Frontiers In Pharmacology[JOURNAL]
Sun
200 papers
Psychosocial and clinical determinants of medication adherence among elderly chronic disease patients in China.
Zhang Y, Han Y, Sun A … +1 more , Wu M
Front Pharmacol · 2026 · PMID 42338964 · Full text
BACKGROUND: Identifying psychosocial factors associated with medication adherence is critical to optimize chronic disease management in elderly patients. This study aimed to explore key psychosocial and clinical determin...
BACKGROUND: Identifying psychosocial factors associated with medication adherence is critical to optimize chronic disease management in elderly patients. This study aimed to explore key psychosocial and clinical determinants of medication adherence and their synergistic interactions among home-dwelling elderly patients with chronic diseases. METHODS: A cross-sectional study was conducted among 952 elderly patients. Data were collected using validated scales including Adherence to Refills and Medications Scale (ARMS), Self-efficacy for Appropriate Medication Use Scale (SEAMS), Social Support Rate Scale (SSRS), Beliefs about Medical Questionnaire (BMQ), and The Adapted Chinese medication literacy measure (ChMLM). Univariate and multivariable logistic regression, together with interaction analysis, were used to explore associated factors and their synergistic effects. RESULTS: Among 952 participants (mean age 70.32 ± 6.95 years, 51.47% male), multivariable analysis showed that living with a caregiver (OR = 6.91, 95% CI: 2.79-17.70, p < 0.001), higher self-efficacy (OR = 1.13, 95% CI: 1.10-1.17, p < 0.001), Support utilization (OR = 1.09, 95% CI: 1.01-1.17, p = 0.027), stronger medication necessity beliefs (OR = 1.06, 95% CI: 1.02-1.11, p = 0.005), and better medication proficiency (OR = 1.02, 95% CI: 1.00-1.04, p = 0.018) were independently associated with good adherence. Conversely, higher medication concerns (OR = 0.94, 95% CI: 0.91-0.98, p = 0.003), Objective support (OR = 0.91, 95% CI: 0.84-0.98, p = 0.020) and more medication knowledge (OR = 0.97, 95% CI: 0.96-0.99, p < 0.001) were associated with poorer adherence. Critically, Six significant synergistic interactions were identified, including Necessity × Concerns and Knowledge × Self-efficacy, suggesting mutual modification between these factors. CONCLUSION: Medication adherence is influenced by a complex network of determinants, where cognitive, behavioral, and social factors do not operate in isolation but interact synergistically. Multidimensional interventions targeting high-risk combinations, such as high medication knowledge with low self-efficacy, may effectively improve adherence.
Effects of inclisiran therapy on metabolomic and lipoproteomic profiles in dyslipidemic patients.
Patrussi J, Vignoli A, Tenori L … +9 more , Sorrentino A, Berteotti M, Lotti E, Crudele F, Ciarrocca Taranta G, Rogolino AA, Barbieri G, Gori AM, Marcucci R
Front Pharmacol · 2026 · PMID 42338963 · Full text
BACKGROUND: Inclisiran is a subcutaneously administered synthetic small interfering RNA directed against proprotein convertase subtilisin-kexin type 9, leading to sustained low-density lipoprotein cholesterol (LDL-C) red...
BACKGROUND: Inclisiran is a subcutaneously administered synthetic small interfering RNA directed against proprotein convertase subtilisin-kexin type 9, leading to sustained low-density lipoprotein cholesterol (LDL-C) reduction with a twice-yearly dosing regimen. While its lipid-lowering efficacy is well established, its broader metabolic effects remain incompletely characterized. This study aimed to comprehensively evaluate serum metabolomic and lipoproteomic changes in patients with dyslipidemia before and after inclisiran treatment using an integrated nuclear magnetic resonance (NMR)-based approach. METHODS: This observational single-center study included 69 patients with dyslipidemia treated with inclisiran in routine clinical practice. Fasting serum samples were collected at baseline and 3 months after treatment initiation. A total of 30 metabolites and 112 lipoprotein-related parameters were quantified using NMR spectroscopy. Paired comparisons between time points were performed using the Wilcoxon signed-rank test with false discovery rate correction. Clustering based on lipoprotein changes was conducted using the KODAMA algorithm to identify distinct response patterns. RESULTS: Inclisiran treatment was associated with extensive and coherent reductions in lipoprotein-related parameters. Seventy-four lipoprotein variables showed significant changes. Reductions were observed across LDL, IDL, and VLDL subclasses, while some HDL-related parameters were increased. In contrast, the global metabolomic profile remained largely unchanged; trimethylamine-N-oxide (TMAO) was the only metabolite significantly increased at follow-up. KODAMA clustering identified three patient groups with heterogeneous responses. Two groups demonstrated marked lipoprotein reductions, particularly those with higher baseline LDL-related parameters, whereas one group exhibited minimal changes. Baseline TMAO levels were lower in the group with the most pronounced lipid response and increased at follow-up, potentially reflecting changes in concomitant lipid-lowering therapy rather than a direct effect of inclisiran. CONCLUSION: Inclisiran induces a broad and consistent improvement in lipoprotein profiles, extending beyond LDL-C reduction, with minimal impact on the overall metabolome. These findings support the highly specific lipid-lowering action of inclisiran and highlight inter-individual variability in treatment response, especially in concomitant lipid-lowering therapies.
