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101
Systematic Review Open Access
Samuel Korsah, John Antwi Apenteng, Derick Kontoh, Nathaniel Nene Djangmah Nortey, Prince Baffour Adofo, Mariam Tagoe, Anna Kwarley Quartey
Published online December 30, 2025
Future Integrative Medicine. doi:10.14218/FIM.2025.00019
Abstract
Amoebiasis, or amoebic dysentery, is a gastrointestinal disorder caused by the parasite Entamoeba histolytica. The disease is endemic in parts of Africa, Asia, North and South America, [...] Read more.

Amoebiasis, or amoebic dysentery, is a gastrointestinal disorder caused by the parasite Entamoeba histolytica. The disease is endemic in parts of Africa, Asia, North and South America, leading to several deaths annually. Reported adverse effects associated with the current first-line treatment for amoebiasis, coupled with the evolution of resistance to it, call for the need to search for plant-based alternatives. This study systematically reviews medicinal plants with activity against Entamoeba histolytica.

The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to retrieve scholarly literature. The study reviewed 70 articles from 7 popular databases: Google Scholar, PubMed, ScienceDirect, Booksc.org, Emerald, Scopus, and MEDLINE, highlighting several plants with anti-amoebic properties.

The primary parts of the plant used in the treatment of Entamoeba histolytica were the leaves (61%), followed by rhizomes (13%), roots (8%), seeds (8%), stems (4%), and fruits (4%). The families Asteraceae (18%) and Zingiberaceae (18%) contain most plants that are effective against Entamoeba histolytica. These medicinal plants families are rich in phytochemicals such as terpenoids and flavonoids that have anti-entamoeba histolytica activity. Maceration is the most commonly used extraction method.

The results suggest that plants are a promising source of new agents to combat amoebiasis caused by Entamoeba histolytica. The most frequently used plant parts were leaves (61%), and the maceration method was the most common extraction technique due to its simplicity and cost-effectiveness. The majority of studies were limited to in vitro models, with only one plant (Adenophyllum aurantium) tested in vivo. Further research is needed to establish their mechanisms of action, toxicities, and clinical potential.

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102
Corrigendum Open Access
Qingqing Liu, Guangchu Pan, Peizhong Liu, Aimeng Zhang, Kaili Wang, Rongyuan Yang, Qing Liu
Published online December 26, 2025
Future Integrative Medicine. doi:10.14218/FIM.2023.00034C
103
Expression of Concern Open Access
Published online December 26, 2025
Future Integrative Medicine. doi:10.14218/FIM.2023.00034E
104
Consensus Open Access
Sujun Zheng, Xiaoyuan Xu, Yuemin Nan, Wei Hou, Jie Bai, Shan Tang, Chen Liang, Lei Luo, Jianshe Wang, Xinhua Li, Min Zhang, Guohong Deng, Hui Liu, Yongfeng Yang, Wen Xie, Xiaojuan Ou, Xinxin Zhang, Lai Wei, Jidong Jia, Zhongping Duan, Inherited Metabolic Liver Disease Collaboration Group, Chinese Society of Hepatology, Chinese Medical Association
Published online December 26, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00440
Abstract
To support clinicians in making informed decisions regarding the diagnosis and management of inherited hyperbilirubinemia, including Gilbert syndrome, Crigler-Najjar syndrome, Dubin-Johnson [...] Read more.

To support clinicians in making informed decisions regarding the diagnosis and management of inherited hyperbilirubinemia, including Gilbert syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, and Rotor syndrome, the Inherited and Metabolic Liver Disease Collaboration Group of the Hepatology Branch of the Chinese Medical Association convened a panel of Chinese experts in this field. This multidisciplinary consortium developed the present expert consensus by integrating the latest advances in both clinical practice and basic research.

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105
Research Letter Open Access
Huiting Wei, Jiangtao Liang, Huijuan Shi, Anjia Han
Published online December 26, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00044
106
Original Article Open Access
Ying Zhang, Long-Fei Wang, Jing Chen, Mindie H. Nguyen, Qi Zheng
Published online December 26, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00443
Abstract
The rate of functional cure (HBsAg loss) remains unsatisfactory following pegylated interferon (PEG-IFN) treatment in chronic hepatitis B. To optimize PEG-IFN administration, this [...] Read more.

