Network. 2025 Mar 24:1-37. doi: 10.1080/0954898X.2025.2472626. Online ahead of print.

ABSTRACT

Plant diseases significantly threaten food security by reducing the quantity and quality of agricultural products. This paper presents a deep learning approach for classifying foliar diseases in apple plants using the Tunicate Swarm Sine Cosine Algorithm-based Deep Residual Network (TSSCA-based DRN). Cluster heads in simulated Internet of Things (IoT) networks are selected by Fractional Lion Optimization (FLION), and images are pre-processed with a Gaussian filter and segmented using the DeepJoint model. The TSSCA, combining the Tunicate Swarm Algorithm (TSA) and Sine Cosine Algorithm (SCA), enhances the classifier's effectiveness. Moreover, Plant Pathology 2020 - FGVC7 dataset is used in this work. This dataset is designed for the classification of foliar diseases in apple trees. The TSSCA-based DRN outperforms other methods, achieving 97% accuracy, 94.666% specificity, 96.888% sensitivity, and 0.0442J maximal energy, with significant improvements over existing approaches. Additionally, the proposed model demonstrates superior accuracy, outperforming other methods by 8.97%, 6.58%, 2.07%, 1.71%, 1.14%, 1.07%, 0.93%, and 0.64% over Multidimensional Feature Compensation Residual neural network (MDFC - ResNet), Convolutional Neural Network (CNN), Multi-Context Fusion Network (MCFN), Advanced Segmented Dimension Extraction (ASDE), and DRN, fuzzy deep convolutional neural network (FCDCNN), ResNet9-SE, Capsule Neural Network (CapsNet), IoT-based scrutinizing model, and Multi-Model Fusion Network (MMF-Net).

PMID:40126079 | DOI:10.1080/0954898X.2025.2472626

Network. 2025 Mar 24:1-26. doi: 10.1080/0954898X.2025.2480294. Online ahead of print.

ABSTRACT

This study aims to enhance the educational security and legitimacy by overcoming the problem of real-time student signature verification. The issue is raised from the growing issue about identity theft and academic fraud in schools, which compromises the validity of tests and other academic evaluations. To overcome these problems, the paper presents a deep learning-based method for signature verification made possible by employing the cutting-edge Convolutional Neural Networks (CNNs). The proposed method utilizes a VGG19 architecture trained and adjusted to handle the unique characteristics of student signatures. Initially, the procedure is pre-processing the image, after the key signature features are extracted. After passing these characteristics across VGG19 network, the signature's authenticity is classified as either unreliable or malicious nodes. The proposed method offers a flexibility and scalability for various educational settings with its capacity to manage both batch and individual processing. The model's efficacy is demonstrated by experiment with accuracy, precision, and recall values, which surpasses the existing techniques. The method ensures dependable performance under circumstances by illustrating resilience to several kinds of noise and distortion. The proposed deep learning model results pay a way for addressing the issue of student signature verification, enhancing the academic institutions' security and legitimacy.

PMID:40126006 | DOI:10.1080/0954898X.2025.2480294

Network. 2025 Mar 24:1-41. doi: 10.1080/0954898X.2025.2480299. Online ahead of print.

ABSTRACT

Breast cancer is the foremost cause of mortality among females. Early diagnosis of a disease is necessary to avoid breast cancer by reducing the death rate and offering a better life to the individuals. Therefore, this work proposes a Parallel Convolutional SpinalNet (PConv-SpinalNet) for the efficient detection of breast cancer using mammogram images. At first, the input image is pre-processed using the Gabor filter. The tumour segmentation is conducted using LadderNet. Then, the segmented tumour samples are augmented using Image manipulation, Image erasing, and Image mix techniques. After that, the essential features, like CNN features, Texton, Local Gabor binary patterns (LGBP), scale-invariant feature transform (SIFT), and Local Monotonic Pattern (LMP) with discrete cosine transform (DCT) are extracted in the feature extraction phase. Finally, the detection of breast cancer is performed using PConv-SpinalNet. PConv-SpinalNet is developed by an integration of Parallel Convolutional Neural Networks (PCNN) and SpinalNet. The evaluation results show that PConv-SpinalNet accomplished a superior range of accuracy as 88.5%, True Positive Rate (TPR) as 89.7%, True Negative Rate (TNR) as 90.7%, Positive Predictive Value (PPV) as 91.3%, and Negative Predictive Value (NPV) as 92.5%.

