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    Original Article Open Access
    Development and Validation of a New Prognostic Model for Predicting Survival Outcomes in Patients with Acute-on-chronic Liver Failure
    Wende Li, Wanshu Liu, Yihui Rong, Dongze Li, Bing Zhu, Shaobo Yang, Shidong Sun, Shaoli You, Yu Chen, Jun Li
    Journal of Clinical and Translational Hepatology, Published online September 30, 2024. doi:10.14218/JCTH.2024.00316
    Abstract
    Early determination of prognosis in patients with acute-on-chronic liver failure (ACLF) is crucial for optimizing treatment options and liver allocation. This study aimed to identify [...] Read more.

    Early determination of prognosis in patients with acute-on-chronic liver failure (ACLF) is crucial for optimizing treatment options and liver allocation. This study aimed to identify risk factors associated with ACLF and to develop new prognostic models that accurately predict patient outcomes.

    We retrospectively selected 1,952 hospitalized patients diagnosed with ACLF between January 2010 and June 2018. This cohort was used to develop new prognostic scores, which were subsequently validated in external groups.

    The study included 1,386 ACLF patients and identified six independent predictors of 28-day mortality through multivariate analysis (all p < 0.05). The new score, based on a multivariate regression model, demonstrated superior predictive accuracy for both 28-day and 90-day mortalities, with Areas under the ROC curves of 0.863 and 0.853, respectively (all p < 0.05). This score can be used to stratify the risk of mortality among ACLF patients with ACLF, showing a significant difference in survival between patients categorized by the cut-off value (log-rank (Mantel–Cox) χ2 = 487.574 and 606.441, p = 0.000). Additionally, the new model exhibited good robustness in two external cohorts.

    This study presents a refined prognostic model, the Model for end-stage liver disease-complication score, which accurately predicts short-term mortality in ACLF patients. This model offers a new perspective and tool for improved clinical decision-making and short-term prognostic assessment in ACLF patients.

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    Original Article Open Access
    In Silico Assessment of Photosystem I P700 Chlorophyll a Apoprotein A2 (PsaB) from Chlorella vulgaris (green microalga) as a Source of Bioactive Peptides
    Md Ariful Amin, Uzzal Chondra, Md Morshedul Alam
    Journal of Exploratory Research in Pharmacology, Published online September 30, 2024. doi:10.14218/JERP.2023.00030
    Abstract
    Chlorella vulgaris is a green, photosynthetic microalga in the phylum Chlorophyta. The goal of our study was to perform a bioinformatics analysis of Photosystem I P700 chlorophyll [...] Read more.

    Chlorella vulgaris is a green, photosynthetic microalga in the phylum Chlorophyta. The goal of our study was to perform a bioinformatics analysis of Photosystem I P700 chlorophyll a apoprotein A2, one of its photosynthesis-related proteins, and to hunt for potent bioactive peptides.

    To generate peptides and estimate the safety and efficacy of each bioactive peptide, we employed the tools BIOPEP-UWM™, PeptideRanker, DBAASP, and ToxinPred. PepDraw was used to understand the physicochemical properties and primary chemical structures of the selected bioactive peptides.

    The liberated peptides exhibit up to 17 distinct bioactivities, as shown by the in silico digestion of the protein using several proteolytic enzymes. The peptides with bioactivities are listed as angiotensin-converting enzyme inhibitor, dipeptidyl peptidase IV inhibitor, dipeptidyl peptidase III inhibitor, antioxidative, renin inhibitor, glucose uptake stimulator, neuropeptide regulator (regulating stomach mucosal membrane activity and ion flow), antithrombotic, anti-amnestic, CaMPDE inhibitor, activators of ubiquitin-mediated proteolysis, alpha-glucosidase inhibitor, immunomodulating, calcium-binding, antibacterial, anti-inflammatory, and hypotensive agent. Using the Database of Antimicrobial Activity and Structure of Peptides (DBAASP) prediction method, the antibacterial activity of the released peptides was predicted, highlighting the existence of potent antibacterial peptides. An examination of their physicochemical properties revealed that most peptides are low molecular weight, mildly acidic, and moderately water-soluble. To further establish the non-toxicity profile of the released peptides (sequence length > 3), a ToxinPred analysis was performed, which revealed that most of the peptides are non-toxic. According to the allergenicity analysis, most of the top-ranked peptides are likely non-allergenic.

    Thus, our study reveals a less labor-intensive method for discovering new therapeutic targets derived from C. vulgaris, which hold both pharmacological and medical significance.

