Serican Journal of Medicine provides a platform for communicating scientific advances in medical sciences globally, serving as a highly regarded source of cutting-edge information and international collaboration. Serican Journal of Medicine covers all aspects of medical fields, including basic, translational, and clinical research. The journal also presents clinical trials, surgical techniques, instrumental innovations and modifications, multi-disciplinary treatment for human diseases, public health concerns, state-of-the-art reviews, case reports, editorial comments, and clinical guidelines.
USCACA Call For 2026 AACR and ASCO Travel Awards
The U.S. Chinese Anti-Cancer Association (USCACA) is pleased to announce the call for nominations for the 2026 USCACA Travel Awards to support attendance at the 2026 AACR and ASCO Annual Meetings. These awards will recognize 2 to 5 outstanding junior Chinese investigators who have been selected for an oral presentation at either the 2026 AACR or 2026 ASCO Annual Meeting. Awardees will be selected based on the significance of their scientific contributions in basic, translational, or clinical cancer research as reflected in their accepted oral presentations.
Copyright (c) 2025 USCACA (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
The role of RNA 2′-O-methylation in prostate cancer
2′-O-methylation (Nm) represents a pervasive RNA modification occurring in multiple RNA species, including messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA). This chemical mark exerts critical regulatory functions in RNA stability, transcriptional control, and translational efficiency. Recent advances in high-throughput sequencing technologies have enabled transcriptome-wide mapping of Nm sites, uncovering increasing evidence that aberrant Nm modifications contribute to oncogenesis and tumor progression. Prostate cancer, the second most commonly diagnosed malignancy in men in the United States, has emerged as a disease context in which dysregulated Nm-related pathways are of particular significance. As sequencing-based investigations continue to expand, delineating the activities of Nm-modifying enzymes across distinct RNA classes in prostate cancer is anticipated to provide mechanistic insights into disease biology, facilitate the discovery of novel therapeutic targets, and ultimately guide the development of Nm-centered anticancer strategies.
This review aims to provide a comprehensive overview of RNA Nm in PCa, with an emphasis on identifying new molecular mechanisms and therapeutic opportunities, particularly in the context of CRPC.
a review to summarize the recent advancement of RNA 2'-O-methylation in PCa
Copyright (c) 2025 Siqi Wu, Rui Wang, yang yi (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
FOXA2 and NKX2-1 Orchestrate Neuroendocrine Lineage Plasticity in Prostate Cancer
Neuroendocrine prostate cancer (NEPC) is a treatment-resistant subtype that arises through lineage plasticity, allowing tumor cells to bypass androgen receptor (AR)–targeted therapies. In a recent study, Lu et al. define a transcriptional and epigenetic hierarchy that drives this transdifferentiation. The pioneer factor FOXA2 initiates enhancer remodeling and regional DNA demethylation, while the neural lineage transcription factor NKX2-1 is required to complete the NE program. Together, these factors reorganize 3D chromatin architecture and activate lineage-specific genes through enhancer–promoter looping. Crucially, the histone acetyltransferase p300/CBP is essential cofactor in this process. Pharmacologic inhibition of p300/CBP with CCS1477 suppresses NE gene expression and impairs tumor growth in NEPC models. These findings offer a mechanistic insight of lineage plasticity and highlight p300/CBP as promising therapeutic targets. The study also raises key questions about the stability and reversibility of chromatin remodeling and sets a framework for understanding enhancer-driven plasticity in other cancers.
Copyright (c) 2025 Ka-wing Fong (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Effects of Interleukin-17 on Expression of CD40 and CD40L in T and B Cell Lines
Interleukin-17 (IL-17, also known as IL-17A) plays a role in immune regulation and pathogenesis of various diseases. Cluster of differentiation 40 (CD40) and its ligand CD40L are critical for T and B cell communications and activation of immune responses. This study investigated the effects of IL-17A on CD40L expression in Jurkat T cells and CD40 expression in Mino B cells. The cells were treated with IL-17A (40 ng/mL for Jurkat cells and 20 ng/mL for Mino cells) for durations ranging from 0 to 24 hours. Protein expression levels were assessed using Western blotting combined with densitometric analysis. IL-17A treatment resulted in an increase in CD40L expression in Jurkat cells, although this change did not reach statistical significance (P > 0.05). In contrast, CD40 expression in Mino cells was significantly decreased at 24 h compared to the control group (*P < 0.05). These findings indicate that IL-17A differentially regulates the expression of co-stimulatory molecules in T and B cells, potentially contributing to its modulatory effects on T–B cell interactions.
