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Multispecies Signatures and Driving Factors of Oral Microbiome Dysbiosis in Pediatric Crohn’s Disease in the United Arab Emirates 阿拉伯联合酋长国儿童克罗恩病口腔微生物群失调的多物种特征和驱动因素
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-31 DOI: 10.1016/j.arcmed.2026.103389
Ghaidaa Mesto , Eman Al Atrash , David Rawat , Hala Elzayat , Mohamad Miqdady , Farah Al-Marzooq

Purpose

Despite the recognized impact of the gut microbiome, research on the oral microbiome is limited, particularly in pediatric patients with Crohn’s disease (CD). This study aims to explore salivary microbiome signatures in pediatric patients with CD from the United Arab Emirates (UAE), compared to healthy controls (HC), by analyzing early-life, lifestyle, and disease-specific factors driving dysbiosis.

Methods

Salivary samples from 52 pediatric patients with CD and HC (n = 26/group) were subjected to 16S rRNA sequencing using Oxford Nanopore technology. Bioinformatics and biostatistical analyses were employed to compare groups and identify microbiota signatures correlated with clinical data.

Results

Enrichment of several species, including Veillonella parvula, Veillonella dispar, and Prevotella denticola, with depletion of beneficial bacteria was observed in CD. Machine learning-based composite biomarker analysis identified 36 species distinguishing CD from HC, most of which are opportunistic pathogens, raising concerns about their potential impact on vulnerable pediatric patients with CD. Multifactorial analysis revealed significant oral microbiome dysbiosis in patients with CD across all 15 analyzed factors, with unique CD-specific biomarkers. The strongest associations with microbial alterations were demonstrated by disease duration, diet, exercise habits, early antibiotic exposure, and delivery method. Among the 19 species analyzed, Capnocytophaga gingivalis demonstrated multifactorial associations, emerging as an integrative biomarker of disease burden. The α-diversity was significantly lower in patients with CD, with distinctive β-diversity patterns.

Conclusion

This is the first comprehensive multifactorial analysis of the oral microbiome in pediatric patients with CD from the Middle East, employing novel machine learning approaches for composite biomarker discovery. Core dysbiotic species in CD may serve as potential diagnostic and prognostic biomarkers requiring validation in larger-scale studies.
目的:尽管肠道微生物组的影响已得到公认,但对口腔微生物组的研究仍然有限,特别是在克罗恩病(CD)的儿科患者中。本研究旨在通过分析早期生活、生活方式和驱动生态失调的疾病特异性因素,探索阿拉伯联合酋长国(UAE)儿科乳糜泻患者与健康对照组(HC)相比的唾液微生物组特征。方法采用牛津纳米孔技术对52例小儿CD和HC患者唾液样本(26例/组)进行16S rRNA测序。采用生物信息学和生物统计学分析进行组间比较,并确定与临床数据相关的微生物群特征。结果CD中包括细小微孔菌、细小微孔菌和齿状普雷沃氏菌等多种菌种的富集,而有益菌的减少。基于机器学习的复合生物标志物分析鉴定出36种将CD与HC区分出来的菌种,其中大多数是条件致病菌。多因素分析显示,在所有15个分析因素中,有独特的CD特异性生物标志物,CD患者口腔微生物群失调显著。微生物改变与疾病持续时间、饮食、运动习惯、早期抗生素暴露和给药方式的相关性最强。在分析的19个物种中,牙龈碳噬菌显示出多因子相关性,成为疾病负担的综合生物标志物。CD患者α-多样性明显降低,β-多样性模式明显。这是首次对中东儿童CD患者口腔微生物组进行综合多因素分析,采用新颖的机器学习方法发现复合生物标志物。乳糜泻的核心益生不良物种可能作为潜在的诊断和预后生物标志物,需要在更大规模的研究中进行验证。
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引用次数: 0
Pro-Tumorigenic Roles of Cyclin Dependent Kinase 2 and its Associated Cyclins in Cholangiocarcinoma Progression under High Glucose Condition 细胞周期蛋白依赖性激酶2及其相关细胞周期蛋白在高糖条件下胆管癌进展中的致瘤作用
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-30 DOI: 10.1016/j.arcmed.2026.103383
Cheerapinya Taebprakhon , Supannika Sorin , Kullanat Khawkhiaw , Chatchai Phoomak , Wunchana Seubwai , Sopit Wongkham , Charupong Saengboonmee

Background

Previous studies have shown that hyperglycemia upregulates cyclin-dependent kinase 2 (CDK2) and its cyclin partners, cyclin E and cyclin A, in cholangiocarcinoma (CCA). However, the effects of targeting these proteins in a hyperglycemic state are unclear.

Aim

This study aimed to investigate the therapeutic effects of inhibiting CDK2 and its cyclin partners under high-glucose conditions.

