{"title":"Editorial commentary on the special issue of cancer research.","authors":"Editorial Board","doi":"10.7555/JBR.38.20240800","DOIUrl":"10.7555/JBR.38.20240800","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":"38 4","pages":"287-288"},"PeriodicalIF":2.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unlocking the novel activation mechanism of human IL-18.","authors":"Yingchao Hu, Yuxian Song, Shuo Yang","doi":"10.7555/JBR.38.20240154","DOIUrl":"10.7555/JBR.38.20240154","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-3"},"PeriodicalIF":2.2,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Zubair Hafiz, Jie Pan, Zhiwei Gao, Ying Huo, Haobin Wang, Wei Liu, Jian Yang
{"title":"Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) <i>via</i> dephosphorylation of the EGFR signaling pathway.","authors":"Muhammad Zubair Hafiz, Jie Pan, Zhiwei Gao, Ying Huo, Haobin Wang, Wei Liu, Jian Yang","doi":"10.7555/JBR.38.20240055","DOIUrl":"10.7555/JBR.38.20240055","url":null,"abstract":"<p><p>The current study aimed to assess the effect of timosaponin AⅢ (T-AⅢ) on drug-metabolizing enzymes during anticancer therapy. The <i>in vivo</i> experiments were conducted on nude and ICR mice. Following a 24-day administration of T-AⅢ, the nude mice exhibited an induction of CYP2B10, MDR1, and CYP3A11 expression in the liver tissues. In the ICR mice, the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration. The <i>in vitro</i> assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6, MDR1, and CYP3A4, along with constitutive androstane receptor (CAR) activation. Treatment with <i>CAR</i> siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression. Furthermore, other CAR target genes also showed a significant increase in the expression. The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice. Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation, with this effect being partially reversed by the ERK activator t-BHQ. Inhibition of the ERK1/2 signaling pathway was also observed <i>in vivo</i>. Additionally, T-AⅢinhibited the phosphorylation of EGFR at Tyr1173 and Tyr845, and suppressed EGF-induced phosphorylation of EGFR, ERK, and CAR. In the nude mice, T-AⅢ also inhibited EGFR phosphorylation. These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"382-396"},"PeriodicalIF":2.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chunming Tang, Yanling Wang, Min Wu, Zhiji Wang, Yupeng Zhou, Ya Lin, Yijun Wang, Huae Xu
{"title":"Cancer cell membrane-camouflaged biomimetic nanoparticles for enhancing chemo-radiation therapy efficacy in glioma.","authors":"Chunming Tang, Yanling Wang, Min Wu, Zhiji Wang, Yupeng Zhou, Ya Lin, Yijun Wang, Huae Xu","doi":"10.7555/JBR.38.20240100","DOIUrl":"10.7555/JBR.38.20240100","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is a highly aggressive and lethal brain tumor with limited treatment options. To improve therapeutic efficacy, we developed a novel multifunctional nanoplatform, GM@P(T/S), comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide (TMZ) and superparamagnetic iron oxide (SPIO) nanoparticles. The successful preparation was confirmed in terms of particle size, morphology, stability, the <i>in vitro</i> drug release, and cellular uptake assays. We demonstrated that GM@P(T/S) exhibited the enhanced homotypic targeting, the prolonged blood circulation, and efficient blood-brain barrier penetration in both <i>in vitro</i> and <i>in vivo</i> studies. The combination of TMZ and SPIO nanoparticles within GM@P(T/S) synergistically improved chemo-radiation therapy, leading to a reduced tumor growth, an increased survival, and minimal systemic toxicity in the orthotopic GBM mouse models. Our findings suggest that GM@P(T/S) holds a great promise as a targeted and efficient therapeutic strategy for GBM.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"87-102"},"PeriodicalIF":2.2,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaqi Tang, Lin Luo, Bakwatanisa Bosco, Ning Li, Bin Huang, Rongrong Wu, Zihan Lin, Ming Hong, Wenjie Liu, Lingxiang Wu, Wei Wu, Mengyan Zhu, Quanzhong Liu, Peng Xia, Miao Yu, Diru Yao, Sali Lv, Ruohan Zhang, Wentao Liu, Qianghu Wang, Kening Li
