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1
Review Article Open Access
Falguni Goel, Neha Sharma, Daksh Kumar
Published online December 9, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00040
Abstract
Harlequin ichthyosis, one of the rarest and most severe skin disorders, is mainly characterized by extreme hyperkeratosis, severely impairing the natural barrier function of the [...] Read more.

Harlequin ichthyosis, one of the rarest and most severe skin disorders, is mainly characterized by extreme hyperkeratosis, severely impairing the natural barrier function of the skin. This congenital disease results from a mutation in the ABCA12 gene responsible for lipid transport, whereby healthy skin development is assured. Harlequin ichthyosis is an autosomal recessive condition that requires parents to carry a defective gene copy for the disorder to manifest in their offspring. Babies born with Harlequin ichthyosis have thick skin plates that crack and flake off; they easily become dehydrated, infected, and may suffer from respiratory complications. With new improvements in neonatal care and systemic therapy, notably retinoid therapy, infants’ survival rates have improved. This review provides an inclusive overview of the pathophysiology, clinical features, diagnostic methods, management, and potential future therapies for Harlequin ichthyosis. In addition, a discussion on genetic counseling and its importance in managing family risk factors is also included, as well as a look into cutting-edge research focused on gene therapy and potential curative treatments.

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2
Review Article Open Access
WenQing Yang
Published online December 9, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00045
Abstract
The association between chronic inflammation and cancer has reshaped our understanding of tumorigenesis and cancer therapy. Inflammatory responses can both promote and suppress [...] Read more.

The association between chronic inflammation and cancer has reshaped our understanding of tumorigenesis and cancer therapy. Inflammatory responses can both promote and suppress cancer, depending on the context and timing. Key molecular players, such as nuclear factor kappa-light-chain-enhancer of activated B cells, interleukin-6, signal transducer and activator of transcription 3, and a variety of immune cell types, including tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, orchestrate an environment conducive to tumor survival, angiogenesis, metastasis, and immune evasion. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. However, its success varies across tumor types and patients, underscoring the need to understand the tumor microenvironment and inflammatory context. This review examines the mechanistic underpinnings of inflammation-driven cancer, discusses translational research efforts targeting inflammatory pathways, and explores clinical applications, including the integration of immunotherapy with anti-inflammatory agents and biomarkers for personalized treatment. Future directions in the field include the application of artificial intelligence, microbiome research, single-cell technologies, and gene editing tools to further tailor therapies and overcome resistance mechanisms.

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3
Original Article Open Access
Yuan-Hung Kuo, Wei Teng, Yen-Hao Chen, Po-Ting Lin, Tsung-Han Wu, Chung-Wei Su, Wei-Ting Chen, Chen-Chun Lin, Chao-Hung Hung, Sheng-Nan Lu, Shi-Ming Lin, Jing-Houng Wang, Chun-Yen Lin
Published online December 8, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00418
Abstract
The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient’s immune-nutritional status and has been proposed as a prognostic [...] Read more.

The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient’s immune-nutritional status and has been proposed as a prognostic marker in hepatocellular carcinoma (HCC). However, its role in advanced HCC patients treated with atezolizumab plus bevacizumab (Ate/Bev) remains unclear. In this study, we aimed to evaluate the prognostic value of PNI in patients receiving first-line Ate/Bev therapy.

We retrospectively analyzed 362 patients with unresectable HCC who received Ate/Bev between November 2020 and June 2023 across two centers. Based on prior literature, a cutoff of 45 was used to classify patients into low-PNI (<45) and high-PNI (≥45) groups. Propensity score matching was performed to balance baseline characteristics.

After propensity score matching, 130 patients (65 per group) were included in the analysis. The high-PNI group showed a significantly lower incidence of grade ≥ 3 treatment-related adverse events (10.8% vs. 24.6%, p = 0.039), a higher objective response rate (38.4% vs. 20.0%, p = 0.037), and significantly longer overall survival (16.7 vs. 7.9 months, p = 0.009). Although progression-free survival was longer in the high-PNI group (4.8 vs. 3.0 months), the difference was not statistically significant (p = 0.597). Multivariate analysis confirmed that PNI was an independent predictor of overall survival (hazard ratio: 0.574, 95% confidence interval: 0.353–0.933, p = 0.025), after adjusting for vascular invasion, alpha-fetoprotein levels, concurrent therapy, and post-treatment interventions.

PNI is an independent prognostic factor for overall survival in advanced HCC patients treated with Ate/Bev in real-world clinical practice. Incorporating PNI into routine assessments may enhance risk stratification and guide therapeutic decision-making.

