Obesity has emerged as a global health crisis in the 21st century, driven by rising obesity rates and associated metabolic disorders. The genome-wide association studies led to the identification of a gene associated with obesity and thus named the fat mass and obesity-associated (FTO) gene. In humans, the FTO gene is expressed in various tissues, including the brain, liver, and adipose tissue. It is known to play a major role in regulating energy balance, appetite, and body fat mass. FTO encodes an N6-methyladenosine RNA demethylase that regulates key biological processes, including adipogenesis, energy homeostasis, and glucose metabolism, through a dynamic RNA modification process involving splicing, export, decay, and/or translation. Polymorphisms in the FTO gene, particularly within intron 1, are strongly associated with increased risk of body mass index and obesity. In addition, FTO has been implicated in the pathogenesis of type 2 diabetes mellitus, cardiovascular disease, chronic kidney disease, and various cancers, where it could function both as an oncogene and a tumor suppressor gene. Pre-clinical studies have established the functional relevance of FTO, where its overexpression promotes obesity, whereas its deletion allows maintenance of a normal body phenotype. This review covers the recent advances in the development of specific FTO inhibitors and highlights their potential as therapeutic agents for obesity and metabolic disorders, although their development is still in its early stages. Despite the significant progress made in understanding the role of FTO in metabolic diseases, further research is needed to elucidate the precise mechanisms linking FTO variants to specific pathological outcomes and to optimize targeted therapies.

Chronic atrophic gastritis (CAG) is a prevalent and progressive gastric disorder that can lead to significant gastric dysfunction and an increased risk of gastric cancer. Oxidative stress plays a central role in the pathogenesis of CAG, contributing to cellular damage and inflammation. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is crucial in cellular defense against oxidative stress by regulating the expression of antioxidant and cytoprotective genes. Activation of this pathway has shown promise in mitigating oxidative damage and promoting mucosal healing in CAG. This review aims to explore the therapeutic potential of Nrf2/ARE pathway activation in the context of CAG. We discuss the mechanisms underlying the activation of Nrf2, its role in regulating antioxidant genes, and its impact on oxidative stress management in the gastric mucosa. Recent advancements in pharmacological agents that activate the Nrf2 pathway, such as rhein and certain traditional Chinese medicines, are also highlighted. These interventions have demonstrated protective effects against oxidative stress, reduced inflammation, and promoted gastric mucosal healing. We, further, explore the potential clinical applications of Nrf2 activators in CAG treatment and the challenges in translating these findings into clinical practice. In addition, we outline future research directions aimed at optimizing Nrf2 activation strategies and exploring combination therapies to enhance therapeutic outcomes in CAG patients. The findings underscore the importance of targeting the Nrf2/ARE pathway as a promising strategy for managing oxidative stress-related gastric diseases.

Nanomedicine, at the convergence of nanotechnology and medicine, holds transformative potential for bone healing through advanced diagnostic and therapeutic strategies. Among various nanomaterials, silver nanoparticles (AgNPs) have gained attention due to their broad-spectrum antimicrobial, anti-inflammatory, and anticancer properties. This review examines the principles of nanomedicine and theranostics, AgNP synthesis methods and physicochemical characteristics, and their application in bone regeneration for infection control, scaffold design, osteoinduction, and angiogenesis. The integration of AgNPs into theranostic platforms for simultaneous therapy and imaging is critically evaluated, highlighting modalities such as micro-computed tomography, magnetic resonance imaging, and photoacoustic imaging. The preclinical and early clinical evidence is analyzed, addressing critical limitations including toxicity, biocompatibility, pharmacokinetics, manufacturing reproducibility, and regulatory hurdles. This review outlines future trends, such as green synthesis, stimuli-responsive systems, and personalized scaffolds. A comprehensive understanding of these multidimensional facets is crucial for advancing AgNP-based nanomedicine from the bench to the bedside in bone healing applications.

