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Review Article Open Access
Roberto Loi, Gabriella Simbula, Monica Pibiri
Published online June 30, 2024
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Gene Expression. doi:10.14218/GE.2023.00175
Abstract
Experimental models using 2/3 partial hepatectomy or chemical injury have helped identify the pathways associated with liver regeneration (LR). Several microRNAs (miRNAs) have been [...] Read more.

Experimental models using 2/3 partial hepatectomy or chemical injury have helped identify the pathways associated with liver regeneration (LR). Several microRNAs (miRNAs) have been identified as modulators of LR, but the molecular mechanisms underlying their activity are still unclear. Given the development of new therapies targeting miRNAs, this is an important question to address. This review discusses recent studies exploring the molecular mechanisms of miRNA-dependent regulation of LR. In particular, the finding that circ-RBM23 promotes LR by sequestering cytoplasmic miRNA139-5p has furthered the understanding of the molecular mechanisms underlying circRNA activity. Interestingly, although miRNAs are generally considered negative regulators of their target mRNAs, miRNAs182-5p promotes LR by upregulating Cyp7a. Furthermore, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) were shown to enhance LR after 2/3 partial hepatectomy by releasing miRNAs that inhibit gene expression to promote an anti-inflammatory response or miRNA-regulatory factors. Since the administration of MSCs-EVs has no hepatotoxic side effects, this may represent a therapeutic strategy to promote LR. miRNAs also mediate LR after chemical injury. This is the case for miR194 and miR21, whose downregulation activates pro-regeneration pathways to ameliorate acetaminophen-induced liver injury. In addition, the downregulation of miR21 has been shown to improve autophagy and haemostasis after acetaminophen overdose. Although further studies are needed to improve their efficacy as therapeutics, the evidence gathered in this review has led to a better understanding of the molecular mechanisms associated with the control of LR by miRNAs.

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Review Article Open Access
Eliete A. Alvin, Anna Victótria Borges, Hugo Félix Perini, Marcos Vinícius da Silva, Anielle Christine A. Silva
Published online December 25, 2024
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00007
Abstract
Neglected tropical diseases (NTDs) encompass a range of infectious diseases prevalent in tropical and subtropical regions, often overlooked despite their substantial health impacts [...] Read more.

Neglected tropical diseases (NTDs) encompass a range of infectious diseases prevalent in tropical and subtropical regions, often overlooked despite their substantial health impacts and high mortality rates. Current treatments for NTDs frequently cause severe side effects due to the pharmacokinetic properties of drugs, which can be harmful even at therapeutic doses. There is a pressing need for innovative diagnostic and therapeutic strategies to mitigate these side effects and improve diagnostic capabilities, as many NTDs lack adequate diagnostic tools. Nanotechnology presents a promising avenue to address these challenges. Nanomaterials possess unique characteristics that enable dual functionality in disease diagnosis and treatment. When conjugated with drugs, nanomaterials can enhance the efficacy of treatments for parasitic diseases while reducing the toxicity associated with conventional medications. Nanomaterial-drug conjugates also serve as efficient carriers, improving drug delivery systems for existing NTD treatments and minimizing adverse effects. This study explores recent advancements in conjugating nanomaterials with drugs for the treatment and diagnosis of NTDs. A comprehensive review of primary database sources reveals significant gaps in current research, underscoring the vast potential for developing novel therapeutic and diagnostic tools. These innovations could revolutionize the management of NTDs, ushering in more effective and safer treatment modalities in the future.

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Original Article Open Access
Yang Zhang, Jiahao Ji, Xiaodong Dou, Rui Wang, Hao Wu, Zhen Li, Tong Zhang
Published online December 25, 2024
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Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00014
Abstract
Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin [...] Read more.

Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin (DHA) has demonstrated anti-inflammatory and immunosuppressive properties, which may benefit individuals with incomplete immune reconstitution. This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs). This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs).

RNA sequencing data (GSE106792) was retrieved from the Gene Expression Omnibus database. R software and Bioconductor packages were used to identify differentially expressed genes (DEGs) among INRs, immune responders (IRs), and healthy controls (HCs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, along with protein-protein interaction (PPI) network construction, were performed. Potential DHA-binding proteins were predicted using the STITCH server and molecular docking studies. Validation experiments were conducted on peripheral blood mononuclear cells from 18 INRs. Cells were treated with varying concentrations of DHA, and CD4+ and CD8+ T cell activation markers (CD38 and HLA-DR) were measured via flow cytometry.