Galactagogue activity of shalukam ( Willd rhizome) compared to domperidone in Wistar albino rats.
Kumar AS, Vimala KS, Priya S … +1 more , Priyalatha B
Front Pharmacol · 2026 · PMID 42333379 · Full text
Breast milk insufficiency is a significant public health concern, as it directly affects infant nutrition and immunity. Inadequate milk production remains a major barrier to effective breastfeeding, and it is reported in...
Breast milk insufficiency is a significant public health concern, as it directly affects infant nutrition and immunity. Inadequate milk production remains a major barrier to effective breastfeeding, and it is reported in approximately 60 -90% of mothers in low- and middle-income countries. Emotional stress, anxiety, lack of sleep, and maternal illness are various psychological and physiological factors that influence breast milk production. Galactagogues are used to induce, maintain, and increase breast milk production. Commonly used galactagogues include domperidone, metoclopramide, chlorpromazine, and sulpiride. These medications are associated with side effects such as xerostomia, gastrointestinal disorders, cardiac arrhythmia, lethargy, sedation, and hypertension. In Ayurvedic classical texts, several drugs possessing sthanya janana properties are described. and mention as . In an article titled "Report on folklore medicinal plants used for female healthcare in Assam", a tablet prepared from the rhizome of Nelumbium speciosum Willd. is reported to be used to increase lactation and to manage painful menstruation. Twenty- four female Wistar albino rats were divided into four groups, with six rats in each group. Two trial drug groups received (finely powdered dried plant material) at single and double doses, while the control group received standard feed, and the standard group received domperidone from the 5th to the 14th day of lactation. All treatments were administered orally in distilled water using an oral gavage needle at 1:30 PM daily. The of is administered by mixing 1.08g/kg of in 10ml distilled water in Single dose group, 2.16g/kg in 20ml distilled water and 1g/kg of Domperidone in 10ml distilled water in standard group. Milk yield was estimated by separating the mothers from the pups for four hours, followed by 60 minutes of suckling, with pre- and post-suckling body weights measured using an electronic balance. The results suggest that the trial drug double-dose group demonstrated better galactagogue activity than the standard drug domperidone group in parameters serum prolactin and cortisol levels and trial drug single dose group demonstrated better galactagogue activity than the standard drug domperidone group in parameters serum prolactin and milk yield of 10 days. The findings suggests that the double dose group demonstrates stronger galactagogue potential.
Editorial: Emerging and reemerging neglected tropical diseases: their epidemiology, transmission, mitigation, and vaccines and chemotherapeutics advancements, volume II.
Mohapatra RK, Mishra S, Kandi V … +2 more , Mohapatra NP, Sirka CS
Front Pharmacol · 2026 · PMID 42328657 · Full text
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Enhancing secondary metabolite accumulation in medicinal plants to improve immunomodulatory activity.
Mkhize P, Morafo V, Mbita Z
Front Pharmacol · 2026 · PMID 42328656 · Full text
Despite progress in enhancing secondary metabolite accumulation to support plant growth and stress tolerance, relatively few studies have established direct links between these increases and enhanced immunoregulatory out...
Despite progress in enhancing secondary metabolite accumulation to support plant growth and stress tolerance, relatively few studies have established direct links between these increases and enhanced immunoregulatory outcomes in humans. Bridging this gap is essential for advancing pharmacological applications and the development of effective plant-based immune therapeutics. Unlike previous reviews that primarily focus on metabolite enhancement strategies in isolation, this review proposes an integrative translational framework linking plant metabolic reprogramming, metabolite bioavailability, and downstream human immunomodulatory relevance. This review evaluates genetic, biochemical, and ecological strategies used to enhance secondary metabolite accumulation in medicinal plants and assesses their potential to translate into immunomodulatory effects. The available evidence indicates that while elicitor- and biostimulant-based approaches consistently enhance metabolite accumulation, their translation into clinically relevant outcomes is constrained by factors such as bioavailability, metabolic stability, and dose-dependent effects. The review further highlights key limitations and knowledge gaps, emphasising the need for integrative and translational research frameworks to link plant metabolic enhancement with human immune outcomes.
The impact of China's drug regulatory reform on access to orphan drugs: a cross-sectional study of diseases listed in the rare disease catalog.
Lan Y, Lin X, Huang Z … +1 more , Zan W
Front Pharmacol · 2026 · PMID 42328655 · Full text
OBJECTIVE: China released two batches of the Rare Disease Catalog in 2018 and 2023, respectively, listing a total of 207 diseases. This study aims to analyze the accessibility of medications for diseases included in the...
