Frontiers of MedicinePub Date : 2025-04-01Epub Date: 2025-03-22DOI: 10.1007/s11684-025-1127-5
Na Kang, Qinghui Duan, Xin Min, Tong Li, Yuxin Li, Ji Gao, Wanli Liu
{"title":"Multifaceted function of B cells in tumorigenesis.","authors":"Na Kang, Qinghui Duan, Xin Min, Tong Li, Yuxin Li, Ji Gao, Wanli Liu","doi":"10.1007/s11684-025-1127-5","DOIUrl":"10.1007/s11684-025-1127-5","url":null,"abstract":"<p><p>B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"297-317"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of cap-dependent endonuclease in influenza virus with ADC189: a pre-clinical analysis and phase I trial.","authors":"Jing Wei, Yaping Deng, Xiaoyun Zhu, Xin Xiao, Yang Yang, Chunlei Tang, Jian Chen","doi":"10.1007/s11684-024-1115-1","DOIUrl":"10.1007/s11684-024-1115-1","url":null,"abstract":"<p><p>ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T<sub>1/2</sub>) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"347-358"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2025-04-01Epub Date: 2025-03-04DOI: 10.1007/s11684-025-1123-9
Wu He, Ke Xu, Yongcui Yan, Gen Li, Bo Yu, Junfang Wu, Kaineng Zhong, Da Zhou, Dao Wen Wang
{"title":"Low dose of hydroxychloroquine is associated with reduced COVID-19 mortality: a multicenter study in China.","authors":"Wu He, Ke Xu, Yongcui Yan, Gen Li, Bo Yu, Junfang Wu, Kaineng Zhong, Da Zhou, Dao Wen Wang","doi":"10.1007/s11684-025-1123-9","DOIUrl":"10.1007/s11684-025-1123-9","url":null,"abstract":"","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"386-390"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2025-04-01Epub Date: 2025-03-24DOI: 10.1007/s11684-024-1113-3
Weibo Zhao, Liqiang Zhou, Yixing Wang, Ji Wang, Yi Eve Sun, Qi Wang
{"title":"Single-cell transcriptome analyses of PBMCs reveal the immunological characteristics of individuals with phlegm-dampness constitution.","authors":"Weibo Zhao, Liqiang Zhou, Yixing Wang, Ji Wang, Yi Eve Sun, Qi Wang","doi":"10.1007/s11684-024-1113-3","DOIUrl":"10.1007/s11684-024-1113-3","url":null,"abstract":"<p><p>Ancient traditional Chinese medicine (TCM) doctrine says \"The superior doctor prevents illnesses,\" pointing out preventative medicine as the ultimate goal for medical care. TCM recognizes that genetic predisposition and environmental and lifestyle influences contribute to diseases. It divides people into eight constitutions in addition to one normal/healthy kind. People with one of the eight subhealth constitutions are prone to develop different kinds of corresponding illnesses. The goal for this type of categorization is to help people take preemptive measures to prevent or delay disease onset. As the peripheral immune system through surveying the body, it can capture information from essentially all organs and reflect anomalies occurring in each organ. Thus, the detailed profiling of the peripheral immune-system function can generally reflect a person's overall heath state. In this study, we performed the single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from individuals with Tanshi (phlegm dampness) constitution. They were prone to develop metabolic disorders including diabetes. scRNA-seq revealed greatly reduced mucosal-associated invariable T cell content and heightened TNFα-NFκB, JAK-STAT, and interferon signaling. These findings indicated heightened chronic inflammation, as well as increased hypoxia/apoptosis responses, likely resulting from frequent sleep apnea that Tanshi individuals experienced. Altogether, this pilot study demonstrated effectiveness in using scRNA-seq to reveal molecular-immunological bases for constitution categorization, thereby substantiating that preventative medicine originated from TCM.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"376-385"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2025-04-01Epub Date: 2025-01-17DOI: 10.1007/s11684-024-1116-0
Ziyi Wang, Hongying Zhu, Wei Xiong
