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Review Article Open Access
Indre Zaparackaite, Shailinder Jit Singh, Debashish Bhattacharya, Swamy Kaki Bale, Rafael Cavalcante Correia, Partap Kumar Midha, Dhaval Govani, Ramnik Vallabh Patel
Published online September 10, 2024
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00092
Abstract
Based on our experimental and clinical research, the gastroschisis is formed by raised intraluminal and intraabdominal pressure in combination with potential weak points. The psycho-neuro-endocrine-target [...] Read more.

Based on our experimental and clinical research, the gastroschisis is formed by raised intraluminal and intraabdominal pressure in combination with potential weak points. The psycho-neuro-endocrine-target organ axis of young mothers, who themselves struggle to meet their macro and micronutrient requirements, places a burden on the placenta. The associated smoking, alcohol, drugs, and other toxins, leads to fetal distress. This activates the same fetal axis, with the final common pathway being activated via the sacral parasympathetic nervous system as a flight or fight response leading to colorectal secreto-motility disorder of the hindgut and small left colon leading to partial functional obstruction of hindgut. This leads to pressure build-up on the proximal colon. An intact ileocecal valve leads to blind loop obstruction, creating the force required to herniate the bowel through the defect at three key points of weakness in the abdominal wall, the most vulnerable being the right paraumbilical region. If the ileocecal valve becomes incompetent, variants of gastroschisis may occur. The fetus, particularly the peritoneum, always has a tendency to heal defects quickly, which forms secondary events in the eviscerated bowel causing the closing and closed gastroschisis with vanishing organs. Recent technological advances in preformed silastic silo innovation, prenatal diagnosis and monitoring for closing gastroschisis, perinatal management, percutaneous central long lines, and innovative minimally invasive bedside procedures, have all made significant contributions. We believe that gastroschisis is the external surgical symptom and peak of the iceberg, secondary to an underlying colorectal motility disorder, providing the force to eviscerate bowel loops through potential weak points and its subsequent sequelae.

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Original Article Open Access
Noor Al Deen A. Elazazi, Mohamed Eltabbakh, Hend Mubarak Hussein, Yasmeen M. Mahmood, Reda Elwakil
Published online September 19, 2024
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00087
Abstract
The treatment of Helicobacter pylori (H. pylori) infection remains a challenge due to the increasing prevalence of drug-resistant bacteria. It is hypothesized that using more potent [...] Read more.

The treatment of Helicobacter pylori (H. pylori) infection remains a challenge due to the increasing prevalence of drug-resistant bacteria. It is hypothesized that using more potent acid suppressants, such as potassium-competitive acid blockers (P-CABs) like Vonoprazan, may improve eradication rates. The aim of this study was to compare the effectiveness of H. pylori eradication regimens containing Vonoprazan with those containing proton pump inhibitors for H. pylori infection.

Two hundred and thirty-two patients were assigned to two groups. Group I (treatment-naïve) included: Arm 1 (intervention arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Vonoprazan 20 mg twice daily; and Arm 2 (comparator arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Esomeprazole 20 mg twice daily. Group II (treatment-experienced) included: Arm 3 (intervention arm) with 58 patients who received Levofloxacin 500 mg once daily, Vonoprazan 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily; and Arm 4 (comparator) with 58 patients who received Levofloxacin 500 mg once daily, Esomeprazole 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily. All patients received their treatment regimens for 14 days. H. pylori eradication was assessed four weeks after treatment.

The successful eradication rate was higher in Arm 1 (58.6%) compared to Arm 2 (50%), and higher in Arm 3 (50%) compared to Arm 4 (43.1%). H. pylori eradication regimens including P-CABs were well-tolerated with a low incidence of adverse events.

The results of P-CAB-based eradication regimens are comparable to those of proton pump inhibitor-based regimens.

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Review Article Open Access
Weizheng Zhang
Published online January 2, 2025
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00199
Abstract
Hyperuricemia (HU), characterized by elevated uric acid (UA) levels in the blood, is a global health concern associated with various conditions, including cardiovascular diseases, [...] Read more.