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4
Original Article Open Access
Yanan Guo, Sisi Dong, Meng Li, Yanyan Tao, Jing Lv, Chenghai Liu
Published online December 5, 2025
Gastroenterology & Hepatology Research. doi:10.14218/GHR.2025.00001
Abstract
PVT is a harmful event in cirrhosis, and the prevention and treatment of PVT are important in the management of cirrhosis and portal hypertension. The study aimed to observe the [...] Read more.

PVT is a harmful event in cirrhosis, and the prevention and treatment of PVT are important in the management of cirrhosis and portal hypertension. The study aimed to observe the efficacy of Danggui Buxue Decoction (DBD) on portal vein thrombosis (PVT) in cirrhosis and to elucidate the related mechanism using a modified animal model.

A model of PVT in cirrhosis was established by partial portal vein ligation and intraperitoneal injection of CCl4 in rats, which showed obvious PVT with intra- and extravenous thrombosis as well as liver cirrhosis. Rats were randomly assigned into four groups and received intragastric administration of DBD (12 g/kg/day) or rivaroxaban (20 mg/kg/day) for 6 weeks.

DBD attenuated collagen deposition and reduced thrombus formation in model livers, increased portal vein blood flow, expanded the portal vein diameter, and reduced prothrombin time and international normalized ratio in the model rats. In addition, DBD reduced hepatic von Willebrand factor and plasminogen activator inhibitor-1 expression and increased hepatic fibrin degradation product content in the liver tissues of model rats.

We modified a model of cirrhotic PVT in rats and found that DBD had a good effect on PVT and liver fibrosis, with the mechanisms related to the enhancement of portal vein blood flow and the protection against endothelial cell injury.

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5
Illuminating and Instructive Clinical Case Open Access
Mario Romeo, Silvio Borrelli, Marcello Dallio, Carlo Garofalo, Fiammetta Di Nardo, Paolo Vaia, Carmine Napolitano, Luca De Nicola, Alessandro Federico
Published online December 2, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00404
Abstract
For individuals with decompensated advanced chronic liver disease (dACLD), the onset of refractory ascites (RA) represents a dramatic event. In this setting, a relevant proportion [...] Read more.

For individuals with decompensated advanced chronic liver disease (dACLD), the onset of refractory ascites (RA) represents a dramatic event. In this setting, a relevant proportion of RA patients develop kidney dysfunction, as well as hepatorenal syndrome-acute kidney injury, with limited therapeutic and survival chances. An 81-year-old woman with dACLD-RA was admitted with severe ascites and stage IV chronic kidney dysfunction. On the second day, hepatorenal syndrome-acute kidney injury occurred, requiring standard medical therapy. Intravenous human albumin (HA) and terlipressin administration were compromised by poor venous access and severe respiratory dysfunction. After excluding transjugular intrahepatic portosystemic shunt and transplantation due to age and comorbidities, peritoneal dialysis (PD) was initiated, leading to renal recovery and ascites resolution. Two weeks later, she was readmitted due to the unfeasibility of accessing peripheral veins for the intravenous administration of HA, which was essential to support circulatory function, preserve oncotic balance, and properly manage both RA and chronic kidney dysfunction. A novel PD+HA protocol was therefore started, with intraperitoneal infusion of HA-enriched dialysate to allow a positive albumin gradient from dialysate to blood. Over 12 months, serum albumin levels increased, and clinical stability and improved nutritional status were observed, with no additional hospitalizations or complications. This is the first case describing the application of HA-enriched PD in managing a dACLD patient with RA and kidney dysfunction. HA-enriched PD may represent a promising strategy in complex dACLD care by guaranteeing frequent and small-volume paracentesis and preservation of oncotic pressure without dialytic albumin loss.

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6
Short Communication Open Access
W.J.A. Banukie N. Jayasuriya, L.D.A. Menuka Arawwawala, N.T. Bhavantha Dias, K. Pararamasingam, N.M.M. Fazlan, K.A. Samarasinghe, T. Sugandhika Suresh
Published online November 28, 2025
Future Integrative Medicine. doi:10.14218/FIM.2025.00029
Abstract
Alpinia calcarata (A. calcarata) Roscoe (Family: Zingiberaceae) is a rhizomatous perennial herb used in traditional medicine to treat inflammatory conditions. This study aimed to [...] Read more.

