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Original Article Open Access
Thyroid Hormone Levels in Mothers and Cord Blood at Delivery in Crude Oil Producing Community in Delta State, Nigeria
Mathias A. Emokpae, Lawrence Ogana
Published online May 29, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00085
Abstract
Harm caused by crude oil spillage and its associated environmental toxicants manifests slowly. This study examined the impact of crude oil environmental toxicants on neonates’ thyroid [...] Read more.

Harm caused by crude oil spillage and its associated environmental toxicants manifests slowly. This study examined the impact of crude oil environmental toxicants on neonates’ thyroid and cognitive functions in crude oil-producing communities.

The case-control study comprised 55 crude oil-exposed expectant mothers and 33 non-crude oil-exposed expectant mothers as controls. Serum Benzo Pyrene Dihydrodiol Epoxide (BPDE), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were assayed in expectant mothers and neonates. Intelligence quotient and APGAR scores were determined in the children using Fagan’s test of infant intelligence.

Serum TSH (p < 0.05) and BPDE (p < 0.001) were higher, while T3 and T3/T4 ratio were significantly lower (p < 0.001) in exposed pregnant women compared to the control. Cord blood TSH and T3/T4 ratio were lower (p < 0.001) while T4 and BDPE were higher (p < 0.001) in prenatally exposed neonates than prenatally non-exposed infants. Serum TSH correlated with BDPE (R2 = 0.080, p < 0.036) and APGAR score (R2 = 0.341, p < 0.012), while T3 and T4 were not associated with BDPE and APGAR score. TSH correlated with T3 (R2 = 0.0.082, p < 0.05), T3 correlated with T4 (R2 = 0.111, p < 0.013) and TSH (R2 = 0.082, p < 0.05). Exactly 54.5% (30/55) of prenatally exposed neonates had a low intelligence quotient compared to 36.4% (12/33) in prenatally non-exposed neonates.

Crude oil and associated environmental pollutants might significantly affect the thyroid function. Environmental surveillance, biomonitoring and environmental cleanup are emphasized. Future research on the mechanisms of the observed toxicological effects on thyroid hormones and targeted protection of pregnant women and their offspring is suggested.

Full article
Review Article Open Access
The Tumor Microenvironment and Tumor-infiltrating Lymphocytes in Solid Tumor: A Comprehensive Review
Zhuoya Sun, Lupeng Qiu, Xiao Zhao, Shunchang Jiao
Published online June 25, 2024
Oncology Advances. doi:10.14218/OnA.2023.00043
Abstract
The tumor microenvironment is a dynamic cellular landscape critical to cancer progression. Within it, tumor-infiltrating lymphocytes hold a dual role, contributing to both tumor [...] Read more.

The tumor microenvironment is a dynamic cellular landscape critical to cancer progression. Within it, tumor-infiltrating lymphocytes hold a dual role, contributing to both tumor suppression and progression. This review synthesized current knowledge on tumor-infiltrating lymphocytes, emphasizing their prognostic significance and therapeutic potential. By dissecting their interactions within the tumor microenvironment and with cancer cells, we sought to uncover the complexities of the immune response in cancer and explored the future direction of immunotherapeutic strategies.

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Original Article Open Access
NOTCH4 Is a New Player in the Development of Pulmonary Fibrosis
Nadezhda Bakalenko, Daria Smirnova, Liana Gaifullina, Polina Kuchur, Daniela Ian, Mikhail Atyukov, Ju Liu, Anna Malashicheva
Published online June 30, 2024
Gene Expression. doi:10.14218/GE.2024.00006
Abstract
Idiopathic pulmonary fibrosis is a chronic, progressive, incurable lung disease, leading to irreversible lung tissue remodeling. The Notch signaling pathway, essential for lung [...] Read more.

Idiopathic pulmonary fibrosis is a chronic, progressive, incurable lung disease, leading to irreversible lung tissue remodeling. The Notch signaling pathway, essential for lung development, has gained attention for its role in pulmonary fibrosis. While Notch1 and Notch3 have been extensively studied, the involvement of other Notch receptors, especially Notch4, remains less explored. This study aimed to evaluate the impact of Notch4 on lung fibroblast activation and its potential interaction with the transforming growth factor-beta 1 (TGFβ1) signaling.

Primary human lung fibroblasts were transduced with lentivirus containing the intracellular domain of NOTCH4 (N4ICD). Changes in gene expression in transduced cells were assessed using real-time polymerase chain reaction, immunofluorescence staining, and Western blotting. Transcriptomic analysis was also performed on N4ICD-transduced lung fibroblasts.