PMID:40125951 | DOI:10.1080/0954898X.2025.2480299

Am J Respir Cell Mol Biol. 2025 Mar 24. doi: 10.1165/rcmb.2024-0342OC. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disorder without curative therapies, underscoring the critical unmet need for identification of novel therapeutics. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a damage-associated molecular pattern protein (DAMP) and Toll-Like Receptor 4 (TLR4) ligand that contributes to the severity of radiation-induced lung fibrosis and NASH-associated hepatic fibrosis. This study investigates eNAMPT as a druggable target in human and preclinical IPF utilizing the eNAMPT-neutralizing ALT-100 monoclonal antibody (mAb). Blood, PBMCs, and lung tissues from IPF patients and from an experimental bleomycin-induced lung fibrosis model in C57Bl6 mice were analyzed. Biochemical and histologic measurements, as well as gene expression through bulk and single-cell RNA sequencing of human PBMCs and murine lung tissues were performed. Human studies revealed NAMPT expression to be significantly elevated in plasma, lung tissues, and in PBMCs from IPF subjects, correlating with disease severity and inversely associated with IPF survival. Bleomycin-exposed mice exhibited increased inflammatory indices associated with lung fibrosis development (including NAMPT levels), as well as physiologic lung stiffening, and TGFβ pathway-related protein and gene expression with each indice significantly mitigated in mice receiving ALT-100 mAb. scRNAseq studies demonstrated the ALT-100 mAb to reverse bleomycin-induced dramatic expansion of alveolar type 2 epithelium (AT2) and indiction of endothelial- and epithelial cell-to-mesenchymal/myofibroblast transitions (EndMT, EMT). These finding support the fundamental involvement of eNAMPT/TLR4 signaling pathway in lung fibrosis pathobiology with eNAMPT neutralization a viable therapeutic strategy to directly address the unmet need for novel IPF treatments.

PMID:40126452 | DOI:10.1165/rcmb.2024-0342OC

Ther Deliv. 2025 Mar 24:1-14. doi: 10.1080/20415990.2025.2478803. Online ahead of print.

ABSTRACT

AIMS: Diltiazem (DIL), a calcium channel blocker, has demonstrated potential ininhibiting fibrosis-related processes, including TGF-β activation, collagen production, and epithelial-mesenchymal transition, making it a promising candidate for idiopathic pulmonary fibrosis (IPF). This study evaluates the anti-fibrotic efficacy of DIL-loaded chitosan (DIL-CHT) and trimethyl chitosan (DIL-TMC) nanoparticles through molecular and experimental approaches.

METHODS: DIL-CHT and DIL-TMC nanoformulations were developed and analyzed particle size, ζ-potential, entrapment efficiency, and in vitro release. Antifibrotic efficacy in bleomycin (BLM)-induced IPF rat model, was tested at subtherapeutic doses (3 mg/kg/day, i.t.) and DIL alone (10 mg/kg/day, p.o.). DFT (B3LYP/6-31 G**) optimization and molecular docking were conducted to assess electronic properties and interactions among CHT, TMC, and DIL.

RESULTS: DIL-TMC and DIL-CHT nanoparticles were 175.6 nm and 267.8 nm, with entrapment efficiencies of 81.72% and 66.0%, respectively; TMC showed a superior 24-hour sustained release. TMC's larger HOMO-LUMO gap (ΔE = -0.260 eV vs. -0.253 eV for CHT) suggests greater stability, supporting its enhanced interaction with DIL. TMC nanoparticles significantly reduced BLM-induced IPF symptoms, i.e. BLM induced increased lung index, hydroxyproline accumulation, oxidative stress in lung tissue, and blood pressure.

