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Review Article Open Access
The Role of the Brain-lymphatic Axis in Traumatic Brain Injury-associated Cognitive Impairment: From Glymphatic System Clearance Dysfunction to Peripheral Lymphatic Stasis
Shiqin Dong, Xiaoyu Li, Yayu Zhuo, Kai Tang, Jianliang Wu, Chenrui Zhang, Junbo Qin, Jianping Sun
Published online December 10, 2025
Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00025
Abstract
Traumatic brain injury (TBI)-associated cognitive impairment is highly prevalent, severely impacting patients’ daily life and social functioning, with its mechanisms incompletely [...] Read more.

Traumatic brain injury (TBI)-associated cognitive impairment is highly prevalent, severely impacting patients’ daily life and social functioning, with its mechanisms incompletely understood. Globally, TBI affects over 69 million people annually, and post-TBI cognitive impairment may last for years, or even a lifetime, imposing heavy burdens on patients’ families. The brain-lymphatic axis (glymphatic + peripheral lymphatic systems, especially meningeal vessels) has gained attention: glymphatic dysfunction (dependent on astrocyte endfeet Aquaporin-4 polarization, key for clearing β-amyloid and other wastes) causes metabolic waste accumulation and neuroinflammation, while peripheral lymphatic stasis worsens cognitive decline. This review aims to summarize their roles, dissect mechanisms, and outline therapies. The review found that most current studies explore the glymphatic system and the peripheral lymphatic system in isolation, lacking understanding of their dynamic interplay (e.g., bidirectional inflammatory factor transmission, immune cell migration, synergistic dysfunction); longitudinal studies that track axis changes across TBI stages (acute, subacute, chronic) are scarce; diagnostic tools are insufficient (non-invasive biomarkers lack large-scale clinical validation, and imaging has limited clinical use); and existing therapeutic strategies mostly target single subsystems, with few combined interventions for the whole axis. In conclusion, this review highlights critical gaps in current knowledge and proposes integrated, axis-targeted approaches as a promising direction for future research and therapeutic development.

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Original Article Open Access
Polyherbal Dietary Supplement MD-1 Ameliorates Severity of Type 2 Diabetes Mellitus in High-fat Diet-fed C57BL/6J Mice by Attenuating Adipose Tissue Inflammation
Telapolu Srivani, Mangathayaru Kalachaveedu, Sugin Lal Jabaris, Cordelia John
Published online June 28, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00013
Abstract
MD-1 is a time-tested polyherbal diabetes supplement in Tamil Nadu, India. It is composed of dried powdered herbs: Phyllanthus amarus Schum. & Thonn, Tinospora cordifolia (Willd.) [...] Read more.

MD-1 is a time-tested polyherbal diabetes supplement in Tamil Nadu, India. It is composed of dried powdered herbs: Phyllanthus amarus Schum. & Thonn, Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms, Emblica officinalis Gaertn., Eugenia jambolana Lam., Gymnema sylvestre R. Br. Ex, and Cassia auriculata Linn. This study aimed to investigate the in vivo effects of MD-1 in high-fat diet (HFD)-induced diabetes mellitus in C57BL/6J mice.

After 10 weeks of HFD induction, diabetic mice (n = 60) were randomized to 21-day treatments with MD-1, metformin, or left untreated on a standard pellet diet. Fasting blood glucose, triacylglycerol (TAG), total cholesterol, and liver tissue markers including superoxide dismutase, glutathione peroxidase, glutathione, thiobarbituric acid reactive substance, glucokinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase expressions were measured. Adipose tissue tumor necrosis factor (TNF)-α infiltration and messenger RNA expression of peroxisome proliferator-activated receptor γ (PPAR-γ) and glucose transporter type 4 (Glut4) were also analyzed.