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    Case Report Open Access
    Gastrocolocutaneous Fistula: A Case Report on a Rare Complication of Gastrostomy Placement
    Nicholas Bell, Trinh Nguyen
    Journal of Translational Gastroenterology, Published online September 30, 2024. doi:10.14218/JTG.2024.00007
    Abstract
    Percutaneous endoscopic gastrostomy (PEG) tube placement is a common procedure used to provide medium- and long-term enteral nutrition to patients. Although generally considered [...] Read more.

    Percutaneous endoscopic gastrostomy (PEG) tube placement is a common procedure used to provide medium- and long-term enteral nutrition to patients. Although generally considered safe, PEG tube placement can be associated with various potential complications. We report a case of gastrocolocutaneous fistula formation in a patient who presented with severe abdominal pain, new-onset diarrhea, and feculent emesis nine days after PEG tube placement. Awareness of this rare complication can facilitate the recognition of colonic perforation during gastrostomy tube placement and enable early detection of the complication post-procedurally. Additionally, we discuss various techniques that may be employed to prevent this complication during PEG tube placement.

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    Review Article Open Access
    Environmental Triggers’ Involvement in the Development of Type 1 Diabetes Mellitus
    Tajudeen Olanrewaju Yahaya, Umar Usman Liman, Caleb Dikko Obadiah, Zafira Illo Zakari, Daniel Anyebe, Boniface Gomo Clement, Balkisu Marafa Muhammad
    Exploratory Research and Hypothesis in Medicine, Published online July 27, 2022. doi:10.14218/ERHM.2022.00051
    Abstract
    The huge burden of type 1 diabetes mellitus (T1DM) has been a source of concern globally since the Industrial Revolution in the 18th–19th centuries. To this end, studies have shown [...] Read more.

    The huge burden of type 1 diabetes mellitus (T1DM) has been a source of concern globally since the Industrial Revolution in the 18th–19th centuries. To this end, studies have shown that certain environmental changes that accompanied the Revolution may have increased the risk and burden of the disease in genetically predisposed individuals. However, documented studies that synthesize these environmental triggers are scarce. As a result, the current study was conceived to synthesize the environmental triggers of T1DM to boost public awareness. Relevant information was retrieved from reputable academic databases; namely, Scopus, PubMed, SpringerLink, and Embase. The results showed that chemical exposure, viral infection, gut microbiome disruption, vitamin and mineral deficiencies, inadequate or exclusive breastfeeding, as well as early exposure to infant feeding formulas could increase the risk and burden of T1DM in genetically predisposed individuals. As a consequence, these triggers could compromise the expression of certain genes involved in insulin synthesis and immune function, such as the human leukocyte antigen (HLA), insulin (INS), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes. This would result in a dysfunctional immune system in which immune cells, such as T-cells and B-cells and molecules, such as cytokines would attack self-tissues, thus causing autoimmunity of the pancreatic beta cells. Environmental triggers could also induce the T1DM pathophysiology by modifying the epigenome of the mentioned genes. Furthermore, some epigenetic changes could be reversed, which would infer that treatment procedures that would include the pathophysiology of the environmental triggers could be more effective.

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    Original Article Open Access
    Overexpression of RBM34 Promotes Tumor Progression and Correlates with Poor Prognosis of Hepatocellular Carcinoma
    Wei Wang, Rui Zhang, Ning Feng, Longzhen Zhang, Nianli Liu
    Journal of Clinical and Translational Hepatology, Published online July 13, 2022. doi:10.14218/JCTH.2022.00166
    Abstract
    Emerging evidence suggests that RNA-binding motif (RBM) proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors. The objective of this study [...] Read more.

    Emerging evidence suggests that RNA-binding motif (RBM) proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors. The objective of this study was to investigate the role of RBM34, an RBM protein, in hepatocellular carcinoma (HCC).

    We first examined the expression of RBM34 across cancers. The correlation of RBM34 with clinicopathological features and the prognostic value of RBM34 for HCC was then investigated. Functional enrichment analysis of RBM34-related differentially expressed genes (DEGs) was performed to explore its biological function. RNA sequencing (RNA-seq) was applied to identify downstream genes and pathways affected upon RBM34 knockout. The correlation of RBM34 with immune characteristics was also analyzed. The oncogenic function of RBM34 was examined in in vitro and in vivo experiments.

