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Original Article Open Access
Md Ariful Amin, Uzzal Chondra, Md Morshedul Alam
Published online September 25, 2024
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Journal of Exploratory Research in Pharmacology. 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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Review Article Open Access
Xuexin Liang, Qingqing Tang, Jiawei Chen, Yanghui Wei
Published online March 25, 2025
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00031
Abstract
Cancer is the leading cause of death globally, with nearly 20 million new cases and 9.7 million deaths in 2022. Due to its vague initial symptoms, cancer is often difficult to detect [...] Read more.

Cancer is the leading cause of death globally, with nearly 20 million new cases and 9.7 million deaths in 2022. Due to its vague initial symptoms, cancer is often difficult to detect in its early stages. Liquid biopsy, a revolutionary approach in oncology, provides a minimally invasive, real-time method for cancer detection, monitoring, and characterization by examining circulating tumor components in body fluids. This review presents current technologies and clinical applications of liquid biopsy, focusing particularly on its value for early cancer diagnosis. Liquid biopsy enables molecular profiling of cancer for precision oncology by isolating circulating extracellular nucleic acids (cell-free DNA), circulating tumor DNA, and circulating tumor cells from blood and other body fluids. Cell-free DNA, which circulates freely in the blood, may or may not be tumor-derived, while circulating tumor DNA is specifically of tumor origin. Additionally, circulating tumor cells can be isolated from blood; these cells, shed from tumors into the bloodstream, typically survive only 1–2.5 h before immune clearance, though a small fraction can persist and metastasize to distant sites. Exosomes, small membrane-bound vesicles secreted by tumor cells, also carry molecular information about the tumor and have become a valuable source of biomarkers in liquid biopsy. Advances in detection technologies for these analytes have expanded the utility of liquid biopsy, facilitating the identification of somatic mutations and actionable genomic alterations in tumors. Finally, this review discusses the opportunities and challenges facing liquid biopsy and offers insights into its future development.

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Original Article Open Access
Xiaobin Chi, Zhijian Chen, Jianda Yu, Xiaohua Xie, Zerun Lin, Yongbiao Chen, Lizhi Lv
Published online October 21, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00270
Abstract
Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Epigenetic mechanisms have revealed that noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), [...] Read more.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Epigenetic mechanisms have revealed that noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in HCC progression. This study aimed to construct a circRNA-miRNA-mRNA network in HCC and validate one axis within the network.

HCC-related transcriptome data were obtained from the Gene Expression Omnibus, and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs. The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted. The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.

We identified six differentially expressed circRNAs in HCC, which were linked to 13 miRNAs and 88 mRNAs. A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed. Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression, possibly through the miR-140-3p/KRAS axis. Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.

The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

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Review Article Open Access
Xiulin Hu, Congjia Ma, Xiangyu Kong
Published online September 25, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00017
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with difficulties in early diagnosis, poor prognosis, and limited effective therapies. Early detection and effective [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with difficulties in early diagnosis, poor prognosis, and limited effective therapies. Early detection and effective treatment offer the optimal chance to improve survival rates. Various studies have shown that gut microbiota dysbiosis is closely related to PDAC, with potential mechanism involving immune regulation, metabolic process impact, and reshaping the tumor microenvironment. A comprehensive understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy such as fecal microbiota transplantation, creating new opportunities and fostering hope for desperate PDAC patients.

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Original Article Open Access
Azad Bakht, Sydney T. Cannon, Joshua D. Waltonen, Trisha M. Shattuck, Wencheng Li
Published online June 18, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00011
Abstract
Molecular testing has emerged as a valuable tool for stratifying cytologically indeterminate thyroid nodules (ITNs), with Harvey rat sarcoma viral oncogene homolog/neuroblastoma [...] Read more.