Copyright (c) 2025 Kunang Liu, Kana Wang, Lin Li, Dongxia Ge, Zongbing You (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Emerging Mechanisms Linking High-Fat Diet and Endometrial Cancer: Insights into the Role of Gut Microbiota and Metabolic Dysregulation
High-fat diet (HFD) consumption has been recognized as a significant risk factor for the development of endometrial carcinoma (EC). Emerging research highlights gut microbiota as crucial mediators of HFD-induced systemic effects, which not only promote metabolic disorders such as obesity, insulin resistance, and systemic inflammation but also lead to profound alterations in gut microbiota composition. These changes subsequently influence estrogen metabolism, inflammatory signaling pathways, and endometrial remodeling, thereby exacerbating cellular proliferation and atypical changes within the endometrium. The underlying mechanisms may involve dysbiotic shifts in intestinal flora that contribute to increased endotoxemia, compromised intestinal barrier function, and chronic low-grade inflammation. This review synthesizes current findings on how HFD-induced gut microbiota dysbiosis and metabolic dysregulation contribute to the pathogenesis of EC while highlighting potential preventive and therapeutic strategies.
High-fat diet; Endometrial carcinoma; Endometrial atypical hyperplasia; Gut microbiota; Estrogen metabolism; Inflammation; Metabolic dysregulation.
Copyright (c) 2025 Kana Wang, Kunang Liu, Lin Li, Dongxia Ge, Zongbing You (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
2025 SAU Annual Meeting Report: Unraveling the Molecular Complexities of Urologic Malignancies
The 2025 Society of Academic Urologists (SAU) annual meeting was held during Jun 15-18, 2025, and showcased the latest discoveries in urologic oncology with a particular emphasis on prostate cancer biology, epigenetic regulation, immunotherapy, and novel therapeutic targets. Featuring an exceptional lineup of keynote speakers, scientific symposia, and interactive forums, the meeting provided a dynamic platform for the exchange of ideas among researchers, clinicians, and trainees dedicated to advancing urologic science and improving patient outcomes.
Copyright (c) 2025 Xiaoqi Liu, Benyi Li (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Accidental Trismus Leading to Failed Endotracheal Intubation and Abandoned Surgery Following Rapid Sequential Induction of General Anesthesia: A Case Report
A 64-year-old female patient, weighing 46 kg, 156 cm tall, and BMI of 18.9 kg/m², was scheduled to have the left tibial intramedullary needle under general anesthesia. General anesthesia induction was performed sequentially using sufentanyl 15 μg, propofol 120 mg, and cis-atracurium 10 mg intravenously. 2.5 minutes after good mask administration of oxygen by artificial ventilation, the anesthesiologist planned to intubate the trachea and found that her mandible and jaw joint were fixed, the masseter muscle was stiff, and the mouth could not open. Propofol 50 mg was added to deepen the anesthesia, which remained so. The surgery was cancelled. After waking up from anesthesia, the patient recovered her spontaneous mouth opening activity with a maximum mouth opening of 3.3 cm. During this period, the patient's nasopharyngeal body temperature monitoring was unchanged. In recent years, there have been a few cases of masseter muscle spasm (MMS) induced by general anesthesia, and the mechanism of which is still unclear. This sudden MMS after general anesthesia induction led to the anesthesiologist’s mental tension and failure of endotracheal intubation. In such an emergency, if the anesthesiologist's skills and associated equipment are inadequate, the patient should be decisively awakened from anesthesia and the abandoned operation.
general anesthesia induction, MMS, trismus, difficult airway, intubation failure
Copyright (c) 2025 Runqiao Fu, Xiaorong Cheng (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
USCACA/ASFC Youth Scholar and ASCO Travel Awards Ceremony Report (2025)
The U.S. Chinese Anti-Cancer Association (USCACA) held its 2025 Annual Awards Ceremonies in Chicago to honor outstanding young Chinese cancer researchers for their contributions to basic, translational, and clinical cancer research. The events took place during two major occasions: the 2025 ACACR/USCACA Joint Annual Meeting on April 26 and The China Summit during the 2025 ASCO Annual Meeting on June 1.