{"title":"Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis.","authors":"Jiaqi Tang, Lin Luo, Bakwatanisa Bosco, Ning Li, Bin Huang, Rongrong Wu, Zihan Lin, Ming Hong, Wenjie Liu, Lingxiang Wu, Wei Wu, Mengyan Zhu, Quanzhong Liu, Peng Xia, Miao Yu, Diru Yao, Sali Lv, Ruohan Zhang, Wentao Liu, Qianghu Wang, Kening Li","doi":"10.7555/JBR.38.20240065","DOIUrl":"10.7555/JBR.38.20240065","url":null,"abstract":"<p><p>Given the extremely high inter-patient heterogeneity of acute myeloid leukemia (AML), the identification of biomarkers for prognostic assessment and therapeutic guidance is critical. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In the current study, we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas (TCGA) based on differential gene expression analysis and univariable Cox proportional hazards regression analysis. By using multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we constructed a 9-CSMs prognostic model for risk stratification of the AML patients. The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels. Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients. The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores. Notably, single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance. Furthermore, PI3K inhibitors were identified as potential treatments for these high-risk patients. In conclusion, we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"397-412"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"hUCMSC-derived extracellular vesicles relieve cisplatin-induced granulosa cell apoptosis in mice by transferring anti-apoptotic miRNAs.","authors":"Wenjing Tang, Haiyan Yan, Xiaojun Chen, Yanan Pu, Xin Qi, Liyang Dong, Chuan Su","doi":"10.7555/JBR.37.20230310","DOIUrl":"10.7555/JBR.37.20230310","url":null,"abstract":"<p><p>Premature ovarian insufficiency (POI) caused by chemotherapy is a common complication in female cancer survivors of childbearing age. Traditional methods, including mesenchymal stem cell (MSC) transplant and hormone replacement therapy, have limited clinical application because of their drawbacks, and more methods need to be developed. In the current study, the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) were investigated in a cisplatin (CDDP)-induced POI mouse model and a human granulosa cell (GC) line. The results showed that hUCMSC-EVs significantly attenuated body weight loss, ovarian weight loss, ovary atrophy, and follicle loss in moderate-dose (1.5 mg/kg) CDDP-induced POI mice, similar to the effects observed with hUCMSCs. We further found that the hUCMSC-EVs inhibited CDDP-induced ovarian GC apoptosis by upregulating anti-apoptotic miRNA levels in GCs, thereby downregulating the mRNA levels of multiple pro-apoptotic genes. In general, our findings indicate that the moderate-dose chemotherapy may be a better choice for clinical oncotherapy, considering effective rescue of the oncotherapy-induced ovarian damage with hUCMSC-EVs. Additionally, multiple miRNAs in hUCMSC-EVs may potentially be used to inhibit the chemotherapy-induced ovarian GC apoptosis, thereby restoring ovarian function and improving the life quality of female cancer patients.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"36-49"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of common genetic variants in <i>KCNQ</i> family genes associated with gastric cancer survival in a Chinese population.","authors":"Yuetong Chen, Chen Li, Yi Shi, Jiali Dai, Yixuan Meng, Shuwei Li, Cuiju Tang, Dongying Gu, Jinfei Chen","doi":"10.7555/JBR.38.20240040","DOIUrl":"10.7555/JBR.38.20240040","url":null,"abstract":"<p><p>The <i>KCNQ</i> family of genes ( <i>KCNQ1</i>- <i>KCNQ5</i>), encoding voltage-gated K <sup>+</sup> (Kv) channels, have been demonstrated to play potential pathophysiological roles in cancers. However, the associations between genetic variants located in <i>KCNQ</i> family genes and gastric cancer survival remain unclear. In this study, a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in <i>KCNQ</i> family genes associated with overall survival (OS). Based on the survival evaluation of all five <i>KCNQ</i> family genes, <i>KCNQ1</i> was selected for subsequent genetic analysis. In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants, we found that <i>KCNQ1</i> rs10832417G>T was associated with an increased OS in gastric cancer patients (adjusted hazards ratio [HR] = 0.84, 95% confidence interval [CI]: 0.72-0.98, <i>P</i> = 0.023). Subsequently, a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants. The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure. Furthermore, we observed that gastric cancer patients with downregulated <i>KCNQ1</i> expression had a poorer survival across multiple public datasets. The findings of the present study indicate that <i>KCNQ1</i> rs10832417 may serve as an independent prognostic predictor of gastric cancer, providing novel insights into the progression and survival of the disease.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"76-86"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuhan Chen, Xuchun Wang, Nan Yang, Yuechi Song, He Cheng, Yujie Sun
