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561
Original Article Open Access
Chun-Hui Jiang, Hong-Yu Wu, Jia-Yun Chen, Wen Huang, Chun-You Huang, Zhao-Shen Li, Xue Fang, Wen-Bin Zou
Published online August 30, 2023
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00026
Abstract
Functional bowel disorders (FBDs) afflict millions of people worldwide. The pathogenesis of FBDs remains unclear and there are no effective treatments currently available. The intestinal [...] Read more.

Functional bowel disorders (FBDs) afflict millions of people worldwide. The pathogenesis of FBDs remains unclear and there are no effective treatments currently available. The intestinal microbiota is deemed a critical etiological factor in FBDs, and microbiota-targeted treatment strategies have promising therapeutic value. However, no comprehensive scientometric analyses related to FBDs and the intestinal microbiota have been performed. This study aimed to employ scientometrics to thoroughly analyze the knowledge base and the viable frontier between the intestinal microbiota and FBDs research fields.

Scientometrics was used to analyze the global research trends and hotspots in the overlapping fields of FBDs and the intestinal microbiota. The Web of Science database was selected as the research tool, and documents written in English and published from database inception to June 26th, 2023, were investigated.

There was a growth in publications from 2007 to 2022, with a total of 2,924 articles identified. China (n = 685, 23.43%) made the greatest contribution, followed by the United States (n = 672, 22.98%) and United Kingdom (n = 276, 9.44%). Co-citation analysis of references reflected the knowledge base in the past 16 years, including updating the understanding of FBDs, unveiling the relationship between the intestinal microbiota and FBDs, and preliminary research on the effects of microbiota-targeted treatment on FBDs.

By utilizing scientometrics, we identified three main research frontiers including microbiome-metabolites-mechanisms in FBDs, microbiota-related biomarkers for FBDs, and mechanism of microbiota-targeted treatments towards FBDs for precise medicine. These findings could provide valuable guidance for future research.

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562
Review Article Open Access
Ryan Dao, Amit Aggarwal
Published online August 28, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00027
Abstract
Major depressive disorder (MDD) continues to be a prevalent disease worldwide. While selective serotonin reuptake inhibitors and other medications continue to be prescribed, further [...] Read more.

Major depressive disorder (MDD) continues to be a prevalent disease worldwide. While selective serotonin reuptake inhibitors and other medications continue to be prescribed, further research has been conducted toward other treatment modalities. Within the past decade, ketamine, an N-methyl-d-aspartate receptor antagonist, has been extensively studied as a new treatment for MDD. Recent studies show that ketamine at subanesthetic doses provides antidepressant effects. An extensive overview of the latest statistics of MDD and treatment plans are emphasized, with a review of current medications and their subsequent side effects. However, an important factor to consider with ketamine is dissociation, and given ketamine’s psychotomimetic side effects, it must be reviewed further. Despite such side effects of hallucinations and depersonalization, studies have shown administration achieves rapid and lasting antidepressant effects. The synergistic effects of ketamine are also analyzed with recent studies to summarize the effects of different treatment modalities. A summary of the latest research studies of ketamine as a possible treatment for MDD is provided. By focusing on the evolution of ketamine as a treatment for MDD, physicians can now utilize newer techniques for depression, with better short-term and long-term outcomes for the patients.

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563
Original Article Open Access
Qian Zhu, Lu Wang, Xiaoxiao Hu, Yingzhi Zhang, Tianquan Huang, Taiyu He, Zhiwei Chen, Gaoli Zhang, Mingli Peng, Min Chen, Dachuan Cai, Xiaofeng Shi, Hong Ren
Published online August 25, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00108
Abstract
Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) booster vaccination in cirrhotic patients who had received the primary [...] Read more.

Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) booster vaccination in cirrhotic patients who had received the primary series.

We performed a longitudinal assessment in 48 patients with cirrhosis, 57 patients with chronic hepatitis B (CHB) and 68 healthy controls (HCs) to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times. A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1, BA.4 and BA.5 from serum samples collected from three cohorts.

