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Review Article Open Access
Megan Lewis, Christopher M. Johnson
Published online June 18, 2024
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00086
Abstract
Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the GI tract. The etiology is unclear, and most clinical [...] Read more.

Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the GI tract. The etiology is unclear, and most clinical symptoms are nonspecific, making the diagnosis and prognosis of IBD challenging as there is no gold-standard diagnostic test. Both endoscopy and imaging are essential diagnostic tools for determining disease state, location, and severity. However, the high cost and invasive nature of these tests make them unrealistic for frequent assessment. Given these limitations, laboratory testing of blood and feces has proven to be a viable alternative for routine disease monitoring. To integrate more efficient and personalized treatment strategies, new studies are consistently emerging to develop minimally invasive testing that can predict disease severity and response to available treatments. The goal is to develop better predictors of disease course, response to therapy, and therapy-related adverse events, thereby establishing a more efficient and personalized treatment strategy. This review aimed to delve into existing literature to assemble a collection of currently used biomarkers that aid in monitoring treatment response, as well as highlight select novel and combined biomarkers that hold promise for future management of IBD.

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Review Article Open Access
Dmitry Victorovich Garbuzenko
Published online March 1, 2024
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00071
Abstract
This review summarizes the current investigations that confirm the significance of liver fibrosis (LF) as an independent cardiovascular risk factor in non-alcoholic fatty liver [...] Read more.

This review summarizes the current investigations that confirm the significance of liver fibrosis (LF) as an independent cardiovascular risk factor in non-alcoholic fatty liver disease (NAFLD). PubMed, Google Scholar, Web of Science platform, Reference Citation Analysis, and Cochrane Systematic Reviews were searched for articles published between 2008 and 2023. Relevant articles were identified using the following keywords: “cardiovascular diseases”, “cardiovascular risk factors”, “non-alcoholic fatty liver disease”, “nonalcoholic steatohepatitis”, and “liver fibrosis”. The reference lists of the identified articles were also searched for other relevant publications. The investigations that described LF as a cardiovascular risk factor in NAFLD met the inclusion criteria. NAFLD occupies a leading position among liver diseases worldwide. Cardiovascular disorders are the most significant cause of unfavorable outcomes in NAFLD patients. Currently, the relationship between them is well established. The pathophysiological mechanisms predisposing to the development of cardiovascular disorders in NAFLD include atherogenic dyslipidemia, impaired glucose metabolism and liver insulin resistance, low-grade systemic inflammation, endothelial dysfunction, cardiovascular remodeling, as well as gut dysbiosis, which are influenced by numerous genetic and epigenetic factors. Identification of cardiovascular risk factors in NAFLD is an important public health issue. At present, there is evidence that the presence of advanced LF may be a strong independent predictor and risk factor for cardiovascular disorders in NAFLD. It is obvious that early diagnosis of LF will allow to stratify NAFLD patients by cardiovascular risk groups and thereby determine the most optimal therapeutic interventions.

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Original Article Open Access
Ashrafun Nessa, Shirin Akter Begum, Saif Ullah Munshi, Ferdousy Begum, Afroza Chowdhury, Noor-E-Ferdous
Published online March 29, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2023.00033
Abstract
The government of Bangladesh adopted visual inspection of the cervix with acetic acid method for cervical cancer screening in the majority of the district and sub-district hospitals. [...] Read more.

The government of Bangladesh adopted visual inspection of the cervix with acetic acid method for cervical cancer screening in the majority of the district and sub-district hospitals. Before alternative screening methods are adopted, the prevalence of high-risk human papillomavirus (HPV) genotypes among various geographical regions must be determined. Therefore, we aimed to determine the prevalence of high-risk HPV genotypes in urban and rural areas of Bangladesh.

This cross-sectional study was carried out at Bangabandhu Sheikh Mujib Medical University, Dhaka from July 2021 to June 2022. Using a multistage sampling method, cervical samples (N = 3,856) were collected from women aged 30–49 years attending visual inspection of the cervix with acetic acid at 16 centers (eight districts and eight sub-districts). HPV tests were performed by real-time PCR amplification. Descriptive analysis and Chi-square test/Fisher’s exact test were performed for associations, and a P value <0.05 was considered significant.

Among the 3,856 women, the overall prevalence of high-risk HPV was 3.6%, with 49 (1.3%) women testing positive for HPV16, 12 (0.3%) women testing positive for HPV18, and 65 (1.7%) testing positive for other high-risk HPV genotypes. There was a significant variation in the prevalence of high-risk HPV among the divisions (P = 0.001), with the highest infection rate (7.1%) observed among women in rural Sylhet and the lowest in rural Mymensingh (0.5%). No significant difference in high-risk HPV prevalence was found between the urban and rural women, except in Mymensingh.

The low prevalence of high-risk HPV (3.6%) among Bangladeshi women with regional variation should be considered by policymakers during the development of cervical cancer prevention policies.