Call for nomination 2025 USCACA/AFCR Youth Award
The USCACA Junior Faculty Awards will recognize 3 to 6 outstanding junior Chinese faculty for their significant contributions to translational or clinical cancer research. Eligibility is open to junior Chinese faculty currently engaged in translational or clinical cancer research, holding the rank of Associate Professor (or equivalent) in China, or Instructor or Assistant Professor (or equivalent) in the United States. In addition, candidates in China must have obtained training in the US and subsequently returned to China within the last three years or confirmed to return China by the end of 2025, and are currently active in (or will be continue their) translational and clinical cancer research in China.
Copyright (c) 2025 https://creativecommons.org/licenses/by-nc-nd/4.0
Mechanisms and Therapeutic Strategies to Overcome Enzalutamide Resistance in Advanced Prostate Cancer
Enzalutamide, a second-generation androgen receptor (AR) inhibitor, has significantly improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC). However, resistance to enzalutamide remains a significant clinical hurdle, driven by diverse mechanisms, including AR amplification, point mutations, and splice variants such as AR-V7, which sustain signaling despite AR inhibition. In parallel, bypass pathways, including glucocorticoid receptor activation, PI3K/Akt/mTOR signaling, noncanonical Wnt activation, and lineage plasticity, contribute to AR-independent resistance. Nonetheless, the tumor microenvironment also plays a vital role in fostering immune evasion and suppressing cytotoxic immune responses. This review summarizes the current understanding of these resistance mechanisms and highlights emerging strategies to overcome them, including combination therapies targeting DNA repair (e.g., PARP inhibitors), epigenetic reprogramming (e.g., EZH2 inhibitors), and immune escape (e.g., checkpoint blockade or fulvestrant). Ongoing clinical trials and drug repurposing efforts, such as the use of artesunate or masofaniten, offer promising avenues for combating resistance. Ultimately, a precision medicine framework that integrates molecular diagnostics, biomarker-guided interventions, and rational drug combinations is essential to improve outcomes for patients with enzalutamide-resistant metastatic castration-resistant prostate cancer (mCRPC).
Copyright (c) 2025 Xinyi Wang, Zhiguo Li, Xiaoqi Liu (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Interleukin-6 regulates expression of estrogen receptors in human colorectal cancer and acute T-cell leukemia cells
Interleukin-6 (IL-6) is a pleiotropic cytokine involved in inflammation, immune regulation, and tumor progression. Estrogen receptors (ERs), particularly ERα and ER, play distinct roles in modulating immune responses and cancer development, yet their regulation by IL-6 in different cancer types remains incompletely understood. In this study, we investigated the effects of IL-6 on expression of ERα and ERβ in human colorectal cancer cells (HCT116) and acute T-cell leukemia cells (Jurkat). The cells were treated with recombinant human IL-6 (at a dosage of 100 ng/ml) for up to 24 hours, and changes in ER expression were assessed using Western blot analysis. We found that IL-6 treatment did not significantly alter ERα or ERβ levels in HCT116 cells, though a non-significant upward trend in ERβ expression was observed. In contrast, Jurkat cells exhibited a statistically significant increase in ERβ expression at 8 and 24 hours after IL-6 stimulation, while ERα expression remained unchanged. These findings suggest a cell-type-specific regulatory role of IL-6 in modulating estrogen receptor expression. The selective upregulation of ERβ in Jurkat cells implies a potential IL-6-ERβ signaling axis in T-cell leukemia, which may contribute to inflammation-driven leukemogenesis and warrants further mechanistic investigation.