Serum anti-receptor-binding domain (RBD) immunoglobulin (Ig)G and neutralizing antibody (NAb) levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days. After receiving the booster dose, both antibody levels were significantly increased to levels comparable to patients with CHB and HCs. Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis. The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibro-cirrhosis grade. However, compared with the primary series, the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4, and was followed by a significant decrease in the titer against BA.5.

A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants. Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.

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564
Original Article Open Access
Jing Zhou, Fa-Da Wang, Lan-Qing Li, Yu-Jin Li, Shi-Yan Wang, En-Qiang Chen
Published online August 25, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00272
Abstract
Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment [...] Read more.

Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment is lacking.

HBeAg-negative patients with normal ALT and positive HBV DNA (≥20 IU/mL) were retrospectively enrolled. The endpoints included virological response (HBV DNA<100 IU/mL), changes in aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), and the incidence of liver nodules, cirrhosis, and hepatocellular carcinoma (HCC).

This cohort (n=194) was divided into three subgroups, untreated (n=67), treatment-continued (n=87), and treatment-discontinued patients (n=40), with a median follow-up of 54 months. The treatment-continued group achieved 100% (95% CI: 94.7–100) virological response, and significantly reduced APRI and FIB-4 scores (both p<0.001). The risk of liver nodules and cirrhosis in that group was reduced by 76% (HR: 0.24, 95% CI: 0.11–0.54, p<0.001) and 89% (HR: 0.11, 95% CI: 0.14–0.91, p=0.041) vs. the untreated group and by 77% (HR: 0.23, 95% CI: 0.10–0.49, p<0.001) and 95% (HR: 0.05, 95% CI: 0.01–0.44, p=0.006) vs. the treatment-discontinued group. For patients with HBV DNA≥2,000 IU/mL, adherence to treatment lowered the risks of liver cirrhosis by 92% (95% CI: 0.01–0.67) and 93% (95% CI: 0.01–0.53) vs. the untreated and treatment-discontinued patients, respectively. No patient adhering to treatment developed HCC, but one in each of the remaining groups did.

Continuous nucleos(t)ide analog (NA) treatment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase, especially in those with HBV DNA≥2,000 IU/mL.

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565
Review Article Open Access
Jasmine Tidwell, George Y. Wu
Published online August 25, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00252
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. About 20% have a normal body mass index (BMI) and a variant known as lean NAFLD. Unlike typical NAFLD [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. About 20% have a normal body mass index (BMI) and a variant known as lean NAFLD. Unlike typical NAFLD cases associated with obesity and diabetes, lean NAFLD causes liver disease by mechanisms not related to excess weight or insulin resistance. Genetic disorders are among the major factors in developing lean NAFLD, and genome-wide association studies have identified several genes associated with the condition. This review aims to increase awareness by describing the genetic markers linked to NAFLD and the defects involved in developing lean NAFLD.

Full article
566
Original Article Open Access
Yingqian Wang, Yujia Li, Yangling Qiu, Min Shen, Ling Wang, Jiangjuan Shao, Feng Zhang, Xuefen Xu, Zili Zhang, Mei Guo, Shizhong Zheng
Published online August 25, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00162
Abstract
Development of fibrosis in chronic liver disease requires activation of hepatic stellate cells (HSCs) and leads to a poor outcome. Artesunate (Art) is an ester derivative of artemisinin [...] Read more.

Development of fibrosis in chronic liver disease requires activation of hepatic stellate cells (HSCs) and leads to a poor outcome. Artesunate (Art) is an ester derivative of artemisinin that can induce ferroptosis in HSCs, and activated transcriptional factor 3 (ATF3) is an ATF/CREB transcription factor that is induced in response to stress. In this study, we examined the role of the Rho-associated protein kinase 1 (ROCK1)/ATF3 axis in Art-induced ferroptosis in HSCs.

HSC activation and ferroptosis were studied in vitro by western blotting, polymerase chain reaction, immunofluorescence, and other assays. ATF3 electrophoretic mobility and ROCK1 protein stability were assayed by western blotting. Immunoprecipitation was used to detect the interaction of ROCK1 and ATF3, as well as ATF3 phosphorylation. A ubiquitination assay was used to verify ROCK1 degradation. Atf3-interfering and Rock1-overexpressing mice were constructed to validate the anti-hepatic fibrosis activity of Art in vivo.

