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Original Article Open Access
Role of ELK3 in Ferroptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes
Yaqun Zhang, Huimin Shi, Lin Wang, Jihong Pan
Published online January 20, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00036
Abstract
Rheumatoid arthritis (RA) is an inflammatory arthritis characterized by chronic joint inflammation, cartilage degradation, and bone erosion. ELK3 is a transcriptional repressor [...] Read more.

Rheumatoid arthritis (RA) is an inflammatory arthritis characterized by chronic joint inflammation, cartilage degradation, and bone erosion. ELK3 is a transcriptional repressor that can affect cell proliferation, migration, invasion, apoptosis, and other cellular processes. The study aimed to clarify the effect of ELK3 in the biological activity and ferroptosis phenotype of RA fibroblast-like synoviocytes (FLS), and to reveal its molecular mechanism in regulating ferroptosis in RA FLS.

We investigated the impact of ELK3 on the biological activity and ferroptosis phenotype of RA FLS using real-time quantitative polymerase chain reaction, immunohistochemistry, Transwell assay, CCK-8 assay, and ferroptosis-related indicator kit. The molecular mechanism of ELK3 in RA FLS was further explored using Western blot, chromatin immunoprecipitation polymerase chain reaction, and other experiments.

ELK3 was highly expressed in RA. Silencing ELK3 inhibited the invasion and proliferation of RA FLS (both p < 0.05). After silencing ELK3 in imidazole ketone erastin-induced RA FLS, intracellular reactive oxygen species, lipid peroxidation levels, ferrous ion content, 4-Hydroxynonenal levels, and Malondialdehyde concentrations all increased. Additionally, ELK3 affects ferroptosis in RA FLS by regulating kelch-like ECH-associated protein 1 (p < 0.05).

Silencing ELK3 leads to decreased invasion and proliferation of RA FLS, affecting their biological activity. ELK3 inhibits ferroptosis by suppressing its transcriptional activity through binding to the kelch-like ECH-associated protein 1 promoter. This suggests that ELK3 may be a potential target for RA therapy.

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Original Article Open Access
Fabrication of Polymethyl Methacrylate Microspheres for Improving Immunogenicity of Tetanus Toxoid
Sellappan Mohan, Arumugam Nagarajan
Published online November 11, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00005
Abstract
The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging [...] Read more.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging from 40 µm to 70 µm in diameter can be formed. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells. This study aimed to use biocompatible polymethyl methacrylate microspheres for the controlled delivery of antigens.

The potency of various formulations containing encapsulated tetanus toxoid (TT) with polymethyl methacrylate polymer microspheres was assessed using the toxin neutralization and challenge methods. The neutralization test was conducted on pooled sera two weeks after the initial immunization and weekly for four weeks following the booster dose administration. Scanning electron micrographs of the microspheres revealed drug leaching from spherical granular matrices.

The injection site showed a higher distribution of smaller microparticles, resulting in depot release. The polymer coating’s thickness was significantly lower compared to the 25% polymer microspheres. Concentrations ranging from 0.00024 mL to 0.00030 mL caused significant tetanic paralysis. Two weeks after the initial immunization, the antigenic activity of TT was below the minimum threshold, possibly due to insufficient levels of antigenic TT within the system within seven days post-immunization. The polymethacrylate microsphere elicited a notable immune response, but only the polymer concentration of 25% w/v met the I.P. requirements; lower polymer concentrations were ineffective.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within microspheres. Consequently, microspheres ranging from 40 µm to 70 µm in diameter can be assembled. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells.

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Mini Review Open Access
Circadian Rhythms in Tumor Regulation: Impacts on Tumor Progression and the Immune Microenvironment
Jinxin Li, Peng Luo, Ying Liu, Yu Fang, Linhui Wang, Aimin Jiang
Published online February 24, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00038
Abstract
The spatial heterogeneity of tumors has long been a subject of significant interest in oncology. Recent research has revealed that tumors and their microenvironments undergo dynamic [...] Read more.