Molecular testing has emerged as a valuable tool for stratifying cytologically indeterminate thyroid nodules (ITNs), with Harvey rat sarcoma viral oncogene homolog/neuroblastoma RAS viral oncogene homolog (HRAS/NRAS) mutations being among the most prevalent molecular alterations. The study aimed to evaluate the malignancy risk of ITNs with these mutations.

We conducted a retrospective study involving ITNs (Bethesda category III and IV) that underwent ThyroSeq testing between February 2016 and January 2022. A smaller subset of ITNs also underwent Afirma testing. We specifically identified nodules with HRAS/NRAS mutations and collected radiological, clinical, histological, and follow-up data.

Our analysis identified 45 ITNs with NRAS (29 cases) and HRAS (15 cases) mutations. Of the 29 nodules with NRAS mutations, 25 underwent surgical treatment (14 total thyroidectomies and 11 hemithyroidectomies), resulting in a surgical resection rate of approximately 86%. Among the resected nodules, six were malignant, yielding a calculated risk of malignancy (ROM) ranging from 20.6% to 25%. Three of these malignant nodules were managed with total thyroidectomy, while the other three underwent hemithyroidectomy. During a follow-up period of 43.8 months for total thyroidectomy and 32.9 months for hemithyroidectomy, no recurrence or metastasis was detected among the patients. Among the four nodules treated conservatively, three remained stable, with an average follow-up duration of 34.7 months, while one patient was lost to follow-up. Regarding HRAS mutations, 15 nodules were identified, with 12 of them undergoing surgical treatment (six total thyroidectomies and 6 hemithyroidectomies), resulting in an 80% surgical resection rate. Two of the resected nodules were malignant, with a calculated ROM of 13.3% to 16.7%. Both malignant nodules were managed with total thyroidectomy, and during a follow-up period of 37.9 months, no recurrence or metastasis occurred. Of the three nodules managed conservatively, all remained stable, with an average follow-up duration of 31.1 months.

The ROM for nodules with NRAS (20.6–25%) or HRAS (13.3–16.7%) mutations was found to be low. Therefore, before opting for total thyroidectomy, conservative management, including limited resection, should be considered as a viable alternative.

Full article
Case Report Open Access
Çiğdem Sercan, Önder Bozdoğan, Ömer Günhan
Published online May 23, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00046
Abstract
Pleomorphic adenoma is the most common benign tumor of the salivary glands. Histologically, it is characterized by the presence of both epithelial and mesenchymal elements and may [...] Read more.

Pleomorphic adenoma is the most common benign tumor of the salivary glands. Histologically, it is characterized by the presence of both epithelial and mesenchymal elements and may contain various metaplastic changes. This paper reported a case of pleomorphic adenoma with extensive mucinous metaplasia, which is histologically very similar to mucoepi- dermoid carcinoma. Pleomorphic adenoma with extensive mucinous and squamous differentiation may be misdiagnosed as mucoepidermoid carcinoma. Immunohistochemistry was ineffective in differential diagnosis, and the diagnosis was confirmed by the absence of mastermind like transcriptional coactivator 2 (MAML2) translocation. The detection of MAML2 translocation can help avoid misdiagnosis of MEC in similar cases. Additionally, the published literature on metaplasia on pleomorphic adenoma was also reviewed and summarized.

Full article
Letter to the Editor Open Access
Sanjoy Majumder, Rutupurna Das, Annapurna Sahoo, Kunja Bihari Satapathy, Gagan Kumar Panigrahi
Published online November 11, 2024
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Gene Expression. doi:10.14218/GE.2024.00058
Original Article Open Access
Yue Chen, Wenkang Gao, Huikuan Chu, Afnan Ahmed Mohamed Al-Asbahi, Shengqi Yan, Hang Yuan, Jiake Che, Zilu Cheng, Zexuan Li, Jin Ye, Rong Lin, Xiaohua Hou, Fan Du, Ling Yang
Published online October 21, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00237
Abstract
The effect of tenofovir amibufenamide (TMF) on blood lipid profiles in patients with chronic hepatitis B (CHB) remains unclear. This study aimed to explore whether TMF affects blood [...] Read more.

