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Review Article Open Access
Fluorescence-guided Surgery for Hepatocellular Carcinoma: From Clinical Practice to Laboratories
Tian Xiao, Didi Chen, Li Peng, Zhuoxia Li, Wenming Pan, Yuping Dong, Jinxiang Zhang, Min Li
Published online January 2, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00375
Abstract
Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine [...] Read more.

Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries, but it cannot distinguish between benign and malignant liver tumors. This review focused on the clinical applications and limitations of indocyanine green, as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC. It covers traditional fluorescent imaging probes such as enzymes, reactive oxygen species, reactive sulfur species, and pH-sensitive probes, followed by an introduction to aggregation-induced emission probes. Aggregation-induced emission probes exhibit strong fluorescence, low background signals, excellent biocompatibility, and high photostability in the aggregate state, but show no fluorescence in dilute solutions. Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.

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Review Article Open Access
Herbal Medicine for the Mind: Traditionally Used Medicinal Plants for Memory Loss from the Indian Subcontinent
Fawad Alam-Siddiqui, Ayesha Ghayur, Zaheer Ul-Haq, Muhammad Nabeel Ghayur
Published online April 23, 2025
Future Integrative Medicine. doi:10.14218/FIM.2024.00050
Abstract
Memory loss is a symptom of several neurological disorders, including dementia and Alzheimer’s disease (AD). It can significantly impact individuals, their loved ones, and society [...] Read more.

Memory loss is a symptom of several neurological disorders, including dementia and Alzheimer’s disease (AD). It can significantly impact individuals, their loved ones, and society as a whole. Current pharmaceutical interventions have shown some improvement in individuals’ quality of life, but more needs to be done to reduce the burden of memory loss and AD. This paper investigates herbal remedies for memory loss, with a particular focus on the mechanisms underlying their effects. By consulting several South Asian printed books, numerous traditionally used medicinal plants with memory-enhancing properties were identified. A review of published studies showed that many of these plants have reported properties related to memory enhancement and the treatment of AD. Some of the relevant mechanistic actions reported for these plants include acetylcholinesterase inhibition, anti-inflammatory activity, antioxidant effects, and neuroprotective properties. There is also evidence that some plants exhibit a combination of different mechanisms, making them especially promising as therapeutic agents for memory loss. Our review shows the existence and potential of medicinal plants in addressing memory loss. Additionally, some reports provide a scientific basis for the use of these plants in conditions characterized by memory decline, such as AD. This study underscores the importance of further research to evaluate the efficacy of traditionally used medicinal plants in the management of memory loss.

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Letter to the Editor Open Access
Epigenetics, Epigenomics, and Personalized Medicine
Sanjoy Majumder, Rutupurna Das, Annapurna Sahoo, Kunja Bihari Satapathy, Gagan Kumar Panigrahi
Published online November 11, 2024
Gene Expression. doi:10.14218/GE.2024.00058
Hot Topic Commentary Open Access
Prolonged Direct Hyperbilirubinemia Following Acute Hepatitis: When Not to Worry?
Danzhu Zhao, George Y. Wu
Published online November 8, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00265
Review Article Open Access
Anticancer Mechanisms of Indigenous Food Plants in Nigeria
Adeoye Bayo Olufunso, Adeyemi Funmilayo Elizabeth, Bolade Damilola Comfort, Oyeleke Ibukun Oyebimpe, Oyerinde Ayodeji Michael, Fadeyi Blessing, Olatinwo Goodness Olusayo, Ukangwa Ngozi Angela, Adeshina Halliyah Celine, Onyeyiriuche Chinecherem Chibundo, Aanu-Bakare Grace Olajumoke, Adeoye Ayodeji David, Akano Oyedayo Phillips, Adelakin Lola Adeola, Achor Cornilluis Bangsi, Ajaere Sandra Onyinyechi, Osundina Oluwaseun Babatunde, Olatinwo Mercy Olajoju, Adebayo Barakat Temitope, Olanrewaju Okikiola Olamide
Published online January 26, 2025
Future Integrative Medicine. doi:10.14218/FIM.2024.00042
Abstract
Cancer continues to pose a substantial public health problem in Nigeria, characterized by rising rates of occurrence and mortality. While there is increasing interest in using natural [...] Read more.