IL-6, estrogen receptor, leukemia, colorectal cancer, immune disease, inflammation
Copyright (c) 2025 Yue Liu, Zongbing You (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Interactions between Pro-inflammatory Cytokines and Estrogen Receptors in Endometrial Cancer
Endometrial cancer (EC) is a hormone-driven malignancy in which estrogen receptor (ER) signaling plays a central role. Meanwhile, chronic inflammation, particularly mediated by pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-17 (IL-17), has emerged as a key contributor to endometrial cancer progression. This review examines the interplay between IL-6, IL-17, and estrogen receptors (ERα and ERβ) in endometrial cancer cells, highlighting how these cytokines regulate ER expression and function through multiple signaling pathways, including the Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. IL-6 and IL-17 have been shown to upregulate ERα and suppress ERβ, thereby enhancing estrogen-mediated tumor proliferation and potentially contributing to hormonal therapy resistance. Moreover, evidence suggests a bidirectional feedback loop in which estrogen signaling further amplifies cytokine production, creating a self-sustaining inflammatory environment that promotes tumor progression. Understanding this cytokine–ER crosstalk provides novel insights into endometrial cancer pathogenesis and reveals potential therapeutic targets. Strategies that combine endocrine therapy with anti-inflammatory agents or cytokine pathway inhibitors may help overcome resistance and improve clinical outcomes in selected patients. Further mechanistic studies and clinical trials are needed to validate the prognostic and therapeutic relevance of IL-6 and IL-17 in hormone-responsive endometrial cancer.
Endometrial cancer; ERα; ERβ; Interleukin-6; Interleukin-17; Inflammation; Hormone signaling; Tumor microenvironment.
Copyright (c) 2025 Lin Li, Kana Wang, Kunang Liu, Sayed Ala Moududee, Dongxia Ge, Zongbing You (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
A Review of Sipuleucel-T in Combination with Other Therapies for Metastatic Castration-Resistant Prostate Cancer
Recent research has expanded the therapeutic landscape for sipuleucel-T by introducing several combination treatments. These include innovative hormone therapies (enzalutamide and abiraterone), immunomodulatory agents (including IL-15, IL-7, atezolizumab, ipilimumab, and indoximod), DNA vaccines, and radiopharmaceuticals, many of which have demonstrated enhanced clinical outcomes and received approval from the U.S. Food and Drug Administration (FDA). These combination therapies present novel opportunities to enhance patient survival and quality of life. Sipuleucel-T, a significant autologous cell immunotherapy, was approved by the FDA in 2010 for the treatment of patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Integration of sipuleucel-T with other therapeutic modalities holds promise for advancing mCRPC treatment. Nevertheless, the optimal sequencing and combination strategies for sipuleucel-T with other therapies remain under investigation, with numerous clinical trials currently exploring new treatment paradigms. Incorporation of these therapies, particularly to develop more effective and personalized treatment strategies, necessitates additional research. Future studies should aim to ascertain the optimal timing and sequencing of treatments and to identify biomarkers that can predict treatment responses, thereby enhancing outcomes for patients with mCRPC. This review underscores potential strategies for the integration of sipuleucel-T with other therapies and examines their therapeutic potential in mCRPC.
prostate cancer, mCRPC, sipuleucel-T, combination therapy.
Copyright (c) 2025 Ye Wang, Fenghong Cao, Zhiyong Zhang, Xuemei Li, Xiaobing Dou, Yuchen Liu, Zongbing You (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
A Review of the Pharmacological Effects of Ginkgo Biloba Extract
As an extract from a traditional medicinal plant, ginkgo biloba extract (GBE) has complex chemical components and diverse pharmacological activities that have always been a research hotspot in the medical field. This article systematically reviews the main components and extraction processes of GBE. From multiple aspects such as cardiovascular and cerebrovascular protection, neural regulation, intervention in metabolic diseases, and respiratory system protection, this review explores GBE’s pharmacological effects and mechanisms of action, combined with clinical research and experimental data. Further, this review analyzes the research progress of GBE in antibacterial activity, drug interactions, and safety evaluation, aiming to provide a comprehensive theoretical reference for clinical application and subsequent research of GBE.