The rate of functional cure (HBsAg loss) remains unsatisfactory following pegylated interferon (PEG-IFN) treatment in chronic hepatitis B. To optimize PEG-IFN administration, this study aimed to evaluate virological markers to predict functional cure and/or hepatitis B e antigen (HBeAg) loss.

Relevant studies assessing virologic markers for predicting functional cure and HBeAg loss after PEG-IFN therapy were systematically retrieved from PubMed, Embase, the Cochrane Library, and Web of Science up to November 2023. Predictive effectiveness was evaluated via the summary receiver operating characteristic curve.

We analyzed 38 studies (6,179 patients). HBsAg decline at week 24 had the greatest discriminative ability according to the area under the receiver operating characteristic curve (AUROC) (0.89) and sensitivity (0.88) for predicting functional cure, whereas baseline HBsAg had a comparable AUROC (0.86) and highest specificity (0.79), with both being significantly better than baseline hepatitis B core-related antigen and hepatitis B virus (HBV) RNA (all P < 0.001). For HBeAg loss or seroconversion, HBV RNA, HBV DNA, HBeAg, and HBeAg decline at week 12, as well as HBV DNA and HBeAg decline at week 24, all exhibited comparable predictive values (AUROC = 0.75–0.78). HBV RNA and HBeAg levels at week 24 showed optimal sensitivity (0.87), and HBeAg decline at week 12 had the highest specificity (0.83).

HBsAg decline at week 24 and baseline HBsAg levels are better predictors of functional cure than novel virologic markers, while on-treatment HBV RNA and HBeAg levels and dynamic changes are the most reliable indicators for HBeAg loss.

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107
Original Article Open Access
Lanyue Huang, Yuzhao Feng, Wei Wang, Wei Liu, Yunhui Liu, Liang Chen, Yuxin Niu, Tingting Liu, Mi Song, Yiwei Xu, Zhongyuan Yang, Guang Chen, Qin Ning, Tao Chen, Lin Zhu
Published online December 26, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00645
Abstract
Infections are frequent and lethal complications of acute-on-chronic liver failure (ACLF). Reliable biomarkers to distinguish fungal from bacterial infections remain limited. Given [...] Read more.

Infections are frequent and lethal complications of acute-on-chronic liver failure (ACLF). Reliable biomarkers to distinguish fungal from bacterial infections remain limited. Given the central role of immune dysfunction in ACLF, we aimed to evaluate the diagnostic value of serum cytokines in differentiating invasive pulmonary aspergillosis (IPA) from bacterial pneumonia (BP) in HBV-associated ACLF.

This retrospective case-control study enrolled ACLF patients admitted to the Tongji Hospital, between 2018 and 2022. Patients were categorized into IPA, BP, and non-infection groups. The BP and non-infection groups were propensity score-matched to the IPA cases. Serum cytokines levels (IL-1β, sIL-2R, IL-6, IL-8, IL-10, TNF-α) and clinical data were collected, with the diagnostic performance of these cytokines as biomarkers assessed via ROC curves.

A total of 32 IPA, 96 BP, and 96 non-infection patients were enrolled, with balanced baseline characteristics. Compared with the non-infection group, the IPA group had higher sIL-2R (1,606.00 vs. 1,211.50 U/mL, P = 0.019) and IL-6 (69.03 vs. 15.98 pg/mL, P < 0.001) levels, but lower IL-8 levels (62.20 vs. 132.00 pg/mL, P = 0.025). The BP group showed elevated sIL-2R (1,792.00 U/mL), IL-6 (49.42 pg/mL), IL-10 (13.40 pg/mL) levels compared to the non-infection group (all P < 0.001). Also, IL-8 was lower in the IPA group than in the BP group (62.20 vs. 176.00 pg/mL, P < 0.001) and its assessment could best distinguish IPA from BP (AUC = 0.743, cut-off = 76.60 pg/mL; sensitivity = 66.7%, specificity = 82.1%).

Serum IL-8 exhibited superior diagnostic value for IPA in patients with HBV-ACLF and could effectively discriminate Aspergillus infections from bacterial infections.