Cancer continues to pose a substantial public health problem in Nigeria, characterized by rising rates of occurrence and mortality. While there is increasing interest in using natural products for cancer treatment, comprehensive data on the specific bioactive compounds in these plants and how they modulate different types of cancer are still lacking. Additionally, although traditional knowledge about these food plants is rich and valuable, it has not been fully integrated with modern scientific research to create standardized treatment protocols. Scientific databases like PubMed, ScienceDirect, Google Scholar, and ResearchGate were explored to retrieve empirical data. The key plants discussed are Spondias mombin, Xanthosoma sagittifolium, Elaeis guineensis, Irvingia gabonensis, Allium cepa, Blighia sapida, Dioscorea dumetorum, Psidium guajava, and Talinum triangulare. These plants demonstrate a wide range of anticancer properties, including the ability to induce apoptosis (cell death), halt the cell cycle, inhibit angiogenesis, and regulate inflammatory responses. They contain a variety of phytochemicals, such as flavonoids, tannins, terpenoids, alkaloids, and organosulfur compounds, which contribute to their anticancer effects. For example, Spondias mombin contains flavonoids that inhibit the formation of tumors, whereas Xanthosoma sagittifolium exhibits cytotoxic effects against leukemia cells. Additionally, Elaeis guineensis exhibits antioxidant properties that counteract oxidative stress, a crucial factor in cancer progression. This review highlights the significance of these plants in developing complementary cancer therapies that can be used alongside conventional treatments. By combining traditional knowledge with contemporary scientific methods, these medicinal plants have the potential to provide innovative approaches to cancer prevention and treatment, addressing the pressing demand for safer and more efficient therapeutic alternatives.

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Review Article Open Access
Understanding Inflammatory Bowel Disease: An Integrative Framework of Microbiome, Metabolome, and Immunological Biomarkers
Prithvi S. Prabhu, Rija Kalita, Vanshika Sharma, Tulika Prakash
Published online March 25, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00030
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and primarily includes ulcerative colitis and Crohn’s disease. As the number [...] Read more.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and primarily includes ulcerative colitis and Crohn’s disease. As the number of patients suffering from IBD increases, diagnosis and treatment have become pressing yet challenging tasks. A major challenge is that patients with IBD often do not exhibit characteristic symptoms, making it difficult to distinguish IBD from other intestinal abnormalities. Endoscopy is the most conventional method used to diagnose IBD; however, this technique is invasive and costly. Therefore, there is a need to develop affordable, non-invasive diagnostic methods, which underscores the importance of identifying biomarkers specific to IBD. It is now well established that the gut microbiome plays a significant role in the development of IBD, and changes in the abundance of various gut organisms have been widely studied to identify microbial signatures associated with the disease. This review discusses the current state of knowledge regarding biomarkers in IBD, with a primary focus on the gut microbiome, associated metabolic signatures, and their links with immunological biomarkers. These biomarkers will help propose an integrative model to better understand the pathophysiology of this complex disease. Such an integrated approach also offers insights into potential therapeutic targets for designing more effective treatment strategies for patients.

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Original Article Open Access
HBx Facilitates Drug Resistance in Hepatocellular Carcinoma via CD133-regulated Self-renewal of Liver Cancer Stem Cells
Xiangshu Jin, Huijun Dong, Juan Wang, Guomin Ou, Xinyuan Lai, Xing Tian, Lei Wang, Hui Zhuang, Tong Li, Kuanhui Xiang
Published online November 25, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00259
Abstract
Hepatitis B virus (HBV) infection contributes to hepatocellular carcinoma (HCC) tumorigenesis, drug resistance, and recurrence, although the underlying molecular mechanisms remain [...] Read more.