The effect of tenofovir amibufenamide (TMF) on blood lipid profiles in patients with chronic hepatitis B (CHB) remains unclear. This study aimed to explore whether TMF affects blood lipids during 48 weeks in patients with CHB.

A total of 91 patients with CHB undergoing TMF treatment for 48 weeks were divided into two groups: Lipid Normal (n = 42) and Lipid Abnormal (n = 49), based on baseline blood lipid levels. Lipid indices, virological responses, and biochemical indicators were compared between the two groups. Clinical observations were further verified through in vitro experiments.

After an average follow-up of 373 ± 121 days, lipid indices in all 91 patients had not significantly changed compared with baseline (total cholesterol: 4.67 vs. 4.69 mmol/L, P = 0.2499; triglycerides: 1.08 vs. 1.04 mmol/L, P = 0.4457; high-density lipoprotein cholesterol: 1.25 vs. 1.25 mmol/L, P = 0.3063; low-density lipoprotein cholesterol: 3.03 vs. 3.02 mmol/L, P = 0.5765). Subgroup comparisons showed lipid indices remained stable. Among treatment-naïve patients (n = 82), complete viral suppression rates were 23.2%, 59.8%, 70.7%, and 86.6% at four, 12, 24, and 48 weeks, respectively. Cellular experiments revealed that TMF did not promote lipid metabolism in primary hepatocytes and AML12 cells.

Regardless of baseline blood lipid characteristics, 48 weeks of antiviral treatment with TMF in patients with CHB had no significant lipid-raising effect.

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Hot Topic Commentary Open Access
Danzhu Zhao, George Y. Wu
Published online November 8, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00265
Original Article Open Access
Huiling Tian, Long Cheng, Yunhui Liang, Yongshen Ren
Published online June 20, 2024
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Future Integrative Medicine. doi:10.14218/FIM.2024.00009
Abstract
Ulcerative colitis (UC) is a chronic autoimmune disease that mainly affects the rectum and colon. The symptoms primarily include abdominal pain, diarrhea, and bloody stools. The [...] Read more.

Ulcerative colitis (UC) is a chronic autoimmune disease that mainly affects the rectum and colon. The symptoms primarily include abdominal pain, diarrhea, and bloody stools. The incidence of UC continues to increase each year. Bear bile powder (BBP) is a well-known traditional medicine that remains in use due to its outstanding efficacy. This study aimed to elucidate the therapeutic effects and molecular mechanisms of BBP on dextran sulfate sodium (DSS)-induced UC.

DSS-induced UC model mice were created and then randomly assigned to the following groups: control, DSS-treated, 5-amino salicylic acid-treated, BBP low dose, and BBP high dose. Treatment was administered by gavage. Disease activity index, body weight loss, colon histopathology, colon length, and the expression of inflammatory cytokines were measured. Samples of the intestinal content were collected, and differences in the gut microbiota were analyzed by 16S rDNA sequencing.

The experimental results demonstrated that BBP significantly alleviated the symptoms and histopathological scores in UC mice, reduced the production of interleukin-6, interleukin-1β, tumor necrosis factor-α, malondialdehyde, nitric oxide, and myeloperoxidase, and upregulated the expression of cyclic adenosine monophosphate (cAMP), protein kinase A, and cAMP-response element binding protein. Moreover, 16S rRNA sequencing revealed that the gut microbiota of mice in the DSS-treated group was disordered compared to the control group. The abundance of gut microbiota in the treatment groups improved to varying degrees.

Together, these results indicate that BBP significantly improves the inflammatory symptoms of mice with acute colitis, which may be related to its upregulation of the cAMP/protein kinase A/cAMP-response element binding protein signaling pathway, inhibition of NOD-like receptor thermal protein domain associated protein 3 inflammasome secretion, and regulation of gut microbiota.

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