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Review Article Open Access
The Hidden Drivers of Aging: Microbial Influence on Genomic Stability and Telomere Dynamics
Swarup K. Chakrabarti, Dhrubajyoti Chattopadhyay
Published online April 17, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00045
Abstract
This review explores the complex interplay between the microbiome and human aging, highlighting how dysbiosis impacts host physiology and health, particularly in relation to genomic [...] Read more.

This review explores the complex interplay between the microbiome and human aging, highlighting how dysbiosis impacts host physiology and health, particularly in relation to genomic stability and telomere attrition. Recent advances in cellular and molecular biology have underscored the role of both intrinsic and extrinsic factors in human aging, with the microbiome emerging as a key determinant of host physiology and health. Dysbiosis—disruptions in microbiome composition—is linked to various age-related diseases and impacts genomic stability and telomere attrition, the progressive shortening of telomeres that limits cell division and contributes to aging. This review examines how microbiome dynamics influence aging by triggering inflammation, oxidative stress, immune dysregulation, and metabolic dysfunction, all of which affect two primary hallmarks of aging: genomic instability and telomere attrition. Understanding these interactions is essential for developing targeted interventions to restore microbiome balance and promote healthy aging, offering potential treatments to extend healthspan and alleviate aging-related diseases. The convergence of microbiome and aging research promises transformative insights and new avenues for improving global population well-being.

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Review Article Open Access
Emerging Serum Biomarkers for Chronic Hepatitis B: Focus on Serum HBV RNA and HBcrAg
Yike Tian, Haibo Yu, Juan Chen
Published online July 22, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00064
Abstract
Chronic hepatitis B virus (HBV) infection remains a major cause of liver diseases, including cirrhosis and hepatocellular carcinoma. Reliable biomarkers for assessing viral replication, [...] Read more.

Chronic hepatitis B virus (HBV) infection remains a major cause of liver diseases, including cirrhosis and hepatocellular carcinoma. Reliable biomarkers for assessing viral replication, liver damage, and predicting clinical outcomes are essential for effective patient management. This review focuses on two promising biomarkers: serum HBV RNA and hepatitis B core-related antigen, both of which show strong correlations with viral replication and disease progression. Serum HBV RNA levels reflect the quantity and transcriptional activity of intrahepatic covalently closed circular DNA, providing insights into viral replication. They also correlate with other markers of replicative activity and have predictive value for key clinical outcomes, including hepatitis B e antigen and hepatitis B surface antigen seroconversion, relapse after therapy cessation, and liver fibrosis. Similarly, hepatitis B core-related antigen is closely associated with covalently closed circular DNA levels, correlates with markers of viral replication, and shows promise in predicting liver fibrosis, cirrhosis, and the risk of hepatocellular carcinoma. This review highlights the potential of both biomarkers for monitoring disease progression and guiding therapeutic decisions, particularly in the context of personalized treatment strategies and risk assessment for liver-related complications.

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Review Article Open Access
Unraveling the Oncogenic Potential of microRNAs in Lung Cancer: A Narrative Review Article
Ali Moradi, Mohammad Bayat, Parvin Pourmasoumi, Sufan Chien
Published online March 19, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00001
Abstract
Lung cancer (LC) remains the leading cause of cancer-related deaths worldwide, characterized by high mortality rates and limited treatment options. MicroRNAs (miRNAs) are critical [...] Read more.

Lung cancer (LC) remains the leading cause of cancer-related deaths worldwide, characterized by high mortality rates and limited treatment options. MicroRNAs (miRNAs) are critical regulators of gene expression and play significant roles in the development of LC. This review aimed to provide a comprehensive analysis of oncogenic miRNAs involved in LC, focusing on their dysregulation, functional roles, and potential implications for diagnosis and therapy. In this review, we collected data from published literature, specifically selecting English articles closely related to the topic. We conducted a thorough review of studies published between 2013 and 2023, utilizing prominent academic databases such as PubMed, Scopus, and Google Scholar to gather relevant data. Our investigation highlights several oncogenic miRNAs that have been shown to play critical roles in lung cancer biology, including miR-9-5p, miR-21, and miR-31. These miRNAs are known to facilitate various key processes, such as tumor cell proliferation, enhanced migratory capabilities, and the development of resistance to chemotherapeutic agents. Additionally, miRNAs present significant diagnostic and therapeutic potential. In conclusion, the unique roles and regulatory networks of miRNAs in LC warrant extensive further research. Further research is essential to uncover the complex networks of miRNAs and to develop innovative miRNA-based therapies for lung cancer.