CONCLUSIONS: These findings indicate the strong therapeutic potential of DIL-TMC for IPF with minimal cardiovascular side effects.

PMID:40125984 | DOI:10.1080/20415990.2025.2478803

Physiol Rev. 2025 Mar 24. doi: 10.1152/physrev.00032.2024. Online ahead of print.

ABSTRACT

Nanosized extracellular vesicles (EVs) are released by all cells to convey cell-to-cell communication. EVs, including exosomes and microvesicles, carry an array of bioactive molecules, such as proteins and RNAs, encapsulated by a membrane lipid bilayer. Epithelial cells, endothelial cells, and various immune cells in the lung contribute to the pool of EVs in the lung microenvironment and carry molecules reflecting their cellular origin. EVs can maintain lung health by regulating immune responses, inducing tissue repair, and maintaining lung homeostasis. They can be detected in lung tissues and biofluids such as bronchoalveolar lavage fluid and blood, offering information about disease processes and can function as disease biomarkers. Here, we discuss the role of EVs in lung homeostasis and pulmonary diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, idiopathic pulmonary fibrosis, and lung injury. The mechanistic involvement of EVs in pathogenesis and their potential as disease biomarkers are discussed. Lastly, the pulmonary field benefits from EVs as clinical therapeutics in severe pulmonary inflammatory disease, as EVs from mesenchymal stem cells attenuate severe respiratory inflammation in multiple clinical trials. Further, EVs can be engineered to carry therapeutic molecules for enhanced and broadened therapeutic opportunities, such as the anti-inflammatory molecule CD24. Finally, we discuss the emerging opportunity of using different types of EVs for treating severe respiratory conditions.

PMID:40125970 | DOI:10.1152/physrev.00032.2024

Fibrosis (Hong Kong). 2025;3(1):10004. doi: 10.70322/fibrosis.2025.10004. Epub 2025 Feb 18.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is marked by progressive alveolar destruction, impaired tissue regeneration, and relentless fibrogenesis, culminating in respiratory failure and death. A diverse array of resident and non-resident cells within the lung contribute to disease pathogenesis. Notably, immune cells, both resident and recruited, respond to cues from sites of lung injury by undergoing phenotypic transitions and producing a wide range of mediators that influence, initiate, or dictate the function, or dysfunction, of key effector cells in IPF pathology, such as alveolar epithelial cells, lung fibroblasts, and capillary endothelial cells. The role of the immune system in IPF has undergone an interesting evolution, oscillating from initial enthusiasm to skepticism, and now to a renewed focus. This shift reflects both the past failures of immune-targeting therapies for IPF and the unprecedented insights into immune cell heterogeneity provided by emerging technologies. In this article, we review the historical evolution of perspectives on the immune system's role in IPF pathogenesis and examine the lessons learned from previous therapeutic failures targeting immune responses. We discuss the major immune cell types implicated in IPF progression, highlighting their phenotypic transitions and mechanisms of action. Finally, we identify key knowledge gaps and propose future directions for research on the immune system in IPF.

PMID:40124525 | PMC:PMC11928166 | DOI:10.70322/fibrosis.2025.10004

Elife. 2025 Mar 24;13:RP93373. doi: 10.7554/eLife.93373.

ABSTRACT

Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there is a subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain a healthy metabolic profile free of metabolic syndrome. The molecular underpinnings of MHO, however, are not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10 modulates weight gain in a striking and sexually dimorphic manner. Female, but not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet, female Ctrp10 knockout (KO) mice show rapid weight gain. Despite pronounced obesity, Ctrp10 KO female mice do not develop steatosis, dyslipidemia, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. Obesity is largely uncoupled from metabolic dysregulation in female KO mice. Multi-tissue transcriptomic analyses highlighted gene expression changes and pathways associated with insulin-sensitive obesity. Transcriptional correlation of the differentially expressed gene (DEG) orthologs in humans also shows sex differences in gene connectivity within and across metabolic tissues, underscoring the conserved sex-dependent function of CTRP10. Collectively, our findings suggest that CTRP10 negatively regulates body weight in females, and that loss of CTRP10 results in benign obesity with largely preserved insulin sensitivity and metabolic health. This female MHO mouse model is valuable for understanding sex-biased mechanisms that uncouple obesity from metabolic dysfunction.