Hepatitis B virus (HBV) infection contributes to hepatocellular carcinoma (HCC) tumorigenesis, drug resistance, and recurrence, although the underlying molecular mechanisms remain unclear. Recent studies suggest that HBV infection may be associated with liver cancer stem cells (LCSCs), but the exact mechanisms are yet to be resolved. In this study, we aimed to analyze the role of HBV infection in regulating the stemness of HCCs, which is closely linked to drug resistance.

Sphere formation assay and real-time Polymerase Chain Reaction quantification were used to isolate and confirm liver cancer stem cells. The inhibitory concentration values of sorafenib and regorafenib were calculated and compared using the Cell Counting Kit-8 assay. HBV infection was used to assess the effect of HBV replication on LCSC markers. Co-immunoprecipitation assay was performed to detect the interaction between CD133 and SRC. Furthermore, we utilized the CRISPR-Cas9 system to knockout CD133 expression in HepG2.2.15 cells.

LCSCs derived from HCCs exhibited high expression of stem cell markers and demonstrated reduced sensitivity to sorafenib and regorafenib. HBV replication promoted both drug resistance and stemness in hepatoma cells and clinical samples. Overexpression of HBx protein in HepG2 cells upregulated the expression of CD133, EpCAM, and CD24, enhancing resistance to sorafenib and regorafenib. Knockout of CD133 expression using the CRISPR-Cas9 system significantly inhibited drug resistance to both sorafenib and regorafenib in HepG2.2.15 cells. Mechanistically, HBV replication promoted CD133 expression, which in turn interacted with the SRC/STAT3 signaling pathway.

Our data suggest that HBV replication enhances the stemness and drug resistance of HCC, providing a strong theoretical foundation for the development of targeted and efficient treatments for HBV-infected HCCs.

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Mini Review Open Access
The Pathophysiological Relationship and Treatment Progress of Obstructive Sleep Apnea Syndrome, Obesity, and Metabolic Syndrome
Jixiang Li, Liang Zeng, Tong Feng
Published online January 7, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00048
Abstract
Patients with obstructive sleep apnea (OSA) and metabolic syndrome (MetS) have a higher prevalence and mortality rate of cardiovascular diseases, posing a significant burden on [...] Read more.

Patients with obstructive sleep apnea (OSA) and metabolic syndrome (MetS) have a higher prevalence and mortality rate of cardiovascular diseases, posing a significant burden on both individuals and society. Although the precise pathophysiological relationship between OSA and MetS remains unclear, their bidirectional interaction may create a harmful cycle of mutual reinforcement. This review explored the current treatment progress for OSA and MetS, including continuous positive airway pressure therapy, weight management, and metabolic surgeries. Studies indicate that while continuous positive airway pressure therapy effectively alleviates OSA symptoms, its impact on metabolic markers is limited, emphasizing the importance of long-term weight control. Metabolic surgeries, such as gastric bypass and sleeve gastrectomy, significantly reduce weight and directly improve metabolic abnormalities associated with MetS, such as insulin resistance and dyslipidemia, thereby lowering the risk of cardiovascular diseases. In contrast, mandibular advancement devices primarily improve symptoms of OSA and indirectly enhance metabolic function by improving sleep quality and reducing intermittent hypoxemia. Although mandibular advancement devices have a limited direct impact on metabolic parameters, they may offer potential benefits in lowering blood pressure and managing MetS. Understanding and breaking the cycle between OSA and MetS can significantly reduce the associated cardiovascular risks.

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Review Article Open Access
A New Approach to Differentiating Large Granular Lymphocytic Leukemias and Their Mimics in Light of Current Updates in the 5th Edition of the WHO Classification
Dylan W. Purkiss, Iris E. Lee, Dan Xu, Jun Wang
Published online January 21, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00043
Abstract
Large granular lymphocytic leukemias (LGLLs), including T-cell LGLL and natural kill (NK)-cell LGLL variants, are rare lymphoproliferative disorders characterized by the chronic [...] Read more.

