Serican journal of medicine最新文献

{"title":"DYRK kinases phosphorylate IL-17RA at S801.","authors":"Sayed Ala Moududee, Andrew A Herppich, Mary Kay H Pflum, Dongxia Ge, Zongbing You","doi":"10.17161/sjm.v3i3.25722","DOIUrl":"10.17161/sjm.v3i3.25722","url":null,"abstract":"<p><p>Interleukin-17 (IL-17) receptor A (IL-17RA) promotes inflammatory reactions by activating kinases and transcription regulators. Our previous studies have demonstrated that glycogen synthase kinase 3 (GSK3) phosphorylates IL-17RA at T780. It is not known whether other kinases also phosphorylate IL-17RA. Here, we identified an association between dual-specificity tyrosine-regulated kinases (DYRKs) and IL-17RA. We found that DYRK1B and DYRK4 interacted with and phosphorylated IL-17RA at serine 801 (S801). Overexpression of DYRK1B and DYRK4 enhanced IL-17RA phosphorylation, whereas siRNA-mediated knockdown of DYRK1B or DYRK4 reduced the phosphorylation. Serum starvation of the cultured cells increased expression levels of DYRK1B/4 and IL-17RA phosphorylation, suggesting stress-dependent modulation of receptor modification. Moreover, selective small-molecule inhibitors of DYRKs effectively suppressed IL-17RA phosphorylation at S801. Our findings indicate a link between DYRK family kinases and IL-17RA phosphorylation, providing new potential therapeutic targets in the management of IL-17-mediated diseases.</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conditionally Reprogrammed Cells Preserve Cellular Diversity and Permit Genetic Manipulation: Implications for Cancer Heterogeneity and Tissue Regeneration.","authors":"Shuang Fang, Guangzhao Li, Dilber Nurmurmet, Xiaokui Mo, Chen Fei, Sujata Choudhury, Nancy Palechor-Ceron, Richard Schlegel, Xuefeng Liu, Jenny Li","doi":"10.17161/sjm.v3i1.24566","DOIUrl":"10.17161/sjm.v3i1.24566","url":null,"abstract":"<p><p>Our previous study demonstrated that a Rho kinase inhibitor (Y-27632), in combination with irradiated fibroblast feeder cells, enables both normal and tumor epithelial cells from various tissues to proliferate indefinitely in vitro, without the need for exogenous viral or cellular gene transduction. These cells are referred to as Conditionally Reprogrammed Cells (CRCs). This approach has shown great promise for applications in regenerative and personalized medicine. In the present study, we first investigated whether CRCs could be genetically manipulated and stably express exogenous genes. Using lentiviral transduction of GFP, we successfully infected human foreskin keratinocytes (HFKs) cultured under CRC conditions. GFP expression was stably maintained over multiple passages and through freeze-thaw cycles. Similar stable GFP expression was also observed in CRCs derived from human tumor specimens, including neuroendocrine cervical carcinoma and prostate cancer. We next explored the use of GFP-labeled CRC-HFKs in co-culture systems with tumor-derived CRCs to evaluate colony formation and cellular heterogeneity. Our data demonstrated that CRCs from different individuals can form heterogeneous colonies, supporting the potential of CRC-based systems for modeling tissue development, regeneration, and tumor heterogeneity. To optimize the CRC platform for translational applications, we further assessed human fibroblasts as an alternative to the mouse feeder layer, using GFP-expressing CRCs as a functional readout. Finally, we demonstrated the capacity for gene knockdown in CRCs by successfully silencing p53 and HPV16 E6 in cervical cancer-derived CRCs using shRNA lentiviral vectors. These results collectively establish that the CRC method supports stable genetic manipulation and underscore its potential for mechanistic studies, disease modeling, and development of cell-based therapeutic strategies.</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate Cancer: Etiology, Diagnosis, and Treatment.","authors":"Chaohao Li, Zhiguo Li, Xiaoqi Liu","doi":"10.17161/sjm.v3i1.24992","DOIUrl":"10.17161/sjm.v3i1.24992","url":null,"abstract":"<p><p>Based on cancer statistics in 2025, 313,780 American men were diagnosed with prostate cancer, and 35,770 of them died from the disease; thus, prostate cancer remains a serious health issue for American men. In this article, we review multiple aspects of the disease, including etiology, diagnosis, and treatment. Regarding disease etiology, we summarize current knowledge of prostate cancer initiation and progression, with a focus on androgen receptor signaling. We discuss the genetic landscape of prostate cancer, including alterations in the DNA damage response pathway, FOXA1, SPOP, the PI3K pathway, WNT signaling, AURKA, and MYCN. We also address the potential contribution of inflammation to prostate cancer development. In the diagnosis of prostate cancer, the Gleason score is discussed. Measurement of prostate-specific antigen (PSA) levels has been the gold standard for diagnosing prostate cancer and monitoring disease progression. We also review additional diagnostic methods, including magnetic resonance imaging, the 4Kscore, the Prostate Health Index, and bone scintigraphy. Various treatments have been used clinically. For localized prostate cancer, active surveillance, radical prostatectomy, radiotherapy, and androgen deprivation therapy are available options. For metastatic prostate cancer, androgen deprivation therapy remains the standard of care. For castration-resistant prostate cancer, cabazitaxel and second-generation androgen receptor inhibitors are the major therapeutic approaches. We also review several non-canonical treatment strategies.