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108
Systematic Review Open Access
Jing Qiao, Junyan Gao, Xinxin Huang, Lun Gu, Yihang Song, Tongchang Wang, Zhaoshen Li, Zixuan He, Shuling Wang, Yu Bai
Published online December 25, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00021
Abstract
Terminal ileum intubation is considered the completion step of colonoscopy and is usually performed to assess the ileum. The histological examination of the ileal mucosa, which [...] Read more.

Terminal ileum intubation is considered the completion step of colonoscopy and is usually performed to assess the ileum. The histological examination of the ileal mucosa, which is acquired during terminal ileum intubation, may allow an accurate diagnosis. However, there is no absolute consensus on when ileoscopy and biopsy should be attempted. As a result, we aimed to evaluate whether terminal ileum intubation and biopsy should be performed routinely.

Systematic searches were performed in the PubMed, EMBASE, and Cochrane Library databases, as well as the Science Citation Index via the Web of Science platform. Reference lists from the identified papers were manually searched. Systematic searches were performed from January 1, 1971, to October 1, 2025. Studies reporting on terminal ileum intubation and biopsy during colonoscopy were included. Case reports, letters, reviews, and animal studies were excluded. The primary outcomes were the diagnostic yield of terminal ileum intubation and the rate of necessitating a change in management. Data were extracted independently by three reviewers.

Thirty-six studies were included. The subtotal diagnostic yield and the rate of necessary change among the selected patients were much greater than those among the unselected patients (5.1% versus 2.5% and 1.5% versus 0.4%, respectively). In addition, the diagnostic yield was found more frequently for inflammatory bowel disease, anemia, abdominal pain, and chronic diarrhea than for the other indications (26.7%, 16.1%, 14.9%, 12.4%, and 3.2%, respectively). The yield of ileal histopathology with a normal endoscopic appearance was low in both unselected and selected patients (3.5% and 2.4%, respectively).

Terminal ileum intubation is recommended as gold standard for completing colonoscopy. Biopsy should be considered in patients with abnormal endoscopic findings or specific high-risk symptoms.

Full article
109
Reviewer Acknowledgement Open Access
Editorial Office of Journal of Exploratory Research in Pharmacology
Published online December 25, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.000RA
110
Review Article Open Access
Victor Pikov
Published online December 25, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2025.00048
Abstract
Dysphagia, a severe comorbidity of many neurological diseases, often lacks targeted therapies. Electrical stimulation of cranial nerves represents a novel therapeutic class. This [...] Read more.

Dysphagia, a severe comorbidity of many neurological diseases, often lacks targeted therapies. Electrical stimulation of cranial nerves represents a novel therapeutic class. This critical review assessed the clinical effectiveness and safety of various approaches for electrical stimulation of the cranial nerves for treating dysphagia, categorized as implantable (directly targeting the nerve), minimally invasive (pharyngeal electrical stimulation), and non-invasive (transcutaneous). A critical literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed database was comprehensively searched, and studies were rigorously assessed for inclusion and exclusion criteria. The Newcastle–Ottawa Scale was used to assess the risk of bias. The analysis included 15 clinical studies: four assessing vagus nerve stimulation (including implantable and transcutaneous approaches) and eleven assessing pharyngeal electrical stimulation. Most evaluated studies, particularly for pharyngeal electrical stimulation and transcutaneous vagus nerve stimulation, demonstrated significant beneficial effects on validated dysphagia outcome measures. Importantly, no long-term severe adverse effects were reported across the evaluated stimulation approaches. Cumulative evidence indicates that vagus nerve stimulation and pharyngeal electrical stimulation approaches can effectively alleviate dysphagia symptoms. The different stimulation approaches appear to be complementary, with distinct profiles rendering them suitable for different therapeutic contexts (e.g., short-term hospital-based vs. long-term at-home treatment). Consequently, they represent distinct and valuable options for individualized dysphagia therapy.

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111
Review Article Open Access
Si-Qi Zhang, Bao-Ping Luo, Ya-Na Zhou, Yong Zhou, Kai-Wen Hu
Published online December 25, 2025
Gastroenterology & Hepatology Research. doi:10.14218/GHR.2025.00005
Abstract
Unlike the traditional staging treatment of tumors, the core of “Green Tumor Treatment” is to divide the treatment of tumors into three stages: Hegemony (directly targeting the [...] Read more.

