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Geography, genes, and germs: An evolutionary entanglement 地理、基因和细菌:进化的纠缠。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-08-01 DOI: 10.1016/j.bj.2025.100888
Aila Akosua Kattner
This journal issue presents an article on genomic surveillance and phylogenetic analysis for monitoring SARS-CoV-2, alongside reviews of recent advances in the treatment of hepatocellular carcinoma and gastric cancer, and current insights into mpox. It includes a perspective on the role of extended reality techniques in pediatric neurosurgery, as well as updates on cleft care and the relationship between mitochondrial bioenergetics and iron. Further contributions explore the link between metastatic potential and cytidine deaminase, miRNA targets involved in hypertrophy and fibrosis during cardiac remodeling, and new deep-learning models for predicting response to cardiac resynchronization therapy. The expression of connexin gap junction proteins in atrial fibrillation is examined in detail, along with a retrospective study on enteral autonomy in pediatric short bowel syndrome. The issue concludes with novel insights into the rare genetic disorder Bietti crystalline dystrophy.
本期杂志发表了一篇关于监测SARS-CoV-2的基因组监测和系统发育分析的文章,同时回顾了肝细胞癌和胃癌治疗的最新进展,以及目前对m痘的见解。它包括对扩展现实技术在小儿神经外科中的作用的看法,以及对腭裂护理和线粒体生物能量学与铁之间关系的更新。进一步的贡献探讨了转移潜能与胞苷脱氨酶之间的联系,心脏重塑过程中涉及肥厚和纤维化的miRNA靶点,以及预测心脏再同步治疗反应的新深度学习模型。我们详细研究了连接蛋白间隙连接蛋白在心房颤动中的表达,并对儿童短肠综合征的肠内自主性进行了回顾性研究。这期杂志总结了对罕见的遗传性疾病比埃蒂结晶性营养不良症的新见解。
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引用次数: 0
Hepatocellular carcinoma systemic treatment update: From early to advanced stage 肝细胞癌系统治疗 2024 年更新:从早期到晚期。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-08-01 DOI: 10.1016/j.bj.2024.100815
Wei Teng , Tai-Chi Wu , Shi-Ming Lin
Hepatocellular carcinoma (HCC) ranks the sixth most common malignancy but the third leading cause of cancer-related mortality in the world. Significant breakthroughs have been made in systemic treatment for HCC over the past two decades, which have improved treatment outcomes. In addition to multiple tyrosine kinase inhibitors (mTKIs), immune checkpoint inhibitors (ICIs) and antiangiogenic drugs are increasingly being applied. The combination of ICI and antiangiogenic or dual ICIs has become the new standard of care due to remarkable response rates. However, currently available systemic regimens are primarily reserved for certain patients in the intermediate and advanced stages who will not benefit from locoregional treatments. Evidence supporting the use of systemic treatment as neoadjuvant or adjuvant therapies in patients with early-stage HCC, especially the high risk of recurrence after curative treatments, remains limited. This review identified recent developments in systemic therapy, including mTKIs and ICIs, considering results on first- and second-line treatment, role of neoadjuvant and adjuvant settings, and combination with loco-regional therapy. Various ongoing clinical trials regarding the role of systemic therapies and potential novel targets in patients with early-, intermediate-, and advanced-stage HCC were also summarized and revealed that systemic therapy is no longer limited to advanced-stage HCC. Moreover, the introduction of T-cell redirecting strategies, including bispecific antibodies and chimeric antigen receptor T cells, has revolutionized the treatment landscape for HCC. Future research should focus on an in-depth exploration of the mechanisms governing the establishment of tumor barriers.
肝细胞癌(HCC)在最常见的恶性肿瘤中排名第六,但却是全球癌症相关死亡的第三大原因。过去二十年来,HCC 的系统治疗取得了重大突破,改善了治疗效果。除了多种酪氨酸激酶抑制剂(mTKIs)外,免疫检查点抑制剂(ICIs)和抗血管生成药物的应用也越来越广泛。ICI 和抗血管生成药物或双 ICIs 的联合应用因其显著的反应率而成为新的治疗标准。然而,目前可用的全身治疗方案主要用于某些无法从局部治疗中获益的中晚期患者。对于早期 HCC 患者,尤其是治愈性治疗后复发风险较高的患者,支持将全身治疗作为新辅助或辅助疗法的证据仍然有限。本综述梳理了包括 mTKIs 和 ICIs 在内的全身治疗的最新进展,考虑了一线和二线治疗的结果、新辅助和辅助治疗的作用以及与局部区域治疗的结合。会议还总结了正在进行的各种临床试验,这些试验涉及全身疗法在早期、中期和晚期 HCC 患者中的作用以及潜在的新靶点,结果表明全身疗法不再局限于晚期 HCC。此外,包括双特异性抗体和嵌合抗原受体T细胞在内的T细胞重定向策略的引入彻底改变了HCC的治疗格局。未来的研究应侧重于深入探索肿瘤屏障的建立机制。
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引用次数: 0
Impact of Vertical Facial Patterns on Three-Dimensional Surgical Outcomes and Stability in Skeletal Class II Malocclusion. 垂直面部模式对骨骼ⅱ类错牙合三维手术效果和稳定性的影响。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-31 DOI: 10.1016/j.bj.2025.100894
Wasuthorn Poolsin, Ellen Wen-Ching Ko, Carol Yi-Hsuan Chen, Cheng-Hui Lin

