Background The rise in HIV prevalence has led to more individuals using antiretroviral therapy (ART). These drugs, together with concurrent lifestyle factors, contribute to metabolic dysfunction, such as an increased risk of prediabetes. The asymptomatic nature of prediabetes may increase the probability of initiating ART without appropriate individualised regimen selection or required metabolic monitoring. Objectives This study evaluated the effects of NRTI‐ and NNRTI‐based fixed‐dose combination regimens used as pre‐exposure prophylaxis (Truvada) and for HIV management (Triovir) on selected markers of glucose homeostasis. Methods Forty‐two male Sprague Dawley rats (150–180 g) were randomly allocated into two main groups: nonprediabetic (NPD) ( n = 21) and prediabetic (PD) ( n = 21). Prediabetes was induced using a high‐fat, high‐carbohydrate (HFHC) diet over 20 weeks, followed by a treatment period lasting 12 weeks. Treatment procedure: the NPD and PD rats were further randomly subdivided into their respective ART regimens ( n = 7/group). After the treatment period, the study was terminated, and tissues and organs of interest were collected for biochemical analyses. Results HFHC feeding effectively induced a PD phenotype, characterised by elevated fasting glucose, glucose intolerance, increased homeostasis model assessment of insulin resistance (HOMA‐IR), hypertriglyceridaemia and weight gain ( p < 0.05). Treatment with Truvada and Triovir attenuated these metabolic markers in PD and NPD groups. However, HOMA‐IR was elevated in NPD animals following both treatments. The administration of either regimen in NPD animals increased plasma C‐peptide levels, whereas plasma glucagon remained unchanged. In PD animals, Truvada treatment increased C‐peptide concentrations, whereas Triovir reduced them. Hepatic glucose exhibited a pattern comparable with the C‐peptide response in NPD animals. However, in PD groups, both treatments lowered glucagon levels and elevated hepatic glucose concentrations. Conclusion Truvada and Triovir caused mixed responses on metabolic dysfunction in diet‐induced PD rats. These findings highlight the complex metabolic interactions of ART, warranting further mechanistic studies, particularly in populations on ART with pre‐existing metabolic risk.
The global rise in antimicrobial resistance, increasing rates of emerging and re‐emerging viral infections, and the persistent burden of fungal and parasitic diseases have intensified the need for alternative anti‐infective therapeutic strategies; a challenge further compounded by the diminishing pipeline of novel therapeutic agents. Historically, numerous compounds showed potent broad‐spectrum activity against bacterial, viral, fungal, and parasitic pathogens but failed to achieve widespread clinical adoption due to significant limitations, including systemic toxicity, poor selectivity, rapid degradation, unfavorable pharmacokinetics, and off‐target host damage. Consequently, many of these promising therapeutic agents were abandoned despite their demonstrated efficacy. Advances in nanotechnology have revitalized interest in these historically neglected compounds by enabling targeted delivery, controlled release, improved biodistribution, and reduced toxicity, offering strategies to improve the therapeutic index of agents once considered clinically impractical. Specifically, this review examines how nanotechnology can reshape the translational potential of therapeutically constrained anti‐infective agents and highlights key examples, including halogen‐based antimicrobials, metal‐derived therapeutics, reactive oxygen and nitrogen species, and membrane‐active compounds. We discuss how these technologies address historical barriers to therapeutic application and critically evaluate the remaining barriers hindering clinical translation and long‐term biological interactions. Collectively, we propose that the next generation of anti‐infective therapeutics may emerge not solely from discovering entirely new compounds, but from strategically reengineering abandoned agents using advanced nanotechnology‐enabled delivery systems.
Diabetic encephalopathy (DE), a prevalent complication of diabetes, is strongly associated with progressive cognitive dysfunction. The iron‐dependent regulated cell death process known as ferroptosis has been implicated in the neurodegeneration observed in DE. Smart soup (SS), a classic Chinese herbal formula, is used to treat memory impairment. In this study, we evaluated the therapeutic potential of SS against DE. We found that oral administration of SS significantly ameliorated learning and memory deficits in a rat model of DE. This cognitive improvement was accompanied by the inhibition of hippocampal ferroptosis, evidenced by decreased lipid peroxidation, iron overload, and reactive oxygen species (ROS), alongside increased levels of the antiferroptotic proteins GPX4 and FTH1. Furthermore, SS treatment mitigated aberrant mitochondrial alterations and reduced the levels of mitophagy‐related proteins (PINK1 and Parkin), suggesting it alleviates the upstream damage that triggers excessive mitophagic activity. Mechanistically, SS appears to target NR3C1 (glucocorticoid receptor), downregulating its transcriptional activation of key iron metabolism factors, LCN2 and NCOA4. Collectively, our findings demonstrate that SS exerts neuroprotective effects in DE likely by suppressing ferroptosis via the NR3C1/LCN2/NCOA4 axis and improving mitochondrial homeostasis, offering a promising therapeutic strategy for this condition.
