Current Drug Targets - Online First

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and the MET exon 14 skipping mutation is a key oncogenic driver, which promotes tumor progression and provides a new direction for precision therapy.

A systematic search of English-language literature and clinical trial data related to the MET exon 14 skipping mutation from 2020-2025 was performed to summarize the role of the mutation and therapeutic advances.

DNA-based next-generation sequencing (NGS), RNA-based NGS, and RT-qPCR were employed as the main detection methods. Preclinical models confirmed that mutations promote tumor progression by activating the RAS/MAPK pathway. Clinical trials have reported objective remission rates (ORR) of 46-68% for first-line treatment with MET inhibitors in NSCLC patients harboring MET exon 14 skipping mutations.

MET exon 14 skipping mutation as a therapeutic target for NSCLC has made significant progress, and MET inhibitors are more advantageous than chemotherapy and immunotherapy, and have been recommended by national and international guidelines as a first-line treatment option. Additionally, NGS technology has the potential to dynamically monitor tumor evolution and drug-resistant mutations, thereby helping to realize precision medicine.

The MET exon 14 skipping mutation is an important target for the precision treatment of NSCLC, and MET-TKIs have remarkable efficacy but a prominent problem with drug resistance. The construction of a precision medicine system encompassing diagnosis, treatment, and drug resistance management through multi-omics research, technological innovation, and international collaboration is a key direction for improving prognosis.

Estrogen deficiency in postmenopausal women influences several physiological processes, notably affecting the gut-brain axis (GBA). Emerging evidence from both preclinical and clinical studies suggests that the loss of estrogen following menopause contributes to GBA dysfunction. The present review aims to explore the clinical and preclinical evidence linking estrogen deficiency-induced gut dysbiosis with GBA dysfunction in postmenopausal women.

A literature survey was conducted using scientific databases such as PubMed, Google Scholar, ResearchGate, and Semantic Scholar to evaluate studies focused on estrogen's role in modulating GBA dysfunction using keywords such as estrogen, GBA, menopause, gut dysbiosis, and GM. Both experimental and observational studies were considered to synthesize current findings.

Estrogen deficiency has been shown to alter the composition and diversity of GM, impair gut barrier function, and dysregulate immune responses involving T cells and microglia within the GIT and CNS. These disruptions are associated with cognitive decline, emotional disturbances, and neurodegenerative conditions. Evidence supports a strong association between menopause-related estrogen loss, gut microbial imbalance, and GBA dysfunction.

The estrogen-GBA plays a crucial role in postmenopausal health, and phytoestrogen- mediated modulation of GM offers a promising therapeutic approach supported by preclinical evidence. However, limited clinical data and population variability highlight the need for well-designed human studies to validate these findings.

Targeting GM modulation presents a promising therapeutic strategy for mitigating GBA dysfunction in postmenopausal women. This review consolidates existing evidence and highlights the need for further research into microbiota-based interventions to alleviate estrogen deficiency-related neurophysiological disorders.

This study aimed to investigate the expression of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) tissues and its association with the frequency of legume food intake.

Clinical data from 93 NSCLC patients at Jiujiang University-affiliated Hospital (2018-2023) were collected. Postoperative recurrence status and legume intake were obtained via telephone follow-up. Fourteen patients with recurrence or metastasis were assigned to the first progression (FP) group. Propensity score matching (1:3) was used to select 42 non-progression (NP) matched patients, totaling 56 for analysis. Patients were divided into low- and high-legume intake groups. EGFR expression was assessed by immunohistochemistry and statistical analysis.

EGFR positivity was higher in the FP group (78.6%, 11/14) than in the NP group (47.6%, 20/42) (P < 0.05). The NP group had a greater proportion of patients with high-frequency legume consumption compared to the FP group (71.4% vs. 35.7%, P < 0.05). Furthermore, patients with high-frequency legume intake (42.9%, 15/35) showed significantly lower EGFR positivity than those in the low-frequency intake group (76.2%, 16/21) (P < 0.05). These results indicate that higher legume intake correlates with both reduced EGFR expression and a decreased postoperative recurrence risk.

These findings suggest that higher legume intake is associated with reduced EGFR expression and better postoperative outcomes in NSCLC patients. Legume consumption may modulate disease progression through EGFR regulation.