Ginkgo Biloba Extract; Pharmacological Effects; Clinical Application; Mechanism of Action; Safety
Copyright (c) 2025 shanwen you (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Case Report: An Exploration of Cadaveric Anatomical Anomalies
In the gross anatomy laboratory at the Tulane University School of Medicine, our group of six Anatomy Master’s Degree students observed several anatomical and pathological findings in a female cadaver. The dissectors were provided with dissection equipment including forceps, hemostats, blunt probes, and scalpels to study the cadaver. Some notable discoveries included severe scoliosis, an ossified lumbar mass, extensive abdominal adhesions, a duodenal stent, a biliary stent, a hysterectomy and oophorectomy procedure, and medical devices such as a subclavian chemotherapy port and ureteral stents. The scoliosis appeared to be caused by the ossified mass spanning the length of her lumbar spine. Histopathological analysis revealed osteoid tissue which indicated a possible diagnosis of osteosarcoma. The subclavian chemotherapy port was found in the supine position within the right superior thoracic region, leading us to speculate a malignant nature of the lumbar mass. During abdominal dissection, reflection of the anterior abdominal wall was difficult due to the many abdominal adhesions found throughout the peritoneal cavity. The greater omentum was unable to be observed due to the adhesions. Dissection of the intraperitoneal organs revealed abnormal coloration of the gallbladder and cystic duct. After identifying the organs of the gastrointestinal tract with multiple intestinal adhesions, a duodenal stent was revealed in the descending duodenum. A second stent was identified in the bile duct, suggesting that it had been placed to alleviate biliary obstruction or pancreatitis due to complications of the duodenal stent placement. During the pelvic cavity dissection, the dissectors noticed a complete hysterectomy and oophorectomy. It is unknown whether the procedure was done to prevent further complications in the treatment of the lumbar mass, or if it was done prior to the formation of the lumbar mass. Dissection of the retroperitoneal space revealed that both kidneys had no anatomical variations, but ureteral stents were found in the renal pelvises of both kidneys. The ureteral stents traveled through the ureters and entered into the urinary bladder. Using literature review, the dissectors explored possible links between these findings.
Cadaveric study; malignant gastric outlet obstruction; anatomical anomalies; duodenal stent; osteosarcoma; gross anatomy; biliary stent; postmortem pathology; anatomical structures; scoliosis; medical dissection; meningioma.
Copyright (c) 2025 Madison Haggard, Noah LaBruyere, Vy Nguyen, Rylie Shook, Wyatt Turner, Yazen Zaben (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Effects of Different Processing Methods on the Content of Rutin and Tannin in Sophora japonica Herb Medicine
Objective: To investigate the effects of different processing methods on the content of rutin and tannin in Sophora japonica herb medicine (Chinese herb medicine name: Huai Mi or Huai Hua). Methods: Huai Mi was processed with different methods. Tannin content was determined using potassium permanganate titration method. Rutin content was quantified using ultraviolet spectrophotometry. Results: The tannin content was the highest in stir-fried-to-coke samples (1.87%), while the highest rutin content was observed in stir-fried-to-yellow samples (0.134%). The stir-fried-to-ash samples had the lowest contents of both rutin and tannin. Conclusion: Processing methods critically impact the contents of bioactive compounds in Sophora japonica herb medicine. Optimizing these methods may enhance medicinal efficacy and utilization
Sophora japonica; Huai Mi; Processing methods; Tannin; Rutin; Chinese herb medicine.
Copyright (c) 2025 Shanwen You, Yingjie Fu (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Unraveling the Role of N6-Methyladenosine in Prostate Cancer: Implications for Prognosis and Tumor Aggression
The epitranscriptomic modification N6-methyladenosine (m6A) has emerged as a central regulator of RNA metabolism, influencing diverse physiological and pathological processes. As the most abundant RNA modification in eukaryotic cells, m6A dynamically modulates gene expression by regulating RNA processing, stability, and translation. Dysregulation of m6A has been implicated in key oncogenic processes, including tumor initiation, progression, metastasis, therapy resistance, and interactions within the tumor microenvironment. Despite these advances, the role of m6A in prostate cancer remains poorly understood, highlighting the need for further investigation. In a recent study, Xu et al. utilized refined m6A meRIP-seq to profile 162 primary prostate cancer patient samples, unveiling novel insights into the epitranscriptomic landscape of this malignancy. These findings not only enhance our understanding of m6A regulation in cancer biology but also underscore its potential to inform diagnostic, prognostic, and therapeutic strategies for prostate cancer.