Unlike the traditional staging treatment of tumors, the core of “Green Tumor Treatment” is to divide the treatment of tumors into three stages: Hegemony (directly targeting the cancer focus), Kingship (supporting the body’s vital energy and eliminating pathogenic factors), and Imperialism (improving the internal environment), based on the urgency of the tumor and the patient’s physical condition. This approach guides the clinical treatment of tumors. Its treatment system incorporates all minimally invasive and low-damage treatment methods, combining internal and external treatments, traditional Chinese medicine and Western medicine, as well as local and systemic treatments. It aims to maximize treatment outcomes while ensuring the patient’s quality of life, which is highly consistent with the treatment goals for primary liver cancer. This review aims to explore the integrated Traditional Chinese and Western medicine treatment model for primary liver cancer under the guidance of the Green Tumor Treatment concept.

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112
Original Article Open Access
Jiaming Fu, Zijing Wang, Yanli Li, Yinhui Deng, Junyi Fu, Jinxiu Yu
Published online December 25, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00034
Abstract
Acromegaly requires multimodal management. While surgery is first-line, many patients have persistent/recurrent disease. Gamma knife radiosurgery (GKRS) offers precise radiation, [...] Read more.

Acromegaly requires multimodal management. While surgery is first-line, many patients have persistent/recurrent disease. Gamma knife radiosurgery (GKRS) offers precise radiation, but data on its use as initial therapy remain limited. This study aimed to review the outcomes and report on our experience in treating patients with acromegaly using initial GKRS.

We retrospectively identified 33 patients with acromegaly who underwent GKRS from 1993 until 2016 at the Department of Radiotherapy, the Second Affiliated Hospital of Guangzhou Medical University. These patients had complete endocrine, radiological, and imaging data before and after GKRS. Furthermore, univariate and multivariate analysis was utilized to analyze the potential prognostic factors of endocrine remission and new-onset hypopituitarism.

Thirty-three patients were enrolled in the study. Fifteen patients (45.5%) were males and 18 (54.5%) were females. The median age was 44.0 years (range, 24.9–66.2 years). During a median follow-up of 65.6 months (range, 12.9–297.6), the median margin dose for GKRS was 15.0 Gy (range, 10.8–20.3 Gy). Endocrine remission was achieved in nine of the 33 patients (27.3%) over a mean follow-up of 85.1 months (range, 12.9–161.3). No prognostic factors demonstrated a significant association with endocrine remission. New-onset hypopituitarism occurred in eight patients (24.2%) after GKRS. The tumor control rate was 100%. Only one patient developed worsening visual dysfunction. No new cranial neuropathy was noted.

Initial GKRS for acromegaly provided effective tumor control and partial endocrine remission with a favorable safety profile, notably a low rate of new-onset hypopituitarism, representing a viable treatment option.

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113
Original Article Open Access
Swati Bhardwaj, Shenyu Wang, Yuxin Liu
Published online December 19, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00013
Abstract
Endometrial polyp (EMP) is one of the most common diagnoses in the evaluation of women with abnormal uterine bleeding. Understanding the malignancy risk associated with EMPs and [...] Read more.

Endometrial polyp (EMP) is one of the most common diagnoses in the evaluation of women with abnormal uterine bleeding. Understanding the malignancy risk associated with EMPs and related risk factors is essential for guiding both pathology practice and clinical management. This study aimed to explore risk factors for malignancy in EMPs.

The pathology database was searched for women diagnosed with EMP between 2021 and 2022. Patient age, polyp size, background endometrium, recurrence, and (if applicable) cancer types were recorded. Immunohistochemistry (IHC) for p53 and p16 was performed on selected cases. Risk factors for malignancy were analyzed using Chi-square and analysis of variance tests.

Among the 740 EMP cases analyzed, 94% were benign, 2% were premalignant, and 4% were malignant. The median patient age was 54 years (range: 19–92). Minimal serous carcinoma (n = 14, 2%) was the most prevalent cancer. Among the 52 cases with p53 IHC, 38 were diagnosed as benign, supported by a wild-type p53 pattern, while 14 were diagnosed as serous carcinoma, supported by a mutant p53 pattern. Malignant polyps were found to be significantly associated with advanced age and malignant background endometrium (p < 0.001). Large size and recurrence were not identified as significant risk factors.

