Endocrine, Metabolic & Immune Disorders-Drug Targets - Volume 25, Issue 15, 2025
Volume 25, Issue 15, 2025
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Network Pharmacology Unveils Multi-Systemic Intervention of Panax notoginseng in Osteoporosis via Key Genes and Signaling Pathways
More LessAuthors: Qiyue Wang, Xiaoping Wang, Kezhou Wu, Weiwei Wu, Zhantu Wei and Weili FengBackgroundPanax notoginseng (Burk.) F. H. Chen (PN) is a traditional Chinese medicine that has been applied to prevent and treat osteoporosis. The mechanism of PN for osteoporosis remained a mystery.
ObjectiveThe objective of this study was to reveal the therapeutic effect and illuminate the possible mechanism of PN for osteoporosis.
MethodsThe Traditional Chinese Medicine Database and Analysis Platform was searched to screen the potent ingredients of the PN and to analyze the potential therapeutic targets for osteoporosis. We excavated four disease databases to collect osteoporosis-related genes. After integrating the gene expression profile of osteoporosis and the chemical-protein data of PN, a protein-protein interaction network was constructed to demonstrate the interactions among the gene products. GO function, KEGG pathway, and docking analyses were executed.
ResultsNetwork pharmacology obtained 31 active ingredients and 134 targets for the treatment of osteoporosis. The key components were beta-elemene, quercetin, methyl palmitate, oleic acid, and hexanal. The results of GO and KEGG analyses showed that Panax notoginseng was beneficial for osteoporosis by influencing the main pathways including AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway, p53 signaling pathway, NF-kappa B signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, FoxO signaling pathway, and Wnt signaling pathway, modulating inflammation, metabolism, cell proliferation, cell survival, growth and angiogenesis. Panax notoginseng intervened in osteoporosis through multi-components, multi-targets, and multi-pathways.
ConclusionThis study illustrates the mechanism of Panax notoginseng for osteoporosis, providing broader insights for novel research and developments of the Panax species for osteoporosis.
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Oral Microbiota Associated with Clinical Efficacy of Ustekinumab in Crohn’s Disease
More LessAuthors: Feiyang Xu, Rui Xie, Le He, Honggang Wang, Yifan Zhu, Xiaozhong Yang and Huiming YuBackgroundCrohn’s Disease (CD) is a chronic inflammatory gastrointestinal disease. Ustekinumab (UST) has been utilized as a therapeutic option for CD patients. However, approximately 40-60% of patients exhibit an inadequate response to UST. Accumulating evidence has confirmed the involvement of oral bacteria in the development of CD. Nevertheless, the relationship between oral microbiota and the efficacy of UST therapy in CD patients has remained unexplored.
Materials and MethodsWe recruited 28 healthy individuals and 53 CD patients, 47 of whom completed the entire UST therapy. Oral samples and clinical data were collected. The clinical response and clinical remission were defined based on the CDAI score. Oral samples were analyzed by 16S rRNA gene sequencing. The analysis of sequence data was performed by QIIME and R.
ResultsWe revealed the oral microbial difference between the Healthy Control (HC) group and the CD group. The enrichment of Fusobacteria, Leptotrichia, Capnocytophaga, and Campylobacter, and the diminution of Haemophilus and Rothia were observed in the CD group. Differences in oral microbiota were also identified among patients with different efficacy of UST. Compared to the response and remission groups, both the non-response and non-remission groups showed significantly higher levels of Fusobacteria and Leptotrichia. Predictive models for clinical response and clinical remission in UST were developed based on oral microbiota, with the Area Under the Curve (AUC) value of 0.944 and 0.930, respectively.
ConclusionOral microbiota was relevant to the UST efficacy in patients with CD based on the predictive model. These findings suggest that oral microbiota could serve as a non-invasive prognostic biomarker for UST treatment in CD patients.
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Bioinformatics Analysis Reveals Microrchidia Family Genes as the Prognostic and Therapeutic Markers for Colorectal Cancer
More LessAuthors: Binghui Liu, Lingbin Chen, Hui Chen, Juhua Pan and Changfa YuAimThe aim of this study is to examine the role of the microrchidia (MORC) family, a group of chromatin remodeling proteins, as the therapeutic and prognostic markers for colorectal cancer (CRC).
BackgroundMORC protein family genes are a highly conserved nucleoprotein superfamily whose members share a common domain but have distinct biological functions. Previous studies have analyzed the roles of MORCs as epigenetic regulators and chromatin remodulators; however, the involvement of MORCs in the development and pathogenesis of CRC was less examined.
ObjectiveThe current work examined the role of the MORCs as the therapeutic and prognostic markers for CRC.