OBJECTIVE: China released two batches of the Rare Disease Catalog in 2018 and 2023, respectively, listing a total of 207 diseases. This study aims to analyze the accessibility of medications for diseases included in the catalog and assess the impact of drug regulatory reforms on the supply of medications for rare diseases. METHODS: This study compiled five categories of information on drugs for 207 rare diseases: basic information on drug availability, the number of drug approvals and production capacity, drug development trends, marketing approval efficiency, and medical insurance coverage. Descriptive statistical analysis was employed. RESULTS: By the end of 2025, out of 207 rare diseases, 98 (47.3%) had drugs approved in China, with a single company being the exclusive supplier for 37 of these diseases. Between 2015 and 2025, the NMPA approved a total of 2,007 Investigational New Drug (IND) applications and 1,134 New Drug Applications (NDAs) for rare diseases, showing an overall upward trend. Following the publication of the catalog, the median review time for NDA applications for rare disease drugs was reduced by 79 days compared to pre-publication (516 vs. 595, P < 0.001); for drugs eligible for Priority Review and Approval (PRA), the median review time was reduced by 73 days compared to non-PRA drugs (493 vs. 566, P < 0.001). The time difference between the market launches of the same drug in China and the United States has been reduced by 1.52 years (5.53 vs. 4.01, P < 0.001). Of the 263 drugs used to treat 98 rare diseases, 181 were included in the medical insurance coverage, and the time to inclusion in the insurance coverage was reduced by 1.01 years following the publication of the directory (2.09 vs. 1.07, P < 0.001). CONCLUSION: With the release of the rare disease catalog and the advancement of drug regulatory reforms, access to orphan drugs in China has improved. However, more than half of all rare diseases still face the dilemma of having no available treatments. It is recommended that the coordination mechanism between drug regulation and medical insurance be maintained to better meet patients' clinical medication needs.
combined with prevents spleen deficiency constipation via the gut microbiota-mediated brain-gut axis.
She M, Sun X, Tan Z
Front Pharmacol · 2026 · PMID 42328654 · Full text
INTRODUCTION: The study evaluates the preventive effects of and (3:1) on spleen deficiency constipation in mice, focusing on the brain-gut axis, gut microbiota, and oxidative stress. The findings aim to inform the prev...
INTRODUCTION: The study evaluates the preventive effects of and (3:1) on spleen deficiency constipation in mice, focusing on the brain-gut axis, gut microbiota, and oxidative stress. The findings aim to inform the prevention and treatment of this condition. METHODS: Thirty male specific pathogen-free (SPF) KM mice (4 weeks old, 20 ± 2 g) were randomized into a normal control group (NC), a model group (NM), and a and group (HF). Serum levels of 5-hydroxytryptamine (5-HT), cholecystokinin (CCK), motilin (MTL), and vasoactive intestinal peptide (VIP) were measured by ELISA. Liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by a spectrophotometer. Gut microbiota was analyzed by 16S rRNA sequencing. RESULTS: Compared to NM, the HF showed significantly increased 5-HT, CCK( < 0.05), and MTL ( < 0.001), and significantly decreased VIP( < 0.05). Liver MDA content was markedly higher in NM than in NC( < 0.01), with a downward trend in HF. Conversely, the liver SOD activity in NM was significantly lower than in NC( < 0.001), and the HF displayed an upward trend. Microbiota analysis revealed higher diversity in HF, as indicated by higher chao1, pielou_e, shannon, and simpson indices. The gut microbiota species composition in the HF was dominated by beneficial bacteria such as and , with a reduction in pathogenic bacteria such as and . The characteristic gut microbiota of the NM was enriched in and its conditional pathogens, while the characteristic gut microbiota of the HF was enriched in beneficial symbiotic bacteria such as , and . The metabolic pathways and the genetic information processing pathway were improved in the HF, and the DNA repair and recombination protein pathways were also repaired. CONCLUSION: The and combination effectively prevents spleen deficiency constipation, an effect associated with the brain-gut axis and gut microbiota. The observed trends in oxidative stress markers warrant further investigation.
: a critical review of the ethnobotany, phytochemistry, pharmacology and challenges in standardization and safety.
Zeng H, Wen J, Chen M … +7 more , Qiu Z, Huang S, Hao E, Du Z, Yao C, Hou X, Deng J
Front Pharmacol · 2026 · PMID 42328653 · Full text
BACKGROUND: var. (Airy Shaw and Suvat.) Niyomdham (), locally known as "White Kwao Krua" or "white kudzu", is a renowned medicinal botanical drug indigenous to Southeast Asia, particularly Thailand and Myanmar. It has...