The spatial heterogeneity of tumors has long been a subject of significant interest in oncology. Recent research has revealed that tumors and their microenvironments undergo dynamic changes over time, particularly in the form of periodic circadian rhythms. Disruptions to these rhythms have been recognized as a pivotal factor in the advancement of tumorigenesis. Such disruptions not only induce dysregulation of gene expression within tumor cells, influencing tumor growth, metabolism, the cell cycle, and vascular homeostasis but also facilitate metastasis. Furthermore, they mediate the remodeling of the tumor immune microenvironment, fostering the development of an immunosuppressive milieu. Additionally, the in vivo metabolism and therapeutic responsiveness of tumor treatments—including chemotherapy, targeted therapy, and immunotherapy—have been shown to be modulated by circadian rhythms. This suggests that time-specific drug administration may enhance treatment efficacy, offering novel insights for precision cancer therapy. In this review, we systematically update contemporary research on the impact of circadian rhythms on tumor biology, encompassing both tumor progression and the efficacy of drug therapies. Building upon these insights, we explore the potential for a synergistic approach that integrates the targeting of rhythmic genes with current tumor treatment modalities. We also discuss the feasibility of tailoring tumor therapy to the rhythmic alterations that define in vivo metabolism and the efficacy of specific therapeutic agents, highlighting the significance of rhythm-based strategies in the personalized treatment of tumors and the prevention of associated diseases.

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Case Report Open Access
Diagnosis of Lung Leishmaniasis by Bronchoalveolar Lavage Cytology in a Human Immunodeficiency Virus-infected Patient: A Case Report
Ahmed A. Ahmed, Y. Helen Zhang
Published online January 17, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00037
Abstract
Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs. We report a case of a 45-year-old male with human immunodeficiency virus infection [...] Read more.

Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs.

We report a case of a 45-year-old male with human immunodeficiency virus infection who presented with abdominal pain and vomiting. Imaging studies revealed minimal bilateral ground-glass opacities in the lungs, hepatosplenomegaly, and diffuse lymphadenopathy. A bronchoscopy with bronchoalveolar lavage cytology evaluation showed abundant macrophages containing numerous intracellular organisms with characteristic dot-like kinetoplasts, confirming the diagnosis of Leishmaniasis. Special stains for other infections were negative.

This case highlights the value of bronchoalveolar lavage cytology in diagnosing non-neoplastic lung pathologies, including parasitic infections like Leishmaniasis, thereby enabling prompt and targeted treatment.

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Mini Review Open Access
Pediatric Bone Marrow Myelofibrosis: A Heterogeneous “Entity” Requiring Refined Classification to Guide Therapy
Jinjun Cheng
Published online December 23, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00035
Abstract
Diagnosing and treating cytopenic myelofibrosis in children is challenging due to the wide spectrum of clinical and pathological features, underlying etiologies, and variable therapeutic [...] Read more.

Diagnosing and treating cytopenic myelofibrosis in children is challenging due to the wide spectrum of clinical and pathological features, underlying etiologies, and variable therapeutic responses. In this review, we summarize the related literature and present our diagnostic algorithm to differentiate pediatric myelofibrosis and guide therapy. In brief, primary myelofibrosis is extremely rare in children, while myelofibrosis secondary to non-neoplastic or neoplastic disorders should be thoroughly ruled out in ambiguous cases. Moreover, it is reasonable to closely follow up patients and repeat bone marrow biopsy before reaching a definitive diagnosis.

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Original Article Open Access
Ursolic Acid Modulates Estrogen Conversion to Relieve Inflammation in Metabolic Dysfunction-associated Steatotic Liver Disease via HSD17B14
Simin Gu, Hui Zhang, Zhekun Xiong, Chong Chen, Junmin Wang, Dan Fang, Yiyuan Zheng, Yong Li
Published online March 10, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00414
Abstract
The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been escalating annually, positioning it as the leading cause of chronic liver disease worldwide. [...] Read more.

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been escalating annually, positioning it as the leading cause of chronic liver disease worldwide. Ursolic acid has demonstrated promising therapeutic efficacy in managing MASLD, thereby justifying the need for an in-depth exploration of its pharmacological mechanisms. This study aimed to investigate elucidate the therapeutic mechanisms by which ursolic acid modulates estrogen conversion in the treatment of MASLD.

Building upon prior studies that have highlighted the potent anti-inflammatory effects of ursolic acid and its specific targeting of 17β-hydroxysteroid dehydrogenase 14 (HSD17B14), this investigation employed a western diet to induce MASLD in murine models with varying severities over different time intervals.