Hyperuricemia (HU), characterized by elevated uric acid (UA) levels in the blood, is a global health concern associated with various conditions, including cardiovascular diseases, gout, hypertension, metabolic syndrome, renal dysfunction, and neurodegenerative diseases. Recent studies highlight the multifaceted origins of HU, implicating genetic predisposition, dietary patterns, lifestyle choices, and environmental influences. Genetic variations affecting enzymes and transporters involved in purine metabolism and UA excretion have been identified, paving the way for personalized treatment strategies. Advances in diagnostic imaging and omics technologies provide enhanced precision in detecting and evaluating risks. While pharmacological interventions remain central to managing HU, persistent challenges such as treatment resistance necessitate the exploration of novel drug targets and lifestyle modifications. Chinese herbal medicines present a potential alternative with fewer side effects. Emerging research on the impact of gut microbiota on UA metabolism opens new therapeutic avenues. Despite progress, challenges such as optimizing treatment duration and understanding long-term effects remain. Collaborative efforts are essential to address these challenges and advance our comprehension of HU. Integrating precision medicine and holistic patient care approaches holds promise for improving outcomes and enhancing the quality of life for individuals with HU. This review provided a contemporary analysis of HU, covering its causes, associated health risks, diagnosis, treatment, and future outlook.

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Original Article Open Access
Md. Asad Khan, Kashif Ali, M. Moshahid A. Rizvi
Published online June 25, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00003
Abstract
Infection with HPV16, a high-risk human papillomavirus (HPV), can cause cervical cancer in humans. These infections carry a high risk of morbidity and mortality globally in females. [...] Read more.

Infection with HPV16, a high-risk human papillomavirus (HPV), can cause cervical cancer in humans. These infections carry a high risk of morbidity and mortality globally in females. This study aimed to conduct an in vivo comparison of Poly (D,L-lactic-co-glycolide) (PLGA)-encapsulated peptide mixture nanoparticles and PLGA microspheres as delivery systems for vaccines.

PLGA polymers were used to form microspheres for a therapeutic vaccine against cervical cancer. The target antigens were the L1 and L2 capsid proteins and the E6 and E7 oncoproteins from HPV16. These antigens were selected based on their immunogenicity, allergenicity, and toxicity. We predicted epitopes for cytotoxic T lymphocytes (CTLs) and helper T lymphocytes. In our investigation of CTL epitopes, we employed synthetic chimeric PLGA microsphere peptides, consisting of multiple H-2Db-restricted HPV16 peptides, coupled with other immune-potentiating adjuvants as predicted by our work.

H-2Db-restricted HPV16 peptides, when administered subcutaneously, enabled CTLs to eliminate in vitro TC-1 tumor cells expressing E6 and E7 of HPV16. Additionally, TC-1 cells protected C57BL/6 mice against in vivo challenges. To address this problem, peptide-based vaccines, which are among the most effective vaccine systems, have been extensively studied. Combining peptide-based vaccinations with microsphere peptide mixture particles and delivery technologies enhances their efficacy in stimulating cellular immune responses and eliminating tumor cells.

This approach may provide a potential therapeutic candidate vaccine based on microsphere-encapsulated peptides for the prevention of cervical cancer caused by HPV.

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Original Article Open Access
Yimeng Zhou, Yang Ding, Yanwei Li, Qiuju Sheng, Chao Han, Yaoxin Fan, Ziyi Wang, Bingchao Lu, Xiaoguang Dou, Chong Zhang
Published online November 8, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00221
Abstract
Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial [...] Read more.

Necroptosis is critical for regulating intestinal epithelial cells (IECs). Butyric acid (BA), produced during intestinal microbial metabolism, protects the intestinal epithelial barrier. However, whether necroptosis occurs in IECs during liver cirrhosis and whether sodium butyrate (NaB) can regulate necroptosis have not yet been reported. In this study, we aimed to investigate whether IECs undergo necroptosis in cirrhosis and whether NaB can regulate necroptosis and the related regulatory mechanisms.

Serum levels of RIPK3, MLKL, and Zonulin, as well as fecal BA levels, were measured and correlated in 48 patients with liver cirrhosis and 20 healthy controls. A rat model of liver cirrhosis was established, and NaB was administered. The expressions of MLKL, p-MLKL, and tight junction proteins were measured. We conducted an in vitro investigation of the effect of NaB on necroptosis in the HT29 cell line.