MethodsThe expressions and prognostic significance of MORC family genes in CRC were explored. The role of these genes in tumor immunity was comprehensively analyzed in terms of their functions in immune cell infiltration, tumor microenvironment (TME), and their interaction with immune regulatory genes such as immunosuppressive genes, immune checkpoints and immunostimulatory genes. The relations between MORC family genes, tumor mutation burden (TMB), DNA, mismatch repair (MMR), RNA methylation, microsatellite instability (MSI), and drug sensitivity were investigated using the R statistical software. The expressions of MORC4 in 150 CRC tissues and 60 paracancer tissues were detected by immunohistochemical method. CRC cell proliferation, migration, and invasion were measured by cell counting kit-8 (CCK-8), scratch assay, and transwell cell invasion assay.
ResultsThe expressions of MORC2 and MORC4 were significantly upregulated, whereas those of MORC1 and MORC3 were noticeably downregulated in CRC in comparison to their expressions in normal colorectal mucosal tissues. Patients with high-expressed MORC2 showed a more unfavorable prognosis than those with a low MORC2 level. Functional annotation analysis identified 100 MORC family genes with the most significant negative or positive correlations to diabetic cardiomyopathy, amyotrophic lateral sclerosis, oxidative phosphorylation, Huntington’s disease, thermogenesis, Parkinson’s disease, olfactory transduction, Alzheimer’s disease, prion disease. MORC3 expression was positively correlated with Stromal score, Immune score and ESTIMATE score, while MORC2 expression was negatively related to the three scores in CRC, these correlations were not statistically significant. Additionally, the MORC family genes were significantly positively correlated with tumor-infiltrating immune cells such as T helper cells and exhibited close relations to some immunosuppressive genes such as CXCR4 and PVR, immunostimulatory genes such as TGFBR1, KDR, and CD160 as well as some immune checkpoint genes. It was found that the expressions of some members of MORC family genes were positively correlated with DNA methylation, MSI, TMB, MMRs, and drug sensitivity in CRC and that the mRNA and protein levels of MORC4 were remarkably upregulated in CRC tissues than in adjacent normal tissues (P<0.05). In the MORC4 knockdown group, DLD-1 cell proliferation was more inhibited than in the negative control (NC) and siRNA groups (P<0.05). Furthermore, the migratory capacity of DLD-1 cells and the number of cells crossing the basement membrane in the MORC4 knockdown group were reduced compared to the NC and siRNA groups (all P<0.05).
ConclusionThe expressions of MORC family genes were significantly different in CRC samples, which was related to the immune cell infiltration and prognosis of CRC. Thus, the MORC family genes were considered as markers for indicating the clinical immunotherapy and prognostic outcome of CRC.
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Protective Effect of Vitamin D Supplementation Against Atherosclerotic Cardiovascular Disease in Type 1 Diabetes Mellitus Model
More LessIntroductionCardiovascular disease (CVD) is a leading cause of mortality on a global scale, with a higher prevalence observed among men. This study investigated the protective effect of vitamin D supplementation on CVD.
MethodsA cohort of thirty mice was divided into three groups: control, T1 diabetic, and T1 diabetic groups that received vitamin D treatment. For each mouse in the three groups, measurements were taken of body weight, blood glucose levels, glycated hemoglobin (HbA1c), lipid profile, cardiac enzymes, troponin I, adropin, nitric oxide (NO), endothelin-1, and Vascular endothelial growth factor (VEGF). In addition, measurements were taken for the overall lymphocyte count, as well as the CD3+, CD4+, CD8+, CD4+, CD25+, and CD8+ CD25+ cell counts in all mice.
ResultsThe diabetic mice that received vitamin D treatment exhibited significant reductions in blood glucose levels, HbA1c levels, lipid profile, cardiac enzymes, troponin I, endothelin-1, and VEGF levels as compared to the untreated diabetic group (p < 0.01). Furthermore, there was an observed rise in adropin and NO levels in diabetic mice that received vitamin D treatment compared to the untreated diabetic group (p < 0.05). The diabetic mice treated with vitamin D exhibited a substantial decrease in total lymphocyte counts compared to the untreated diabetic and control animals (p < 0.0001). Regarding the CD3+ subset, it was shown that diabetic mice subjected to vitamin D treatment had notably elevated levels of these cells compared to both the untreated diabetic and control groups (p < 0.0001). In addition, the administration of vitamin D resulted in a substantial decrease in the numbers of CD4+ and CD8+ cells in the group of individuals with diabetes (p < 0.0001). The diabetes group that received vitamin D treatment had significantly reduced populations of CD4+ CD25+ and CD8+ CD25+ compared to the untreated diabetic group (p < 0.0001).
ConclusionVitamin D maintains the integrity of the cardiovascular system through the reduction of blood glucose levels and lipid profile. Moreover, its supplementation prevents atherosclerotic CVD by suppressing inflammatory reactions.