Large granular lymphocytic leukemias (LGLLs), including T-cell LGLL and natural kill (NK)-cell LGLL variants, are rare lymphoproliferative disorders characterized by the chronic proliferation of cytotoxic lymphocytes. Despite recent advancements, challenges remain in distinguishing these entities from one another and from related disorders, such as T-cell prolymphocytic leukemia, adult T-cell leukemia/lymphoma, Sézary syndrome, and aggressive NK-cell leukemia, owing to overlapping clinical and morphologic features. This article aims to review the role of molecular and immunophenotypic markers in guiding diagnosis and prognosis of LGLLs, with brief review of their clinical and morphologic features by synthesizing current advances in molecular pathogenesis, immunophenotypic profiling, and updated World Health Organization (WHO) classification criteria in order to enhance diagnostic precision, improve prognostic assessment, and inform personalized treatment strategies for these challenging disorders.

Literature was searched through Pubmed and the recently published 5th WHO classification criteria. Articles were reviewed and analyzed with emphasis on recent molecular and cytogenetic insights.

A total of 106 publications were reviewed, and the recent molecular insights—focusing on those concerning STAT3 mutations in T-cell LGLL and TET2 mutations in NK-cell LGLL which have refined diagnostic frameworks, though gaps persist in understanding their clinical relevance and variability.

By providing a comparative analysis of large granular lymphocytic leukemias and their differential diagnoses in cooperation of the current advances in molecular pathogenesis, immunophenotypic profiling, and updated WHO classification criteria, this work aimed to enhance diagnostic precision, improve prognostic assessment, and inform personalized treatment strategies for these challenging LGLLs.

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Original Article Open Access
Risk of Coronary Artery Disease in Patients with Liver Cirrhosis: A Systematic Review and Meta-analysis
Chunru Gu, Liyan Dong, Lu Chai, Zhenhua Tong, Fangbo Gao, Walter Ageno, Fernando Gomes Romeiro, Xingshun Qi
Published online November 21, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00226
Abstract
Coronary artery disease (CAD) is increasingly observed in patients with liver cirrhosis. However, data on the incidence and prevalence of CAD in cirrhotic patients are heterogeneous, [...] Read more.

Coronary artery disease (CAD) is increasingly observed in patients with liver cirrhosis. However, data on the incidence and prevalence of CAD in cirrhotic patients are heterogeneous, and the association remains uncertain. In this study, we aimed to conduct a systematic review and meta-analysis to address these issues.

PubMed, EMBASE, and Cochrane Library databases were searched. Incidence, prevalence, and factors associated with CAD were pooled using a random-effects model. Risk ratio (RR) and odds ratio (OR), with their 95% confidence interval (CI), were calculated to evaluate differences in CAD incidence and prevalence between patients with and without liver cirrhosis.

Fifty-one studies were included. The pooled incidences of CAD, acute coronary syndromes, and myocardial infarction (MI) were 2.28%, 2.02%, and 1.80%, respectively. Liver cirrhosis was not significantly associated with CAD incidence (RR = 0.77; 95% CI = 0.46–1.28) or MI (RR = 0.87; 95% CI = 0.49–1.57). The pooled prevalence of CAD, acute coronary syndromes, and MI was 18.87%, 12.54%, and 6.12%, respectively. Liver cirrhosis was not significantly associated with CAD prevalence (OR = 1.29; 95% CI = 0.83–2.01) or MI (OR = 0.58; 95% CI = 0.28–1.22). Non-alcoholic steatohepatitis, hepatitis C virus, advanced age, male sex, diabetes mellitus, hypertension, hyperlipidemia, smoking history, and family history of CAD were significantly associated with CAD in cirrhotic patients.

CAD is common in cirrhotic patients, but cirrhosis itself may not be associated with an increased CAD risk. In addition to traditional risk factors, non-alcoholic steatohepatitis and hepatitis C virus infection are also associated with CAD presence in cirrhotic patients.

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