Background: The surgical outcomes and stability of patients with skeletal Class II malocclusion determine the success of treatment. Variations in surgical interventions, patient responsiveness, and growth patterns across vertical facial morphologies result in varying treatment outcomes and postoperative stability.

Methods: This retrospective study recruited 52 adults diagnosed with skeletal Class II malocclusion treated with bimaxillary surgery; these adults were divided into two groups according to their vertical facial patterns. Cone-beam computed tomography images were collected before surgery (T0), after surgery (T1), and after orthodontic treatment (T2). Reconstructed three-dimensional images were used for cephalometric measurements and analysis.

Results: From T0 to T1, the Frankfort-mandibular plane angle decreased in the high-angle group but increased in the low-medium-angle group. The mandible advanced 9.02 and 6.21 mm in the high-angle and low-medium-angle groups, respectively. From T1 to T2, significant changes were observed in the anterior mandible horizontal movement of the high-angle group (-1.91 ± 3.63 mm) compared with the low-medium-angle group (-0.57 ± 1.04 mm). There were more patients exhibit clinically significant relapse (> 2 mm) in the high-angle group (44%) than in the low-medium-angle group (20%).

Conclusion: The relapse patterns in the two groups were similarly upward and backward. However, the high angle group exhibited greater average postoperative changes. The proportion of patients who exhibited a clinically significant relapse was higher in the high angle group.

背景:骨骼ⅱ类错牙合患者的手术结果和稳定性决定了治疗的成功与否。手术干预、患者反应性和垂直面部形态的生长模式的变化导致治疗结果和术后稳定性的变化。方法:本回顾性研究招募了52例经双颌手术治疗的成人骨骼II类错颌畸形;这些成年人根据他们的垂直面部模式被分成两组。收集术前(T0)、术后(T1)和正畸治疗后(T2)的锥束ct图像。重建的三维图像用于头部测量和分析。结果:T0 ~ T1时,高角度组法兰克福-下颌平面角减小,低-中角度组法兰克福-下颌平面角增大。高、中、低角度组下颌骨分别前进9.02、6.21 mm。从T1到T2,高角度组下颌骨前水平运动(-1.91±3.63 mm)较中低角度组(-0.57±1.04 mm)有显著变化。高角度组出现临床显著复发(> 2mm)的患者(44%)多于中低角度组(20%)。结论:两组患者的复发模式均呈上升和下降趋势。然而,高角度组表现出更大的术后平均变化。在高角度组中表现出临床显著复发的患者比例更高。
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引用次数: 0
Anisomeles indica enriched with ovatodiolide protects against aspirin-induced gastric ulcers through gut microbiota modulation. 富含卵泡内酯的印度茴香通过调节肠道微生物群来预防阿司匹林诱导的胃溃疡。
IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-23 DOI: 10.1016/j.bj.2025.100893
Hsiu-Man Lien, Yu-Yen Wang, Shiao-Wen Li, Hwai-Jeng Lin, Hui-Yu Wu, Yu-Tsen Huang, Chun-Ya Chen, Chia-Chang Chen, Cheng-Hsun Chiu, Chih-Ho Lai