N4ICD overexpression significantly upregulated key fibrotic markers such as ACTA2 and COL1A1. It also induced the TGFβ1 pathway, as evidenced by SMAD2 phosphorylation and elevated TGFβ1 mRNA level. Transcriptomic analysis revealed that N4ICD-induced cells exhibited characteristics of highly invasive myofibroblasts.

This study establishes Notch4 as a novel contributor to pulmonary fibrosis, by demonstrating its ability to induce myofibroblast differentiation and interact with the TGFβ1 pathway.

Full article
Original Article Open Access
Peripheral Blood CD4+/CD8+ T Cell Ratio Predicts HBsAg Clearance in Inactive HBsAg Carriers Treated with Peginterferon Alpha
Fengping Wu, Chenrui Liu, Ling He, Yikai Wang, Xin Zhang, Miaoxian Li, Rui Lu, Pei Kang, Mei Li, Yaping Li, Xiaoli Jia, Shuangsuo Dang
Published online December 6, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00240
Abstract
T lymphocytes play a pivotal role in resolving hepatitis B virus infection. This study aimed to investigate the dynamics of peripheral blood T lymphocyte subsets during peginterferon [...] Read more.

T lymphocytes play a pivotal role in resolving hepatitis B virus infection. This study aimed to investigate the dynamics of peripheral blood T lymphocyte subsets during peginterferon alpha (peg-IFN-α) therapy and their association with hepatitis B surface antigen (HBsAg) clearance in inactive HBsAg carriers (IHCs).

This prospective observational study enrolled 197 IHCs treated with peg-IFNα-2a/2b for 48 weeks and followed for 24 weeks (treatment group), and 221 IHCs who were regularly monitored for 72 weeks without treatment (IHC control group). Peripheral blood T lymphocyte subsets were evaluated using flow cytometry at baseline, and at 12, 24, 48, and 72 weeks in both groups. At 72 weeks, IHCs in the treatment group were categorized into an HBsAg clearance group and an HBsAg persistence group. Differences in T lymphocyte subsets among these groups were compared, and correlations between T lymphocyte subsets and HBsAg clearance were analyzed.

At 72 weeks, intention-to-treat analysis showed significantly higher HBsAg clearance (46.7%) and seroconversion rates (34.5%) in the treatment group compared to the IHC control group (HBsAg clearance rate of 1.4%, seroconversion rate of 0.9%; both p < 0.001). The median absolute counts of CD3+, CD4+, and CD8+ cells significantly decreased at 12, 24, and 48 weeks in both the HBsAg clearance and persistence groups, returning to baseline at 72 weeks (all p < 0.001). IHCs with HBsAg clearance had higher median percentages of CD3+ CD8+ cells and lower median percentages of CD3+ CD4+ cells and CD4+/CD8+ ratios at 12, 24, and 48 weeks compared to the HBsAg persistence and IHC control groups (all p < 0.001). Baseline HBsAg levels (below 2.0 log10 IU/mL) and hepatitis B virus DNA levels (below 20 IU/mL), alanine aminotransferase elevation at 12 weeks (greater than 2×upper limit of normal), and CD4+/CD8+ ratios (less than 1.5 at 12 weeks and below 1.4 at 24 weeks) were predictive of HBsAg clearance.

Peripheral blood CD4+/CD8+ ratios at 12 and 24 weeks may serve as predictive markers for HBsAg clearance in IHCs treated with peg-IFN-α.

Full article
Original Article Open Access
SOX9 Overexpression Ameliorates Metabolic Dysfunction-associated Steatohepatitis Through Activation of the AMPK Pathway
Juan Deng, Kai Ding, Shuqing Liu, Fei Chen, Ru Huang, Bonan Xu, Xin Zhang, Weifen Xie
Published online December 20, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00197
Abstract
The transcription factor sex-determining region Y-related high-mobility group-box gene 9 (SOX9) plays a critical role in organ development. Although SOX9 has been implicated in [...] Read more.

The transcription factor sex-determining region Y-related high-mobility group-box gene 9 (SOX9) plays a critical role in organ development. Although SOX9 has been implicated in regulating lipid metabolism in vitro, its specific role in metabolic dysfunction-associated steatohepatitis (MASH) remains poorly understood. This study aimed to investigate the role of SOX9 in MASH pathogenesis and explored the underlying mechanisms.

MASH models were established using mice fed either a methionine- and choline-deficient (MCD) diet or a high-fat, high-fructose diet. To evaluate the effects of SOX9, hepatocyte-specific SOX9 deletion or overexpression was performed. Lipidomic analyses were conducted to assess how SOX9 influences hepatic lipid metabolism. RNA sequencing was employed to identify pathways modulated by SOX9 during MASH progression. To elucidate the mechanism further, HepG2 cells were treated with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor to test whether SOX9 acts via AMPK activation.