BACKGROUND: var. (Airy Shaw and Suvat.) Niyomdham (), locally known as "White Kwao Krua" or "white kudzu", is a renowned medicinal botanical drug indigenous to Southeast Asia, particularly Thailand and Myanmar. It has long been utilized in ethnomedicine for estrogen-related conditions and age-associated functional decline. This review critically evaluates the nexus between its botanical characteristics, traditional ethnopharmacological uses, and contemporary evidence regarding its therapeutic potential. MATERIALS AND METHODS: A structured literature search was conducted across multiple international and Chinese databases up to 2025, with screening based on predefined inclusion and exclusion criteria focusing on botanical identity, chemical composition, pharmacological activity, toxicological evidence, and clinical findings. Taxonomic validity and geographic distribution were verified using Plants of the World Online (POWO) and the Global Biodiversity Information Facility (GBIF). The names and chemical formulas of secondary metabolites were verified using the PubChem database, and the structures were drawn using ChemDraw 22.2. RESULTS: Phytochemical studies on the rhizomes of showed that it contains 106 kinds of secondary metabolites, including benzopyrans, isoflavones and their glycosides, coumarins, steroids, fatty acids and their derivatives, and other metabolites. Pharmacological evidence demonstrates that exhibits potent estrogenic, anti-osteoporotic, and antioxidant activities, alongside neuroprotective and immunomodulatory effects. Clinical data suggest that its high concentration of potent phytoestrogens effectively mitigates vasomotor symptoms and urogenital syndromes in menopausal women, while positively influencing lipid metabolism and bone mineral density. CONCLUSION: represents a high-potency phytoestrogenic candidate for menopause management. Nevertheless, the translation from traditional use to clinical standardization is hindered by a lack of rigorous pharmacokinetic data and inconsistent quality control of metabolites. Future research should move beyond descriptive summaries toward mechanistic studies that define long-term safety margins and standardized dose-response relationships in order to ensure therapeutic reliability.
Mechanistic elucidation of Wuling Powder targeting macrophage polarization to ameliorate renal ischemia-reperfusion injury via multidimensional computational systems pharmacology coupled with experimental validation.
Wang QQ, Gong YF, Wang ZF … +12 more , Pu X, Li X, Bai L, Zhang J, Xie J, Li J, Jiang W, Liu LM, Zuo JW, Zhao YY, Zheng DH, Li HL
Front Pharmacol · 2026 · PMID 42328652 · Full text
INTRODUCTION: The blurry mechanism of Wuling Powder (WLP) in treating renal ischemia-reperfusion injury (R-IRI) has greatly hindered its clinical promotion and application as well as the development of modern preparation...
INTRODUCTION: The blurry mechanism of Wuling Powder (WLP) in treating renal ischemia-reperfusion injury (R-IRI) has greatly hindered its clinical promotion and application as well as the development of modern preparations. This study applied computational systems pharmacology combined with experimental validation to reveal the mechanism of Wuling Powder (WLP) in ameliorating renal ischemia reperfusion injury (R-IRI) by regulating macrophage polarization (MP). METHODS: Firstly, the core target mechanism of WLP in treating R-IRI by regulating MP was clearly identified through using multidimensional AI computational systems pharmacology, including network pharmacology, the Gene Expression Omnibus database analysis, machine learning, molecular docking etc. RESULTS: As a result, the core target of WLP in improving MP for treating R-IRI was confirmed to be PLAUR, HSPA1A, and FOS. Then, molecular dynamics simulation revealed that the 3,4-Dihydroxybenzaldehyde-PLAUR complex, which exhibited the least negative docking score, could still bind stably. On this basis, in vivo experiments combined with multivariate statistics and correlation analysis further demonstrated that WLP and its main active compound 3,4-Dihydroxybenzaldehyde could significantly modulate MP by regulating PLAUR to improve R-IRI. DISCUSSION: These findings collectively support PLAUR, HSPA1A, and FOS as core therapeutic targets through which WLP modulates MP to alleviate R-IRI. This systematic research provides a solid theoretical basis for the clinical application and modern drug development of WLP in the prevention and treatment of R-IRI.
Targeting the JAK/STAT pathway with isoliquiritigenin in ovarian cancer: molecular mechanisms and therapeutic implications.
Ding M, Guo F, Lin P
Front Pharmacol · 2026 · PMID 42328651 · Full text
Ovarian cancer, one of the most common gynecological malignancies, ranks as the fifth leading cause of cancer death in women. To investigate the mechanism by which isoliquiritigenin (ISL) regulates the JAK/STAT signaling...
Ovarian cancer, one of the most common gynecological malignancies, ranks as the fifth leading cause of cancer death in women. To investigate the mechanism by which isoliquiritigenin (ISL) regulates the JAK/STAT signaling pathway in ovarian cancer intervention, this review integrates cellular, animal, and preclinical studies on ISL treatment for ovarian cancer, explores how ISL modulates the JAK/STAT pathway and affects ovarian cancer cell behavior and the tumor immune microenvironment, and summarizes the related mechanisms and research progress. The results show that ISL exerts significant anti-ovarian cancer effects through multitarget regulation of the JAK/STAT pathway. With the advantages of low toxicity and multi-pathway modulation, ISL is a promising natural candidate for targeted therapy, reversal of drug resistance, and combination therapy in ovarian cancer, thus holding great value for basic research and clinical translation.
Sigma-1 and Sigma-2 receptors exhibit divergent genome-wide Co-expression architectures in human brain despite shared subcellular localization.
Harbert DH
Front Pharmacol · 2026 · PMID 42328650 · Full text
The sigma-1 receptor (SIGMAR1) and sigma-2 receptor (TMEM97) are both enriched at the mitochondria-associated membrane (MAM) and have been pharmacologically co-classified for decades, yet their functional relationship at...