EMPs carry a low risk of malignancy, which is not significantly influenced by the polyp’s size or its recurrence. Our findings highlight the significantly elevated risk of malignancy in elderly patients and the importance of p53 IHC in improving diagnostic accuracy.

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114
Review Article Open Access
Marwan Al-Raeei
Published online December 19, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00034
Abstract
Artificial intelligence (AI) is transforming the diagnosis, treatment, monitoring, and research of soft tissue disorders, which include muscles, tendons, ligaments, fascia, nerves, [...] Read more.

Artificial intelligence (AI) is transforming the diagnosis, treatment, monitoring, and research of soft tissue disorders, which include muscles, tendons, ligaments, fascia, nerves, and blood vessels. Traditional diagnostic methods often rely on imaging, histopathology, and clinical evaluation, which can be time-consuming and prone to human error. This review aims to explore the impact of AI on enhancing soft tissue care. The review examines the application of deep learning algorithms in medical imaging, pathology, predictive analytics, and treatment planning. It also evaluates AI’s role in monitoring and rehabilitation, as well as its contributions to research in soft tissue disorders. AI significantly improves the accuracy of medical imaging analysis, facilitating the detection of abnormalities such as tumors and tears. AI-powered pathology tools automate slide analysis, enhancing diagnostic consistency and efficiency. Predictive analytics enable early risk assessment and personalized patient management. In surgical contexts, AI supports preoperative simulations and robotic-assisted procedures, leading to improved outcomes. Additionally, AI enhances patient monitoring through wearable devices and telemedicine. The integration of AI into soft tissue diagnostics and therapeutics presents transformative potential for personalized and efficient healthcare. However, challenges related to data security, algorithm bias, interpretability, and ethical considerations must be addressed. Overall, AI holds promise for improving patient outcomes and advancing medical science in the field of soft tissue disorders.

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115
Original Article Open Access
Xiaoliang Jin, Jing Zhao, Yuenian Chen, Li Xu, Ming Cheng, Ting Ye, Haifeng Jin, Liang Huang, Yue Hu, Haibiao Bao, Bin Lyu
Published online December 19, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00025
Abstract
Accumulating evidence indicates that fecal syndecan-2 (SDC2) methylation is a promising biomarker for early detection of colorectal cancer. This study aimed to investigate the diagnostic [...] Read more.

Accumulating evidence indicates that fecal syndecan-2 (SDC2) methylation is a promising biomarker for early detection of colorectal cancer. This study aimed to investigate the diagnostic efficacy of fecal SDC2 methylation testing for adenomas and evaluate the risk stratification efficacy of the Asia-Pacific Colorectal Screening Scoring (APCS) combined with SDC2 methylation status.

This was a prospective, multicenter diagnostic study. Adult participants with no history of colonoscopy within the past three years were enrolled. Demographic data were collected, and APCS scores were evaluated. All participants underwent fecal SDC2 methylation testing and colonoscopy. Colonoscopy outcomes and pathological results of any polyps served as reference standards. The fecal SDC2 methylation test and reference standard assessments were conducted in a blinded manner. The APCS-SDC2 scoring system was developed by integrating fecal SDC2 methylation results with APCS scores, and its efficacy was assessed.

In total, 985 participants were enrolled, among whom 62 (6.3%) tested positive for fecal SDC2 methylation. The sensitivity and specificity of fecal SDC2 methylation in detecting advanced adenomas were 31.3% (95% confidence interval (CI): 21.6–42.7%) and 96.1% (95% CI: 94.6–97.2%), respectively. The APCS-SDC2 scoring system demonstrated superior discriminatory performance for advanced adenomas (area under the curve: 0.7032; 95% CI: 0.5869–0.8195). For advanced adenoma screening, the specificity of the APCS-SDC2 score was higher than that of the APCS score (86.7% vs. 66.7%; P < 0.001).

A positive fecal SDC2 methylation test indicated a higher risk of advanced adenoma, and colonoscopy should be prioritized. The APCS-SDC2 scoring system demonstrated superior risk stratification performance for advanced adenomas.