This commentary provides an in-depth discussion of the study *“The Landscape of N6-Methyladenosine in Localized Primary Prostate Cancer”*, analyzing its findings on the role of N6-methyladenosine (m6A) in prostate cancer and their implications for prognosis and tumor aggressiveness.
Copyright (c) 2025 Xin Xu, Xinqiao Zheng, Housheng Hansen He (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Mushroom Polysaccharides as Natural Modulators of IL-17: Implications for Gut Microbiota, Autoimmune Diseases and Cancer Therapy
Interleukin-17 (IL-17, also known as IL-17A) is a member of the pro-inflammatory cytokine family that plays a pivotal role in immune defense, inflammatory responses, and tissue homeostasis. It contributes to host protection, autoimmune diseases, and cancer progression. Recent studies have highlighted the critical role of gut microbiota in immune regulation and tumor progression. Alterations in its composition can disrupt protective mechanisms, increase infection risk, and elevate the likelihood of metabolic and immune-related diseases. Mushroom polysaccharides are biological macromolecules extracted from the fruiting bodies, mycelia, or fermentation broth of mushrooms. These compounds achieve anti-tumor, anti-inflammatory, anti-oxidative, and immune-regulatory effects by modulating gut microbiota, increasing short-chain fatty acid production, enhancing intestinal mucosal barrier function, regulating lipid metabolism, and activating specific signaling pathways. Mushroom polysaccharides have been shown to regulate IL-17 both directly through key signaling pathways and indirectly by modulating gut microbiota, thereby influencing immune-related diseases and tumor progression. Therefore, mushroom polysaccharides, acting as natural regulators of IL-17, possess extensive application potentials in cancer therapy and immune disease management.
Mushroom Polysaccharides, IL-17, Gut Microbiota, Autoimmune Disease, Cancer.
Copyright (c) 2025 Kunang Liu, Kana Wang, Zongbing You (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Novel Roles of Mitochondrial Outer Membrane Protein TOMM20 in Prostate Cancer
Copyright (c) 2025 Linglong Yin, Xiong Li (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Aurora kinases are a family of serine/threonine kinases of whom function to preserve the integrity and fidelity of chromosomal segregation. In mammals, aurora kinase A (AurkA) is vital to the mitotic phase of the cell cycle as a consequence of its spatial and timely interactions with various types of cell cycle substrates. Since AurkA is present in all of the mammalian somatic cell cycles, it is also detectable in many different types and stages of cancers. Specific activation sites, feedback loops, and substrate interactions have been identified and linked to the progression of urological cancers. It is inarguable that the slightest hint of disorder among AurkA can disrupt the cell cycle’s ability to regulate the growth and progression of cells in all conditions due to its direct interactions with tumor suppressing molecules. Discovering that AurkA interacts with FOXO3a, PLK1, TPX2, TPX2, SPOP, YBX1 and CXCR7 in ways that were unknown before 2019 has revealed new targeted treatment options that may surpass current methodology in efficiency and length of remission. The aim of this paper is to highlight AurkA’s oncogenic role in urological cancers, in addition to emphasizing newfound pathways and mechanisms that introduce the prostate cancer research field to more options for therapeutic approaches.
urological cancer, phosphorylation, aurora kinase
Copyright (c) 2025 Jennifer Grasso, Cheng Zhang, Ka-wing Fong (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Appropriate normalization is critical to improve reproducibility of tissue ChIP-seq
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.
Copyright (c) 2025 Qi Chu, Liu Peng, Lourdes Brea, Viriya Keo, Xiaodong Lu, Jindan Yu, Jonathan Zhao (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Long-Read Sequencing Outperforms Short-Read Sequencing in Detecting Most Structural Variations
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.
Copyright (c) 2025 Xinyue Chen, Xiaodong Lu, Xianglin Sh, Shaojun Yu, Jonathan Zhao (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Impact of Nanopore Flow Cell Types on DNA Methylation Detection
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.