PMID:40126547 | DOI:10.7554/eLife.93373

Cancer Sci. 2025 Mar 24. doi: 10.1111/cas.70056. Online ahead of print.

ABSTRACT

Tumor-derived exosomes (TDEs) have emerged as vital biomarkers of multiple cancers. However, the diagnostic and stage-predicting effects of exosomal pyruvate kinase isoenzyme type M2 (PKM2) in peripheral blood and its mechanism in promoting gastric cancer (GC) remain unclear. Here, we analyzed plasma exosomal PKM2 in 216 blood samples collected from GC patients and healthy donors (HD). The area under the curve (AUC) of plasma exosomal PKM2 demonstrated superior performance in early GC diagnosis compared with that of widely used clinical biomarkers. Kaplan-Meier analysis revealed that high exosomal PKM2 expression was associated with poor prognosis in patients with GC (HR = 1.623, p = 0.029). Single-cell transcriptome sequencing analysis showed that PKM2 was enriched in tumor-associated macrophages (TAM). We further confirmed that the polarization of TAM to the pro-tumoral M2 phenotype induced by exosomal PKM2 promoted the proliferation, migration, and invasion of GC cells. Mechanistically, exosomal PKM2 enhanced lipid synthesis in TAM by inhibiting SCAP polyubiquitination, which triggered the nuclear accumulation of SREBP1, thereby upregulating fatty acid synthesis enzymes, such as FASN, ACACA, and ACLY. In conclusion, plasma exosomal PKM2 is a promising novel biomarker for the clinical diagnosis of GC. Importantly, exosomal PKM2 shapes the tumor microenvironment by activating the SREBP1-related lipid synthesis pathway in macrophages, thereby contributing to GC development.

PMID:40126044 | DOI:10.1111/cas.70056

New Phytol. 2025 Mar 24. doi: 10.1111/nph.70100. Online ahead of print.

NO ABSTRACT

PMID:40125595 | DOI:10.1111/nph.70100

Lancet Reg Health West Pac. 2025 Mar 6;56:101509. doi: 10.1016/j.lanwpc.2025.101509. eCollection 2025 Mar.

ABSTRACT

BACKGROUND: The incidence of tuberculosis (TB) decreased significantly in recent years in China. However, the declining in the burden of tuberculosis infection (TBI) have not been systematically evaluated. The aim of this study was to elucidate the changes of TBI prevalence during the past decade.

METHODS: Based on a population-based, multicenter cohort study (LATENTTB-NSTM), a 10-year follow-up survey was conducted among registered residents (≥18 years old) at two study sites (Zhongmu and Danyang) using open-cohort design. After excluding active TB, tuberculin skin test (TST) and interferon-γ release assay (IGRA) were used to determine TBI status of each participant.

FINDINGS: Overall, 5924 eligible participants who completed the follow-up survey were included in the analysis. Compared to the age- and gender-standardized TBI prevalence determined by IGRA in 2013, the prevalence of TBI was observed to be decreased by 22·24% (from 15·11% to 11·75%) in Danyang site and by 40·86% (from 16·57% to 9·80%) in Zhongmu site in 2023. A consistently declining trend was observed as well for TBI prevalence determined by TST test. The acquisition of TBI in 10 years was assessed by the conversion rate of IGRA result in 4648 participants who participated in both the 2013 and 2023 surveys. The IGRA conversion rate in Danyang site was significantly higher than that in Zhongmu site (4% vs. 2%, p < 0·0001). The reversion rate of IGRA result was assessed as well, and no statistically significant difference was observed between the two study sites (29% in Danyang site vs. 31% in Zhongmu site, p = 0·577). Male gender was found to be associated with an increased risk of IGRA conversion as compared to female, with adjusted odds ratio (OR) of 1·46 (95% confidence interval [CI]: 1·00-2·13). In addition, never smokers were observed to be associated with significantly higher IGRA reversion rates (OR = 2·91, 95% CI: 1·52-5·57) (p = 0.001) as compared to current smokers. We also found the influence of BCG vaccination at birth on TST positivity was non-significant among individuals aged 15 and above.