</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and Therapeutic Strategies to Overcome Enzalutamide Resistance in Advanced Prostate Cancer.","authors":"Xinyi Wang, Zhiguo Li, Xiaoqi Liu","doi":"10.17161/sjm.v2i4.24058","DOIUrl":"10.17161/sjm.v2i4.24058","url":null,"abstract":"<p><p>Enzalutamide, a second-generation androgen receptor (AR) inhibitor, has significantly improved survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). However, resistance to enzalutamide emerges in nearly all patients, posing a major clinical challenge. This review comprehensively examines the multifaceted mechanisms underlying enzalutamide resistance, including AR amplification, point mutations, splice variants such as AR-V7, and the activation of bypass signaling pathways, including glucocorticoid receptor signaling, PI3K/Akt/mTOR, and Wnt signaling. Additionally, the tumor microenvironment, lineage plasticity, and neuroendocrine differentiation contribute to therapy resistance through immune evasion and epigenetic reprogramming. We further discuss promising therapeutic strategies aimed at overcoming resistance, including combination treatments with PARP inhibitors, epigenetic modulators, and next-generation androgen receptor (AR) inhibitors. Biomarkers and personalized medicine approaches increasingly guide ongoing clinical trials to optimize treatment efficacy. This review also highlights drug repurposing as a practical avenue for targeting noncanonical vulnerabilities in resistant prostate cancer. Together, these insights provide a foundation for developing more durable and individualized treatment strategies for patients with enzalutamide-resistant metastatic castration-resistant prostate cancer (mCRPC).</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13278092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appropriate normalization is critical to improve reproducibility of tissue ChIP-seq.","authors":"Qi Chu, Liu Peng, Lourdes Brea, Viriya Keo, Xiaodong Lu, Jindan Yu, Jonathan C Zhao","doi":"10.17161/sjm.v2i3.23692","DOIUrl":"10.17161/sjm.v2i3.23692","url":null,"abstract":"<p><p>Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) is a powerful technology for studying genetic and epigenetic regulation. However, ChIP-seq data can be heavily affected by variations in chromatin amount and composition, ChIP enrichment, library preparation, and sequencing depth, affecting its overall reproducibility across biological replicates. Here, we evaluated four ChIP-seq normalization methods utilizing triplicate Foxa1 ChIP-seq data performed in prostate cancer tissues from three mice. We found that count-per-million (CPM) normalization, although not affecting peak calling in individual samples, is very useful for visualization and comparison of peak distribution and intensity across samples. By contrast, equal-read normalization improves both peak identification and intensity comparison. Moreover, spike-in normalization took advantage of spike-in chromatin ChIP to correct technical variations in ChIP-seq, including ChIP enrichment, sample preparation, and sequencing. Lastly, input-adjusted spike-in normalization further accounts for differences in input chromatin amount across samples, which is especially crucial for tissue ChIP-seq that often starts with different amounts of input chromatin. Overall, our study demonstrated that appropriate normalization is essential to improve the reproducibility and comparability of ChIP-seq experiments and highlighted the importance of input-adjusted spike-in normalization for tissue ChIP-seq.</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12880172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic targeting of Aurora Kinase A in advanced prostate cancer.","authors":"Maroun Bou Zerdan, Mehmet Asim Bilen, Jindan Yu","doi":"10.17161/sjm.v2i2.23274","DOIUrl":"10.17161/sjm.v2i2.23274","url":null,"abstract":"","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12881931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Nanopore Flow Cell Types on DNA Methylation Detection.","authors":"Xianglin Shi, Xiaodong Lu, Xinyue Chen, Shaojun Yu, Rebecca S Arnold, Viraj A Master, Jonathan C Zhao","doi":"10.17161/sjm.v2i2.23664","DOIUrl":"10.17161/sjm.v2i2.23664","url":null,"abstract":"<p><p>Third-generation sequencing technologies have revolutionized the study of epigenetic characteristics in human diseases, with Oxford Nanopore Technologies (ONT) at the forefront of long-read sequencing. ONT has made rapid improvements in flow cell designs, which greatly increased its sequencing accuracy but, at the same time, led to some projects utilizing different flow cell types, mainly R9 vs. R10, across samples. Whether and how the flow cell types affect genome-wide DNA methylation detection remains incompletely understood. Here, we used both flow cell types to analyze 6 human renal cell carcinoma (RCC) samples and compared the results. While there was a highly significant correlation between 5-methylcytosine (5mC) detected by R9 and R10 flow cells, we also observed substantial differences. R9 flow cells over-estimated 5mC levels at hypomethylated chromatin regions, mostly at promoters, while under-estimated 5mC at hypermethylated chromatin regions, enriched at intronic and intergenic regions. Such deviations in detection were likely caused by substantially lower sequencing accuracy of R9 flow cells, due to its mechanics, especially having problems sequencing homopolymeric DNA elements, such as CpG islands, leading to both higher false-positive and false-negative detections. Interestingly, such systematic errors were largely mitigated by batch-correction software, improving data comparability. In summary, our study reports superior performance of R10 flow cells, leading to much higher accuracy in base sequencing and DNA methylation detection.