Serum levels of RIPK3, MLKL, and Zonulin in the liver cirrhosis group were higher, while fecal BA levels were lower than those in the control group. Zonulin levels were positively correlated with RIPK3 and MLKL levels, while fecal BA levels were negatively correlated with serum MLKL levels, but not with RIPK3 levels. NaB reduced the mRNA and protein expression of MLKL but had no effect on RIPK1 and RIPK3 in vitro. Rescue experiments demonstrated that NaB inhibited necroptosis through E2F1-mediated regulation of MLKL.

NaB alleviates intestinal mucosal injury and reduces necroptosis in IECs in liver cirrhosis. It also inhibits the necroptosis of IECs and protects the intestinal barrier by reducing E2F1 expression and downregulating MLKL expression levels. These results can be employed to develop a novel strategy for treating complications arising from liver cirrhosis.

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Original Article Open Access
Robert Lam, Dhanpat Jain, Yanhong Deng, Eesha Acharya, Joseph K. Lim
Published online October 17, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00189
Abstract
Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed [...] Read more.

Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed to investigate the role of clinical and histologic risk factors on long-term outcomes in patients with MASLD.

A retrospective cohort study of 451 adults with biopsy-proven MASLD was conducted at a U.S. academic hospital from 2012 to 2020. An experienced pathologist evaluated the index liver biopsy. Patients with a prior liver transplant or alternative etiologies of chronic liver disease were excluded. The duration of the risk exposure was determined from the date of the index liver biopsy to an outcome event or the last follow-up examination. Outcome events of interest included incident liver-related events, liver decompensation, and all-cause mortality.

In the final cohort of 406 patients followed for a median of 3.7 years (interquartile range: 4.8 years), 35 patients died, 41 developed hepatic decompensation, and 70 experienced a liver-related event. Among histologic risk factors, stage 3 (adjusted Hazard ratio (aHR) 2.68, 95% confidence interval (CI) 1.18–6.11) and stage 4 (aHR 6.96, 95% CI 3.55–13.64) fibrosis were associated with incident liver-related events compared to stage 0–1 fibrosis. Stage 4 (aHR 8.46, 95% CI 3.26–21.99) fibrosis alone was associated with incident liver decompensation events compared to stage 0–1 fibrosis. Among clinical risk factors, hypertension (aHR 2.58, 95% CI 1.05–6.34) was associated with incident liver decompensation.

In a U.S. single-center cohort of patients with biopsy-proven MASLD, advanced fibrosis was the primary risk factor for incident liver decompensation and liver-related events.

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Letter to the Editor Open Access
Shuai Ren, Lina Song, Marcus J. Daniels, Ying Tian, Zhongqiu Wang
Published online August 22, 2024
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00016
Original Article Open Access
Yuxin Chen, Tianqing Huang, Fei Li, Ehu Liu
Published online August 23, 2024
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00012
Abstract
Isofraxidin, an important coumarin compound found in the medicinal plant Sarcandra glabra, is reported to have anti-inflammatory activity. However, its natural concentration is [...] Read more.

Isofraxidin, an important coumarin compound found in the medicinal plant Sarcandra glabra, is reported to have anti-inflammatory activity. However, its natural concentration is insufficient to meet the existing demand for this valuable molecule. Therefore, biotechnological approaches are necessary to enhance the isofraxidin content.

Endophytes were isolated from the roots, stems, and leaves of Sarcandra glabra and fermented with Sarcandra glabra, respectively. The target strains capable of increasing isofraxidin content were screened using high-performance liquid chromatography. Their genes were amplified, and the polymerase chain reaction products were sequenced. BLAST analysis was used to compare the sequences with those in GenBank, and a phylogenetic tree was constructed for species identification.

Fifteen endophytic bacteria and six endophytic fungi were isolated from the roots, stems, and leaves of Sarcandra glabra. Among them, Enterobacter, Bacillus wiedmannii, Trametes versicolor from the roots, and Diaporthe celeris and Diaporthe hongkongensis from the leaves increased the isofraxidin content in Sarcandra glabra. The isofraxidin content in Sarcandra glabra fermented by endophytes Enterobacter, Bacillus wiedmannii, Trametes versicolor, Diaporthe celeris, and Diaporthe hongkongensis was 1.37, 1.27, 1.11, 1.40, and 1.16 times higher than in the blank samples, respectively.