MD-1 treatment significantly reduced elevated fasting blood glucose, TAG, and total cholesterol in HFD-fed mice and countered HFD-induced weight gain despite unchanged caloric intake. Improved adipose tissue function was evidenced by reduced TNF-α infiltration and increased messenger RNA expression of PPAR-γ and Glut4. MD-1 attenuated HFD-induced fatty liver disease by reducing oxidative stress and TAG accumulation, suggesting a possible two-hit mechanism.

MD-1 administration primarily targets adipose tissue TNF-α signaling in HFD mice, restoring function via PPAR-γ/Glut4 expression. These findings support its glycemic intervention potential and justify its supplementation in diabetes.

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Original Article Open Access
Serum-derived hsa_circ_101555 as a Diagnostic Biomarker in Non-hepatocellular Carcinoma Chronic Liver Disease: A Phase II Cross-sectional Study
Nourhan Badwei, Amal Tohamy Abdel Moez, Nashwa El-Khazragy, Mohammed Soliman Gado
Published online September 5, 2025
Gene Expression. doi:10.14218/GE.2025.00040
Abstract
Circular RNAs (circRNAs) are non-coding RNAs characterized by a strictly closed-loop covalent structure. They are abundantly detected in various cells due to their conserved nature. [...] Read more.

Circular RNAs (circRNAs) are non-coding RNAs characterized by a strictly closed-loop covalent structure. They are abundantly detected in various cells due to their conserved nature. Studies have reported their potential association with chronic liver disease (CLD), including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), with possible roles as diagnostic and prognostic markers. This study aimed to analyze the potential use of serum-derived hsa_circ_101555 as a diagnostic tool for CLD without HCC, and to compare it with other known non-invasive parameters for liver disease severity and inflammation. Additionally, it aimed to evaluate its expression among non-HCC CLD patients, CLD with HCC cases reported in our published (phase I) study, and healthy controls.

A cross-sectional study (phase II) was conducted involving 30 clinically, laboratory, and radiologically diagnosed Egyptian non-HCC CLD patients and 30 healthy subjects. The serum expression level of hsa_circ_101555 was measured using real-time polymerase chain reaction. The diagnostic accuracy was assessed through receiver operating characteristic curve analysis, calculating the area under the curve to determine sensitivity and specificity. The study also compared hsa_circ_101555 levels with established non-invasive parameters such as the Child-Turcotte-Pugh and model for end-stage liver disease scores, as well as inflammatory markers like the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

hsa_circ_101555 demonstrated high diagnostic accuracy (area under the curve of 0.970) at a cutoff point of 2.088 for differentiating non-HCC CLD patients from healthy controls. Elevated circRNA levels were noted in patients with hepatic encephalopathy and ascites, correlating with advanced liver disease scores (Child-Turcotte-Pugh/model for end-stage liver disease scores). Mean circRNA values were highest in HCC cases, followed by non-HCC CLD patients, and lowest in healthy controls.

Serum-derived hsa_circ_101555 demonstrates high diagnostic accuracy in differentiating non-HCC CLD patients from healthy controls. These findings suggest that hsa_circ_101555 has the potential to serve as a reliable non-invasive biomarker for the early diagnosis of CLD, correlating with disease severity and inflammation markers. Further research with larger sample sizes is warranted to validate its clinical utility and enhance the management of CLD.

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Original Article Open Access
Protective effects of Sclerocarya birrea in vivo
Renaud Nonmarmbaye, Alcherif Hamid Mahamat, Sidiki Neteydji, Fadoul Mahamat Fadoul, Touo’yem Nkemmo Willy Stéphane, Elisabeth Ngo Bum
Published online September 1, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00039
Abstract
Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae) is a plant widely used by traditional healers in several African countries to treat numerous illnesses such as Alzheimer’s disease, [...] Read more.

Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae) is a plant widely used by traditional healers in several African countries to treat numerous illnesses such as Alzheimer’s disease, schizophrenia, inflammation, infections, arterial hypertension, headaches, and others. This study aimed to determine the therapeutic efficacy of Sclerocarya birrea (S. birrea) against glutamate-induced neurotoxicity.