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116
Review Article Open Access
Danzhu Zhao, George Y. Wu
Published online December 18, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00476
Abstract
ATP-binding cassette (ABC) transporters are transmembrane proteins involved in the translocation of bilirubin, bile acids, phospholipids, and cholesterol into bile canaliculi. Mutations [...] Read more.

ATP-binding cassette (ABC) transporters are transmembrane proteins involved in the translocation of bilirubin, bile acids, phospholipids, and cholesterol into bile canaliculi. Mutations in particular genes encoding these transporters—including BSEP (ABCB11 gene), MDR3 (ABCB4 gene), sterolin-1 and sterolin-2 (ABCG5/8 genes), and MRP2 (ABCC2 gene)—result in a wide spectrum of liver diseases, ranging from benign conditions such as Dubin-Johnson syndrome to more severe presentations like progressive familial intrahepatic cholestasis. The severity of disease is influenced by many factors, including zygosity, mutation type, and environmental modifiers such as hormones, consanguinity, and founder effects. Homozygous and compound heterozygous mutations typically result in severe and early-onset diseases, while heterozygous single-allelic mutants generally result in milder diseases. Next-generation genetic testing has proven to have high diagnostic value and is important for prognostication. With knowledge of the underlying specific mutations, there is also potential for future targeted therapy for many severe diseases. The aim of this review is to update and discuss the hepatic diseases associated with ABC transporter mutations, the genetic and environmental effects that influence the severity of disease, typical presentations of these cholestatic hepatic diseases, diagnostic considerations, and treatment options.

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117
Research Letter Open Access
Jinyan Chen, Ruijie Zhao, Chiyu He, Huigang Li, Yajie You, Zuyuan Lin, Ze Xiang, Jianyong Zhuo, Wei Shen, Zhihang Hu, Shusen Zheng, Xiao Xu, Di Lu
Published online December 18, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00238
118
Reviewer Acknowledgement Open Access
Editorial Office of Journal of Clinical and Translational Hepatology
Published online December 18, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.000RA
119
Editorial Open Access
Can-Lin Hong, Zong-Chao Liu, Wen-Qing Li
Published online December 18, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2025.00027
120
Review Article Open Access
Bani Bandana Ganguly, Nitin N. Kadam
Published online December 18, 2025
Gene Expression. doi:10.14218/GE.2025.00051
Abstract
Full or partial trisomy of human chromosome 21 results in dysregulation of gene expression, leading to the manifestation of specific phenotypes described in individuals with Down [...] Read more.

Full or partial trisomy of human chromosome 21 results in dysregulation of gene expression, leading to the manifestation of specific phenotypes described in individuals with Down syndrome (DS). Defects in brain development, coupled with impairment in neurogenesis, are ultimately expressed as cognitive deficiency, Alzheimer disease (AD), and dementia. Amid the triplication of all human chromosome 21 (HSA21) genes, dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A)-mediated neurogenesis and dendritic development have been attributed to the learning and memory deficits and cognitive impairment in the DS population. Upregulated DYRK1A perturbs the development and function of the brain, collectively affecting neurogenesis, synaptogenesis, synaptic transmission, and cell signaling pathways, which might disproportionately produce inhibitory neurotransmission and contribute to the cognitive phenotype. However, the lack of distinct gene-phenotype associations acts as a potential barrier to therapeutic improvement of cognitive performance and amelioration of AD-related neurodegeneration. The present review aims to summarize the neurogenetic consequences of triplicated DYRK1A in the DS population in relation to sexual dimorphism and expression of the Apolipoprotein Eε4 (APOE ε4) genotype. Notably, normalization of trisomic DYRK1A demonstrated improved synaptic plasticity, glutamatergic/GABAergic (excitatory/inhibitory) balance, and learning and memory in DS mouse models. Therapeutic approaches using inhibitors of DYRK1A, including catechins present in green tea extract and several other natural and synthetic agents, produced variable outcomes in cognitive improvement, depending on age and dose of administration. Mitigation of impairment in neurogenetic differentiation and cognitive performance might help control AD-related dementia and enhance quality of life. This review highlights the consequences of upregulated DYRK1A kinase on impairment of neurogenesis and cognitive deficits, and the therapeutic challenges associated with DYRK1A inhibitors for ameliorating dysregulated gene expression in DS models and human DS.

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