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Mini Review Open Access
Nitin Srivastava, Aaruni Saxena, Anil K. Saxena
Published online September 20, 2024
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Oncology Advances. doi:10.14218/OnA.2024.00019
Abstract
Despite the large number of cancer chemotherapeutics, cancer treatment is still not very satisfactory. Immune checkpoint inhibition has emerged as a new ray of hope in the immunotherapy [...] Read more.

Despite the large number of cancer chemotherapeutics, cancer treatment is still not very satisfactory. Immune checkpoint inhibition has emerged as a new ray of hope in the immunotherapy approach for cancer treatment. Immune checkpoint inhibitors are molecules located on the surface of immune cells that regulate unnecessary immune responses and keep autoimmune reactions in check. Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 and anti-programmed cell death ligand-1, have been employed to activate receptors on immune cells like T-cells, which can deactivate the immune checkpoint and thus reactivate them against cancer cells. However, ICI therapy has limitations, including resistance development in patients, its suitability for all patients, multiple organ disorders, and hyper-progression. Therefore, understanding the chemical structures of small molecule ICIs may aid in designing and developing novel ICIs with improved efficacy and efficiency for cancer chemotherapy. This review’s novelty lies in its summary of the U.S. Food and Drug Administration-approved drugs, repurposed drugs, candidate drugs used alone or in combination with monoclonal antibodies, and novel potential lead molecules under preclinical investigation, which may be useful for designing new chemical entities as ICIs. The review describes 10 different drugs approved by the U.S. Food and Drug Administration that have demonstrated immune checkpoint inhibition targeting the programmed cell death ligand-1/programmed cell death protein-1 signaling, CTLA-4/CD28, TIGIT/PVR, and CD47/SIRPα pathways, as well as three repurposed drugs, 11 candidate drugs, and nine drugs in combination with monoclonal antibodies that are in various phases of clinical trials.

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Review Article Open Access
Mohd Yusuf
Published online March 29, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2023.00041
Abstract
Cervical cancer is a significant public health concern worldwide. Current screening approaches include Pap smears, human papillomavirus testing, visual inspections, and emerging [...] Read more.

Cervical cancer is a significant public health concern worldwide. Current screening approaches include Pap smears, human papillomavirus testing, visual inspections, and emerging molecular techniques, aimed at enhancing precision and accessibility. The landscape also includes the increasing prominence of self-sampling and telemedicine, which broaden the reach of screening services. Human papillomavirus vaccination programs targeting young girls have the potential to significantly reduce long-term risk. These evolving strategies are supported by global initiatives such as the World Health Organization’s Cervical Cancer Elimination Initiative, aiming to increase screening efforts and reduce the global impact of cervical cancer. The key findings of this study suggested that current methodologies for the detection and prevention of cervical cancer are a little beneficial and there is a pressing need to use advanced technologies such as highly sophisticated equipment integrated with artificial intelligence. In addition, the detection of cervical cancer screening provides insights into evolving methodologies, promising prospects, and nuanced challenges that must be addressed to prevent this condition in females worldwide. Looking forward, future cervical cancer screening involves further refinements in molecular testing, expanded vaccine coverage, and the integration of telehealth solutions, promising increased accessibility and improved early detection to overcome insightful challenges.

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Original Article Open Access
Michel Planat, Marcelo Amaral, David Chester, Fang Fang, Raymond Aschheim, Klee Irwin
Published online January 31, 2024
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Gene Expression. doi:10.14218/GE.2023.00079
Abstract
Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able [...] Read more.

Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able to differentiate between “healthy” nucleotide sequences and disrupted sequences that may be associated with various diseases. In this paper, we extend our efforts to the study of messenger RNA (mRNA) metabolism, showcasing the power of our approach.

To achieve this, we used: (a) infinite (finitely generated) groups , with generators representing the distinct nucleotides and a relation between them [e.g., the consensus sequence in the mRNA translation (i), the poly(A) tail in item (ii), and the microRNA seed in item (iii)]; (b) aperiodicity theory, which connects healthy groups to free groups of rank r and their profinite completion , and (c) the representation theory of groups over the space-time-spin group SL2(C), highlighting the role of surfaces with isolated singularities in the character variety.

We investigate (1) mRNA translation in prokaryotes and eukaryotes, (2) polyadenylation in eukaryotes, which is crucial for nuclear export, translation, stability, and splicing of mRNA, (3) microRNAs involved in RNA silencing and post-transcriptional regulation of gene expression, and (4) identification of disrupted sequences that could lead to potential illnesses.

Our approach could potentially contribute to the understanding of the molecular mechanisms underlying various diseases and help develop new diagnostic or therapeutic strategies.

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Systematic Review Open Access
Gabriela Silva Neubern de Oliveira, Cassia Senger, Rodrigo Cardoso de Oliveira
Published online March 11, 2024
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Future Integrative Medicine. doi:10.14218/FIM.2023.00042
Abstract
Medicinal plants have been recognized as a promising alternative treatment against some types of cancer, being rich sources of effective biochemical agents. The aim of this study, [...] Read more.