Copyright (c) 2025 Xianglin Shi, Xiaodong Lu, Xinyue Chen, Shaojun Yu, Rebecca Arnold, Viraj Master, Jonathan Zhao (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
T Cell Immunity in Pathogenesis, Progression, and Malignant Transformation of Endometriosis
Endometriosis is a common gynecological condition characterized by special features such as invasive growth, recurrence, and potential distant metastasis. Recent studies indicate an increasing incidence of malignant transformation of endometriosis. The mechanisms underlying the occurrence, progression, and malignancy of endometriosis are multifactorial, involving genetic alterations, environmental factors, hormonal imbalances, and immuno-inflammatory responses. Various T cell subsets play crucial roles in regulating immune responses and influencing disease progression and malignant risk. CD4+ T cells, including T helper (Th) cells (Th1, Th2, and Th17), regulatory T (Treg) cells, follicular helper T (Tfh) cells, and Th9 cells, alongside CD8+ T cells are essential for maintaining the immune microenvironment in endometriosis. Disruption of the balance among these T cell subtypes can promote chronic inflammation, immune evasion, and tissue remodeling that may facilitate malignant transformation. Therapeutic strategies targeting T cell function or restoring immune homeostasis hold promise for managing endometriosis through immunomodulation or checkpoint blockade therapy to prevent its malignant progression. This article reviews the role of T cells in the malignant transformation of endometriosis and proposes potential immunoregulatory treatment approaches.
Endometriosis; malignant transformation; endometriosis-associated ovarian cancer; CD4+ T cells; CD8+ T cells; immune microenvironment; T cell imbalance; immunotherapy.
Copyright (c) 2025 Kana Wang, Kunang Liu, Zelan Liao, Zongbing You (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Safety Evaluation of Albumin-Bound Paclitaxel in Patients with Non-Small Cell Lung Cancer Based on CHPS：A single institution retrospective study
Copyright (c) 2025 Shuke Long, Jinping Wang, Haixia Xu (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
The Safety and Protective Effects of Intravitreal Injection of Human Adipose-Derived Mesenchymal Stem Cells in a Rat Model of Retinal Ischemia/Reperfusion Injury
Purpose: The purpose of this study was to evaluate the safety and protective effects of intravitreal injection of human adipose-derived mesenchymal stem cells (ADMSCs) in a rat model of retinal ischemia/reperfusion (I/R) injury induced by anterior chamber perfusion. Methods: Two weeks after induction of I/R injury, rats received a single intravitreal injection of human ADMSCs at doses of 2×10⁴ cells or 5×10⁴ cells suspended in 3 μL saline. Control rats received 3 μL saline or no injection. Retinal and optic nerve changes were assessed at two weeks after injection using immunofluorescence, hematoxylin and eosin staining, toluidine blue staining, and polymerase chain reaction to evaluate inflammation-related and neurotrophic factors. Results: Intravitreal injection of human ADMSCs significantly reduced the number of apoptotic retinal ganglion cells after I/R injury, preserved the ganglion cell layer, and increased expression of neurotrophic factors such as brain-derived neurotrophic factor and insulin-like growth factor 1. The high-dose group (receiving 5×10⁴ cells) demonstrated superior neuroprotective effects compared to the low-dose group (receiving 2×10⁴ cells) as evidenced by less retinal ganglion cell apoptosis. In addition, histopathological analysis revealed localized tissue remodeling and increased microglial infiltration, particularly in the low-dose group. Conclusion: The safety of intravitreal human adipose-derived mesenchymal stem cell transplantation requires further investigation, particularly with regard to potential proliferative responses and their long-term effects. In addition, the optimal dosage of adipose-derived mesenchymal stem cells needs to be explored to balance therapeutic efficacy and minimize adverse outcomes. which was associated with structural retinal damage. In addition, the high-dose group exhibited a potential risk of inflammation or maladaptive changes.
Copyright (c) 2025 Baiyu Hu, Jing Shu, Hanying Fan, Mei Xin, Liuzhi Zeng, MD (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
Disparities in Response to the All of Us Research Program COVID-19 Participant Experience (COPE) Survey
This study demonstrated the successful longitudinal recruitment of a large number of diverse participants to the COPE survey in a very short time, empowered by the All of Us Research Program, its infrastructure, and databases. Despite the disparity of response rates across demographic groups, the data collected in the COPE surveys will enable researchers to investigate how the pandemic differentially affects diverse populations and their health status across the United States. Additionally, the findings highlight the need for future research aimed at improving response rates among underrepresented groups, ensuring the All of Us Research Program achieves its goals of diversity and inclusivity in research.