The protein expression of HSD17B14 initially increased, followed by a subsequent decrease. This trend was accompanied by corresponding changes in 17β-estradiol (E2) and estrone (E1) levels. Intervention with ursolic acid resulted in a reduction in HSD17B14 and E1 levels during the phase of high HSD17B14 expression, while simultaneously elevating E2 levels. In steatotic hepatocytes, E1 promoted cellular inflammation, whereas E2 exhibited anti-inflammatory effects. However, the alleviated effects of E2 were antagonized by HSD17B14. As expected, ursolic acid modulated HSD17B14, thereby mitigating the inflammatory response in steatotic hepatocytes.

HSD17B14, a crucial enzyme regulating the balance between E1 and E2, catalyzes the conversion of estrogen E2 into E1, thereby exacerbating tissue inflammation induced by metabolic stress. Ursolic acid, by modulating HSD17B14-mediated estrogen conversion, appears to ameliorate immune-related inflammation in MASLD.

Full article
Original Article Open Access
Acupuncture Protects Brain Regions in an Alzheimer’s Disease Mouse Model by Inhibiting Apoptosis and Reducing Tau Protein
Huiling Tian, Yujie Li, Shun Wang, Zidong Wang, Jiayi Yang, Hao Liu, Jingyu Ren, Jiheng Zuo, Yushan Gao, Ruosang Du, Zhigang Li, Xin Wang, Jing Jiang
Published online December 31, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00028
Abstract
Acupuncture treatment on the DU channel has shown therapeutic effects for Alzheimer’s disease (AD), but the underlying mechanisms are not yet clear. The purpose of this study was [...] Read more.

Acupuncture treatment on the DU channel has shown therapeutic effects for Alzheimer’s disease (AD), but the underlying mechanisms are not yet clear. The purpose of this study was to comprehensively observe the protective effects of acupuncture on different brain regions in AD model mice, providing laboratory evidence for clinical acupuncture intervention in AD.

Eleven senescence-resistant strain 1 male mice were used as the normal control group. The senescence-accelerated prone strain 8 (SAMP8) male mice were used as AD model mice. Thirty-three SAMP8 mice were randomly divided into three groups: AD model group (group M), drug treatment group, and acupuncture treatment group (group A). The effect of acupuncture on learning and memory capabilities of SAMP8 mice was assessed by the Morris water maze test. Nissl staining was employed to provide a general view of the brain structure in AD model mice. Additionally, Western blot analysis was used to quantify Caspase-3 and tau protein levels.

In the spatial navigation test, the ratio of time mice spent in the goal quadrant in group M remained low, even lower than 25%. The ratio of time spent in the goal quadrant by mice in the acupuncture group on day 4 was higher than that on day 1 (P < 0.01). There was a trend indicating that the time ratio of mice in the acupuncture group during the probe trial was higher than in group M, though there was no statistically significant difference. Most traces of mice in group A were in the goal platform quadrant and across the platform in different, yet effective, ways. Compared to group M, most of the cells in the frontal cortex, hippocampus, and temporal cortex of mice in group A were round with clear stratification, regular arrangement, and increased Nissl bodies. The content of Caspase-3 in the frontal cortex and hippocampus of mice in the acupuncture group was lower than in group M (P < 0.01, P < 0.05). The content of tau in the hippocampus and temporal cortex of mice in group A was lower than in group M (P < 0.05; P < 0.01).

Acupuncture at the DU channel can improve learning and memory abilities to a certain degree by reducing apoptosis in the frontal cortex and hippocampus and decreasing tau deposition in the hippocampus and temporal cortex of AD model mice.

Full article
Mini Review Open Access
Optimal Management of Erosive Esophagitis: An Evidence-based and Pragmatic Approach
Maxwell M. Chait
Published online March 25, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00006
Abstract
Erosive Esophagitis (EE) is the most common complication of gastroesophageal reflux disease. Patients with EE can be asymptomatic or present with severe symptoms such as dysphagia [...] Read more.

Erosive Esophagitis (EE) is the most common complication of gastroesophageal reflux disease. Patients with EE can be asymptomatic or present with severe symptoms such as dysphagia and gastrointestinal bleeding. Approximately 10-15% of patients with EE have refractory disease. Optimal management of EE requires understanding its pathophysiology, clinical presentation, and available evaluation and treatment modalities. While pharmacologic treatment of EE is often successful, procedural options such as surgery and endoscopic therapy may be necessary. This article presents an evidence-based and pragmatic approach to the management of EE, the most common complication of gastroesophageal reflux disease.

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Letter to the Editor Open Access
Original Article Open Access
Evolution and Current Challenges of Gastrointestinal Endoscopy in Nigeria: Insights from a Nationwide Survey
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
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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