Medicinal plants have been recognized as a promising alternative treatment against some types of cancer, being rich sources of effective biochemical agents. The aim of this study, therefore, was to gather, through a systematic literature review, articles related to plants from the Brazilian Cerrado biome that have an action on different tumor cells.

Different keywords were used in the search mechanisms of Pubmed, Scielo, Science Direct, Scopus, and Lilacs databases. Of the studies found, titles that did not reflect the purpose of this review, those that did not provide access to the full text, and those that were published before 2005 were excluded. Articles referring to the activity of Cerrado plants in tumor cells published in the last sixteen years were selected, totaling thirty-nine articles. Registration number of this review: #CRD42020205579.

The extracts from the studied plants demonstrated significant antiproliferative effects against several tumor cell lines. 39 species of plants were identified belonging to the families: Combretaceae, Annonaceae, Celastraceae, Verbenaceae, Solanaceae, Myrtaceae, Rubiaceae, Bignoniaceae, Erythroxylaceae, Sapotaceae, Asteraceae, Elaeocarpaceae, Apocynaceae, Anacardiaceae, Calophyllaceae, Lythraceae, Mimosaceae, and Morseraceae. The extracts were obtained from different parts of the plants and different fractions were used.

It can be concluded that the Cerrado contains a wide variety of plants with antitumor actions, and further studies are needed to discover other species with anticancer potential, in addition to in vivo studies.

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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
Charlene Deane, Orla Kelly, Colm O’Morain
Published online August 1, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00008
Abstract
Gastric cancer is the third most common cause of cancer-related death globally. The highest incidence is encountered in Asia, followed by Europe which has the second highest incidence [...] Read more.

Gastric cancer is the third most common cause of cancer-related death globally. The highest incidence is encountered in Asia, followed by Europe which has the second highest incidence worldwide. In Europe, gastric cancer is typically diagnosed at an advanced stage, with an estimated five-year survival rate of 24%, compared to 59% in Japan. This disparity is largely attributed to the significant role of screening in Japan. Given the expected rise in absolute numbers of gastric cancer cases, there has been a demand for gastric cancer screening programmes in high-intermediate risk countries, advocated by the International Agency for Research on Cancer, the Science Advice for Policy by European Academies, the European Commission as part of the Europe Beating Cancer Plan, and the Maastricht VI/Florence consensus guidelines. This review article summarizes the current disparities in screening strategies between countries in the East and West and comments on future developments in population-based screening research in this field. The references for this article were identified through PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Controlled Register of Trials using the search terms “gastric cancer”, “stomach cancer”, “Helicobacter pylori”, and “screening” over the period from 1995 until March 2024. Overall, this review identifies three potential approaches to screening: primary, secondary, and opportunistic. It highlights the lack of a uniform consensus on the best approach to screening, the disparity in the information available in different populations, and upcoming research to address this disparity.

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Original Article Open Access
Kumaran Kasianthan, Janardanan Subramonia Kumar, Kandasamy Nagarajan ArulJothi
Published online May 15, 2024
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Gene Expression. doi:10.14218/GE.2023.00184
Abstract
Familial hypercholesterolemia (FH) is characterized by an elevated level (>155 mg/dL) of LDL (low-density lipoprotein)-Cholesterol in the blood circulation and is one of the [...] Read more.

Familial hypercholesterolemia (FH) is characterized by an elevated level (>155 mg/dL) of LDL (low-density lipoprotein)-Cholesterol in the blood circulation and is one of the major causes of premature atherosclerotic cardiovascular diseases. The significant genes responsible for this lipid deposition are LDL-Receptor (LDLR), Apolipoprotein B-100 (APOB), and proprotein convertase subtilisin/kexin type 9 genes (PCSK9). Other than these 3 genes, 64 gene loci have been identified as polygenic causes. The aim of the study is to analyze the other genes involved in this condition. This can be obtained using differential expression analysis of the already existing FH mRNA expression dataset.

In this study, three datasets representing the markers of monocyte, T lymphocyte, and iPSC in atherosclerosis and FH were selected from the pool of hypercholesterolemia datasets, and differential expression analysis was done using networkanalyst.ca.

The monocyte and t-lymphocytes datasets each had 743 differentially expressed genes (DEGs), while the iPSCs dataset contained 691 DEGs. RPS7, AKRIC3, PL9, and OSM are among the genes that are expressed in the majority of Gene ontology annotations.

According to the findings, genes with varied levels of expression are associated with a variety of functions, including membrane transport, ubiquitin-protein ligase activity, the COP9 signalosome complex, the mitochondrial respiratory chain, and copper metabolism. Analyzing these critical genes lays the groundwork for investigating potential therapeutic targets that could alleviate the impact of cardiovascular disease in individuals diagnosed with FH.

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