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Original Article Open Access
Evaluation of Plasma Neurodegenerative Biomarkers for Diagnosing Minimal Hepatic Encephalopathy and Predicting Overt Hepatic Encephalopathy in Chinese Patients with Hepatic Cirrhosis
Qiuyu Cheng, Yunhui Liu, Zhongyuan Yang, Meng Zhang, Tingting Liu, Yuxin Niu, Wei Liu, Lanyue Huang, Yuzhao Feng, Xiaoyun Zhang, Xiaoping Luo, Qin Ning, Tao Chen
Published online December 12, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00413
Abstract
The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in [...] Read more.

The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in diagnosing minimal hepatic encephalopathy (MHE) has not been systematically evaluated, simultaneously, nor have their associations with the development of overt hepatic encephalopathy (OHE). This study aimed to evaluate the performance of plasma NfL, GFAP, tau, and UCHL1 in diagnosing MHE and predicting the development of OHE in Chinese patients with hepatic cirrhosis.

In this prospective study, 124 patients with hepatic cirrhosis were recruited. The Psychometric Hepatic Encephalopathy Score was used to diagnose MHE, and OHE development was observed during a 30-day follow-up period. Plasma levels of NfL, GFAP, tau, and UCHL1 were measured using the highly sensitive single-molecule array when MHE was diagnosed. Additionally, serum interleukin-6 (IL-6) levels and the model for end-stage liver disease (MELD) and MELD-Na scores were also measured.

MHE was diagnosed in 57 (46.0%) patients. Patients with MHE had significantly higher plasma levels of NfL and GFAP (34.2 vs. 22.4 pg/mL and 173 vs. 97.6 pg/mL, respectively; both p < 0.001) and lower tau levels (8.4 vs. 11.6 pg/mL, p = 0.048) compared to those without MHE. Plasma NfL (odds ratios = 1.027, 95% confidence interval [CI]: 1.006–1.048; p = 0.013) and serum ammonia levels (odds ratios = 1.021, 95% CI: 1.006–1.036; p = 0.007) were independently associated with MHE occurrence. A combination of NfL, GFAP, tau, and UCHL1 was effective in diagnosing MHE in all cirrhotic patients (area under the receiver operating characteristic curve [hereinafter referred to as AUROC]: 0.748, 95% CI: 0.662–0.821), with an accuracy, sensitivity, and specificity of 71.0%, 71.9%, and 71.6%, respectively. In patients without previous OHE, the combination had an AUROC of 0.764 (95% CI: 0.673–0.840), with an accuracy, sensitivity, and specificity of 72.5%, 71.7%, and 73.0%, respectively. Furthermore, GFAP (hazard ratio (HR) = 1.003, 95% CI: 1.000–1.005; p = 0.044), IL-6 (HR = 1.003, 95% CI: 1.001–1.004; p < 0.001), and MELD score (HR = 1.139, 95% CI: 1.072–1.210; p < 0.001)—but not NfL, tau, and UCHL1—were identified as risk factors for 30-day OHE development.

The combination of plasma levels of NfL, GFAP, tau, and UCHL1 performs well in diagnosing MHE. Additionally, MELD score, IL-6, and GFAP appear to be significant predictors of OHE development in patients with hepatic cirrhosis.

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Research Letter Open Access
Development and Validation of a Novel Noninvasive Model to Predict Liver Fibrosis Staging in Untreated Patients with Chronic Hepatitis B
Jianhua Hu, Xiaoli Zhang, Zhibo Zhou, Fangfang Geng, Hongyu Jia, Linfeng Jin, Weixiang Zhong, Guodong Yu, Xue Wen, Hainv Gao, Yida Yang
Published online July 7, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00175
Illuminating and Instructive Clinical Case Open Access
Virological Response to Lamivudine and Tenofovir Treatment in a Mono-infected Chronic Hepatitis B Patient with Potential Tenofovir Resistance: A Case Report
Monica Dahiya, Teresa Tai, Trana Hussaini, Gordon Ritchie, Nancy Matic, Eric M. Yoshida, Christopher F. Lowe
Published online December 12, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00248
Abstract
Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected [...] Read more.

Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected patient with potential tenofovir resistance who required combined lamivudine and tenofovir therapy to achieve adequate viral suppression. The patient’s viral load (plasma) was monitored using the cobas® hepatitis B virus Test on the cobas® 6800 system. Hepatitis B antiviral drug resistance (AVDR) mutations were assessed by amplicon-based sequencing. Plasma was extracted using the MagNa Pure 24 system, and polymerase chain reaction targeting the polymerase gene (860bp) was performed. Sequencing was conducted on GridION R10.4.1 flow cells, and the resulting FASTQ files were analyzed using DeepChek®-HBV Software. We describe a female patient in her 60s with chronic hepatitis B who was e-antigen positive. She met treatment criteria in May 2020, when her alanine transaminase levels were 1.5 times above the upper limit of normal. She was initially started on entecavir but had to switch to tenofovir alafenamide in June 2020 due to a rash. Despite three years of tenofovir therapy, her viral load remained unsuppressed. AVDR testing identified two suspected tenofovir resistance mutations (V191I and A317S). Since no mutations associated with lamivudine resistance were detected, the patient was treated with a combination of lamivudine and tenofovir, achieving viral suppression after four months. Although rare, tenofovir resistance should be considered in patients with persistent viremia despite long-term therapy. AVDR sequencing facilitated the detection of potential tenofovir resistance and guided treatment decisions, leading to successful viral suppression in this case.

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Review Article Open Access
Macromolecular Gene Delivery Systems: Advancing Non-viral Therapeutics with Synthetic and Natural Polymers
Pratikeswar Panda, Sangita Ranee Gouda, Disha Boxi, Gourab Saha, Rajaram Mohapatra
Published online June 25, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00009
Abstract
Macromolecular-based gene delivery systems have emerged as viable alternatives to non-viral vectors for gene therapy due to their versatility, biocompatibility, and capacity to [...] Read more.

Macromolecular-based gene delivery systems have emerged as viable alternatives to non-viral vectors for gene therapy due to their versatility, biocompatibility, and capacity to efficiently deliver therapeutic cargo. These systems, primarily based on synthetic and natural polymers, offer significant advantages in terms of safety, controlled gene release, and targeted delivery. This review explores the design and synthesis of macromolecular carriers, focusing on their chemical and physical architectures, which play a key role in improving gene delivery. Catanionic polymers and their derivatives (comb, brush, and star polymers) have been extensively researched for their capacity to condense and protect genetic material. Furthermore, natural polymers like chitosan and hyaluronic acid have been modified to enhance gene delivery capabilities. These macromolecular carriers are engineered to boost circulation time, increase cellular uptake, and facilitate the controlled release of genetic material at the target site. Strategies such as incorporating targeting ligands, stimuli-responsive elements, and reducing cytotoxicity are being pursued to improve the overall efficiency and specificity of these systems. This review highlights the current state of macromolecular gene delivery systems, their applications, and the ongoing research aimed at overcoming existing challenges, paving the way for more effective non-viral gene therapies.

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Original Article Open Access
Efficacy and Safety of Neuroendoscopic Surgery versus Craniotomy for Supratentorial Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Biwu Wu, Haoyue Yuan, Qiang Yuan, Gang Wu, Jin Hu
Published online April 3, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00006
Abstract
Surgical management of supratentorial spontaneous intracerebral hemorrhage (sICH) remains controversial. Craniotomy (CT) reduces mortality but offers limited functional benefits. [...] Read more.

Surgical management of supratentorial spontaneous intracerebral hemorrhage (sICH) remains controversial. Craniotomy (CT) reduces mortality but offers limited functional benefits. Neuroendoscopic surgery (NE) has emerged as a viable alternative, providing improved outcomes. Recent randomized controlled trials (RCTs) strengthen ongoing comparisons between these approaches. This meta-analysis systematically evaluates the efficacy and safety of NE versus CT for supratentorial sICH.

RCTs comparing NE versus CT for supratentorial sICH were systematically identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science databases. Evaluated outcomes included functional outcome (favorable or unfavorable), hematoma evacuation rate, mortality, intraoperative blood loss, operation time, rebleeding, infection (including pulmonary and intracranial), and total complications. Cochrane’s Risk of Bias-2 tool was employed to assess the risk of bias across the included studies.