Background: Gastric ulcers are commonly caused by improper use of aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or Helicobacter pylori infection. Anisomeles indica (L.) Kuntze, a traditional herbal medicine enriched with ovatodiolide, possesses potent anti-bacterial and anti-inflammatory properties and has demonstrated efficacy in improving gastric ulcers in animal models. However, its impact on the gut microbial ecosystem remains unclear. This study aimed to evaluate the therapeutic effects of A. indica fractions enriched with ovatodiolide on aspirin-induced gastric ulcers and to investigate their influence on gut microbiota composition.

Materials and methods: Aspirin-induced gastric ulcers were established in mice, followed by treatment with various A. indica fractions. The severity of gastric ulceration was assessed using histopathological analysis. Additionally, 16S rRNA V3-V4 sequencing and 16S amplicon library construction were performed to characterize gut microbiota composition.

Results: Our results showed that mice treated with ovatodiolide-enriched A. indica fractions exhibited significant amelioration of gastric ulcers compared to untreated controls. The treatment also enhanced the relative abundance of beneficial gut microbiota, including Lactobacillus and Adlercreutzia. Furthermore, histopathological examination revealed that A. indica treatment significantly upregulated mucin expression in ulcerated gastric tissues, suggesting a protective role in gastric mucosal integrity.

Conclusions: This study provides insights into the mechanisms by which A. indica alleviates gastric ulcers, highlighting its ability to modulate gut microbiota and enhance mucosal protection.

背景:胃溃疡通常是由不正确使用阿司匹林、非甾体抗炎药(NSAIDs)或幽门螺杆菌感染引起的。茴香(L.)中药Kuntze是一种富含卵泡内酯的传统草药,具有有效的抗菌和抗炎特性,并在动物模型中显示出改善胃溃疡的功效。然而,其对肠道微生物生态系统的影响尚不清楚。本研究旨在评价富含卵泡内酯的籼米提取物对阿司匹林性胃溃疡的治疗作用,并探讨其对肠道菌群组成的影响。材料与方法:建立阿斯匹林致小鼠胃溃疡模型,并给予不同成分的籼稻提取物治疗。采用组织病理学分析评估胃溃疡的严重程度。此外,通过16S rRNA V3-V4测序和16S扩增文库构建来表征肠道微生物群组成。结果:我们的研究结果表明,与未治疗的对照组相比,用富含卵泡二聚醚的籼稻提取物治疗的小鼠胃溃疡有显著改善。该治疗还提高了有益肠道菌群的相对丰度,包括乳酸杆菌和克氏Adlercreutzia。此外,组织病理学检查显示,籼稻处理显著上调了溃疡胃组织中粘蛋白的表达,表明其对胃粘膜完整性有保护作用。结论:本研究揭示了籼稻缓解胃溃疡的机制,突出了其调节肠道微生物群和增强粘膜保护的能力。
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引用次数: 0
Discrepant Treponemal Test Results: Identification of Associated Risk Factors Through Machine Learning Technology in 18-Year Electronic Medical Records and National Claims Data. 不一致的密螺旋体测试结果:通过机器学习技术在18年电子医疗记录和国家索赔数据中识别相关风险因素。
IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-19 DOI: 10.1016/j.bj.2025.100890
Hsin-Yao Wang, Ru-Fang Hu, Ting-Wei Lin, Wan-Ying Lin, Yu-Chiang Wang, Jang-Jih Lu, Yi-Ju Tseng

Background: Syphilis is a prevalent disease diagnosed primarily through serological tests. Although one confirmatory treponemal tests (TT), including Treponema pallidum particle agglutination (TPPA) or fluorescent treponema antibody absorption (FTA-Abs), is required for syphilis diagnosis, multiple TTs are commonly administered throughout the disease course. Discrepant TT results can cause confusion and delay treatment. In this study, we identified the clinical characteristics of patients with discrepant TT results and developed a machine learning tool to evaluate the risk of TT discrepancies.