Alpinia calcarata (A. calcarata) Roscoe (Family: Zingiberaceae) is a rhizomatous perennial herb used in traditional medicine to treat inflammatory conditions. This study aimed to develop a topical emulgel dosage form by incorporating the essential oil of A. calcarata rhizome and to investigate it’s in vitro anti-inflammatory activity. A thin-layer chromatographic fingerprint of the essential oil of A. calcarata rhizome was developed. Then, an emulsion base containing plant oil was formulated and incorporated within a Carbopol gel base. The physical characteristics of this formulation were evaluated subsequently. The anti-inflammatory mechanism of the emulgel was determined by in vitro blood cell membrane stabilization assay and thrombolytic activity assay. The results were statistically analyzed by one-way analysis of variance. The thin-layer chromatographic fingerprint of the test oil demonstrated several bands with unique retention factor values. The formulated herbal emulgel was white, viscous, and homogeneous in appearance. The spreadability was 118 g·cm/M, and the pH of the emulgel was 6.30 at 25°C. The A. calcarata emulgel significantly (p < 0.05) inhibited heat-induced in vitro hemolysis, with the highest activity at a 50 µg/mL dose (87.68 ± 0.35%) compared to the placebo. Furthermore, this activity was found to be dependent on the essential oil concentration (r2 = 0.99) of the emulgel. Therefore, it was concluded that the essential oil of A. calcarata rhizome is an effective active ingredient to be used in a topical emulgel formulation, whereas the diverse phytochemicals present in the essential oil would be the underlying source of its anti-inflammatory activity.

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7
Original Article Open Access
Lina Yue, Xuying Xu, Shujie Cui, Ran Xie, Conghui Shi, Changyue Wang, Guangyu Wang, Shidong An, Shurui Xie, Shuo Wang, Xiaolu Pei
Published online November 27, 2025
Future Integrative Medicine. doi:10.14218/FIM.2025.00037
Abstract
The existing wound assessment tools, which are based on modern medical theory, limit the clinical application of traditional Chinese medicine (TCM) nursing. This research aimed [...] Read more.

The existing wound assessment tools, which are based on modern medical theory, limit the clinical application of traditional Chinese medicine (TCM) nursing. This research aimed to develop a scientific, standardized, and characteristic TCM nursing evaluation form for chronic wounds.

Based on a literature review and research group discussions, an initial draft of an expert consultation questionnaire, based on literature from the past five years (2017–2021) from databases such as CNKI, Wanfang, VIP, and SinoMed, was formulated. The authority of the experts was expressed using the authority coefficient, derived from self-evaluations, which is critical for ensuring the scientific validity and rationality of the indicator system. After three rounds of Delphi expert consultation, the TCM nursing assessment form for wound surfaces was finalized.

The effective response rate for the three rounds of expert consultation questionnaires was 100%. The judgment coefficient was 0.85, the familiarity coefficient was 0.89, and the authority coefficient was 0.87. The coefficients of variation for the three rounds were 0.172, 0.044, and 0.013, respectively, while the Kendall’s coefficients of concordance were 0.406, 0.269, and 0.502, respectively, with statistically significant differences (p < 0.001). The final TCM nursing assessment form for wound surfaces included four basic information items, two primary indicators, 17 secondary indicators, and 13 tertiary indicators.

The TCM nursing assessment form integrates TCM syndrome differentiation principles and provides a standardized tool for the assessment of chronic wounds.

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8
Original Article Open Access
Shilong Dong, Luyuan Ma, Chuan Shen, Ruolan Gu, Xinyang Li, Ying Xiao, Caiyan Zhao
Published online November 26, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00343
Abstract
Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by systemic inflammation and immune dysregulation, in which macrophages play a key role in organ [...] Read more.

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by systemic inflammation and immune dysregulation, in which macrophages play a key role in organ injury. This study aimed to investigate the role and mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in ACLF to identify therapeutic targets that modulate macrophage function and mitigate ACLF progression.

Single-cell RNA sequencing data from healthy and ACLF liver tissues were analyzed from the Sequence Read Archive database. Transcriptomic data of peripheral blood mononuclear cells from ACLF patients (GSE168048) were also examined. In vitro experiments assessed PDK4 expression and macrophage polarization, and conditioned-medium studies evaluated effects on LO2 hepatocytes. In vivo validation was performed in ACLF mouse models treated with a PDK4 inhibitor.

Single-cell analysis revealed a predominance of M1-polarized hepatic macrophages in ACLF with marked upregulation of PDK4. Peripheral blood mononuclear cell transcriptomics showed that higher PDK4 expression correlated with 28-day mortality. In vitro, PDK4 expression increased in M1 macrophages; PDK4 inhibition attenuated M1 polarization and reduced cytotoxic effects on LO2 cells. In vivo, pharmacologic inhibition of PDK4 suppressed M1 polarization in macrophages, alleviated liver inflammation, and reduced tissue injury. Mechanistically, PDK4 promoted M1 polarization via activation of signal transducer and activator of transcription 1 signaling.