The prevalence and spread of antimicrobial resistance genes (ARGs) and virulence‐associated genes (VAGs) in bacterial pathogens is a major public health burden. Escherichia coli is an opportunistic pathogen that has garnered significant attention because of the emergence and dissemination of resistance to antibiotics of human and veterinary importance. The objective of this study was to characterize ARGs and VAGs in 3963 E. coli genomes released in complete level by the NCBI from 2006 to 2025. A total of 293 distinct ARGs and 351 distinct VAGs were identified from the genomes of E. coli isolates. Among the 293 ARGs, presence of 41 were found in the genomes of E. coli strains submitted since 2006, and the remaining 252 ARGs were identified in the genomes submitted in subsequent years. The genomes were enriched with ARGs corresponding to the drug classes fluoroquinolones, penam, tetracyclines, cephalosporins, and macrolides. The analysis identified that in 2037 (51.4%) isolates ARGs represented at least 1.29% of the genome, and in 1987 (50.13%) isolates accounted for at least 1.35% of their genome for virulence genes. Analysis of the distinct ARGs showed that 123 of them were found only on plasmids and 141 were shared between chromosomes and plasmids, whereas VAGs showed a greater tendency for chromosomal localization. Single‐copy occurrences of crp and cpxA were commonly found across all 3963 isolates, whereas multiple‐copy variants (≥ 2 copies) of sul1 , tet(A) , and bla TEM-1 were detected in approximately 5% of the isolates. Sequence type analysis showed that ST10 was most frequently represented sequence type in higher level ARG Group III and IV, whereas almost all the strain in ST11 and ST73 were harbouring higher level of Group IV virulence. Weighted linear regression indicated an increase of 0.00292 percentage points per year in the genomic proportion encoding ARGs in E. coli . The results suggest a need for continuous genomic surveillance to tackle AMR, and the development of alternative approaches to overcome the burden of AMR and virulence.
Background Neurological diseases (NDs), including Alzheimer′s disease (AD), Parkinson′s disease (PD), stroke, and brain tumors, impose a substantial global health burden. Although these disorders have distinct clinical manifestations and etiologies, accumulating evidence suggests that they share certain molecular mechanisms. However, their common molecular signatures and the therapeutic potential of turmeric‐derived bioactive compounds have not been systematically investigated. Objectives This study is aimed at identifying shared molecular mechanisms and key hub genes across AD, PD, stroke, and glioblastoma (GBM) using an integrative bioinformatics framework and at investigating turmeric‐derived compounds as potential multitarget common therapeutic candidates. Materials and Methods Gene expression datasets (GSE22491, GSE5281, GSE122709, and GSE4290) were retrieved from the Gene Expression Omnibus (GEO) database. Common host differentially expressed genes (cHDEGs) were identified through integrated bioinformatics analysis. Protein–protein interaction (PPI) networks were subsequently constructed to identify common hub genes (cHubGs), followed by functional enrichment and transcription factor (TF) and miRNA‐mediated regulatory network analyses. The interactions between the identified cHubGs and turmeric‐derived compounds were further investigated using molecular docking and 500‐ns molecular dynamics simulations (MDS). Results A total of 81 cHDEGs and four cHubGs (CCNB1, CDK1, CYCS, and STAT3) were identified. Functional enrichment and regulatory network analysis revealed shared biological processes and signaling pathways, as well as key TFs and miRNAs potentially associated with ND pathogenesis. Among the 77 turmeric‐derived compounds that passed the toxicity screening, demethoxycurcumin, cyclocurcumin, and (1E,4E)‐1‐(4‐hydroxy‐3‐methoxyphenyl)‐5‐(4‐hydroxyphenyl)‐1,4‐pentadien‐3‐one exhibited the strongest predicted binding affinities. The selected compound–target complexes also showed stable behavior during the MDS. Conclusion This study provides insights into the shared molecular features across AD, PD, stroke, and GBM and prioritizes turmeric‐derived compounds as potential multitarget therapeutic candidates. These computational findings require further validation through independent datasets and experimental studies.