Materials and methods: In this retrospective cohort study, electronic health records were linked to national claims records collected from 2001 to 2018. Variables of interest in risk factor identification and machine learning model development included medical histories and demographic characteristics. The association between syphilis treatment and discrepant TT results was assessed.

Results: Among 5,780 eligible patients tested for syphilis, 133 (2.30%) had discrepant TT results. HIV and AIDS were identified as prominent risk factors associated with discrepant TT results (adjusted odds ratio = 2.6, 95% confidence interval = 1.4-4.7). Patients with a top 5% risk probability in the LightGBM model were 10 times more likely than others to have discrepant TT results. TPPA was more likely than FTA-Abs to become negative after treatment among patients with discrepant TT results (odds ratio = 9.18, 95% confidence interval = 2.05-41.07).

Conclusions: Risk factor identification and machine learning model development can support the interpretation of serological tests for syphilis, enabling accurate diagnosis and clinical decision-making.

背景:梅毒是一种主要通过血清学检查诊断的流行疾病。虽然梅毒诊断需要进行一次确认性梅毒螺旋体试验(TT),包括梅毒螺旋体颗粒凝集(TPPA)或荧光螺旋体抗体吸收(FTA-Abs),但在整个病程中通常需要进行多次梅毒螺旋体试验。不同的TT结果可能导致混乱和延误治疗。在这项研究中,我们确定了TT结果不一致的患者的临床特征,并开发了一种机器学习工具来评估TT差异的风险。材料和方法:在这项回顾性队列研究中,电子健康记录与2001年至2018年收集的国家索赔记录相关联。风险因素识别和机器学习模型开发中感兴趣的变量包括病史和人口统计学特征。评估了梅毒治疗与不同TT结果之间的关系。结果:在5780例符合条件的梅毒检测患者中,133例(2.30%)TT结果不一致。HIV和AIDS被确定为与TT结果差异相关的重要危险因素(校正优势比= 2.6,95%可信区间= 1.4-4.7)。在LightGBM模型中,风险概率最高为5%的患者出现TT结果差异的可能性是其他患者的10倍。在TT结果不一致的患者中,TPPA比FTA-Abs更容易在治疗后变为阴性(优势比= 9.18,95%可信区间= 2.05-41.07)。结论:危险因素识别和机器学习模型开发可以支持梅毒血清学检测的解释,从而实现准确的诊断和临床决策。
{"title":"Discrepant Treponemal Test Results: Identification of Associated Risk Factors Through Machine Learning Technology in 18-Year Electronic Medical Records and National Claims Data.","authors":"Hsin-Yao Wang, Ru-Fang Hu, Ting-Wei Lin, Wan-Ying Lin, Yu-Chiang Wang, Jang-Jih Lu, Yi-Ju Tseng","doi":"10.1016/j.bj.2025.100890","DOIUrl":"https://doi.org/10.1016/j.bj.2025.100890","url":null,"abstract":"<p><strong>Background: </strong>Syphilis is a prevalent disease diagnosed primarily through serological tests. Although one confirmatory treponemal tests (TT), including Treponema pallidum particle agglutination (TPPA) or fluorescent treponema antibody absorption (FTA-Abs), is required for syphilis diagnosis, multiple TTs are commonly administered throughout the disease course. Discrepant TT results can cause confusion and delay treatment. In this study, we identified the clinical characteristics of patients with discrepant TT results and developed a machine learning tool to evaluate the risk of TT discrepancies.</p><p><strong>Materials and methods: </strong>In this retrospective cohort study, electronic health records were linked to national claims records collected from 2001 to 2018. Variables of interest in risk factor identification and machine learning model development included medical histories and demographic characteristics. The association between syphilis treatment and discrepant TT results was assessed.</p><p><strong>Results: </strong>Among 5,780 eligible patients tested for syphilis, 133 (2.30%) had discrepant TT results. HIV and AIDS were identified as prominent risk factors associated with discrepant TT results (adjusted odds ratio = 2.6, 95% confidence interval = 1.4-4.7). Patients with a top 5% risk probability in the LightGBM model were 10 times more likely than others to have discrepant TT results. TPPA was more likely than FTA-Abs to become negative after treatment among patients with discrepant TT results (odds ratio = 9.18, 95% confidence interval = 2.05-41.07).