High legume intake correlates with improved prognosis and lower EGFR expression in NSCLC. Further large-scale prospective studies are needed to validate these associations and explore their clinical implications.

Medicinal plants and phytocompounds targeting skeletal muscle wasting in humans are under-represented in the majority of databases reporting plant/herb-diseases association. However, a large body of literature exists wherein plant extracts or active pharmaceutical ingredients thereof demonstrate potential benefit in skeletal muscle wasting diseases across model organisms. Underscoring the relevance of a repertoire documenting such medicinal plants, we introduce PDMD (Plants Database for Muscle Wasting Diseases), a manually curated plants database reported for muscle wasting diseases such as cachexia, sarcopenia, muscle atrophy, muscle frailty, impaired muscle regeneration, and muscle fatigue.

PDMD was developed through systematic manual collection and curation of published studies from PubMed, Science Direct, etc, retrieving literature on plants conferring pharmacological efficacy against muscle wasting across experimental model organisms. Phytochemical and taxonomic information were extracted via tools like ClassyFire, PubChem. To handle the storage of an annotated listing of plants, MS-Excel and MySQL were used. Frontend was designed in Visual Studio Code and HTML/CSS. An Apache/PHP server was used to integrate MS-Excel data and charts.

PDMD encompasses 206 medicinal plants and 230 APIs reported across 18 model organisms, offering taxonomical information, phytochemical classes, SMILES structures, geographical distribution, and other bioactivity indications. PDMD is cross-referenced with standard databases, such as PubChem and PubMed, to enhance functionality.

PDMD catalogs plant-skeletal muscle links in a user-friendly, cross-referenced, free database. PDMD bridges the gaps between ethnopharmacology and botany and aids hypothesis generation for the discovery or screening of phyto-pharmaceuticals.

PDMD highlights overlooked plant-muscle links, bridging ethnopharmacology and botany gaps, and can aid hypothesis generation. PDMD is freely available at https://www.jiit.ac.in/biotechhighlightes/Research-Databases/PDMD/index.html, and was last updated in September 2025.

Biomarkers have revolutionized diagnostics and therapeutics by enabling early detection, prognosis, and treatment monitoring across a range of diseases, including cancer and neurodegenerative disorders. Their role in personalized medicine underscores their importance in modern healthcare.

This review consolidates findings from diverse sources, exploring the classes, mechanisms, and emerging technologies for biomarker discovery. Techniques such as next-generation sequencing, immunohistochemistry, and mass spectrometry were critically evaluated for their efficiency in biomarker validation.

The study identifies various cancer biomarkers, including genetic, proteomic, and metabolomic markers, and highlights their clinical applications. It underscores significant breakthroughs in non-invasive diagnostic tools, such as exosomal proteins, miRNAs, and saliva-based markers. Challenges such as limited sample sizes, regulatory hurdles, and clinical translation bottlenecks were also discussed.

Despite significant advancements, integrating biomarkers into clinical practice remains challenging due to issues of specificity, sensitivity, and cost-effectiveness. Emerging approaches such as immune checkpoint inhibitors, tumor mutational burden assessments, and chemokine profiling have shown potential in enhancing cancer immunotherapy outcomes.

Biomarkers are pivotal in advancing personalized medicine by refining diagnostic and therapeutic strategies. Addressing current limitations through innovative technologies and interdisciplinary collaboration can unlock their full potential, transforming disease management and patient care.

Immunotherapy has revolutionized cancer treatment, however, its effectiveness remains limited by weak tumor immunogenicity and immunosuppressive microenvironments. Mitochondria have emerged as a strategic therapeutic target, given their central role in regulating immune cell activation, proliferation, and function through metabolic reprogramming and signaling pathway modulation. Mitochondria-targeted nanoformulations offer a promising approach to amplify anti-tumor immunity by enhancing immune responses at the cellular and molecular levels.

We searched the PubMed and Web of Science databases using keywords and combinations related to mitochondrial targeting, cancer, immunotherapy, and nanoformulations. The primary search timeframe focused on the last five years. The literature screening process mainly involved an initial screening based on titles and abstracts, followed by a full-text screening.