Art induced ferroptosis in HSCs following glutathione-dependent antioxidant system inactivation resulting from nuclear accumulation of unphosphorylated ATF3 mediated by ROCK1-ubiquitination in vitro. Art also decreased carbon tetrachloride-induced liver fibrosis in mice, which was reversed by interfering with Atf3 or overexpressing Rock1.

The ROCK1/ATF3 axis was involved in liver fibrosis and regulation of ferroptosis, which provides an experimental basis for further study of Art for the treatment of liver fibrosis.

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567
Research Letter Open Access
Evelina Maines, Caterina Rizzardi, Marco Bolognani, Fiorenza Soli, Giovanni Piccoli, Massimo Soffiati, Roberto Franceschi
Published online August 24, 2023
Gene Expression. doi:10.14218/GE.2023.00023
568
Original Article Open Access
Priyal Gupta, Kajal Patel, Garima Garg, Bijina J. Mathew, Dipesh Kale, Jitendra Singh, Sagar Khadanga, Shashank Purwar, Debasis Biswas, Anirudh K. Singh, Ashish Kumar Vyas
Published online August 23, 2023
Gene Expression. doi:10.14218/GE.2023.00016
Abstract
Coronavirus disease (COVID-19) exhibits a range of clinical symptoms, including viral pneumonia, which can progress to acute respiratory distress syndrome, substantial alveolar [...] Read more.

Coronavirus disease (COVID-19) exhibits a range of clinical symptoms, including viral pneumonia, which can progress to acute respiratory distress syndrome, substantial alveolar destruction, and even multi-organ failure in severe cases. Disease pathology is greatly influenced by the host immune response. Several studies reported the perturbation of T-cell responses in COVID-19 patients. Activation and differentiation of CD4+ T cells into various subsets depend on the expression of lineage-specific transcription factors and overall cytokine milieu. Hence, a thorough evaluation of T helper cell lineage-specific transcription factors and pro-inflammatory cytokines can provide crucial insight into COVID-19 pathogenesis and may aid in developing strategies to prevent disease severity. Here, we performed a cross-sectional study to delineate the dysfunctional T helper cell subset immune response associated with COVID-19 disease severity.

We assessed T helper cell responses in SARS-CoV-2 infected individuals who presented with either asymptomatic, mild, or severe disease. mRNA profiling of lineage specific transcription factors and associated cytokines was done using real-time qPCR. Cytokine profiling was done using ELISA.

mRNA levels of FOXP-3 were significantly decreased in patients with severe COVID-19. No significant difference was observed for T-bet and GATA-3 among all of the groups. Bcl-6, the transcription factor for Tfh cell subsets, showed an increased trend in its association with disease progression. Furthermore, mRNA levels of IL-21 were significantly increased with disease severity. We also observed a significant increase in the concentration of pro-inflammatory cytokines IL-6 and IL-1β in patients with severe COVID-19.

These findings provide new insight into COVID-19 disease pathology and may aid in developing effective strategies to manage/control disease severity.

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569
Original Article Open Access
Baisali Nag, Somasundaram Arumugam, V. Ravichandiran, Prasanta Kumar Sarkar
Published online August 21, 2023
Future Integrative Medicine. doi:10.14218/FIM.2023.00031
Abstract
Semisolid oral preparations (Avaleha) are used in Ayurvedic therapeutics. The problems with these preparations include a bitter taste and the use of a sugar base. Here, we aimed [...] Read more.

Semisolid oral preparations (Avaleha) are used in Ayurvedic therapeutics. The problems with these preparations include a bitter taste and the use of a sugar base. Here, we aimed to modify the semisolid Vasavaleha (VA) preparation to an oral solution (syrup) and to observe the efficacy of the VA syrup on patients with bronchial asthma.

VA syrup was prepared by dissolving the water-soluble extracts of Adhatoda vasica leaves and Piper longum fruits in purified water; sorbitol solution and honey were used as sweeteners. Organoleptic tests as well as pH, specific gravity, and viscosity measurements were performed. Liquid chromatography-mass spectrometry analysis of the VA syrup was carried out using an Agilent UHPLC-MS/Q-TOF (6545) system coupled with a Dual AJS ESI source. An open-label clinical trial of the VA syrup was performed on 13 patients with bronchial asthma at a dose of 10 mL (oral, twice a day) for 30 days.