INTERPRETATION: Our findings suggest that the prevalence of TBI in rural residents from China has significantly decreased along with the declining of TB incidence in the last decade. The downward trend shows regional differences, which might be partly explained by the difference in new infection rates across regions.

FUNDING: The CAMS Innovation Fund for Medical Sciences and the National Natural Science Foundation of China.

PMID:40125311 | PMC:PMC11930089 | DOI:10.1016/j.lanwpc.2025.101509

Front Chem. 2025 Mar 7;13:1523712. doi: 10.3389/fchem.2025.1523712. eCollection 2025.

ABSTRACT

ToF-SIMS is a high spatial resolution imaging technique for cellular or subcellular analysis of biological samples. Accurate molecular data in single-cell studies depend on proper cell morphology and chemical integrity, highlighting the importance of sample preparation. In this work, we standardized a more efficient freeze-drying method using standard lab materials and improved the sample preparation process. Our comprehensive freeze-drying protocol for cellular samples, encompassing washing, fixation, and drying steps, facilitates the acquisition of enhanced cellular information and ensures high reproducibility. These improvements are poised to significantly advance single-cell mass spectrometry imaging research.

PMID:40124708 | PMC:PMC11925917 | DOI:10.3389/fchem.2025.1523712

iScience. 2025 Feb 13;28(3):112012. doi: 10.1016/j.isci.2025.112012. eCollection 2025 Mar 21.

ABSTRACT

The protein universe is the collection of all proteins on earth from all organisms both extant and extinct. Classical studies on protein folding suggested that proteins exist as a unique three-dimensional conformation that is dictated by the genetic code and is critical for function. In this perspective, we discuss ideas and developments that emerged over the past three decades regarding the protein structure-function paradigm. It is now clear that ordered (active/functional) and disordered/denatured (and hence inactive/non-functional) represent a continuum of states rather than binary states. Some proteins can switch folds without sequence change. Others exist as conformational ensembles lacking defined structure yet play critical roles in many biological processes, including forming membrane-less organelles driven by liquid-liquid phase separation. Numerous diverse proteins harbor segments with the potential to form amyloid fibrils, many of which are functional, and some possess prion-like properties enabling conformation-based transfer of heritable information. Taken together, these developments reveal the remarkable complexity of the protein universe.

PMID:40124498 | PMC:PMC11926713 | DOI:10.1016/j.isci.2025.112012

JBMR Plus. 2025 Feb 8;9(4):ziaf030. doi: 10.1093/jbmrpl/ziaf030. eCollection 2025 Apr.

ABSTRACT

Obesity is known to influence the circulating 25(OH)D level but less is known about whether it influences the time required to reach a stable 25(OH)D level after initiating vitamin D supplementation. This observational study was done to investigate whether BMI modified the time required to reach a steady-state 25(OH)D level in response to vitamin D supplementation. Participants in the Boston STOP IT study who were treated for 12 mo with 700 IU of vitamin D3 and 500 mg of calcium daily and had 25(OH)D measures at 0, 6, and 12 mo, were included. We assessed the trajectory of 25(OH)D levels by baseline BMI category (normal weight, BMI 18.5-24.9 kg/m2, n = 62; overweight and obese, BMI ≥ 25 kg/m2, n = 105). Baseline 25(OH)D levels were 78 ± 31.3 nmol/L (normal weight) and 74.7 ± 36.5 nmol/L (overweight and obese). In a linear mixed model examining the influence of time and baseline BMI category on change in the mean 25(OH)D level, there was a significant time x BMI group interaction (p = .024. The normal weight participants had reached steady-state 25(OH)D levels by 6 mo whereas 25(OH)D levels continued to rise between 6 and 12 mo in the overweight and obese participants. This analysis suggests that the time required to reach a steady-state 25(OH)D level after initiating vitamin D supplementation in overweight and obese adults is greater than the usual 3-mo time point commonly used in clinical practice. A more refined definition of the time course of circulating 25(OH)D response to supplementation is needed in overweight and obese individuals in order to optimize clinical monitoring of vitamin D status.