Thirty naïve white mice (Mus musculus Swiss, Muridae), of both genders and weighing between 18 and 25 g, were used in the experiments. Different doses (102.5, 205, and 410 mg/kg) of the extract and vitamin C (100 mg/kg) were administered to the animals one hour before administration of monosodium glutamate (4 mg/kg) for 15 consecutive days. T-maze and Y-maze tests were conducted over three days to assess the animals’ behavioral performance. After behavioral testing, the animals were sacrificed and their brains removed for analysis of oxidative stress parameters.

S. birrea extract reversed glutamate-induced behavioral alterations by significantly (P < 0.001) reducing the latency to reach the platform in the T-maze and significantly increasing the percentage of spontaneous alternation in the Y-maze. The extract also significantly counteracted (P < 0.001) glutamate-induced oxidative stress parameters. The 102.5 and 205 mg/kg doses of the extract significantly (P < 0.001) reduced catalase and reduced glutathione levels, as well as the increase in malondialdehyde levels induced by glutamate.

S. birrea root bark extract exhibits neuroprotective properties that facilitate memory and ameliorate glutamate-induced cognitive deficits in white mice. The results provide partial justification for the traditional medicinal use of S. birrea extract.

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Guideline Open Access
Chinese Guidelines for Clinical Diagnosis, Treatment, and Management of Cirrhosis (2025)
Xiaoyuan Xu, Huiguo Ding, Hong You, Yujuan Guan, Jinghang Xu, Wengang Li, Ying Han, Yaping Wang, Yifan Han, Jidong Jia, Lai Wei, Zhongping Duan, Yuemin Nan, Hui Zhuang, Chinese Society of Hepatology, Chinese Medical Association
Published online January 13, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00517
Abstract
The Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise and rename the 2019 “Chinese Guidelines on the Management of [...] Read more.

The Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise and rename the 2019 “Chinese Guidelines on the Management of Liver Cirrhosis” to “Chinese Guidelines for Clinical Diagnosis, Treatment, and Management of Cirrhosis (2025)”. These updated guidelines are aimed at providing recommendations for the clinical diagnosis and management of liver cirrhosis across the compensated, decompensated, and recompensated stages, as well as guidance on cirrhosis reversal and associated complications.

Full article
Original Article Open Access
ATR-FTIR Spectroscopy for Differentiating Metaplastic Breast Carcinoma, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma: A Retrospective Study
Samuel T. Adeleke, Christopher Igbeneghu
Published online July 31, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00014
Abstract
Metaplastic breast carcinoma, a rare entity (<1% of breast neoplasms), lacks comprehensive spectroscopic characterization. This study aimed to address this gap by providing a [...] Read more.

Metaplastic breast carcinoma, a rare entity (<1% of breast neoplasms), lacks comprehensive spectroscopic characterization. This study aimed to address this gap by providing a qualitative and quantitative spectroscopic profile of metaplastic carcinoma in comparison to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).

A retrospective analysis was conducted on archival tissue blocks of metaplastic carcinoma (n = 10), DCIS (n = 12), and IDC (n = 31). Sections were stained with hematoxylin and eosin for histological confirmation. Attenuated total reflectance Fourier-transform infrared spectroscopy was performed on adjacent unstained sections, with normal breast tissue (n = 10) serving as the control. Spectral data were analyzed using t-tests to identify significant differences in peak intensities and ratios. Hierarchical clustering analysis and receiver operating characteristic curves were generated to assess the diagnostic potential of selected spectral features.