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Associative Learning in Subclinical Hypothyroidism at Different Ranges of Thyroid Stimulating Hormone: A Cambridge Neuropsychological Test Automated Battery (CANTAB) Study of Visual Paired Association Learning Task
More LessAuthors: Satkarjit Kaur Jhandi, Shweta Shenoy and Ajaypal SinghBackgroundAssociative learning deficits are constantly found in subclinical hypothyroidism (SCH). Despite achieving normal thyroid stimulating hormone (TSH) levels, a considerable number of patients undergoing levothyroxine (LT-4) treatment frequently complain about memory retrieval. The Paired Association Learning (PAL) task involves computerised testing on the CANTAB- Cambridge Neuropsychological Test Automated Battery, also considered a screening tool for Alzheimer’s disease (AD).
PurposeThis study aimed to investigate the impact of different levels of TSH on visual associative learning in SCH and determine if these impairments were reversed with LT-4.
MethodsA total of 134 participants were included in this cross-sectional study. Group 1: 35 healthy controls; patients with SCH (Group 2: 33 newly identified cases; Group 3: 32 patients on LT-4 with elevated TSH; Group 4: 34 euthyroid but on LT-4). A thyroid profile and a neuropsychological clinical assessment were done. The visual PAL task was performed on CANTAB.
ResultsPAL was significantly impaired (p = <0.05) in all 3 patient groups as compared to Group 1. The PAL total errors (adjusted) scores were significantly higher in Groups 2 and 3, indicating that associative learning is definitely impaired in SCH, reaching levels previously seen in patients with AD.
ConclusionOur findings encourage screening for visual associative learning or memory retrieval in patients with SCH. The study present has established a more reasonable threshold of TSH 2.5mIU/L to encourage examination of associative learning and the initiation of LT-4 in SCH. Poor PAL task performance in patients with SCH may have significant implications in clinical settings for suspecting AD.
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Evaluation and Association of Hematological and Biochemical Parameters of Untreated COVID-19 Patients on the basis of Differences in Ethnicity and Curcumin as a Possible Treatment
More LessAuthors: Munir Akhtar, Rubaida Mehmood, Mukhtar Hussain, Momna Warraich, Hafeez Ullah, Zahida Batool, Sumara Ashraf and Rida SanaBackgroundCBC (complete blood count) tests, along with RPM (Renal parameters) and LFT (Liver function tests), are clinically important for coronavirus patients; curcumin can serve as a possible treatment for SARS- CoV.
ObjectiveThe objective of the study was to determine the relationship of CBC parameters with renal parameters and liver function tests and to develop the hypothesis that curcumin may be the best and non-invasive drug for coronavirus.
Materials & MethodsThe differences between the results of 91 confirmed cases of COVID-19 (symptomatic and asymptomatic) and 100 controls were assessed by an independent t-test and Mann-Witney U Wilcoxon test. Microscopy, hematological tools, and techniques were used to assess the improvements/abnormalities in blood components and parameters.
ResultsThis is a case control study along with the feasibility of curcumin as COVID treatment. The association between parameters was assessed by Pearson & Spearman correlation analysis. The level of significance was p < 0.05. Changes were observed in urea (p = 0.000), creatinine (p = 0.02), total bilirubin (p = 0.000), SGPT (ALT) (p = 0.000), RBC (p = 0.001), HGB (p = 0.001), MCV (p = 0.002), MCH (p = 0.03), MPV, PDW, NE%, LY%, and MO% EO% (p = 0.00), in comparison to normal controls. Differences in the correlation of electrolytes, RPM, and LFT tests along with CBC parameters in Pakistani and Chinese individuals provided a new idea for using various diagnostic and therapeutic tools in different ethnic groups. The COVID-19 infected blood components and parameters showed rapid improvement/recovery, especially the total count of platelets and WBCs (lymphocytes and basophils), HGB, HCT, MCV, and MCH.
ConclusionCurcumin drugs can be used as an immediate remedy/treatment to cure COVID-19 patients.
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Volumes & issues
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Volume 26 (2026)
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Volume 25 (2025)
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Volume 24 (2024)
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Volume 23 (2023)
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Volume 22 (2022)
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Volume 21 (2021)
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Volume 20 (2020)
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Volume 19 (2019)
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Volume 18 (2018)
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Volume 17 (2017)
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Volume 16 (2016)
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Volume 15 (2015)
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Volume 14 (2014)
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Volume 13 (2013)
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Volume 12 (2012)
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Volume 11 (2011)
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Volume 10 (2010)
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Volume 9 (2009)
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Volume 8 (2008)
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Volume 7 (2007)
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Volume 6 (2006)
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