PDK4 is a key pro-inflammatory regulator in ACLF by promoting M1 macrophage polarization. Targeting PDK4 may be a promising strategy to attenuate inflammation and improve clinical outcomes in ACLF.

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9
Original Article Open Access
Yue Xu, Siqian Lu, Hongpei Wu, Haifeng Wu, Ming Li, Meng Zhou, Ting Chen, Xun Wang, Lishuai Qu, Qin Jin, Jinxia Liu
Published online November 26, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00213
Abstract
As the leading cause of chronic liver disease globally, metabolic dysfunction-associated steatotic liver disease (MASLD) lacks effective therapies. This study aimed to investigate [...] Read more.

As the leading cause of chronic liver disease globally, metabolic dysfunction-associated steatotic liver disease (MASLD) lacks effective therapies. This study aimed to investigate the therapeutic potential and molecular mechanisms of oxytocin (OXT) in MASLD.

Integrated bioinformatics analysis of MASLD datasets was carried out to identify OXT-related metabolic disturbances. Serum OXT levels were quantified using an enzyme-linked immunosorbent assay in 113 MASLD patients and 63 healthy controls. Mechanistic assays were conducted using oleic acid (OA)-induced, lipid-loaded HepG2 cells and high-fat diet-fed C57BL/6 mice, and OXT was administered intraperitoneally in vivo and supplemented in vitro.

Bioinformatics analysis revealed significant changes in OXT expression levels, particularly in fatty acid metabolism. Elevated OXT expression levels in MASLD patients were identified as an independent prognostic factor. In vitro, OXT significantly reduced OA-induced lipid accumulation in HepG2 cells, while in vivo, it decreased body weight, liver injury, and serum cholesterol levels in high-fat diet-fed mice. Mechanistically, OXT enhanced the expression level of phosphorylated AMP-activated protein kinase (AMPK) and suppressed the levels of sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS). Blockade of AMPK with the chemical inhibitor Compound C reversed the ability of OXT to suppress the SREBP1c/FAS axis and reduce lipid accumulation in hepatocytes. Additionally, OXT inhibited the nuclear translocation of SREBP1c in OA-treated cells.

The findings demonstrate that OXT may serve as a potential therapeutic agent for MASLD by regulating the AMPK/SREBP1c/FAS pathway in lipid metabolism.

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10
Short Communication Open Access
Arsal Khan, Aaron Jaynes, Fatema Ali, Yamini Virkud, Timothy Sun, Isabel O’Connell, Wayne Shreffler, Qian Yuan, Victoria Martin
Published online November 26, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00026
Abstract
Guaiac fecal occult blood test (gFOBT) is often used to evaluate evidence of food protein-induced allergic proctocolitis (FPIAP) in children in primary care and gastroenterology [...] Read more.

Guaiac fecal occult blood test (gFOBT) is often used to evaluate evidence of food protein-induced allergic proctocolitis (FPIAP) in children in primary care and gastroenterology settings; however, it has not been validated for this diagnosis, and little is known about the positivity rates in early infancy. In this study, we used samples from healthy asymptomatic infants aged two weeks to two months to evaluate the gFOBT positivity rate compared to those diagnosed with FPIAP.

This was a nested case-control study. Frozen stool samples from infants aged two days to five months enrolled in the Gastrointestinal Microbiome and Allergic Proctocolitis study were evaluated using gFOBT (n = 123). The results were interpreted by three blinded staff members, including a trained clinical research coordinator, a pediatric gastroenterologist, and an experienced medical assistant. Additionally, the samples were analyzed using a quantitative fecal immunochemical test (FIT) for hemoglobin to compare with gFOBT results.

Eight percent of samples from the 100 healthy asymptomatic infants were gFOBT positive (11% when including positive and equivocal results). Seventy-four percent of samples from infants diagnosed with FPIAP were gFOBT positive. The interrater reliability of gFOBT interpretation was 81%. Of the healthy samples that yielded a positive gFOBT result, 50% also yielded a positive FIT result. Of the 23 FPIAP samples that yielded a positive gFOBT result, 29% yielded a positive FIT result.

Healthy asymptomatic infants in early infancy were gFOBT positive up to 11% of the time. Caution should be used when interpreting gFOBT results in young infants in a diagnostic setting.

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11
Systematic Review Open Access
Muaz Ali, Abdaal Munir, Jamal Montaser, Srihas Tumu, Venkata Yashashwini Maram Reddy, Navod Jayasuriya, Iana Malasevskaia
Published online November 26, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00035
Abstract
Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with many patients developing drug-resistant epilepsy. Surgical interventions, including stereoelectroencephalography [...] Read more.