The prepared VA syrup was brown in color and sweet in taste. The pH, specific gravity, and viscosity of the prepared VA syrup were 7.52, 1.10, and 1.922, respectively. Piperine, piperdardine, vasicine, vasicol, vasicinol, and vasicinone were determined to be the major phytochemical compounds. This preparation significantly improved all clinical symptoms of asthma and lung function test results in patients with bronchial asthma. It had mucolytic, bronchodilator, and anti-allergic properties. It had no adverse effects at the indicated dose.

The oral solution (syrup) might be an effective alternative for Ayurvedic semisolid preparations. The VA syrup may be taken as an alternative for VA as it was found to be an effective formulation for the management of bronchial asthma.

Full article
570
Original Article Open Access
Songming Li, Qijie Luo, Shirui Chen, Zehua Jia, Tielong Wang, Xinyu Yu, Wenjing Wang, YuyiZhang, Jiaxing Zhu, Feiwen Deng, Qiang Sun, Zhiyong Guo, Xiaoshun He
Published online August 17, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00178
Abstract
Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft [...] Read more.

Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft failure is lacking.

A retrospective, multicenter study was performed to validate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers. L-GrAFT (L-GrAFT7 and L-GrAFT10) was compared with existing models: the Early Allograft Failure Simplified Estimation (EASE) score, the model of early allograft function (MEAF), and the Early Allograft Dysfunction (EAD) model. Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group.

L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival, significantly superior to MEAF [area under the curve (AUC=0.78, p=0.044)] and EAD (AUC=0.78, p=0.006), while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE (AUC=0.84, p>0.05). Furthermore, L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index (DRI) cases (AUC=0.83 vs. MEAF, p=0.007 vs. EAD, p=0.014) and recipients of donors after cardiac death (AUC=0.92 vs. EAD, p<0.001). Through multivariate analysis, pretransplant bilirubin level, units of packed red blood cells, and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group.

The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort, indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

Full article
571
Original Article Open Access
Jia Huang, Yiyi Gong, Ke Liu, Jun Chen, Xiaobo Zhou
Published online August 16, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00037
Abstract
Asiaticoside reduces inflammatory reactions and oxidative stress, the primary causes of photoaging. The authors speculated that asiaticoside might contain therapeutic potential [...] Read more.

Asiaticoside reduces inflammatory reactions and oxidative stress, the primary causes of photoaging. The authors speculated that asiaticoside might contain therapeutic potential for photoaging.

Network pharmacology and molecular docking were used to explore the mechanisms of asiaticoside in treating photoaging. After achieving the targets of asiaticoside using PharmMapper, SwissTargetPrediction, CTD and BATMAN databases, as well as, targets of photoaging using GeneCards database, the co-targets interaction network was formed and a network of asiaticoside, photoaging, and common targets were constructed by Cytoscape. Next, the common targets were analyzed using GO and KEGG enrichment.

The analysis highlighted 202 core targets of asiaticoside were involved in the pathogenesis of photoaging. KEGG indicated asiaticoside performed an anti-photoaging effect through inflammation- and apoptosis-related signalling pathways, especially the PI3K-AKT and NF-κB pathways. Furthermore, the anti-photoaging effect of asiaticoside was verified by human dermal fibroblasts with UVA irradiation in vitro.

Asiaticoside may alleviate UVA-induced cell proliferation inhibition, reverse the abnormal gene expressions involved in the PI3K-AKT and NF-κB pathways, and have a high affinity with those core targets.

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572
Guideline Open Access
Hong You, Fusheng Wang, Taisheng Li, Xiaoyuan Xu, Yameng Sun, Yuemin Nan, Guiqiang Wang, Jinlin Hou, Zhongping Duan, Lai Wei, Jidong Jia, Hui Zhuang, Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association
Published online August 15, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00320
Abstract
To facilitate the achieving of the goal of “eliminating viral hepatitis as a major public health threat by 2030” set by the World Health Organization, the Chinese Society of Hepatology [...] Read more.

To facilitate the achieving of the goal of “eliminating viral hepatitis as a major public health threat by 2030” set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.