For centuries, humans have long sought plant-based remedies derived from barks, seeds, and fruits in their enduring battle against illness. Over time, traditional medicines have evolved to become more effective and safer through pharmacological validation. One key area where these remedies have shown promise is in treating skin infections, as the skin is often the first point of contact for microorganisms and particularly vulnerable to infections caused by bacteria, fungi, viruses, and parasites. Currently, topical infections are primarily treated using ointments and creams, which deliver high concentrations of antimicrobials directly to the affected area. Studies reveal that ethanolic extracts have potent antibacterial activity against Pseudomonas aeruginosa and Staphylococcus species. This effect is ascribed to moderate to high concentrations of saponins, known for their antibacterial qualities. The present study investigates the antibacterial properties of ethanolic and aqueous extracts of Xylopia aethiopica for the formulation of a topical ointment. To determine their minimum inhibitory concentrations (MICs), cultures of Staphylococcus aureus and P. aeruginosa were tested against the extracts, which exhibited MIC values ranging from 2.5 mg/mL to 10 mg/mL for both the ethanolic and aqueous forms. The ointments and creams formulated from these extracts demonstrated notable antibacterial activity, alongside excellent physicochemical properties, including a smooth texture, appealing appearance, uniform consistency with no phase separation, characteristic brown color, excellent spreadability, stability, and suitable pH values (6.3 for the ointment and 7 for the cream), as well as non-irratating effects on the skin. The findings confirm that X. aethiopica possesses effective antibacterial properties against S. aureus and P. aeruginosa, supporting its potential for further in vivo studies and broader therapeutic applications.

The growing demand for natural therapeutic agents has intensified interest in plant-based compounds with potential pharmacological applications. Alcea rosea, traditionally employed in various ethnomedical systems, particularly for inflammatory and respiratory conditions, remains underexplored at the phytochemical level, especially concerning its seeds. The current study aims to bridge this gap by evaluating the chemical constituents of A. rosea seeds and assessing their potential bioactive significance using advanced analytical techniques. Ethyl acetate extraction was chosen for its efficiency in isolating semi-polar compounds, followed by gas chromatography-mass spectrometry to identify the chemical content of the extract. This method enabled the detection of over 50 distinct molecular entities, among which 15 were identified as major components based on peak abundance and database matching using the National Institute of Standards and Technology mass spectral library and the Wiley Registry of Mass Spectral Data. The chemical landscape of the extract included a range of fatty acids, esters, and complex organic molecules, many of which are known to possess anti-inflammatory, antioxidant, antimicrobial, and cytotoxic properties. Notable among these were linoleic acid, oleic acid, and palmitic acid compounds, which are widely recognized for their contributions to cellular signaling, oxidative stress modulation, and tumor suppression. The identification of bis(2-ethylhexyl) phthalate and A13-09519 (chemically ethyl N-methylcarbamate) also points to lesser-known or unconventional phytoconstituents that may hold biomedical interest, although their origin and activity warrant further validation. This investigation reveals A. rosea seeds as a chemically rich botanical source with a diverse array of compounds that could support therapeutic applications. The study sets a precedent for future bioactivity-driven analyses and highlights the value of integrating traditional knowledge with modern phytochemical screening to uncover novel drug leads from botanical sources.

Osteoarthritis (OA) is characterized by the activation of nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) by thioredoxin-interacting protein (TXNIP), which promotes inflammation and pyroptosis. This study investigates whether treadmill exercise (TE) enhances melatonin-mediated regulation of the TXNIP/NLRP3 pathway and attenuates OA progression by modulating pyroptosis in a destabilization of the medial meniscus (DMM) rat model. A total of 32 male Sprague-Dawley rats (6 weeks old; 220 ± 20 g) were randomly assigned to four groups: Sham, DMM, DMM + melatonin, and DMM + melatonin + TE. The intervention lasted for 8 weeks. Morphological staining, immunofluorescence (IF), microcomputed tomography with three-dimensional reconstruction, Western blot, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay were used to assess protein and gene expression. Compared with the DMM + melatonin group, the DMM + melatonin + TE group showed greater reductions in cartilage-subchondral bone damage and OA progression through modulation of the pyroptosis pathway. IF staining revealed that TXNIP protein expression was significantly reduced in the DMM + melatonin + TE group. Both the DMM + melatonin and combination treatment groups significantly regulated TXNIP/NLRP3 signaling and inhibited OA progression through pyroptosis. Furthermore, combining TE with melatonin significantly reduced the expression of pyroptotic cytokines compared with the DMM + melatonin group. This study suggests a potential therapeutic approach for managing OA by combining melatonin treatment with moderate TE.