    RBM34 was highly expressed in hepatocellular carcinoma and correlated with poor clinicopathological features and prognosis. RBM34 was positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. A positive correlation was also observed between RBM34, T cell exhaustion, and regulatory T cell marker genes. Knockout of RBM34 significantly inhibited cell proliferation, migration, and xenograft tumor growth, and sensitized HCC cells to sorafenib treatment. RBM34 inhibition reduced FGFR2 expression and affected PI3K-AKT pathway activation in HCC cells.

    Our study suggests that RBM34 may serve as a new prognostic marker and therapeutic target of HCC.

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    Original Article Open Access
    Naringenin is a Potential Immunomodulator for Inhibiting Liver Fibrosis by Inhibiting the cGAS-STING Pathway
    Li Chen, Siwei Xia, Shuqi Wang, Yuanyuan Zhou, Feixia Wang, Zhanghao Li, Yang Li, Desong Kong, Zili Zhang, Jiangjuan Shao, Xuefen Xu, Feng Zhang, Shizhong Zheng
    Journal of Clinical and Translational Hepatology, Published online April 28, 2022. doi:10.14218/JCTH.2022.00120
    Abstract
    Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease. The mechanism specific to its antifibrosis activity needs further investigation This [...] Read more.

    Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease. The mechanism specific to its antifibrosis activity needs further investigation This study was to focused on the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) pathway in hepatic stellate cells and clarified the antifibrosis mechanism of naringenin.

    The relationship between the cGAS-stimulator of interferon genes (STING) pathway and liver fibrosis was analyzed using the Gene Expression Omnibus database. Histopathology, immunohistochemistry, fluorescence staining, Western blotting and polymerase chain reaction were performed to assess gene and protein expression levels associated with the cGAS pathway in clinical liver tissue samples and mouse livers. Molecular docking was performed to evaluate the relationship between naringenin and cGAS, and western blotting was performed to study the expression of inflammatory factors downstream of cGAS in vitro.

    Clinical database analyses showed that the cGAS-STING pathway is involved in the occurrence of chronic liver disease. Naringenin ameliorated liver injury and liver fibrosis, decreased collagen deposition and cGAS expression, and inhibited inflammation in carbon tetrachloride (CCl4)-treated mice. Molecular docking found that cGAS may be a direct target of naringenin. Consistent with the in vivo results, we verified the inhibitory effect of naringenin on activated hepatic stellate cells (HSCs). By using the cGAS-specific agonist double-stranded (ds)DNA, we showed that naringenin attenuated the activation of cGAS and its inflammatory factors affected by dsDNA. We verified that naringenin inhibited the cGAS-STING pathway, thereby reducing the secretion of inflammatory factors by HSCs to ameliorate liver fibrosis.

    Interrupting the cGAS-STING pathway helped reverse the fibrosis process. Naringenin has potential as an antihepatic fibrosis drug.

    Full article
Special Features

Call for Papers for Special Issue 'Updates of Cytopathology Reporting Systems'

Journal: Journal of Clinical and Translational Pathology
Special Issue: Updates of Cytopathology Reporting Systems
Submission deadline: November 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue 'Frontier research on the toxicity and efficacy of Chinese medicine'

Journal: Future Integrative Medicine
Special Issue: Frontier research on the toxicity and efficacy of Chinese medicine
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘New Translational Challenges in Primary Biliary Cholangitis’

Journal: Journal Clinical and Translational Hepatology
Special Issue: New Translational Challenges in Primary Biliary Cholangitis
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘A Spotlight on Progress and Pitfalls in NAFLD/MAFLD Studies, 2022’

Journal: Journal of Clinical and Translational Hepatology
Special Issue: A Spotlight on Progress and Pitfalls in NAFLD/MAFLD Studies, 2022
Submission deadline: March 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue 'Comparative study of traditional medicine in the world'

Journal: Future Integrative Medicine
Special Issue: Comparative study of traditional medicine in the world
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue 'Therapeutic effects of herbal medicines on neurological impairment and related mental disorders based on the evidence of clinical and basic studies'

Journal: Future Integrative Medicine
Special Issue: Therapeutic effects of herbal medicines on neurological impairment and related mental disorders based on the evidence of clinical and basic studies
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted

Call for Papers for Special Issue ‘Immunoregulatory Mechanisms of Herbal Medicines in Cancer and Infectious Diseases’

Journal: Future Integrative Medicine
Special Issue: Immunoregulatory Mechanisms of Herbal Medicines in Cancer and Infectious Diseases
Submission deadline: June 30, 2023
Publication date: An article will be published online as soon as it is accepted
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