Copyright (c) 2025 Sophia Zhao, Zhuo Chen (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
The hTERT N-terminal DNA binding is necessary but not sufficient for maintaining telomere and cellular immortalization
Telomerase is a reverse transcriptase that adds telomeric DNA repeats at the end of chromosomes and prevents senescence, apoptosis and genome instability. The core components of TERT are a catalytic protein subunit, the telomerase reverse transcriptase (TERT), and an RNA subunit, the telomerase RNA (TR). The N-terminus of TERT has been implicated in processive DNA synthesis that is facilitated by telomere-binding domains in TERT called anchor sites. In this study, we characterized three evolutionarily conserved residues in human TERT, G145, Q169 and G172. We performed site-directed mutagenesis and created hTERT G145A, Q169A and G172A mutants. All three hTERT mutants were not able to immortalize human foreskin fibroblasts (HFFs) and maintain telomere length in cells. The G145A mutant did not abrogate hTERT enzymatic activity, while Q169 and G172 mutants exhibited severely reduced levels and enzymatic activity. When compared to wild type hTERT, the G145 mutant still could interact with telomeric DNA in cells. In contrast, substitutions of Q169 and G172 impaired the interaction between hTERT and telomeres in cells. Thus, characterization of these three conserved residue mutants in GQ motif suggested that the hTERT N-terminal DNA binding is necessary for telomerase function, but not sufficient for maintaining telomere length and immortalizing cells.
Telomerase, telomeres, cell immortalization, DNA-binding, RNA Binding domain, human primary cells
Copyright (c) 2025 Renxiang Chen, Guangzhao Li, Aleksandra Dakic, Yun-Ling Zheng, Jenny Li, Xuefeng Liu (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
An Overview of ADAR Inhibitors: Mechanisms, Applications, and Future Directions
Adenosine deaminases acting on RNA (ADARs) are enzymes responsible for converting adenosine to inosine in double-stranded RNA through a process known as A-to-I editing. This modification is essential for regulating RNA function, impacting key processes such as immune response, gene expression, and RNA stability. ADARs, especially ADAR1, have been linked to several diseases, including cancer, viral infections, and autoimmune disorders, making them promising targets for therapeutic development. Currently, no FDA-approved drugs are specifically marketed as ADAR inhibitors. This review offers a brief analysis of known ADAR inhibitors, with a focus on their mechanisms of action, structural properties, and potential applications. We explore a range of inhibitors, including small molecules, peptide-based inhibitors, natural compounds, and RNA-based inhibitors, and discuss their ability to selectively modulate ADAR activity. The review also addresses the therapeutic implications of these inhibitors in cancer, viral infections, and inflammatory diseases. In addition, we examine future directions for developing more selective and potent ADAR inhibitors, emphasizing both the challenges and opportunities in the field. By consolidating current findings and identifying existing gaps, this review aims to enhance the understanding and therapeutic potential of ADAR inhibition.
A-to-I RNA editing; ADAR inhibitors; drug discovery; high-throughput screening; cancer therapeutics
Copyright (c) 2025 Taufeeque Ali, Qi Cao (Author) https://creativecommons.org/licenses/by-nc-nd/4.0
RFDiffusion: Revolutionizing Protein Design with Generative AI
Protein design is an intricate and essential frontier in biotechnology, offering the potential to revolutionize medicine, materials science, and our understanding of biological systems. At its core, protein design involves crafting proteins with specific structural or functional properties. These tasks include creating enzymes with catalytic activity, designing protein binders to interact with specific targets, and engineering scaffolds that stabilize biologically relevant motifs. For years, traditional methods of protein design relied heavily on physics-based simulations and iterative experimental testing. While groundbreaking, these approaches were often computationally expensive and limited in their ability to explore the vast diversity of protein structures.
Copyright (c) 2025 Zhangzhi(Fred) Peng (Author) https://creativecommons.org/licenses/by-nc-nd/4.0