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with many patients developing drug-resistant epilepsy. Surgical interventions, including stereoelectroencephalography (SEEG)-guided temporal lobe resection (TLR) and SEEG-guided responsive neurostimulation (RNS), are key treatment options. This systematic review compares the efficacy and safety of these interventions in drug-resistant TLE.

A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. A comprehensive search of multiple databases was performed (January 23–February 14, 2025). Eligible studies included adult patients with drug-resistant TLE undergoing SEEG-guided TLR or RNS (where SEEG was used pre-implant for localization). Primary outcomes assessed included seizure freedom, seizure reduction, adverse events, and quality of life (QoL) improvements. Quality assessments were performed using appropriate tools for randomized and observational studies.

Fifteen studies met the inclusion criteria, with sample sizes ranging from 10 to 440 participants. SEEG-guided TLR achieved an average seizure freedom rate of 58.5% (range: 32–85%) and a mean seizure reduction of 75% (range: 60–90%). SEEG-guided RNS resulted in an average seizure freedom rate of 12.85% and seizure reduction of 63.2%, with variability across studies. QoL improvements were reported in 80–82% of patients. Adverse events were infrequent but varied between interventions.

This review highlights the effectiveness of SEEG-guided TLR and RNS in managing drug-resistant TLE. While both interventions reduce seizure burden and improve QoL, seizure freedom rates are higher with resection. However, gaps remain in understanding long-term cognitive outcomes and demographic influences on treatment response. Future research should address these factors to refine patient selection and optimize epilepsy care.

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12
Commentary Open Access
Xu Zhao, Jingyi Chen, Haowen Zhang, Mengyuan Li
Published online November 26, 2025
Future Integrative Medicine. doi:10.14218/FIM.2025.00043
13
Original Article Open Access
Manashi Aditya, Silpa Gangopadhyay, Soumen Bhattacharjee
Published online November 26, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00037
Abstract
Amaranth is conventionally consumed as a significant source of nutrients and bioactive compounds and is a potential alternate crop. The present study aimed to validate the folklore [...] Read more.

Amaranth is conventionally consumed as a significant source of nutrients and bioactive compounds and is a potential alternate crop. The present study aimed to validate the folklore and ethnomedicinal claims regarding the utilization of foliar tissues of the pseudocereal Amaranthus hypochondriacus L. for their pharmacological propensities, primarily focusing on bioactive polyphenolic compounds and associated anti-degenerative properties, in view of the scarce evidence available on the same.

Reverse-phase high-performance liquid chromatography coupled with a photodiode array assay of nineteen significant bioactive polyphenolic compounds, along with their in vitro antioxidant-based pharmacological properties (superoxide and hydroxyl radical scavenging properties, metal-chelating and reducing properties, radical scavenging properties, anti-lipid peroxidation and protein coagulation properties, and α-glucosidase and α-amylase inhibitory activities), were assessed and compared for foliar extracts of ten promising experimental accessions of Amaranthus hypochondriacus, grown in two different seasons (summer and winter).

The results exhibited germplasm-specific variations in the pharmacological potential of foliar tissues of the experimental amaranths, which can be substantiated by data showing a close correlation between the abundance of bioactive polyphenolic compounds (naringin, myricetin, naringenin, apigenin, rutin, catechin, quercetin) and in vitro antioxidant (2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay, hydroxyl radical scavenging, reducing, and metal-chelating) properties, as well as anti-diabetic (inhibition of α-glucosidase and α-amylase activities) and anti-inflammatory (anti-lipid peroxidation) attributes. Accessions IC107144 and IC47434 stood out as the most promising medicinal crops based on overall in vitro anti-degenerative properties and the bioavailability of polyphenolic compounds.

Overall, the results validated the traditional ethnomedicinal claim regarding the utilization of foliar tissues of the underutilized pseudocereal Amaranthus hypochondriacus L., and identified lead germplasms (IC107144 and IC47434) as low-cost natural sources of bioactive compounds, potentially promoting their pharmacological utilization.

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14
Original Article Open Access
O. Vishnevsky, K. Kuzminykh, I. Yatsyk, E. Kondratyuk, I. Chadaeva
Published online November 25, 2025
Gene Expression. doi:10.14218/GE.2025.00050
Abstract
Empirical and theoretical studies can be distinguished among the areas of investigation of the renin-angiotensin-aldosterone system (RAAS) and its relationship with the development [...] Read more.

