potential in revolutionizing fields such as medicine, catalysis, and electronics, promising groundbreaking applications with enhanced efficiency and tailored functionalities in future technologies. This exploration is essential for harnessing the unique properties of metallic nanoparticles to address pressing challenges and advance innovations across diverse scientific and industrial domains.

Non-coding RNA: A key regulator in the Glutathione-GPX4 pathway of ferroptosis.

Ferroptosis, a form of regulated cell death, has emerged as a crucial process in diverse pathophysiological states, encompassing cancer, neurodegenerative ailments, and ischemia-reperfusion injury. The glutathione (GSH)-dependent lipid peroxidation pathway, chiefly governed by glutathione peroxidase 4 (GPX4), assumes an essential part in driving ferroptosis. GPX4, as the principal orchestrator of ferroptosis, has garnered significant attention across cancer, cardiovascular, and neuroscience domains over the past decade. Noteworthy investigations have elucidated the indispensable functions of ferroptosis in numerous diseases, including tumorigenesis, wherein robust ferroptosis within cells can impede tumor advancement. Recent research has underscored the complex regulatory role of non-coding RNAs (ncRNAs) in regulating the GSH-GPX4 network, thus influencing cellular susceptibility to ferroptosis. This exhaustive review endeavors to probe into the multifaceted processes by which ncRNAs control the GSH-GPX4 network in ferroptosis. Specifically, we delve into the functions of miRNAs, lncRNAs, and circRNAs in regulating GPX4 expression and impacting cellular susceptibility to ferroptosis. Moreover, we discuss the clinical implications of dysregulated interactions between ncRNAs and GPX4 in several conditions, underscoring their capacity as viable targets for therapeutic intervention. Additionally, the review explores emerging strategies aimed at targeting ncRNAs to modulate the GSH-GPX4 pathway and manipulate ferroptosis for therapeutic advantage. A comprehensive understanding of these intricate regulatory networks furnishes insights into innovative therapeutic avenues for diseases associated with perturbed ferroptosis, thereby laying the groundwork for therapeutic interventions targeting ncRNAs in ferroptosis-related pathological conditions.