PMID:40124405 | PMC:PMC11929376 | DOI:10.1093/jbmrpl/ziaf030

Front Immunol. 2025 Mar 7;16:1533044. doi: 10.3389/fimmu.2025.1533044. eCollection 2025.

ABSTRACT

Allogeneic natural killer (NK) cell therapy has demonstrated significant potential in cancer immunotherapy by harnessing NK cells to target malignancies. CD138-targeting chimeric antigen receptor (CAR)-engineered NK cells offer a promising therapeutic option for multiple myeloma (MM). However, sustaining CAR expression on CAR-NK cells during ex vivo expansion poses a challenge to developing effective immunotherapies. In this study, primary NK cells were isolated, cryopreserved, and modified to express anti-CD138 CARs through retroviral transduction. Histone deacetylase inhibitors (HDACi), particularly entinostat (ENT), were applied to enhance CAR expression stability in CAR-NK cells. Our findings indicate that ENT treatment significantly improves and maintains CAR expression, thereby enhancing the cytotoxic activity of CAR-NK cells against CD138-positive multiple myeloma cells. ENT-treated CAR-NK cells exhibited prolonged persistence and more significant tumor reduction in an MM tumor-bearing mouse model, highlighting the therapeutic potential of HDACi-treated CAR-NK cells. This study provides the first evidence that HDAC inhibitors can sustain CAR expression in CAR-NK cells in a promoter-dependent manner, potentially enhancing anti-tumor efficacy in multiple myeloma and underscoring the possible need for further clinical evaluation.

PMID:40124378 | PMC:PMC11925867 | DOI:10.3389/fimmu.2025.1533044

Front Immunol. 2025 Mar 7;16:1572273. doi: 10.3389/fimmu.2025.1572273. eCollection 2025.

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2021.789317.].

PMID:40124368 | PMC:PMC11926803 | DOI:10.3389/fimmu.2025.1572273

Skin Health Dis. 2025 Feb 14;5(1):70-74. doi: 10.1093/skinhd/vzae023. eCollection 2025 Feb.

ABSTRACT

Immune checkpoint inhibitors are a class of drugs used in cancer treatment that promote the immune system's response by blocking the inhibitor signals from tumour cells, such as programmed cell death protein 1/programmed death ligand 1 and cytotoxic T-lymphocyte associated protein 4. Despite their clinical benefit, these monoclonal antibodies unspecifically activate the immune system and can lead to the development of 'immune-related adverse events'. Cutaneous toxicities are the most frequent immune-related adverse events, reported in approximately 30-50% of patients treated with immunotherapy; the most common dermatological toxicities are represented by rash, vitiligo, pruritus and lichenoid reactions. Usually, these reactions are mild and it is not necessary to suspend immunotherapy. Potentially life-threatening skin toxicities, such as immunobullous eruption, are rare and may appear in approximately 1% of patients. In this report we describe a case of bullous pemphigoid, the most frequent bullous disease, that developed after treatment with pembrolizumab for a metastatic melanoma. The diagnosis, first suspected by the referring clinic, was confirmed by performing serology and biopsy with direct immunofluorescence. The patient was first treated with high doses of systemic corticosteroids, without suspending the immunotherapy treatment. Subsequently, due to the continuous relapses, we decided to suspend pembrolizumab and systemic corticosteroid and to begin off-label treatment with dupilumab. The following case gives cause for reflection about the management of a drug-induced disease in an immunocompromised patient, while exploring the therapeutic options.

PMID:40125009 | PMC:PMC11924371 | DOI:10.1093/skinhd/vzae023

Ann Gastroenterol. 2025 Mar-Apr;38(2):174-181. doi: 10.20524/aog.2025.0944. Epub 2025 Feb 25.

ABSTRACT

BACKGROUND: Patients' and gastroenterologists' views on the relative importance of treatment outcomes and medication attributes for ulcerative colitis (UC) may differ. We aimed to explore which treatment outcomes and medication attributes are considered important by both for therapeutic decisions.