Empirical and theoretical studies can be distinguished among the areas of investigation of the renin-angiotensin-aldosterone system (RAAS) and its relationship with the development of cardiovascular diseases. Theoretical work is based mainly on the bioinformatic analysis of key elements of RAAS (genes, proteins, metabolites), on calculations and predictions of protein interactions, and on mechanisms of RAAS gene expression regulation. An associative gene network based on big data analysis allows us to reveal relationships among the proteins, regulatory pathways, and biological processes acting in RAAS, as well as to identify new diagnostic markers, therapeutic targets, putative molecular mechanisms of the development of RAAS-associated diseases, drug interactions, and drug toxicity.

The reconstruction and analysis of associative gene networks were performed using ANDSystem. The regulation of RAAS-associated gene expression was analyzed by transcription factor (TF) binding sites (TFBSs) prediction in the proximal promoters of these genes and by studying interactions between TFs themselves using the Ensembl Biomart web service and AnimalTFDB 4.0. The recognition of potential TFBSs in RAAS gene promoters was performed using MoLoTool.

According to the centrality criteria of the RAAS associative gene network, the following proteins were identified as exerting a significant influence on information interplay between network components: IL6, EDN1, TNFA, MK01, LEP, and JUN. Analysis of the ten identified TFs and their TFBSs among the genes in the RAAS network under study revealed clusters of three to 26 genes regulated by them.

Components with the highest values of centrality and vertex degrees were identified in the reconstructed associative gene network of the RAAS, and ten TFs supposed to regulate 26 RAAS genes were determined.

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15
Review Article Open Access
Vinit H. Majmudar, Kyle Nguyen-Ngo, Michael Tadros
Published online November 24, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00038
Abstract
Celiac disease is a chronic, immune-mediated enteropathy precipitated by gluten exposure in genetically predisposed individuals, with a global prevalence of approximately 1%. Though [...] Read more.

Celiac disease is a chronic, immune-mediated enteropathy precipitated by gluten exposure in genetically predisposed individuals, with a global prevalence of approximately 1%. Though diagnostic workflows incorporate serologic techniques with both histologic and genetic evaluation, each approach carries key pitfalls that contribute to diagnostic inaccuracy. Serology testing is limited by selective immunoglobulin A deficiency and low-titer antibodies, in addition to interlaboratory variability of calibration standards and specimen concentrations. While duodenal biopsy is considered the gold standard for celiac diagnosis, patchy villous atrophy (e.g., ultrashort celiac disease) mimics other enteropathies, and the inherent subjectivity of histologic interpretation can compromise accuracy. Furthermore, celiac predisposition is highly correlated with two human leukocyte antigen (HLA) alleles, HLA-DQ2 and HLA-DQ8. However, nearly 30–40% of the general population expresses one of these alleles, thus introducing the risk of overdiagnosis and limiting the practical implications of genetic testing. There exist special celiac presentations, such as seronegative or potential celiac disease, overlap syndromes, and enteropathy-associated T-cell lymphoma, that introduce additional challenges to diagnostic success. The serologic-histologic discordance and nonspecific symptoms associated with these cases may require divergence from the traditional workflow, as well as supplemental investigations, such as a gluten challenge or breath testing, to confirm a celiac diagnosis. These challenges in celiac diagnosis have driven research into novel biomarkers and molecular assays that can not only enable earlier, more accurate detection but also provide longitudinal disease monitoring. Such markers include intestinal fatty acid-binding proteins, specific microRNA expression, and microbiome signatures that are strongly linked to celiac disease, which may one day serve as adjunctive screening tools to optimize diagnostic yield. This narrative review identifies the key pitfalls in adult celiac disease diagnosis — from pre-analytic serology issues to patchy histology and overinterpretation of HLA — and proposes a guideline-aligned, stepwise algorithm (with emerging biomarkers) to enhance accuracy and reduce missed or delayed cases. Ultimately, continued refinement of a comprehensive, multimodal diagnostic strategy that can integrate with emerging molecular tools is necessary for overcoming the current limitations of individual approaches to celiac diagnosis.

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16
Original Article Open Access
Forough Sargolzaeiaval, Xi Cao, Richard L. Wong, Michelle D. Don, Huan-You Wang
Published online November 21, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00009
Abstract
Bone marrow metastasis (BMM) from non-hematolymphoid malignancies with resultant cytopenia(s) can mimic primary hematolymphoid disorders. This study aimed to investigate the clinical [...] Read more.

Bone marrow metastasis (BMM) from non-hematolymphoid malignancies with resultant cytopenia(s) can mimic primary hematolymphoid disorders. This study aimed to investigate the clinical and pathological characteristics of BMM from non-hematopoietic tumors.