</p><p><strong>Conclusions: </strong>Risk factor identification and machine learning model development can support the interpretation of serological tests for syphilis, enabling accurate diagnosis and clinical decision-making.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100890"},"PeriodicalIF":4.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681857","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}
引用次数: 0
PAI-1 is a common driver of aging and diverse diseases PAI-1是衰老和多种疾病的共同驱动因素。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-18 DOI: 10.1016/j.bj.2025.100892
Alireza Khoddam , Toshio Miyata , Douglas Vaughan
Plasminogen activator inhibitor-1 (PAI-1) is a key driver of aging and contributes to diverse pathologies. This review examines PAI-1's multifaceted contributions to aging. At the cellular level, PAI-1 amplifies senescence, exhausts stem cell niches, and disrupts metabolism. These cellular alterations translate into physiological decline: PAI-1 drives cardiovascular aging by promoting vascular senescence and arterial stiffening, contributes to cognitive decline by impairing amyloid-beta clearance, fuels cancer progression through angiogenesis and immune suppression, and exacerbates muscle atrophy by hindering regeneration. A rare loss-of-function SERPINE1 mutation extends lifespan, illustrating how lifelong PAI-1 reduction can positively impact the human healthspan. Looking forward, targeting PAI-1 with inhibitors could mitigate senescence, restore stem cell function, improve metabolic profile, enhance physiological health, and promise a longer healthspan.
纤溶酶原激活物抑制剂-1 (PAI-1)是衰老的关键驱动因素,并参与多种病理。本文综述了PAI-1对衰老的多方面贡献。在细胞水平上,PAI-1会加速衰老,耗尽干细胞壁龛,扰乱新陈代谢。这些细胞改变转化为生理衰退:PAI-1通过促进血管衰老和动脉硬化来驱动心血管老化,通过损害淀粉样蛋白清除来促进认知能力下降,通过血管生成和免疫抑制来促进癌症进展,并通过阻碍再生来加剧肌肉萎缩。一种罕见的SERPINE1功能缺失突变可以延长寿命,说明终身PAI-1减少如何对人类健康产生积极影响。展望未来,利用抑制剂靶向PAI-1可以延缓衰老,恢复干细胞功能,改善代谢谱,增强生理健康,并有望延长健康寿命。
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引用次数: 0
Vomocytosis of Cryptococcus neoformans from Macrophages: from discovery to current understanding. 巨噬细胞引起的新型隐球菌呕吐:从发现到现在的认识。
IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-16 DOI: 10.1016/j.bj.2025.100891
Chinaemerem U Onyishi

The entry of pathogens into host cells is a critical and widely appreciated step in host-pathogen interactions. While significant progress has been made in understanding the various mechanisms by which microbes are taken up by host cells, an appreciation of exit strategies remains limited. Nearly two decades ago, in 2006, two independent groups observed the non-lytic expulsion of the opportunistic fungal pathogen C. neoformans from macrophages, a process also termed vomocytosis. Over the years, various host and pathogen factors have been implicated in modulating vomocytosis; however, a clear understanding of the triggers, the downstream signaling cascades driving expulsion, and the consequences of vomocytosis on pathogenesis remain elusive. In this review, I provide a historical account of vomocytosis in macrophages, summarize our current understanding of its mechanism, discuss its biological significance, and offer suggestions for future research directions.