METHODS: Eight gastroenterologists and 23 patients with UC in Greece participated in semi-structured interviews and focus groups, respectively. The focus groups and interviews were audio-recorded, transcribed and coded, utilizing thematic analysis until data saturation was achieved.

RESULTS: Themes that were discussed included the impact of UC on daily life, UC-related outcomes, drug-related attributes and the patient-doctor relationship. Within these themes, disparities between the perspectives of gastroenterologists and patients were evident on 2 main issues. Gastroenterologists prioritized clinical remission and emphasized long-term objectives, such as mucosal healing, while patients focused on shorter-term outcomes, such as the early and sustained relief of symptoms. Regarding medication attributes, important factors for patients were primarily those that impacted their daily life, such as route of administration, dosage and the need for hospital visits. In contrast, gastroenterologists were more concerned about potential adverse events and non-responsiveness to treatment. There was a consensus regarding the importance of shared decision-making for UC management, emphasized by both patients and clinicians.

CONCLUSIONS: Gastroenterologists mostly prioritize objective measures of remission, while patients mainly focus on factors related to their quality of life and overall well-being. Enhancing communication regarding different goals and expectations may strengthen the physician-patient relationship, ultimately resulting in better shared therapeutic decision-making.

PMID:40124436 | PMC:PMC11928895 | DOI:10.20524/aog.2025.0944

Comput Struct Biotechnol J. 2025 Mar 1;27:887-895. doi: 10.1016/j.csbj.2025.02.036. eCollection 2025.

ABSTRACT

Clostridioides difficile infection (CDI) is a major public health issue, driven by antibiotic resistance and frequent recurrence. CD2068, an ABC protein in C. difficile, is associated with drug resistance, making it a potential target for novel therapies. This study explored FDA-approved non-antibiotic drugs for their ability to inhibit CD2068 through drug screening and experimental validation. Thioridazine exhibited moderate binding affinity to CD2068 and inhibited its ATP hydrolysis activity. It also suppressed the growth of multiple C. difficile ribotypes at 64-128 µg/mL, with rapid-killing effects. When combined with sub-MIC levels of standard antibiotics, thioridazine significantly reduced bacterial growth. In a mouse CDI model, thioridazine demonstrated potential in restoring gut microbial balance and improving survival, although it did not show superiority to vancomycin. These findings suggest that thioridazine has potential as a novel therapeutic for CDI, either as an adjunct to existing antibiotics or as part of a combination therapy to combat antibiotic resistance. Further research, including replication studies and dose optimization, is needed to fully evaluate thioridazine's therapeutic potential.

PMID:40123799 | PMC:PMC11928863 | DOI:10.1016/j.csbj.2025.02.036

Chin Med. 2025 Mar 24;20(1):40. doi: 10.1186/s13020-025-01075-4.

ABSTRACT

In the past, the drug research and development has predominantly followed a "single target, single disease" model. However, clinical data show that single-target drugs are difficult to interfere with the complete disease network, are prone to develop drug resistance and low safety in clinical use. The proposal of multi-target drug therapy (also known as "cocktail therapy") provides a new approach for drug discovery, which can affect the disease and reduce adverse reactions by regulating multiple targets. Natural products are an important source for multi-target innovative drug development, and more than half of approved small molecule drugs are related to natural products. However, there are many challenges in the development process of natural products, such as active drug screening, target identification and preclinical dosage optimization. Therefore, how to develop multi-target drugs with good drug resistance from natural products has always been a challenge. This article summarizes the applications and shortcomings of related technologies such as natural product bioactivity screening, clarify the mode of action of the drug (direct/indirect target), and preclinical dose optimization. Moreover, in response to the challenges faced by natural products in the development process and the trend of interdisciplinary and multi-technology integration, and a multi-target drug development strategy of "active substances - drug action mode - drug optimization" is proposed to solve the key challenges in the development of natural products from multiple dimensions and levels.

PMID:40122800 | DOI:10.1186/s13020-025-01075-4