Eight RCTs were included, comprising 1,354 patients. NE demonstrated a significant advantage in achieving a favorable functional outcome (risk ratio: 1.43; 95% confidence interval (CI) 1.22, 1.68; p < 0.001) and a notably higher hematoma evacuation rate (mean difference (MD): 7.60; 95% CI 3.59, 11.61; p < 0.001). Additionally, NE was associated with a marked reduction in intraoperative blood loss (MD: −152.95; 95% CI −261.68, −44.22; p = 0.006) and a substantial reduction in operative time (MD: −118.49; 95% CI −147.30, −89.67; p < 0.001). The incidences of unfavorable functional outcome and total complications, including pulmonary infection, were significantly lower in the NE group. However, NE did not lead to an improvement in the mortality rate, and there were no significant differences in the incidences of postoperative rebleeding or intracranial infection between the two groups.

These findings suggest that NE offers distinct advantages in terms of functional outcomes and surgical efficiency for patients with supratentorial sICH. Future studies should involve larger, higher-quality RCTs, and neuroendoscopic techniques should be continuously optimized.

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Review Article Open Access
Molecular and Histological Profiles and Relevant Imaging Signatures of Intrahepatic Cholangiocarcinoma
Huizhen Huang, Feng Chen
Published online April 30, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00410
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer, characterized by insidious onset and high malignancy. Many patients are diagnosed at an [...] Read more.

Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer, characterized by insidious onset and high malignancy. Many patients are diagnosed at an inoperable stage, and the effectiveness of chemotherapy and radiotherapy remains limited. This study aimed to provide a comprehensive review of the histological classification, genetic alterations, molecular subtypes, and corresponding imaging signatures of iCCA, highlighting its heterogeneity and offering insights into targeted therapy and personalized treatment. The heterogeneity of iCCA poses significant challenges to both targeted therapy and immunotherapy, necessitating in-depth exploration at the molecular and subtyping levels. Investigating genetic variations, signaling pathway alterations, and molecular subtypes can aid in patient stratification. Stratifying iCCA patients allows for more precise treatment selection, ultimately improving survival outcomes. Imaging, as a non-invasive tool, holds substantial potential for predicting subtypes and molecular profiles. It is possible to infer histological and molecular features from imaging, or to interpret imaging signatures in light of known histological and molecular data. This integrative approach, combining external imaging with internal molecular insights, fosters a comprehensive understanding of iCCA’s characteristics and enhances clinical management.

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Original Article Open Access
Effects of Electroacupuncture Combined with Chinese Herbal Medicine on Gut Microbiota and Metabolomics in Amyotrophic Lateral Sclerosis: A Prospective Study
Hai Cui, Tianyi Liang, Xudong Yang, Yiwen Zhang, Ruqi Zhou, Tianqi Wang
Published online February 20, 2025
Future Integrative Medicine. doi:10.14218/FIM.2024.00055
Abstract
Recent studies have highlighted a link between amyotrophic lateral sclerosis (ALS) and gut microbiota. This prospective study aimed to evaluate the effects of electroacupuncture [...] Read more.

Recent studies have highlighted a link between amyotrophic lateral sclerosis (ALS) and gut microbiota. This prospective study aimed to evaluate the effects of electroacupuncture combined with Chinese herbal medicine on gut microbiota and metabolomics in ALS patients.

Ten ALS patients were randomly assigned to either a treatment group (electroacupuncture with Chinese herbal medicine, n = 6) or a control group (waiting treatment, n = 4). Healthy controls (age- and sex-matched, n = 10) were also included. Data were collected after 12 sessions of electroacupuncture and follow-ups at three and six months. ALS functional rating scale scores were documented pre- and post-treatment. Stool samples were collected at two time points (T0 and T4 weeks) and analyzed, and metabolomic profiles from urine samples were analyzed post-treatment. Heatmap correlation analysis was used to explore relationships between microbiota, metabolomics, and clinical outcomes.

Treatment with electroacupuncture reduced Eisenbergiella abundance in the treatment group. A significant positive correlation was found between Lachnospiraceae and ALS functional rating scale scores (P < 0.005 and P < 0.001, respectively). Differential expression of purine metabolism was observed in ALS patients (P = 0.0017).

Imbalances in the gut microbiome and metabolic disorders have been found among patients with ALS. These imbalances appear to be partially mitigated by treatment with electroacupuncture combined with Chinese herbal medicine. Our research suggests that Eisenbergiella might be a diagnostic biomarker and a potential therapeutic target for ALS.

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