{"title":"Metabolism and metabolomics in senescence, aging, and age-related diseases: a multiscale perspective.","authors":"Ziyi Wang, Hongying Zhu, Wei Xiong","doi":"10.1007/s11684-024-1116-0","DOIUrl":"10.1007/s11684-024-1116-0","url":null,"abstract":"<p><p>The pursuit of healthy aging has long rendered aging and senescence captivating. Age-related ailments, such as cardiovascular diseases, diabetes, and neurodegenerative disorders, pose significant threats to individuals. Recent studies have shed light on the intricate mechanisms encompassing genetics, epigenetics, transcriptomics, and metabolomics in the processes of senescence and aging, as well as the establishment of age-related pathologies. Amidst these underlying mechanisms governing aging and related pathology metabolism assumes a pivotal role that holds promise for intervention and therapeutics. The advancements in metabolomics techniques and analysis methods have significantly propelled the study of senescence and aging, particularly with the aid of multiscale metabolomics which has facilitated the discovery of metabolic markers and therapeutic potentials. This review provides an overview of senescence and aging, emphasizing the crucial role metabolism plays in the aging process as well as age-related diseases.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"200-225"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression.","authors":"Zhuo Zheng, Yongfang Lin, Hua Guo, Zheng Liu, Xiaoliang Jie, Guizhen Wang, Guangbiao Zhou","doi":"10.1007/s11684-024-1122-2","DOIUrl":"10.1007/s11684-024-1122-2","url":null,"abstract":"<p><p>The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"318-328"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decreased neurotensin induces ovulatory dysfunction via the NTSR1/ERK/EGR1 axis in polycystic ovary syndrome.","authors":"Dongshuang Wang, Meiling Zhang, Wang-Sheng Wang, Weiwei Chu, Junyu Zhai, Yun Sun, Zi-Jiang Chen, Yanzhi Du","doi":"10.1007/s11684-024-1089-z","DOIUrl":"10.1007/s11684-024-1089-z","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"149-169"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2025-02-01Epub Date: 2024-12-20DOI: 10.1007/s11684-024-1109-z
Boram Lee, Chan-Young Kwon, Hye Won Lee, Arya Nielsen, L Susan Wieland, Tae-Hun Kim, Stephen Birch, Terje Alraek, Myeong Soo Lee
{"title":"Does the outcome of acupuncture differ according to the location of sham needling points in acupuncture trials for migraine? A systematic review and network meta-analysis.","authors":"Boram Lee, Chan-Young Kwon, Hye Won Lee, Arya Nielsen, L Susan Wieland, Tae-Hun Kim, Stephen Birch, Terje Alraek, Myeong Soo Lee","doi":"10.1007/s11684-024-1109-z","DOIUrl":"10.1007/s11684-024-1109-z","url":null,"abstract":"<p><p>Various acupuncture clinical trials have been conducted on migraine; however, the conclusions remain controversial especially when acupuncture was compared with sham acupuncture. Sham acupuncture is sometimes performed at the same acupuncture points used for verum acupuncture despite the evidence on acupuncture point specificity. Four databases were searched for sham acupuncture or waiting list-controlled acupuncture trials for migraine on December 25, 2023. Sham acupuncture was classified according to the needling points: sham acupuncture therapy at verum points (SATV) or at sham points (SATS). Network meta-analysis was performed based on the frequentist framework for headache pain intensity and response rate. A total of 18 studies involving 1936 participants were analyzed. Headache pain intensity and response rate were significantly improved in verum acupuncture compared with SATS. However, there was no significant difference between SATV and verum acupuncture. When comparing SATS and SATV, there was no significant difference in headache pain intensity and response rate; however, the results were in favor of SATV. The effect of the risk of bias on the certainty of evidence between verum and sham acupunctures was judged to be generally low. SATV should not be misused as a placebo control to evaluate the efficacy of acupuncture.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"53-63"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2025-02-01Epub Date: 2024-12-11DOI: 10.1007/s11684-024-1101-7
Keke Huang, Qingkai Liu, Ruoxi Zhang, Hua Nian, Ying Luo, Yue Luo, Xiaoya Fei, Le Kuai, Bin Li, Yimei Tan, Su Li, Xin Ma
{"title":"Preclinical and clinical studies on Qin-Zhu-Liang-Xue decoction: insights from network pharmacology and implications for atopic dermatitis treatment.","authors":"Keke Huang, Qingkai Liu, Ruoxi Zhang, Hua Nian, Ying Luo, Yue Luo, Xiaoya Fei, Le Kuai, Bin Li, Yimei Tan, Su Li, Xin Ma","doi":"10.1007/s11684-024-1101-7","DOIUrl":"10.1007/s11684-024-1101-7","url":null,"abstract":"<p><p>To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"134-148"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}