The sigma-1 receptor (SIGMAR1) and sigma-2 receptor (TMEM97) are both enriched at the mitochondria-associated membrane (MAM) and have been pharmacologically co-classified for decades, yet their functional relationship at the transcriptomic level remains uncharacterized. We performed genome-wide co-expression analysis for both receptors across five brain regions from the GTEx v8 dataset (n = 209 in the primary region, 16,225 expressed genes) using Spearman correlations. Three Weighted Jaccard (WJ) formulations on continuous correlation vectors - (r+1)/2 shifted, unsigned |r|, and signed-all revealed that SIGMAR1 and TMEM97 share the majority of their global transcriptional architecture (WJ shifted = 0.964, unsigned = 0.907, signed = 0.906; all three rank-identical across 21 pairwise comparisons, ρ = 1.000), yet their top 5% co-expression networks overlap by only 10.0% (binary Jaccard = 0.100). Cosine similarity on raw vectors confirmed metric robustness (ρ = 0.856 with WJ, p = 7.5 × 10). Dissociation gap analysis across all 21 gene pairs showed the WJ-binary gap varies 2.1-fold (0.431-0.927), tracking known biological relatedness rather than reflecting a fixed methodological property. Gene Ontology analysis identified SIGMAR1-specific enrichment for mitochondrial translation and TCA cycle, and TMEM97-specific enrichment for ubiquitin-mediated proteolysis and neurodegeneration pathways. Multi-region replication confirmed the pattern across five brain regions, with the hippocampus showing tail-specific convergence. These findings are consistent with the hypothesis that dual sigma-1/sigma-2 ligands engage two functionally distinct co-expression programs within a shared cellular context, providing a transcriptomic rationale for subtype-selective pharmacological strategies.
Precision management of cenobamate in drug-resistant epilepsy: integrating pharmacogenetics, therapeutic drug monitoring, and real-world clinical strategies.
d'Orsi G, Di Claudio MT, Cafaro A … +12 more , Barco S, Robustella M, Locatelli N, Liantonio A, Imbrici P, Ciavarella G, Rinaldi A, Fania G, Costantino U, Carella M, Cangemi G, Miscio G
Front Pharmacol · 2026 · PMID 42328649 · Full text
Cenobamate (CNB) demonstrates high efficacy in drug-resistant focal epilepsy, yet optimal management requires personalized strategies. This exploratory case series describes five patients selected from a cohort of 125 in...
Cenobamate (CNB) demonstrates high efficacy in drug-resistant focal epilepsy, yet optimal management requires personalized strategies. This exploratory case series describes five patients selected from a cohort of 125 individuals treated with CNB, examining the relationship between pharmacogenetic (PGx) profiles and clinical outcomes. Clinical data and therapeutic drug monitoring (TDM) were integrated with targeted Next-Generation Sequencing of key metabolic genes (UGT2B7, UGT2B4, CYP2E1, CYP2B6, CYP2A6, CYP3A4, CYP2C19) to predict metabolizer phenotypes. Three patients (Cases 1, 3, 4) achieved seizure freedom or ≥50% response at sub-target or target doses (100-200 mg/day enabling early de-escalation of concomitant sodium channel blockers and valproate. This success was supported by a proactive digital communication protocol and a mandatory 100 mg clinical checkpoint. Case 2-a non-responder at 400 mg/day despite therapeutic plasma levels (28.22 mg/L)-exhibited a predicted "Ultrarapid Metabolizer" (UM) phenotype characterized by UGT2B7 Haplotype 4 and CYP2E1 duplication, suggesting possible pharmacokinetic contribution to non-response. Case 5 experienced dose-limiting toxicity at 100 mg/day; we hypothesized this toxicity could be driven by a drug-drug-gene interaction involving CNB-mediated inhibition that impairs clearance of N-desmethylclobazam (the active metabolite of clobazam) in a patient with impaired activity and intermediate function. As an exploratory case series, these findings require validation in adequately powered prospective studies. Associations between UM phenotype and non-response, and between PM phenotype and dose-limiting toxicity, represent preliminary observations that may reflect pharmacokinetic variability. Nevertheless, our experience is consistent with a personalized, sub-target dose titration strategy that may help minimize adverse events in complex polypharmacy settings.
Human leukocyte antigen pharmacogenetics in infectious diseases: anti-infective drug toxicity and host immune response.
Negrini S, Nicola S, Badiu I … +4 more , Quinternetto A, Vitali I, Lo Sardo L, Brussino L
Front Pharmacol · 2026 · PMID 42328648 · Full text
Human leukocyte antigen (HLA) polymorphisms are central to anti-infective pharmacogenetics and to inter-individual variability in infection outcomes and vaccine responses, but clinical relevance depends on whether an ass...