The fermentation of Sarcandra glabra with specific endophytes can increase its isofraxidin content. These findings provide preliminary scientific evidence for the potential of using microorganisms to enhance the quality of traditional Chinese medicine.

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Original Article Open Access
Mengxia Yang, Chunming Zhao, Tengfei Chen, Xiaolong Xu, Qingquan Liu
Published online August 30, 2024
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Future Integrative Medicine. doi:10.14218/FIM.2024.00030
Abstract
Shufeng Jiedu Capsules (SFJD), a traditional Chinese medicine preparation, are widely used in the clinical treatment of influenza, yet their mechanism of action remains unclear. [...] Read more.

Shufeng Jiedu Capsules (SFJD), a traditional Chinese medicine preparation, are widely used in the clinical treatment of influenza, yet their mechanism of action remains unclear. This study aimed to systematically explore the molecular mechanism of SFJD in the treatment of influenza using network pharmacology and bioinformatics techniques.

The active ingredients of SFJD were retrieved from traditional Chinese medicine databases, and their targets were identified using the Swiss Target Prediction and TCMSP databases. Influenza disease genes were obtained from the GEO, GeneCards, and DisGeNET databases, and a Venn diagram was used to identify potential targets by mapping SFJD targets to influenza disease genes. Network construction and analysis of potential therapeutic targets were performed using the STRING12.0 database and Cytoscape3.9.1 software, leading to the identification of key targets. The expression of potential therapeutic targets in tissues and cells was retrieved using the BioGPS database. Functional enrichment analysis of these targets was conducted using the DAVID database. Molecular docking was then used to assess the interactions between key targets and core active ingredients.

SFJD contains 193 active ingredients and 985 targets. There are 510 influenza disease genes, 97 of which are potential therapeutic targets for SFJD in treating influenza, with 27 key targets identified through network construction and analysis. Tissue/cell-specific analysis revealed that 39 potential therapeutic targets are highly expressed in 37 specific tissues/cells. Functional enrichment analysis highlighted pathways such as the C-type lectin receptor signaling pathway, tumor necrosis factor signaling pathway, and hypoxia-inducible factor-1 signaling pathway. Molecular docking results indicated strong interactions between the core active ingredients and the key targets.

This study systematically reveals that the mechanism of action of SFJD in treating influenza is complex, involving multiple targets and pathways related to antiviral, anti-inflammatory, and immune regulation effects. The findings provide valuable reference information for future clinical treatment and basic research on influenza.

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Review Article Open Access
Sihan Zhang, Zhipeng Yao, Na Zeng, Zheng Liu, Qidong Xia, Shaogang Wang
Published online July 25, 2024
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00022
Abstract
Peroxisome proliferator-activated receptors (PPARs) participate in the fatty acid oxidation, the homeostasis of lipid and glucose metabolism, the regulation of insulin sensitivity, [...] Read more.

Peroxisome proliferator-activated receptors (PPARs) participate in the fatty acid oxidation, the homeostasis of lipid and glucose metabolism, the regulation of insulin sensitivity, and numerous metabolic processes, making them novel and important therapeutic targets for cancer treatment. However, PPARs manifest dual functions, wherein their activation and inhibition engender diverse outcomes in different types of tumors. The specificity of drugs for tumors is also a challenge when targeting PPARs. In recent years, proteolysis targeting chimeras (PROTACs) have gained significant attention in the field of cancer therapy, demonstrating potent therapeutic potential in both basic and clinical research. Furthermore, heterobifunctional molecules derived from PROTACs have ventured into domains that extend beyond protein degradation. Currently, there are no developed PPAR-targeting PROTACs. Therefore, our review delves into various aspects, including the dual roles of PPARs, known inhibitors, agonists, ligands, and co-crystal structures, and explores the feasibility and advantages of PPAR-targeting PROTACs and other heterobifunctional molecules in cancer therapy.

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