{"title":"p53 exerts anticancer effects by regulating enhancer formation and activity.","authors":"Shuhan Chen, Xuchun Wang, Nan Yang, Yuechi Song, He Cheng, Yujie Sun","doi":"10.7555/JBR.37.20230206","DOIUrl":"10.7555/JBR.37.20230206","url":null,"abstract":"<p><p>The abnormality of the p53 tumor suppressor is crucial in lung cancer development, because p53 regulates target gene promoters to combat cancer. Recent studies have shown extensive p53 binding to enhancer elements. However, whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood. In the current study, we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established <i>TP53</i> knockout (KO) human bronchial epithelial cells (BEAS-2B). A total of 943 active regular enhancers and 370 super-enhancers (SEs) disappeared upon the deletion of p53, indicating that p53 modulates the activity of hundreds of enhancer elements. We found that one p53-dependent SE, located on chromosome 9 and designated as <i>KLF4</i>-SE, regulated the expression of the Krüppel-like factor 4 ( <i>KLF4</i>) gene. Furthermore, the deletion of p53 significantly decreased the <i>KLF4</i>-SE enhancer activity and the <i>KLF4</i> expression, but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model. Subsequently, in <i>TP53</i> KO cells, the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency. Consistently, <i>KLF4</i> expression also decreased in lung cancer tissues and cell lines. It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells. Collectively, our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function. Therefore, our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"334-347"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ya Xie, Zifeng Xu, Yumin Zhang, Yisheng Li, Pengyu Du, Chun Wang
{"title":"First-episode psychiatric disorder risk from SARS-CoV-2 infection: A clinical analysis with Chinese psychiatric inpatients.","authors":"Ya Xie, Zifeng Xu, Yumin Zhang, Yisheng Li, Pengyu Du, Chun Wang","doi":"10.7555/JBR.38.20240005","DOIUrl":"10.7555/JBR.38.20240005","url":null,"abstract":"<p><p>The extensive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout China in late 2022 has underscored the correlation between this virus and severe psychiatric disorders. However, there remains a lack of reported clinical and pathological features. Accordingly, we retrospectively reviewed the electronic medical records of psychiatric inpatients for seven days from early January 2023. Twenty-one inpatients who developed first-episode psychiatric disorders within two weeks after SARS-CoV-2 infection were recruited, while 24 uninfected first-episode psychiatric inpatients were selected as controls. Comparative analyses of clinical manifestations, routine laboratory tests, and imaging examinations were performed. Our investigation demonstrated a 330% increase in the incidence of first-episode psychiatric inpatients after SARS-CoV-2 infection in 2023, compared with the preceding year without SARS-CoV-2 infections. Most cases exhibited psychiatric symptoms within one week of SARS-CoV-2 infection, which resolved after approximately two weeks, with no residual symptoms after three months. One-way ANOVA demonstrated a significant difference in the highest fever temperature between inpatients with and without psychotic symptoms. Infected inpatients displayed elevated levels of interleukin-4, interleukin-8, and interferon-α, but decreased levels of eosinophils and basophils. These findings suggest that SARS-CoV-2 may contribute to the development of psychiatric disorders, likely mediated by the virus-induced inflammatory response and neuronal dysfunction in the context of psychological distress.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"50-60"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phase separation and transcriptional regulation in cancer development.","authors":"Yan Gu, Ke Wei, Jun Wang","doi":"10.7555/JBR.37.20230214","DOIUrl":"10.7555/JBR.37.20230214","url":null,"abstract":"<p><p>Liquid-liquid phase separation, a novel biochemical phenomenon, has been increasingly studied for its medical applications. It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes. During transcriptional regulation, dynamic condensates are formed through interactions between transcriptional elements, such as transcription factors, coactivators, and mediators. Cancer is a disease characterized by uncontrolled cell proliferation, but the precise mechanisms underlying tumorigenesis often remain to be elucidated. Emerging evidence has linked abnormal transcriptional condensates to several diseases, especially cancer, implying that phase separation plays an important role in tumorigenesis. Condensates formed by phase separation may have an effect on gene transcription in tumors. In the present review, we focus on the correlation between phase separation and transcriptional regulation, as well as how this phenomenon contributes to cancer development.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":"38 4","pages":"307-321"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}