Human leukocyte antigen (HLA) polymorphisms are central to anti-infective pharmacogenetics and to inter-individual variability in infection outcomes and vaccine responses, but clinical relevance depends on whether an association changes treatment or prevention decisions. This narrative review is organized around two complementary pillars: first, severe, typically T cell-mediated adverse drug reactions to anti-infective agents, where HLA can support prevention when genetic effect, phenotype precision, and therapeutic alternatives converge; and second, selected, replicated HLA-region associations with infection outcomes or vaccine immunogenicity, where biological effects may be robust yet individual-level clinical translation is often limited. Within the adverse drug reaction pillar, the clearest preventive paradigm remains HLA-B*57:01-guided abacavir prescribing, with additional high-signal examples including dapsone hypersensitivity and flucloxacillin-induced liver injury that illustrate how large effect sizes do not always justify routine screening. Within the infection and vaccine pillar, HIV, HCV, and hepatitis B vaccine response provide the strongest evidence that HLA shapes clinically relevant host-response heterogeneity. Across both domains, the key pharmacological distinction is between mechanistically persuasive associations and those that are sufficiently robust, transportable, and decision-relevant to change practice.
Metal-based nanomaterials for cancer phototherapy: current advancements and translational challenges.
Su H, Zhao X, Xu W … +6 more , Sa H, Li X, Liu Z, Ning F, Li M, He Z
Front Pharmacol · 2026 · PMID 42328647 · Full text
Cancer remains a leading global health challenge, with limitations in chemotherapy, radiotherapy, and immunotherapy driving interest in alternative modalities. Phototherapy, comprising photodynamic therapy and phototherm...
Cancer remains a leading global health challenge, with limitations in chemotherapy, radiotherapy, and immunotherapy driving interest in alternative modalities. Phototherapy, comprising photodynamic therapy and photothermal therapy, has shown promising antitumor efficacy, yet conventional photosensitizers and photothermal agents often suffer from poor stability, limited tissue specificity, and suboptimal performance. Metal-based nanomaterials effectively address the above limitations and bottlenecks by providing tunable optical properties, catalytic activity for reactive oxygen species generation, and multifunctional platforms for imaging and combination therapies. In this review, we systematically discuss recent advances in precious metal and non-precious metal nanomaterials for cancer phototherapy, elucidating their diverse mechanisms of action and anticancer efficacy, and highlighting the pivotal role of materials design in performance optimization. We further summarize strategies to design and improve these nanomaterials, with an emphasis on enhancing biocompatibility, tumor targeting, and photothermal conversion efficiency, all of which are critical for clinical translation. We also highlight synergistic therapeutic paradigms that combine metal-based phototherapy with other anticancer modalities, providing representative examples of how such combinations can improve treatment outcomes. Finally, we discuss future directions, particularly the development toward intelligent, multifunctional, and low-toxicity metal-based nanoplatforms through stimulus-responsive designs, functional integration, green synthesis, and artificial intelligence-assisted approaches. Overall, this review aims to provide a solid theoretical and technical reference to accelerate the clinical application of metal-based nanomaterials in cancer phototherapy.
Drug-induced hyperuricemia: multi-pathway regulation, causative drugs, and individualized management strategies.
Xiong B, Duan C, Xu S … +4 more , Xu S, Yang C, He D, Luo C
Front Pharmacol · 2026 · PMID 42328646 · Full text
Hyperuricemia, a prevalent metabolic disorder, is not only the primary cause of gout but also an independent risk factor for various chronic conditions, including hypertension, cardiovascular and cerebrovascular diseases...
Hyperuricemia, a prevalent metabolic disorder, is not only the primary cause of gout but also an independent risk factor for various chronic conditions, including hypertension, cardiovascular and cerebrovascular diseases, and diabetes mellitus, thereby posing a significant threat to multi-organ health. Iatrogenic factors represent a key pathogenic trigger for hyperuricemia. With the expanding spectrum of clinical medications and the widespread adoption of polypharmacy, drug-induced hyperuricemia (DIH) now affects up to 25% of hospitalized patients and over 80% of transplant recipients on cyclosporine, emerging as a critical challenge to medication safety and therapeutic efficacy. We conducted a comprehensive literature search across PubMed, Embase, and Web of Science, systematically analyzed 76 relevant high-quality studies, and summarized the core pathogenic pathways, causative drugs, and individualized management strategies of DIH. Focusing on pharmacological mechanisms and clinical translation, this review delineates two pivotal pathogenic pathways of DIH: one involving dysregulation of key transporters that control renal uric acid reabsorption and secretion, and the other characterized by enhanced uric acid production via disruption of purine metabolism. We summarize over 10 classes of causative drugs and their molecular mechanisms, thereby advancing current understanding of DIH pathogenesis. Finally, we integrate management strategies encompassing medication adjustment, urate-lowering therapy, and non-pharmacological interventions, providing a scientific basis for rational prescribing, screening of high-risk populations, and the development of safer therapeutic agents.
Donepezil ameliorates fatigue and depression in PASC patients with HHV-6B SITH-1-induced acetylcholine deficiency.
Oka N, Nakamura K, Hirahata K … +7 more , Ishii A, Yamakawa K, Ie K, Goto T, Shimada K, Fujitani S, Kondo K
Front Pharmacol · 2026 · PMID 42328645 · Full text
INTRODUCTION: The pathogenesis of post-acute sequelae of SARS-CoV-2 infection (PASC) remains poorly understood, and no effective treatment has been established. Reactivation of latent herpesviruses, particularly human he...