SOX9 expression was significantly elevated in hepatocytes of MASH mice. Hepatocyte-specific SOX9 deletion exacerbated MCD-induced MASH, whereas overexpression of SOX9 mitigated high-fat, high-fructose-induced MASH. Lipidomic and RNA sequencing analyses revealed that SOX9 suppresses the expression of genes associated with lipid metabolism, inflammation, and fibrosis in MCD-fed mice. Furthermore, SOX9 deletion inhibited AMPK pathway activation, while SOX9 overexpression enhanced it. Notably, administration of an AMPK inhibitor negated the protective effects of SOX9 overexpression, leading to increased lipid accumulation in HepG2 cells.

Our findings demonstrate that SOX9 overexpression alleviates hepatic lipid accumulation in MASH by activating the AMPK pathway. These results highlight SOX9 as a promising therapeutic target for treating MASH.

Full article
Original Article Open Access
Sociodemographic Factors Associated with Depression among People Living with Human Immunodeficiency Virus on Antiretroviral Therapy at a University Teaching Hospital in a Nigerian Cosmopolitan City
Jeremiah Onubi, Oluwagbenga Adebayo Adeola, Patricia Eseigbe, Adesegun Elisha, Grace O Sheyin, Anyuku A George Chima
Published online September 6, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00018
Abstract
Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus [...] Read more.

Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus (PLHIV), especially in low-and middle-income countries. This study was designed to investigate the sociodemographic factors associated with depression among PLHIV on antiretroviral therapy in a Nigerian cosmopolitan city.

A hospital-based, cross-sectional study was conducted among 592 consenting, randomly selected adult PLHIV receiving treatment at a university teaching hospital in Jos, Nigeria, in 2022, using the PHQ-9 questionnaire and an interviewer-administered sociodemographic questionnaire. Associated variables in univariate analysis were used in multivariable binary logistic regression to obtain adjusted odds ratios (AOR) with a significance level set at α = 0.05.

Depression was found to be highly prevalent among study participants, with 44.9% of them affected. Findings revealed that being male [AOR = 0.62; 95% confidence interval (CI): 0.42–0.92], being employed (AOR = 0.55; 95%CI: 0.31–0.97), and earning a monthly income of ₦50,000–100,000 ($65–130) (AOR = 0.49; 95% CI: 0.27–0.91) and >₦100,000–200,000(>$130–260) (AOR = 0.33; 95% CI: 0.13–0.77) were significantly associated with reduced odds of depression.

The significant association of being male, having formal employment, and earning a moderate monthly income with reduced odds of depression may have implications for policy and strategies for managing mental health issues among PLHIV in cosmopolitan areas like Jos, which face peculiar challenges such as cultural tensions, traffic congestion, and gentrification. PLHIV categories with a relatively higher likelihood of depression may benefit from targeted mental health support systems, in addition to other mental health management strategies generally available to PLHIV.

Full article
Case Report Open Access
Achalasia and Esophageal Cancer: A Case Report and Literature Review
Weiguang Qiao, Qiling Liang, Fachao Zhi
Published online November 12, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00005S
Abstract
Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and the absence of normal esophageal peristalsis. This [...] Read more.

Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and the absence of normal esophageal peristalsis. This condition leads to difficulties in swallowing (dysphagia), regurgitation of food, and chest pain. Clinical observations suggest an association between achalasia and esophageal tumors, as achalasia can increase the risk of developing esophageal cancer. We explore the pathophysiology of achalasia, its clinical manifestations, and the associated risk of esophageal malignancies, supported by recent research and clinical evidence, including specific case studies.

Full article
Original Article Open Access
Patient Portal Utilization Improves Outcomes in Patients with Multiple Myeloma
Elisa Quiroz, Aren Ebrahimi, Alberto Godinez, Leah Puglisi, Samantha Bagsic, Marin Xavier
Published online September 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00015
Abstract
A growing body of literature has demonstrated improved quality of life in cancer patients who utilize web-based patient portals; however, no studies have investigated their impact [...] Read more.

A growing body of literature has demonstrated improved quality of life in cancer patients who utilize web-based patient portals; however, no studies have investigated their impact on objective clinical measures. The study aimed to evaluate the impact of patient portal utilization on clinical outcomes in cancer care. Patient portal platforms provide patients with direct access to their providers through messaging, medication requests, and other tools. There is a knowledge gap in the literature regarding whether electronic patient portals enhance outcomes in cancer care.

This study is a retrospective analysis of 791 patients with multiple myeloma within the Scripps Health system. The effect of MyScripps electronic patient portal use on unplanned hospital visits and mortality was assessed. Outcomes were also evaluated in relation to the age-adjusted Charlson comorbidity index and chemotherapy use.