We conducted a retrospective cohort study of patients diagnosed with BMM by non-hematolymphoid malignancies at our institution over the past 10 years. Demographic and clinical characteristics, histopathological findings of bone marrow, types of metastatic tumors, and prognosis were analyzed.

A total of 54 cases were included. The four most common malignancies with BMM, regardless of gender, were prostatic adenocarcinoma (29.6%), breast carcinoma (25.9%), colorectal adenocarcinoma (5.5%), and lung carcinoma (5.5%). The main clinical and laboratory manifestations were anemia (90.7%), reticulocytosis (80.5%), thrombocytopenia (73.9%), bone pain (55.5%), disseminated intravascular coagulation (39.6%), leukoerythroblastosis (35.3%), and leukopenia (24%). The vast majority (96.3%) of metastatic tumors were identified by morphology alone; however, in approximately 2.7% of cases, immunohistochemistry was required due to subtle morphologic features. In 29.6% (16/54) of patients, BMM was identified prior to or concurrently with other metastatic sites. The median time interval between the initial diagnosis of non-hematolymphoid malignancies and BMM was 29 months. Although patients who received anti-tumor treatment after BMM diagnosis showed significantly improved prognosis (P < 0.01), no significant differences were observed between those treated with immunotherapy versus chemotherapy and/or radiotherapy (P = 0.145).

Prostate and breast carcinomas are the most common malignancies associated with BMM, with anemia, reticulocytosis, and thrombocytopenia being the most frequent clinical manifestations. While our data demonstrate that anti-neoplastic treatments, regardless of regimen, significantly improve overall survival after BMM, no significant survival differences were observed when prostate and breast carcinomas were compared with other types of BMM.

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17
Scoping Review Open Access
Davi Porfirio da Silva, Adriana dos Santos Silva, José Vinicius Melo da Silva, Letícia Mirely de Melo Silva, José Joaquim da Silva Neto, Iramirton Figueredo Moreira, Rossana Teotônio de Farias Moreira, Anielle Christine Almeida Silva
Published online November 14, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00029
Abstract
Nanobiotechnology has driven transformative advancements in healthcare, particularly in the development of innovative solutions for wound treatment, a persistent and costly global [...] Read more.

Nanobiotechnology has driven transformative advancements in healthcare, particularly in the development of innovative solutions for wound treatment, a persistent and costly global health concern. Among these advancements, the combination of biopolymers and metallic nanoparticles has attracted considerable interest due to their excellent biocompatibility and potent antimicrobial activity. This scoping review explores recent technological progress in wound care, with a focus on alginate-based dressings functionalized with metallic nanoparticles. Alginate, a highly versatile biopolymer, was frequently employed in diverse formats, including hydrogels, sponges, beads, films/membranes, and fibers, across the analyzed studies. Silver nanoparticles were the most extensively investigated agents, owing to their well-established efficacy and the development of strategies to mitigate associated risks. Other metallic nanoparticles were also reported, contributing to a growing body of evidence supporting their therapeutic relevance. The synergistic integration of alginate and metallic nanoparticles has shown promising potential to enhance the performance of wound dressings, representing a significant step forward in the design of next-generation materials for effective and targeted wound management.

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18
Original Article Open Access
Pei Wang, Xuerui Yang, Danfeng Li, Bing Li, Yali Wan, Ye Yuan, Gefen Yue, Yuxin Zhan
Published online November 11, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00018
Abstract
Stroke patients have a high incidence of venous thromboembolism (VTE). Improving the prevention and control rates of VTE in stroke patients can enhance their quality of life. The [...] Read more.

Stroke patients have a high incidence of venous thromboembolism (VTE). Improving the prevention and control rates of VTE in stroke patients can enhance their quality of life. The aim of this study was to analyze the effect of 4R crisis management combined with the health belief model in the prevention and control of VTE in stroke patients.

A randomized controlled trial was conducted on 86 stroke patients in the neurosurgery department of a tertiary hospital in Wuhan. The control group was treated with the routine VTE prevention and control strategy, while the experimental group was treated with 4R crisis management combined with the health belief model. The primary outcome measures were the incidence rates of deep vein thrombosis and pulmonary thromboembolism, while the secondary outcome measures were the Short Form Health Belief Model Scale score, medical quality evaluation, and stroke patients’ health behavior scale score. The statistical analysis methods included t-tests and non-parametric tests.