INTRODUCTION: The pathogenesis of post-acute sequelae of SARS-CoV-2 infection (PASC) remains poorly understood, and no effective treatment has been established. Reactivation of latent herpesviruses, particularly human herpesvirus 6B (HHV-6B), has been proposed as a possible contributor to the neuropsychiatric symptoms observed in PASC. SITH-1, a latency-associated protein expressed during HHV-6B reactivation in olfactory bulb astrocytes, induces specific antibody responses that can be detected in peripheral blood. Importantly, SITH-1 has also been identified as a risk factor for depression, suggesting a mechanistic link between HHV-6B reactivation and the development of neuropsychiatric symptoms. METHODS: We measured serum anti-SITH-1 antibody titers in 156 PASC patients and compared them to healthy controls. In this PASC cohort, neuropsychiatric symptoms were assessed using numerical rating scales. In parallel, we developed a mouse model in which SITH-1 was transiently expressed in the olfactory bulb to assess its impact on brain function and behavior. We also conducted a subgroup analysis of a previously reported randomized clinical trial (RCT) of donepezil, stratifying PASC patients by anti-SITH-1 antibody status. RESULTS: Anti-SITH-1 antibody positivity was observed in 62.8% of PASC patients, a significantly higher proportion than in controls. Seropositive patients exhibited more severe fatigue and depressive symptoms. In the mouse model, SITH-1 expression led to reduced acetylcholine production and depression-like behavior, both of which were ameliorated by donepezil. In the clinical trial subgroup of 73 PASC patients, 71.7% were seropositive for anti-SITH-1 antibodies. Among these individuals, donepezil significantly improved fatigue and depression scores, as measured by the Chalder Fatigue Scale and the depression subscale of the Hospital Anxiety and Depression Scale (HADS). CONCLUSION: These findings suggest that HHV-6B reactivation in the olfactory bulb, as indicated by anti-SITH-1 antibody titers, may contribute to fatigue and depression in a subset of PASC patients. Donepezil may be effective in this subgroup, and these findings support the use of anti-SITH-1 antibody titers as a companion diagnostic marker for targeted treatment in PASC.
Formononetin: a promising therapeutic agent targeting the gut-lung axis in acute lung injury.
Batu W, Liu D, Ren C … +3 more , Bi W, Wang J, Wang Y
Front Pharmacol · 2026 · PMID 42328644 · Full text
BACKGROUND: Acute lung injury (ALI) is a common acute inflammatory lung disease in critical clinical conditions, with a complex pathogenesis and limited available treatment options. Although the gut-lung axis has been id...
BACKGROUND: Acute lung injury (ALI) is a common acute inflammatory lung disease in critical clinical conditions, with a complex pathogenesis and limited available treatment options. Although the gut-lung axis has been identified as an emerging field of host-related microbiota in various chronic lung diseases, it remains unclear whether gut microbiota is associated with the development and progression of ALI. OBJECTIVE: This study aims to investigate the therapeutic effects of formononetin on ALI mice and elucidate how formononetin ameliorates ALI by regulating the gut-lung axis. METHODS: Pathological changes in lung and intestinal tissues of LPS-induced ALI mice were first examined using histopathological detection. Reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot (WB) were employed to assess lung/intestinal inflammation and intestinal barrier integrity. 16S rRNA sequencing was used to evaluate the intestinal microbial microenvironment, and metabolomics was applied to detect changes in serum metabolites. RESULTS: Formononetin effectively ameliorated lung injury in ALI mice, reduced the expression of lung/intestinal inflammatory factors, and protected the integrity of the lung-intestinal barrier in ALI mice. Gut microbiota analysis revealed that the anti-ALI effect of formononetin may be associated with Parabacteroides. Metabolite pathway enrichment involved bile acid metabolism and ABC transporters. CONCLUSION: Formononetin reverses lung injury and repairs the gut-lung barrier in ALI mice. These effects are accompanied by changes in Parabacteroides abundance, as well as alterations in ABC transporters and bile secretion. This study provides new insights and potential applications for the clinical intervention of ALI.
Real-world bleeding risk and molecular interaction profiles of direct oral anticoagulants: a comparative study integrating clinical outcomes and docking.
Onar LC, Guner E, Yilmaz I
Front Pharmacol · 2026 · PMID 42328643 · Full text
BACKGROUND: Differences in bleeding risk among direct oral anticoagulants (DOACs) may reflect not only exposure-related factors but also molecule-specific drug-target interaction characteristics. This study aimed to eval...