Results showed that older, male, Hispanic, and Spanish-speaking patients had lower portal utilization. Those with inactive portal status had higher rates of unplanned hospital visits and mortality. Inactive portal status was an independent predictor of unplanned hospital visits in two multivariable logistic regression analyses. A logistic regression model investigating the interaction between patient portal use and age-adjusted Charlson comorbidity index revealed that active portal status remained a predictor of unplanned hospital visits.

This study highlights the potential to improve clinical outcomes among patients with multiple myeloma, particularly in vulnerable communities, by increasing access to electronic patient portals.

Full article
Original Article Open Access
Pentraxin 3 as a Noninvasive Biomarker of Fibrosis and Carotid Intima-media Thickness in Patients with Metabolic Associated Fatty Liver Disease
Alshymaa A. Hassnine, Yasser Fouad, Zienab M. Saad, Alaa M. Mostafa, Hend M. Moness, Nehal I. Abbas, Nasr M. Osman, Wafaa Abdelghany
Published online May 29, 2024
Gene Expression. doi:10.14218/GE.2023.00047
Abstract
Metabolic-associated fatty liver disease (MAFLD) may increase the risk of cardiovascular events. In this study, we assessed the predictive value of pentraxin 3 (PTX3) for severe [...] Read more.

Metabolic-associated fatty liver disease (MAFLD) may increase the risk of cardiovascular events. In this study, we assessed the predictive value of pentraxin 3 (PTX3) for severe fibrosis and carotid intima-media thickness (CIMT) in patients with MAFLD.

188 patients (114 with MAFLD, 74 with dual etiology MAFLD and chronic hepatitis C) were included. All participants underwent clinical history and examination, metabolic parameter assessment, serum level evaluation of PTX3, Fibrosis-4 index and nafld fibrosis score scores, abdominal ultrasound, and CIMT assessment.

The serum PTX3 was significantly elevated in patients with advanced fibrosis compared to those with mild/moderate fibrosis (1.8 vs 1.4, p = 0.006). The PTX3 level was independently associated with advanced fibrosis (odds ratio = 1.26, 95% confidence interval 1.008–1.040). In MAFLD patients, the PTX3 levels in patients with low fibrosis compared to those with advanced fibrosis were 1.4 (1–2.1) and 1.9 (1.3–3.8), respectively (p = 0.027). A significantly greater CIMT was noted in patients with elevated PTX3 levels (3.85 (3.42–4) vs 4.05 (3.7–4.67), p = 0.0001) compared to those with low PTX3 levels.

Serum PTX3 levels can accurately predict advanced fibrosis and CIMT in MAFLD patients. Thus, it could be useful for management and risk stratification.

Full article
Original Article Open Access
Impact of Intermediate-term Oral Contraceptive Use on Oxidative Stress, Lipid Profile, and Liver Function in Iraqi Women: A Comprehensive Biochemical Assessment
Hayder Hatem Sultan, Amir Teimourpour, Ziba Majidi, Fariba Nabatchian
Published online January 25, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00035
Abstract
Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study [...] Read more.

Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study aimed to evaluate the impact of intermediate-term OCP use (Yasmin) on oxidative stress, lipid profile, and liver function, with particular emphasis on antioxidant markers, lipid metabolism, and hepatic enzyme activity, to better understand the potential metabolic and hepatic effects.

A case-control study was conducted in Maysan Governorate, Iraq, involving 150 women (100 OCP users and 50 non-users). Blood samples were collected from Al-Sadr Teaching Hospital and a specialized clinic between February and April 2023. Serum levels of antioxidants, lipids, and liver enzymes were measured using biochemical assays.

OCP users had significantly lower levels of glutathione peroxidase vitamin E and uric acid (p < 0.001) compared to non-users. Lipid profiles showed that OCP users had higher levels of triglyceride and low-density lipoprotein (p < 0.05), whereas total cholesterol was significantly higher in non-users (p < 0.05). Liver enzyme activity, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total serum bilirubin, did not show statistically significant differences (p > 0.05). Longer duration of OCP use was significantly negatively correlated with vitamin E levels (r = −0.67), glutathione peroxidase activity (r = −0.56), uric acid levels (r = −0.45) and high-density lipoprotein (r = −0.54). Positive correlations were found between the duration of OCP use and total cholesterol (r = 0.62), triglyceride (r = 0.58), low-density lipoprotein (r = 0.60), and liver enzymes alanine aminotransferase (r = 0.66) and aspartate aminotransferase (r = 0.64).

Intermediate-term OCP use was associated with changes in oxidative stress and lipid metabolism, potentially increasing cardiovascular and metabolic risks. Regular monitoring of these parameters is recommended for OCP users.

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