Enrichment and PPI network analysis identified 119, 56, and 189 DEGs in the INR vs. HC, INR vs. IR, and IR vs. HC comparisons, respectively. Enrichment and PPI analyses showed that DEGs were mainly involved in immune response pathways. DHA was predicted to interact with multiple target proteins, indicating anti-inflammatory effects. In vitro, DHA significantly reduced the frequency of CD38− HLA-DR+ CD4+ T cells and CD38+ HLA-DR+ CD8+ T cells at 1,000 µM and 500 µM compared to the control.

This study provides insights into the biological mechanisms underlying incomplete immune reconstitution and supports DHA’s potential as a therapeutic agent. DHA effectively inhibits T cell activation in INRs, presenting a novel and promising treatment strategy.

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Letter to the Editor Open Access
Ivan Rankovic, Vladimir Milivojevic, Jelena Martinov Nestorov, Nikola Panic, Jovanka Trifunovic, Christer Bäck, Elena Curakova Ristovska, Stefan Stojkovic, Salma Mudawi, Keith Siau
Published online December 15, 2024
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00013
Original Article Open Access
Yusuf Musa, Abubakar Sadiq Maiyaki, Yusuf Shehu Umar, Pantong Mark Davwar, Kolawole Oluseyi Akande, Chinwe Philomena Onyia, Kenechukwu Chukwuemeka Okonkwo, Muhammad Manko, Adamu Alhaji Samaila
Published online December 25, 2024
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00010
Abstract
Gastrointestinal endoscopy has revolutionized the entire practice of gastroenterology worldwide, including Nigeria. Endoscopy was introduced in Nigeria more than four decades ago, [...] Read more.

Gastrointestinal endoscopy has revolutionized the entire practice of gastroenterology worldwide, including Nigeria. Endoscopy was introduced in Nigeria more than four decades ago, and it has been a story of varying successes and challenges. This study explored the various experiences of endoscopists, the challenges they face, and the efforts put in place to maintain the practice in Nigeria.

This cross-sectional survey was conducted from October to December 2023 among endoscopists practicing in Nigeria. It involved a 30-part self-administered online questionnaire that inquired about individual experiences in endoscopy practice. These included qualifications, competency, facility settings, challenges faced, and innovations employed to address them. At the end of the survey, responses were analyzed using descriptive statistics, Chi-square, and likelihood ratios at the 0.05 level of significance.

A total of 41 respondents participated in the survey from 19 states across the six geopolitical zones of Nigeria, with a mean age ± standard deviation of 43 ± 7 years. Male respondents made up 80.5%, with Nigerian-trained gastroenterologists via the residency program constituting the predominant population, and an average endoscopy experience of five to nine years (39.02%). Most of the respondents work in public institutions (73.17%), with 43.9% working in at least two centers. There was an average of five endoscopists and three to seven endoscopy centers per state. Most centers perform 11–12 upper and four to five lower GI endoscopies per week, respectively, with a predominance of diagnostic procedures. The most common endoscopic intervention was variceal band ligation. The most common challenge faced was the high cost of procedures, accessories, and maintenance of endoscopes.

Endoscopy practice cuts across all the zones and most states of the federation. Both diagnostic and therapeutic procedures are available in most centers. However, the practice is faced with a myriad of challenges, mainly poor financing and inadequate training, among others. As a result, some innovations were locally developed to ease the practice and prevent it from collapsing.

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Review Article Open Access
Weiqiang Zhao
Published online December 25, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00042
Abstract
The number of molecular abnormalities identified in hematopoietic and lymphocytic neoplasms has grown exponentially over the past decades. Patients with genetic biomarker-matched [...] Read more.

The number of molecular abnormalities identified in hematopoietic and lymphocytic neoplasms has grown exponentially over the past decades. Patients with genetic biomarker-matched targeted therapies have experienced significantly improved survival rates. Modern molecular laboratories, equipped with advanced technologies such as next-generation sequencing, can simultaneously test hundreds of genes and thousands of hotspots in a single run with multiple samples analyzed side by side. Bioinformatics tools provide seamless, evidence-based information to determine whether the detected mutations are benign or pathogenic, somatic or germline, druggable or diagnostic. This review is divided into five sections, each aiming to provide a comprehensive overview of the genetic landscape of myeloid and lymphocytic neoplasms. It highlights the challenges and proposes potential solutions to facilitate interpretation and maximize the clinical utility of molecular profiling results.

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Review Article Open Access
Xiaohui Zhang, Sara Niyazi, Huazhang Guo, Ling Zhang
Published online March 24, 2025
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00047
Abstract
Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. It is categorized into distinct pathological and clinical [...] Read more.

Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. It is categorized into distinct pathological and clinical subtypes, including localized unicentric CD, idiopathic multicentric CD, and human herpesvirus 8-associated or human herpesvirus 8-negative variants. Diagnosing CD requires adherence to internationally recognized guidelines that integrate clinical, laboratory, and histological findings. However, distinguishing CD from other diseases can be complex, as numerous benign and malignant conditions can mimic its features. Additionally, individuals diagnosed with CD are at an elevated risk of developing various malignancies. In this article, we reviewed benign and malignant conditions that can mimic CD.

Literature search is conducted and reviewed.

Mimickers of CD include follicular hyperplasia, indolent B-cell lymphoproliferative disorders, peripheral T-cell malignancies, classic Hodgkin lymphoma, follicular dendritic cell tumors, plasma cell disorders, immunoglobulin G4 -related lymphadenopathy, autoimmune-associated lymphadenopathy, infectious causes of lymphadenopathy, and systemic syndromes like POEMS and TAFRO. Various malignancies are associated with CD, including plasma cell proliferations, lymphomas, follicular dendritic cell neoplasms, and Kaposi sarcoma.

This review explores the differential diagnoses and neoplasms linked to CD, emphasizing their role in accurate classification, treatment decisions, and patient management. A comprehensive understanding of CD and its mimickers is crucial for ensuring accurate diagnosis and appropriate patient management in clinical practice.

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Case Report Open Access
Amanda Meindl, M. Sambasiva Rao, Guang-Yu Yang
Published online December 24, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00038
Abstract
Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder predominantly affecting individuals of Puerto Rican descent. It is characterized by oculocutaneous albinism, [...] Read more.

Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder predominantly affecting individuals of Puerto Rican descent. It is characterized by oculocutaneous albinism, platelet storage pool deficiency, and lysosomal ceroid accumulation in tissues. Lysosomal dysfunction has been shown to be associated with pulmonary fibrosis and granulomatous colitis in HPS patients, accounting for a significant portion of morbidity and mortality in this population. Clinical and endoscopic gastrointestinal manifestations in HPS patients are similar to those of active Crohn’s disease, including abdominal pain, bleeding, fissures, fistulas, and perianal involvement. Histology reveals granulomatous colitis that can be difficult to distinguish from Crohn’s disease. Identifying distinct morphologic features from Crohn’s disease is crucial for the diagnosis of HPS. Here, we present a case of a 27-year-old male with a history of HPS and refractory granulomatous colitis with severe perianal disease, who underwent total proctocolectomy and perianal excision. The unique, distinguishing morphologic features from Crohn’s disease in this case are: 1) grossly diffuse ulceration in the ano-rectum and cecum, 2) ulcerative and granulomatous inflammation predominantly involving the mucosa and submucosa of the colon, and 3) accumulation of ceroid pigment in the histiocytes of the lamina propria throughout the entire gastrointestinal tract. Immunohistochemical stains for CD3 and FoxP3-positive T cells in the granulomatous colitis were further analyzed. Thus, we fully document the extent of disease involvement and morphologic features in this patient and extensively discuss the similarities and differences between HPS and Crohn’s disease.

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Original Article Open Access
Shuang Wu, Changmi Deng, Yufeng Han, Wen Fu, Ruixi Hua
Published online December 24, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00024
Abstract
Wilms tumor is the most common kidney tumor in children aged 0-14 years. MicroRNAs are small, noncoding RNAs linked to the development of malignant tumors. Several studies have [...] Read more.

Wilms tumor is the most common kidney tumor in children aged 0-14 years. MicroRNAs are small, noncoding RNAs linked to the development of malignant tumors. Several studies have shown the association between single nucleotide polymorphism in miR-27a and cancer risk. This study aimed to explore the potential impact of the miR-27a rs895819 T>C polymorphism on Wilms tumor susceptibility.

The rs895819 T>C polymorphism was genotyped using the TaqMan method in 145 patients with Wilms tumors and 531 controls. Logistic regression models were used to assess the association between this polymorphism and Wilms tumor risk. A stratified analysis was also performed based on age, sex, and clinical stage.

The rs895819 T>C polymorphism showed genotypic distribution consistent with Hardy-Weinberg equilibrium (P = 0.749). The differences were not statistically significant. The miR-27a rs895819 T>C polymorphism was not significantly associated with Wilms tumor susceptibility, and the stratified analysis did not yield any significant differences.

Our study provides evidence of a lack of association between the miR-27a rs895819 T>C polymorphism and Wilms tumor susceptibility. Further validation through larger sample sizes and additional genetic polymorphisms is warranted.

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Opinion Open Access
Xinbo Xu, Yi Hu, Nonghua Lv
Published online December 25, 2024
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00007
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