After the intervention, the incidence rate of deep vein thrombosis in the control group was 14.6% (6/41), while in the experimental group it was 2.4% (1/41). The difference was statistically significant (χ2 = 3.905, P = 0.048). The incidence rates of pulmonary thromboembolism in both groups were 0%. The scores of all dimensions of the Short Form Health Belief Model Scale in the experimental group were higher than those in the control group, and the difference was statistically significant (P < 0.05, P < 0.01). The medical quality for each item showed that the experimental group performed better than the control group, with the difference being statistically significant (P < 0.05, P < 0.01). The scores on the stroke patients’ health behavior scale in the experimental group were higher than in the control group, except for responsibility, tobacco, and alcohol (P < 0.01).

The application of 4R crisis management combined with the health belief model can effectively improve the health beliefs and health behaviors of stroke patients to prevent VTE, thereby reducing the incidence of VTE.

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Original Article Open Access
Pedro Ribeiro, João Alexandre Lobo Marques, Marconi Pereira Brandão, Octávio Barbosa Neto, Camila Ferreira Leite, Pedro Miguel Rodrigues
Published online November 6, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00037
Abstract
Cardiovascular diseases account for approximately 80% of all deaths caused by known medical conditions, making them the leading cause of mortality worldwide. The present study investigates [...] Read more.

Cardiovascular diseases account for approximately 80% of all deaths caused by known medical conditions, making them the leading cause of mortality worldwide. The present study investigates the use of electrocardiogram (ECG) non-linear features and different topological medical features (heart rate, anthropometry, blood, glucose, and lipid profile, and heart rate variability) to discriminate between different Framingham Cardiovascular Risk Scale status groups in adult obesity using machine learning.

We conducted a cross-sectional study between November 2023 and May 2024 in Fortaleza, Ceará, Brazil. Based on the Framingham Cardiovascular Risk Scale, patients were categorized into three cardiovascular risk groups: Low (22 participants), Moderate (14 participants), and High (17 participants). From ECG signals at two different positions (ECG_Down and ECG_UP), 27 non-linear features were extracted using multi-band analysis. Additionally, 42 medical features provided by physicians were included. From a pool of 19 machine learning classifiers, models were trained and tested within a nested leave-one-out cross-validation procedure using information solely from ECG, solely from medical features, and combining both (multimodal), respectively, to distinguish between Low vs. Moderate, Low vs. High, Moderate vs. High, and All vs. All.

The multimodal model presented the best results for every comparison group, reaching (1) 88.89% Accuracy and 0.8831 area under the curve (AUC) for Low vs. Moderate; (2) 97.44% Accuracy and 0.9706 AUC for Low vs. High; (3) 93.55% Accuracy and an AUC of 0.9412 for Moderate vs. High; (4) 86.79% Accuracy and 0.9346 AUC for All vs. All.

The multimodal model outperformed single-source models in cardiovascular risk classification. ECG-derived non-linear features, especially from ECG_Down, were key drivers, with medical features adding complementary value. The results support its potential use in clinical triage and diagnosis.

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Review Article Open Access
Acharya Balkrishna, Deepika Srivastava, Razia Parveen, Ankita Kukreti, Nidhi Sharma
Published online November 6, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00030
Abstract
Gastrointestinal (GI) health is essential for maintaining systemic balance, influencing digestion, immunity, and neuroendocrine signaling. However, GI disorders such as irritable [...] Read more.

Gastrointestinal (GI) health is essential for maintaining systemic balance, influencing digestion, immunity, and neuroendocrine signaling. However, GI disorders such as irritable bowel syndrome, inflammatory bowel disease, gastroesophageal reflux disease, peptic ulcers, and constipation are increasingly prevalent, significantly affecting global health and healthcare economics. Although conventional pharmacological treatments offer symptomatic relief, their long-term use is often associated with adverse effects, resistance, and limited efficacy, prompting a shift toward alternative and complementary therapies. Traditional systems of medicine, such as Ayurveda, Traditional Chinese Medicine, Unani, and Siddha, emphasize holistic approaches, including herbal formulations that target underlying causes rather than just symptoms. This review provides a comprehensive analysis of the role of natural products and traditional herbals in GI health. It discusses key bioactive constituents, flavonoids, alkaloids, terpenoids, and polyphenols, known for their anti-inflammatory, antimicrobial, gastroprotective, and prebiotic properties. Widely used herbal remedies such as Triphala, licorice root, peppermint oil, turmeric, and psyllium are highlighted for their proven therapeutic actions. Additionally, the review documents more than 300 medicinal plants traditionally used in diverse cultures worldwide for managing GI conditions, based on ethnopharmacological evidence. While the therapeutic promise is substantial, challenges such as formulation standardization, herb-drug interactions, and limited clinical data remain. The review underscores the need for integrating traditional wisdom with modern scientific validation, offering a path forward for safe, effective, and personalized GI healthcare.

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