病原体进入宿主细胞是宿主-病原体相互作用中一个关键且被广泛认可的步骤。虽然在理解微生物被宿主细胞吸收的各种机制方面取得了重大进展,但对退出策略的认识仍然有限。近20年前,在2006年,两个独立的研究小组观察到机会性真菌病原体C.新生形式从巨噬细胞中非溶解性排出,这一过程也被称为呕吐细胞作用。多年来,各种宿主和病原体因素已参与调节呕吐细胞;然而,对触发因素、下游信号级联驱动的排出以及呕吐细胞病在发病机制中的影响的清楚理解仍然是难以捉摸的。本文综述了巨噬细胞呕吐作用的历史,总结了目前对其机制的认识,讨论了其生物学意义,并对未来的研究方向提出了建议。
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引用次数: 0
Photodynamic therapy-induced inflammation and adverse effects: An updated review. 光动力疗法引起的炎症和不良反应:最新综述。
IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-15 DOI: 10.1016/j.bj.2025.100889
Kave Moloudi, Heidi Abrahamse, Blassan P George

Photodynamic therapy (PDT) is a non-invasive medical treatment that uses a photosensitizing agent and light to treat various medical conditions and ophthalmology including chronic central serous chorioretinopathy, cancer, skin disorders, and infections. Local inflammation in tumor environment after PDT can be effective in eliciting an immune response to improve treatment efficiency but it causes some early and long-term side effects in local and surround tissues, resulting leads to incidental effects and unwilling consequences such as pain, erythema and infection. Moreover, the mechanism of inflammation in PDT is not clear. Employment of non-optimized protocol including cytotoxic photosensitizer (PS) and fluence and fluence rate during PDT can bring biased outcomes for patients in terms of inflammation and treatment. In PDT, the minimum cytotoxicity and side effects of normal tissue depend on several factors, including the type and location of the tumor to be treated, the PS used, laser power, oxygen level, tumor properties and the patient's individual characteristics. Therefore, careful consideration and adjustment of these parameters are essential for achieving successful PDT outcome. However, in this topical review, various databases, including PubMed, ScienceDirect, and Google Scholar, were used to find relevant studies for this purpose. We highlighted various parameters that influence on cytotoxicity and inflammation response of normal tissue after PDT. Additionally, various pathways that PDT induced inflammation summarized as well as associated side effects have been categorized and finally, we proposed some factors to reduce the side effects and cytotoxicity to the normal tissue in future.

光动力疗法(PDT)是一种非侵入性医学治疗,它使用光敏剂和光来治疗各种疾病和眼科,包括慢性中枢性浆液性脉络膜视网膜病变、癌症、皮肤病和感染。PDT后肿瘤环境局部炎症可有效引发免疫应答,提高治疗效率,但其对局部及周围组织的早期和长期副作用,可导致疼痛、红斑、感染等偶发效应和不愿发生的后果。此外,炎症在PDT中的作用机制尚不清楚。在PDT期间使用非优化方案,包括细胞毒性光敏剂(PS)和影响力和影响力率,可能会给患者带来炎症和治疗方面的偏倚结果。在PDT中,正常组织的最小细胞毒性和副作用取决于几个因素,包括待治疗肿瘤的类型和位置、使用的PS、激光功率、氧气水平、肿瘤特性和患者的个体特征。因此,仔细考虑和调整这些参数对于实现成功的PDT结果至关重要。然而,在这篇专题综述中,我们使用了各种数据库,包括PubMed、ScienceDirect和谷歌Scholar,来查找相关的研究。我们强调了影响PDT后正常组织细胞毒性和炎症反应的各种参数。此外,总结了PDT诱导炎症的各种途径以及相关的副作用,并提出了未来减少PDT对正常组织的副作用和细胞毒性的一些因素。
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引用次数: 0
Drug Repurposing Targeting miRNA-mRNA Networks to Mitigate Areca Nut-Induced Head and Neck Cancer. 靶向miRNA-mRNA网络的药物再利用减轻槟榔诱导的头颈癌。
IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-08 DOI: 10.1016/j.bj.2025.100886
Hung-Han Huang, Joseph T Chang, Guo-Rung You, Yi-Chen Li, Yi-Fang Huang, Yu-Chen Huang, Eric Yi-Liang Shen, Yin-Ju Chen, Ching-Chi Chiu, Ann-Joy Cheng