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573
Systematic Review Open Access
Xudong Yang, Tianqi Wang
Published online August 14, 2023
Future Integrative Medicine. doi:10.14218/FIM.2023.00019
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is often diagnosed when affected individuals die with respiratory failure. Currently, there are few bibliometrics [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is often diagnosed when affected individuals die with respiratory failure. Currently, there are few bibliometrics studies on ALS.

In this study, a comprehensive literature search using the PubMed, WangFang, China National Knowledge Infrastructure, and Chinese Science and Technology Periodical databases was conducted. The Core Collection database for scientific output related to ALS from 1990 to 2022 was also searched. The retrieved dataset was analyzed using.

Bibliometrix. A total of 12,450 articles published since 1990 were retrieved, and 243 articles were included in this study. Thirty-two countries contributed to ALS research, among which Italy had the dominant position with the highest number of publications. In addition, keyword co-occurrence was analyzed. As the three indirect subjects of this article, the sources, affiliations, as well as authors of the study were included in the analysis.

In recent years, ALS research has made some progress in terms of elucidating the mechanism of the disease and providing clinical treatment, but the results are concentrated in the United States and European countries. For more complicated research results, critical analysis must be performed.

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574
Original Article Open Access
Franklyn Nonso Iheagwam, Olawumi Toyin Iheagwam, Olubanke Olujoke Ogunlana, Shalom Nwodo Chinedu
Published online August 11, 2023
Gene Expression. doi:10.14218/GE.2023.00053
Abstract
Insulin resistance and hyperinsulinemia in type 2 diabetes mellitus induced dyslipidemia. This study aims to investigate the abrogative role of Terminalia catappa (T. catappa) leaf [...] Read more.

Insulin resistance and hyperinsulinemia in type 2 diabetes mellitus induced dyslipidemia. This study aims to investigate the abrogative role of Terminalia catappa (T. catappa) leaf aqueous extract (TCLAE) on diabetes-induced dyslipidaemia in type 2 diabetic rats.

Diabetic rats were induced by fat-rich feed for eight weeks and intraperitoneal streptozotocin (STZ, 30 mg/kg) injection, while glibenclamide (10 mg/kg) and TCLAE-graded doses were orally administered for four weeks. Then, the biomarkers for diabetes, liver function, lipid profile, cardiovascular indices, and liver histology were measured, in addition to the hepatic expression of some lipid metabolic genes.

TCLAE reduced the diabetes-induced fasting blood glucose, weight loss, plasma insulin, alanine transaminase, bilirubin, cholesterol (CHOL), triglyceride (TRIG), low-density lipoprotein-CHOL and low-density lipoprotein-TRIG. TCLAE also decreased the abnormal cardiovascular indices. TCALE significantly enhanced the high-density lipoprotein-CHOL, the expression of peroxisome proliferator-activated receptor alpha (PPAR-α), PPAR delta (PPAR-δ), and carnitine palmitoyltransferase 1a, and decreased the hepatic expression of C-reactive protein of type 2 diabetic rats.

TCLAE alleviates diabetes-induced dyslipidaemia in type 2 diabetic rats by ameliorating the altered expression of lipid metabolic genes.

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575
Review Article Open Access
Zaibo Li, Paul E. Wakely
Published online August 9, 2023
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00014
Abstract
Thymic epithelial neoplasms, comprised of thymoma, thymic carcinoma, and others, account for less than 1% of human tumors. Fine needle aspiration (FNA) is performed to diagnose [...] Read more.

Thymic epithelial neoplasms, comprised of thymoma, thymic carcinoma, and others, account for less than 1% of human tumors. Fine needle aspiration (FNA) is performed to diagnose thymic lesions due to its minimal invasiveness. Since classification of thymic epithelial neoplasms usually requires thorough histologic examination of the entire lesion, it is necessary to understand the information FNA can provide as well as its limitations. The advantage of FNA lies in its comparable diagnostic accuracy and minimal invasiveness, but it is almost impossible to subtype thymomas with this technique owing to its sampling issues. This review summarizes the cytologic features of thymoma and thymic carcinoma as well as the potential diagnostic pitfalls associated with FNA.