BACKGROUND: Differences in bleeding risk among direct oral anticoagulants (DOACs) may reflect not only exposure-related factors but also molecule-specific drug-target interaction characteristics. This study aimed to evaluate real-world bleeding outcomes and to complement these findings with molecular docking analyses as supportive, hypothesis-generating mechanistic context for safety differences among factor Xa inhibitors and a direct thrombin inhibitor. METHODS: A retrospective cohort of 5,721 patients treated with apixaban, rivaroxaban, edoxaban, or dabigatran was analyzed using real-world clinical data. Demographic characteristics, comorbidities, non-life-threatening complications, life-threatening hemorrhagic events, and overall bleeding outcomes were systematically compared. Multivariable logistic regression modeling was used to identify independent predictors of bleeding, with apixaban as the reference agent. Molecular docking analyses were performed using AutoDock 4.2.6 to assess comparative binding energy profiles, hydrogen bond interactions, and root-mean-square deviation values between each DOAC and factor Xa or thrombin. RESULTS: Life-threatening bleeding occurred in 3.1% of patients, while any bleeding event was observed in 13.5% of the cohort. Compared with apixaban, rivaroxaban (OR 1.52), dabigatran (OR 1.29), and edoxaban (OR 1.44) were independently associated with higher odds of bleeding. Advanced age and renal dysfunction were identified as additional independent predictors. Docking analyses indicated that apixaban exhibited the lowest docking-derived binding energy toward factor Xa (ΔG = -14.46 kcal/mol), whereas dabigatran showed selective interaction with thrombin (ΔG = -11.91 kcal/mol). These molecular findings are exploratory and hypothesis-generating and should be interpreted as supportive mechanistic context rather than direct predictors of clinical outcomes. CONCLUSION: In this retrospective cohort, apixaban was associated with a comparatively lower observed bleeding risk compared with other DOAC agents. Docking findings provide exploratory, hypothesis-generating mechanistic context that may help to contextualize observed clinical patterns.
Targeting STAT3 in systemic lupus erythematosus and lupus nephritis: mechanisms, therapeutic advances, and structure-informed perspectives.
Yi F, Tu X, Jin R … +8 more , Zhou J, Li Y, Liao H, Xu W, Yuan Y, Wu M, Bi P, Yin J
Front Pharmacol · 2026 · PMID 42328642 · Full text
This review summarizes the mechanistic and therapeutic relevance of Signal Transducer and Activator of Transcription 3 (STAT3) in systemic lupus erythematosus (SLE) and lupus nephritis (LN), with an emphasis on how struc...
This review summarizes the mechanistic and therapeutic relevance of Signal Transducer and Activator of Transcription 3 (STAT3) in systemic lupus erythematosus (SLE) and lupus nephritis (LN), with an emphasis on how structural information can inform drug development. STAT3 integrates cytokine- and growth factor-driven JAK-STAT signaling, supports pathological T cell differentiation, B cell activation, and renal inflammation, and has therefore emerged as a potential therapeutic node in lupus. Current pharmacological evidence includes traditional Chinese medicine-derived compounds, repurposed or conventional immunomodulators, and clinically advancing JAK-STAT pathway inhibitors; however, most agents act through upstream or indirect modulation rather than direct STAT3 targeting. Structure-informed analyses of candidate compounds further suggest differential druggability across STAT3 domains, with the CCD and SH2 domain providing plausible binding surfaces, whereas the DBD remains comparatively inaccessible. Together, current evidence supports STAT3 as a mechanistically important and therapeutically tractable axis in SLE and LN, while highlighting the need for biochemical, cellular, and validation of domain-selective inhibitors, dual-domain engagement strategies, and degrader-based approaches.
Interplay between the gut microbiota and MAPK/NF-κ B/Nrf2 signaling in depression: pharmacological insights from traditional Chinese medicine.
Yin J, Yin J, Zhang S … +3 more , Xu X, Wang X, Liu Z
Front Pharmacol · 2026 · PMID 42328641 · Full text
Depression is a major global health burden. However, conventional pharmacotherapies often face limitations in efficacy and tolerability. In recent years, the relationship between the gut microbiota and depression has gra...
Depression is a major global health burden. However, conventional pharmacotherapies often face limitations in efficacy and tolerability. In recent years, the relationship between the gut microbiota and depression has gradually emerged as a major research hotspot, offering new perspectives for the treatment of depression. The gut microbiota and the brain are connected through a bidirectional communication system known as the microbiota-gut-brain axis. Within this regulatory network, gut microbiota dysbiosis can disrupt intestinal barrier integrity, triggering systemic and central neuroinflammation. This neuroinflammatory cascade forms the critical pathological basis of depression. These pathological mechanisms underlying depression are driven by the dysregulation of key immune-inflammatory and oxidative stress signaling pathways, such as the mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. Therefore, targeting these pathways has become a promising strategy. Traditional Chinese Medicine (TCM), including botanical drug formulas and bioactive compounds, has demonstrated notable therapeutic efficacy. By altering the gut microbiota and strengthening the gut barrier, TCM can modulate the inflammatory signaling pathways mentioned above and decrease the levels of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6). Consequently, inflammation in the central nervous system can be alleviated, excessive microglial activation can be inhibited, and depressive symptoms can be effectively improved. Owing to its multitarget and multicomponent characteristics, TCM has unique advantages in reshaping the gut microbiota; regulating key signaling pathways, such as MAPK, NF-κB, and Nrf2; and providing a promising therapeutic strategy for depression.
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