Background: Areca nut is a significant risk factor for head and neck cancer (HNC), yet its molecular mechanisms, particularly miRNA-mediated regulation, remain poorly understood. This study investigates the regulatory networks underlying areca nut-induced HNC and explores therapeutic strategies through computational drug repurposing.

Materials and methods: Arecoline was used to assess its effects on invasion, migration, and cisplatin resistance in HNC cells and normal keratinocytes. Differentially expressed miRNAs and mRNAs were identified using high-throughput profiling, followed by integrative network analysis using TCGA-HNSC dataset and multiMiR. OncoPredict was used for drug repurposing to identify therapeutic agents targeting dysregulated miRNA-mRNA networks.

Results: Arecoline exposure promoted invasion and cisplatin resistance, with more pronounced effects in normal keratinocytes, indicating a potential role in early tumorigenesis. Integrative transcriptomic analysis revealed a miRNA-mRNA regulatory network comprising 1,971 oncogenes, 604 tumor suppressors, 35 oncogenic miRNA (OncomiRs), and 36 tumor suppressive miRNA (TSmiRs) regulating pathways related to cell motility and stress response. A tumor-suppressive network with miR-212-3p as a central hub and an oncogenic network modulated by miR-410 and miR-1-3p as critical hubs were identified. Drug repurposing analysis identified four potential therapeutic candidates (MK-2206, BYL-719, MG-132, and FGIN-1-27), with MK-2206 emerging as the most promising. MK-2206 effectively reversed arecoline-induced miRNA-mRNA dysregulation, mitigated malignant phenotypes, and selectively targeted HNC cells while sparing normal keratinocytes.

Conclusions: This integrative approach elucidates areca nut-driven carcinogenesis through miRNA-mRNA interactions and highlights MK-2206 as a promising therapeutic strategy for areca nut-associated HNC.

背景:槟榔果是头颈癌(HNC)的重要危险因素,但其分子机制,特别是mirna介导的调控机制尚不清楚。本研究探讨槟榔果诱导HNC的调控网络,并通过计算药物再利用探索治疗策略。材料和方法:槟榔碱对HNC细胞和正常角质形成细胞的侵袭、迁移和顺铂耐药性的影响。通过高通量分析鉴定差异表达的mirna和mrna,然后使用TCGA-HNSC数据集和multiMiR进行综合网络分析。OncoPredict用于药物再利用,以确定靶向失调的miRNA-mRNA网络的治疗剂。结果:槟榔碱暴露促进了侵袭和顺铂耐药性,对正常角质形成细胞的影响更为明显,表明其在早期肿瘤发生中可能起作用。综合转录组学分析揭示了一个由1971个癌基因、604个抑癌基因、35个致癌miRNA (OncomiRs)和36个抑癌miRNA (TSmiRs)组成的miRNA- mrna调控网络,这些miRNA调节与细胞运动和应激反应相关的途径。发现了一个以miR-212-3p为中心枢纽的肿瘤抑制网络和一个由miR-410和miR-1-3p作为关键枢纽调节的致癌网络。药物再利用分析确定了四种潜在的治疗候选药物(MK-2206, BYL-719, MG-132和FGIN-1-27),其中MK-2206最有希望。MK-2206有效逆转槟榔碱诱导的miRNA-mRNA失调,减轻恶性表型,选择性靶向HNC细胞,同时保留正常角质形成细胞。结论:这种综合方法通过miRNA-mRNA相互作用阐明了槟榔果驱动的致癌作用,并强调了MK-2206是一种有希望的治疗槟榔果相关HNC的策略。
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引用次数: 0
ShinySC: An R/Shiny-based desktop application for seamless analysis of scRNA-Seq data ShinySC:基于R/ shine的桌面应用程序,用于无缝分析scRNA-Seq数据。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-07-01 DOI: 10.1016/j.bj.2025.100885
Po-Jung Huang , Fang-Yu Tsai , Yi-Ju Wu , Yi-Chen Weng , Chi-Ching Lee , Sin-Hong Shih , Shih Sheng Jiang