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576
Editorial Open Access
Kamran Abbasi, Parveen Ali, Virginia Barbour, Kirsten Bibbins-Domingo, Marcel GM Olde Rikkert, Andy Haines, Ira Helfand, Richard Horton, Bob Mash, Arun Mitra, Carlos Monteiro, Elena N. Naumova, Eric J. Rubin, Tilman Ruff, Peush Sahni, James Tumwine, Paul Yonga, Chris Zielinski
Published online August 7, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00000A
577
Original Article Open Access
Lingyu Ma, Jiayu Jiang, Qin Si, Chong Chen, Zhaojun Duan
Published online August 1, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00184
Abstract
Overexpression of IGF2BP3 is associated with the prognosis of hepatocellular carcinoma (HCC). However, its role in regulating tumor immune microenvironment (TME) is not well characterized. [...] Read more.

Overexpression of IGF2BP3 is associated with the prognosis of hepatocellular carcinoma (HCC). However, its role in regulating tumor immune microenvironment (TME) is not well characterized. Here, we investigated the effects of IGF2BP3 on macrophages and CD8+ T cells within the TME of HCC.

The relationship between IGF2BP3 and immune cell infiltration was analyzed using online bioinformatics tools. Knockout of IGF2BP3 in mouse hepatoma cell line Hepa1-6 was established using CRISPR/Cas9 technology. In vitro cell coculture and subcutaneously implanted hepatoma mice model were used to explore the effects of IGF2BP3 on immune cells. Expression of CCL5 or transforming growth factor beta 1 (TGF-β1) was detected with quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The binding of IGF2BP3 and its target RNA was verified by trimolecular fluorescence complementation system and RNA immunoprecipitation followed by quantitative or semiquantitative polymerase chain reaction.

IGF2BP3 expression was elevated in HCC and was positively correlated with macrophage infiltration. Patients with higher IGF2BP3 expression and lower macrophage infiltration had a better survival rate. We found that IGF2BP3 could bind to the mRNA of CCL5 or TGF-β1, increasing their expression, and inducing macrophage infiltration and M2 polarization while inhibiting the activation of CD8+ T cells. Furthermore, inhibition of IGF2BP3 combined with anti-CD47 antibody treatment significantly suppressed the growth of hepatoma in Hepa1-6 xenograft tumor mice.

IGF2BP3 promoted the infiltration and M2-polarization of macrophages and suppressed CD8+ T activation by enhancing CCL5 and TGF-β1 expression, which facilitated the progression of Hepa1-6 xenograft tumor.

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578
Corrigendum Open Access
Fan Gao, Yukun Lin, Mengdi Zhang, Yuju Niu, Luyao Sun, Wenwen Li, Haojie Xia, Haihong Lin, Zhenzhen Guo, Gangjun Du
Published online August 1, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2022.00014C
579
Letter to the Editor Open Access
David Starostka, Richard Dolezilek, Katerina Chasakova
Published online July 31, 2023
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00015
580
Review Article Open Access
Desislava K. Tsoneva, Martin N. Ivanov, Manlio Vinciguerra
Published online July 27, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00040
Abstract
Liver diseases are a major burden worldwide, the scope of which is expected to further grow in the upcoming years. Clinically relevant liver dysfunction-related blood markers such [...] Read more.

Liver diseases are a major burden worldwide, the scope of which is expected to further grow in the upcoming years. Clinically relevant liver dysfunction-related blood markers such as alanine aminotransferase and aspartate aminotransferase have limited accuracy. Nowadays, liver biopsy remains the gold standard for several liver-related pathologies, posing a risk of complication due to its invasive nature. Liquid biopsy is a minimally invasive approach, which has shown substantial potential in the diagnosis, prognosis, and monitoring of liver diseases by detecting disease-associated particles such as proteins and RNA molecules in biological fluids. Histones are the core components of the nucleosomes, regulating essential cellular processes, including gene expression and DNA repair. Following cell death or activation of immune cells, histones are released in the extracellular space and can be detected in circulation. Histones are stable in circulation, have a long half-life, and retain their post-translational modifications. Here, we provide an overview of the current research on histone-mediated liquid biopsy methods for liver diseases, with a focus on the most common detection methods.

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