Spectral analysis revealed that mean peak intensities were generally lower in all carcinoma subtypes compared to normal breast tissue. Specific ratios, including A1237/A1080 (phosphate; p < 0.01), A1043/1543 (glycogen; p < 0.01), and A1080/A1632 (nucleocytoplasmic index; p < 0.03), were significantly elevated in carcinomatous tissues. Receiver operating characteristic analysis identified peak 3,280 (area under the curve (AUC) = 0.93–0.96) as highly effective in differentiating normal from carcinomatous tissues. Peak 2,922 showed specificity for distinguishing normal tissue from IDC (AUC ≈ 0.7). Peak 1,744 effectively discriminated between DCIS and metaplastic carcinoma (AUC = 0.7). The ratio 1,080/1,632 (nucleocytoplasmic ratio) demonstrated exceptional diagnostic accuracy, distinguishing normal from carcinomatous tissues (AUC ≈ 1.0), DCIS from IDC (AUC ≈ 0.86), and DCIS from metaplastic carcinoma (AUC ≈ 0.8).

Attenuated total reflectance Fourier-transform infrared spectroscopy, particularly using peak 3,280 (Amide A) and the 1,080/1,632 ratio (nucleocytoplasmic index), offers a promising approach for discriminating between normal breast tissue and carcinoma, as well as differentiating pre-IDC from metaplastic carcinoma. These spectral markers demonstrate both statistical significance and diagnostic potential.

Full article
Letter to the Editor Open Access
A Potential Mechanism for Lactoferrin to Prevent and Inhibit Organ Fibrosis
Mengqin Guo, Yang Liu, Jiezuan Cen, Chuanbin Wu, Zhengwei Huang
Published online August 21, 2025
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00028
Original Article Open Access
Gene–environment Interaction of GWAS Loci and Reproductive History in Uterine Fibroid Risk: A Case-control Study
Liubov Ponomareva, Ekaterina Barysheva, Anna Dorofeeva, Ksenia Kobzeva, Olga Bushueva
Published online October 14, 2025
Gene Expression. doi:10.14218/GE.2025.00056
Abstract
Uterine fibroids (UFs) are common hormone-dependent tumors with a complex etiology involving both genetic and environmental factors. This study aimed to investigate, for the first [...] Read more.

Uterine fibroids (UFs) are common hormone-dependent tumors with a complex etiology involving both genetic and environmental factors. This study aimed to investigate, for the first time, the associations between loci from genome-wide association studies (GWAS) and environmental risk factors in UF development, with a particular focus on gene–environment interactions.

DNA samples from 737 women with UF and 451 healthy controls were genotyped for ten UF-associated GWAS single nucleotide polymorphisms (SNPs) using probe-based polymerase chain reaction in this case-control study.

SNP rs66998222 (LOC102723323, G/A) was associated with decreased UF risk in the total sample (odds ratio (OR) = 0.81, p = 0.038) and in patients with a history of induced abortion (OR = 0.70, p = 0.009). SNP rs11031731 (THEM7P, WT1, G/A) increased UF risk overall (OR = 1.39, p = 0.01), and in women with abortion history (OR = 1.60, p = 0.008) or without pelvic inflammatory disease (OR = 1.43, p = 0.02). SNPs rs641760 (PITPNM2, C/T) and rs2553772 (LOC105376626, G/T) showed protective effects depending on abortion history. SNP rs1986649 (FOXO1, C/T) was associated with later UF onset (p = 0.049) and slower growth (p = 0.017). GWAS loci influence UF-related genes involved in proliferation, inflammation, and hormone metabolism, underscoring their pathogenic role.

Induced abortions and inflammation modify the effects of GWAS-identified UF risk loci, with allele-specific impacts on hormonal, inflammatory, and repair pathways. Replication in diverse cohorts is needed to validate these population-specific effects.

Full article
Research Letter Open Access
Longitudinal Profile of HBsAg Isoforms and Circulating Immune Complexes in the Natural History of Chronic Hepatitis B Infection
Lung-Yi Mak, Mark Anderson, Tiffany Fortney, Danny Ka-Ho Wong, Rex Wan-Hin Hui, Wai-Kay Seto, Gavin Cloherty, Man-Fung Yuen
Published online September 24, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00379
Original Article Open Access
A Clinicopathologic Analysis of 740 Endometrial Polyps: Risk of Premalignant Changes and Malignancy
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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