Background

Single-cell RNA sequencing (scRNA-seq) enables detailed profiling of cellular heterogeneity, but complex workflows and diverse data formats limit accessibility for clinicians and researchers without programming expertise.

Results

We introduce ShinySC, an R/Shiny-based desktop application designed to streamline comprehensive scRNA-seq analysis through an intuitive graphical interface. ShinySC supports various input formats, including 10x Genomics, Seurat, Scanpy, BD Rhapsody, and CellView. The tool integrates essential analytical procedures such as quality control, normalization, dimensionality reduction, clustering, marker gene identification, batch correction, differential expression analysis, and trajectory inference. Notably, ShinySC implements multiple automatic cell-type annotation methods—reference-based (SingleR), marker-based (ScType, scCATCH), and GPT-based (GPTCelltype)—with features for side-by-side comparison and manual label refinement. Benchmarking indicates robust performance for datasets containing up to 200,000 cells on standard desktop systems with 64 GB RAM, with analysis duration dependent on specific tasks and annotation methods. Demonstrative analyses of PBMC and interferon-stimulated datasets confirm ShinySC's efficacy in accurately annotating cell types and capturing condition-specific transcriptional dynamics.

Conclusions

ShinySC provides a unified, user-friendly, and scalable platform for scRNA-seq analysis explicitly tailored for non-programming users. It surpasses existing limitations by accommodating multiple data formats, employing versatile annotation strategies, and generating high-quality, publication-ready figures. Available freely across Windows, macOS, and Linux platforms, ShinySC enhances the accessibility and reproducibility of single-cell transcriptomic research.

Availability

http://tardis.cgu.edu.tw/ShinySC.
背景:单细胞RNA测序(scRNA-seq)能够详细分析细胞异质性,但复杂的工作流程和多样化的数据格式限制了没有编程专业知识的临床医生和研究人员的可访问性。结果:我们介绍了ShinySC,一个基于R/ shine的桌面应用程序,旨在通过直观的图形界面简化全面的scRNA-seq分析。ShinySC支持各种输入格式,包括10x Genomics, Seurat, Scanpy, BD Rhapsody和CellView。该工具集成了必要的分析程序,如质量控制、标准化、降维、聚类、标记基因鉴定、批量校正、差异表达分析和轨迹推断。值得注意的是,ShinySC实现了多种自动单元格类型注释方法——基于引用的(SingleR)、基于标记的(ScType、scCATCH)和基于gpt的(GPTCelltype)——具有并排比较和手动标签优化的功能。基准测试表明,在具有64 GB RAM的标准桌面系统上,包含多达200,000个单元格的数据集具有强大的性能,分析持续时间取决于特定的任务和注释方法。对PBMC和干扰素刺激数据集的论证性分析证实了ShinySC在准确注释细胞类型和捕获条件特异性转录动力学方面的功效。结论:ShinySC为非编程用户提供了一个统一的、用户友好的、可扩展的scRNA-seq分析平台。它通过容纳多种数据格式、采用通用注释策略和生成高质量、可发布的图形,超越了现有的限制。ShinySC可在Windows、macOS和Linux平台上免费使用,增强了单细胞转录组学研究的可访问性和可重复性。可用性:http://tardis.cgu.edu.tw/ShinySC。
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引用次数: 0
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Biomedical Journal
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