Mitochondria critically govern anti-tumor immunity by controlling the activation and function of immune cells, modulating immune signaling pathways, and adjusting mitochondrial dynamics and metabolism. Recent advancements in mitochondria-targeted nanoformulations have shown potential to enhance immunity by inducing immunogenic cell death (ICD), regulating mitochondrial dynamics and metabolism, and activating key immune pathways.

Mitochondrial-targeted is a novel strategy for activating anti-tumor immunity. Despite promising preclinical results, clinical translation remains unrealized. Future research must prioritize integrating basic and clinical studies to advance mitochondrial immunomodulation from bench to bedside.

Although preclinical studies demonstrate the promise of mitochondria-targeted nanoformulations, clinical translation remains unrealized. Advances in nanotechnology, immunometabolism, and AI-driven drug design hold immense potential to overcome current barriers, particularly in solid tumors. Future efforts may establish mitochondrial immunomodulation as a transformative strategy in oncology.

Preeclampsia (PE) is the second-leading global cause of maternal mortality, affecting 5% of primigravidas. Owing to the substantial heterogeneity of clinical manifestations in PE, an urgent need arises to quantitatively evaluate the efficacy of existing diagnostic methods based on positive proteinuria (PRO) and to develop novel biomarkers to enhance diagnostic accuracy.

We based 1,215 pregnant women obtained from who delivery at the hospital in January 2018 and April 2022 and involved predictors of 66 routine clinical laboratory tests (RCLTs). In addition, from 362 peripheral blood proteomic samples obtained from published datasets. Compared, evaluated, and explored the performances of 5 machine learning models to constructed prediction models.

We pioneered the application of machine learning to assess the diagnostic efficiency of PRO quantitatively, AUROC of 0.771. Next, a more comprehensive assessment was discussed, including 66 RCTIs from blood and urine test items, the AUROC increased to 0.920. Furthermore, the feature selection strategy trained a superior routine clinical prediction model with 5 RCLTs (PRO, alkaline phosphatase (ALP), amylase (AMY), Uric Acid (UA), and Lactate Dehydrogenase (LDH)) for PE to ensure practicality and high performance. In addition, we constructed a protein prediction model for PE based on peripheral blood proteome. Subsequently, EphA1 has been identified as a protein candidate marker for PE, and is highly expressed in placentals. Finally, we established a user-friendly and interpretable PE risk prediction webserver (http://bioinfor.imu.edu.cn/lbppe/) to assist improve the PE diagnosis efficiency.

he predictive platform developed in this study enhances PE early detection, addressing the clinical need for rapid screening tools. Future multi-center trials should validate the models' generalizability.

This study assessed the diagnostic efficiency of proteinuria quantitatively and constructed a cost-effective PE prediction system, which is crucial for improving the diagnostic accuracy of PE.

The global prevalence of Diabetes Mellitus is rising; this complex metabolic disorder marked with hyperglycemia comes with increased morbidity and more associated health risks. Type 1 Diabetes Mellitus, an autoimmune disorder primarily affecting young individuals, lacks innovative pharmacological therapies. While current treatments for Type 2 Diabetes Mellitus-including lifestyle interventions and medications-can be effective, many patients still struggle with glycemic control. This review aims to highlight recent advances in diabetes mellitus management, emphasizing novel therapeutics and drug delivery systems that aim to decrease dosage frequency, target the manifestation of side effects, and enhance anti-diabetic effectiveness.

We conducted a comprehensive review of over 300 articles published between 2017 and 2025, utilizing databases such as PubMed and ScienceDirect.

Recent therapeutic innovations include nanocarrier-mediated drug delivery, microneedle patches, and mRNA- and gene-based systems.

These technologies aim to improve glycemic control, reduce dosing frequency, and minimize side effects. The 2024 American Diabetes Association Standards of Care introduced updated diagnostic criteria and management recommendations, which are summarized herein.

This review outlines key developments in pharmacological and delivery strategies of the past 5 years, targeting all types of diabetes. Special focus is placed on emerging therapies such as mRNA, nanotechnology, and innovative delivery systems, which may transform future diabetes management. The content is designed to support clinicians, researchers, and healthcare professionals in developing future therapeutic strategies.