</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12880221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Read Sequencing Outperforms Short-Read Sequencing in Detecting Most Structural Variations.","authors":"Xinyue Chen, Xiaodong Lu, Xianglin Shi, Shaojun Yu, Jonathan Zhao","doi":"10.17161/sjm.v2i2.23671","DOIUrl":"10.17161/sjm.v2i2.23671","url":null,"abstract":"<p><p>Structural variations (SV) are common in the cancer genome and play critical roles in regulating tumorigenesis. In the past decades, many SVs have been detected through analyses of whole-genome sequencing (WGS) data generated mainly by Illumina paired-end short-read sequencing (SRS). Recent advances in long-read sequencing (LRS) techniques provide exciting opportunities for SV detection. However, a comprehensive analysis of the pros and cons of LRS and SRS in detecting SVs in a cancer genome is still lacking. Here, we performed WGS of the LNCaP prostate cancer cell line through LRS using the Oxford Nanopore Technology and called main SVs, which were compared to those derived from publicly available LNCaP SRS data. Strikingly, LRS is superior in detecting insertions of all sizes and deletions of <1000 bp long, whereas SRS is very useful in capturing long deletions, taking advantage of its paired-end reads. LRS identified more precise breakpoints of detected SVs. In addition, we found that SRS called many duplications and inversions, most of which were not confirmed by LRS, likely due to ambiguity in SRS read alignment to repetitive regions, leading to errors in SV calling. In conclusion, LRS outperformed SRS in detecting most SVs, except deletions longer than LRS read lengths. Our study highlights the advantages of LRS in resolving complex genomic rearrangements and underscores its potential for improving SV detection in cancer genomics.</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating the roles of HOXB13 X285K variant in prostate cancer.","authors":"Xiaodong Lu, Samantha Ye, Mingyang Liu, Jindan Yu","doi":"10.17161/sjm.v2i1.23160","DOIUrl":"10.17161/sjm.v2i1.23160","url":null,"abstract":"<p><p><i>HOXB13</i> X285K is a frameshift mutant caused by the deletion of one nucleotide, c.853delT, within the <i>HOXB13</i> stop codon, resulting in an extension of HOXB13 protein by 96 amino acids on the C terminus. It was found primarily in men of West African ancestry and associated with early-onset prostate cancer (PCa) and more advanced stage. Whether and how X285K contributes to PCa progression remains largely unknown. Here, we established isogenic 22Rv1 cell lines with heterozygous wildtype/X285K HOXB13, which recapitulates the genotypes of X285K in PCa patients. In addition, using the unique C-terminal region of X285K as an antigen, we developed an antibody that specifically recognizes the HOXB13 X285K protein. Lastly, we demonstrated that X285K, similar to wildtype HOXB13, was able to rescue the effects of <i>HOXB13</i> knockdown on both induced and repressed genes, such as <i>FASN</i> and <i>PSA</i>, in PCa cells. In summary, our study reports that X285K retained the transcriptional regulation ability of wildtype HOXB13 and provides isogenic PCa cell lines with wildtype and/or X285K HOXB13 expression and an X285K-specific antibody for a comprehensive investigation of X285K function in PCa.</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetate Metabolism in Urological Health and Disease.","authors":"Jianhua Xiong","doi":"10.17161/sjm.v1i1.23080","DOIUrl":"10.17161/sjm.v1i1.23080","url":null,"abstract":"<p><p>Acetate, the simplest short-chain fatty acid, serves key roles in urological health as both a nutrient and an endogenous molecule. It originates from gut microbial fermentation of dietary fiber and is found in common foods like dairy products, pasta, coffee, and vinegar. Additionally, acetate is synthesized internally to support energy metabolism and cell signaling pathways. This review highlights recent advancements in understanding acetate's function as a signaling molecule in regulating cell fate and activity, with implications for urological health and disease treatment. The potential of acetate as a biomarker for urological health is examined, offering valuable insights that could enhance strategies for disease diagnosis, management, and therapeutic development. Furthermore, the review explores the application of non-invasive imaging techniques to monitor acetate metabolism for the diagnosis, staging, and management of urological cancers.</p>","PeriodicalId":521234,"journal":{"name":"Serican journal of medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}