Methods

CCA cells were cultured in normal glucose (NG) and high glucose (HG) conditions. Expression of CDK2 and the associated cyclins was analyzed using online public databases and verified by Western blot. Cell proliferation and cytotoxicity were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. CDK2 activity was inhibited using tagtociclib. Cyclin E and cyclin A expression was suppressed using siRNA. Molecular mechanisms were analyzed using flow cytometry and Western blot.

Results

CDK2, cyclin E, and cyclin A were upregulated in CCA tissues and cells cultured in the HG condition compared with normal bile ducts. Tagtociclib significantly suppressed CCA cell growth, with HG cells being more sensitive than NG cells. Partial suppression of cyclin E and cyclin A expression minimally affected cell growth but significantly reduced the metastatic phenotypes of CCA cells by suppressing the epithelial-mesenchymal transition.

Conclusion

CCA cells with upregulated CDK2 and its cyclin partners in HG were more sensitive to tagtociclib at a higher dose. Cyclin E and cyclin A also regulated CCA metastasis by controlling epithelial-mesenchymal transition. Targeting CDK2 and its associated cyclins in CCA cells demonstrated therapeutic potential that requires further translational and clinical verification.
先前的研究表明,在胆管癌(CCA)中,高血糖可上调细胞周期蛋白依赖性激酶2 (CDK2)及其细胞周期蛋白伙伴细胞周期蛋白E和细胞周期蛋白A。然而,在高血糖状态下靶向这些蛋白的效果尚不清楚。目的探讨抑制CDK2及其周期蛋白伴侣在高糖条件下的治疗作用。方法在正常葡萄糖(NG)和高糖(HG)条件下培养scca细胞。使用在线公共数据库分析CDK2和相关细胞周期蛋白的表达,并通过Western blot验证。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)和硫代丹胺B (SRB)测定细胞增殖和细胞毒性。他托西尼可抑制CDK2活性。使用siRNA抑制Cyclin E和Cyclin A的表达。采用流式细胞术和Western blot分析其分子机制。结果与正常胆管相比,HG条件下CCA组织和细胞中scdk2、cyclin E和cyclin A表达上调。Tagtociclib显著抑制CCA细胞生长,HG细胞比NG细胞更敏感。部分抑制cyclin E和cyclin A表达对细胞生长影响最小,但通过抑制上皮-间质转化显著降低了CCA细胞的转移表型。结论CDK2及其周期蛋白伴侣在HG中表达上调的cca细胞对大剂量他托西尼更敏感。细胞周期蛋白E和细胞周期蛋白A也通过控制上皮-间质转化来调节CCA转移。在CCA细胞中靶向CDK2及其相关细胞周期蛋白显示出治疗潜力,需要进一步的转化和临床验证。
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引用次数: 0
Comparability of Interstitial and Capillary Blood Glucose Values: A Cross-Sectional Study of Samples from Patients with Multiple Organ Failure 间质和毛细血管血糖值的可比性:多器官衰竭患者样本的横断面研究
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-30 DOI: 10.1016/j.arcmed.2026.103382
Julio Edgardo Gonzalez-Aguirre, Hector Alejandro Medina-Ramirez, Berenice Soto-Moncivais, Sofia Rebeca Sanchez-Ruiz, Carlos Garcia-Arroyo, Juan Francisco Moreno-Hoyos-Abril, Homero Nañez-Terreros

Purpose

Several studies have evaluated the use of interstitial flash glucose (IFG) monitors in critically ill patients. IFG offers potential advantages over capillary blood glucose (CBG) measurements. This study examined the agreement between IFG and CBG values in patients with multiple organ failure (MOF) who required vasopressors and were admitted to the intensive care unit (ICU).

Methods

This cross-sectional study included 394 pairs of CBG and IFG determinations corresponding to 11 ICU-admitted patients. All patients had MOF and required an IV vasopressor infusion. IFG accuracy against CBG was assessed using the Bland-Altman method and by calculating the median absolute relative difference (MARD). Clinical accuracy was assessed using the Clarke Consensus Error Grid (CEG).

Results

The MARD between IFG and CBG was –4.90 (IQR –18.05 to 9.75) mg/dL. Only 76 (19.3%) glucose pairs had MARD above the recommended value of 14%. A positive cumulative balance and intravenous insulin administration were associated with an increased MARD. Bland-Altman analysis revealed a mean difference of 4.79% (SD = 24.06%, 95% CI 2.34–7.24%), with upper and lower limits of agreement of 51.93% (95% CI 47.0–55.56%) and –42.36% (95% CI –46.7 to –37.9%), respectively. A total of 186 (49.9%) IFG were above the recommended threshold value of 12.5% compared to the CBG reference. Only 246 (62.6%) determinations were in the risk zone of the CEG.

Conclusion

IFG does not demonstrate analytical or clinical accuracy equivalent to CBG in patients with MOF requiring vasopressor infusion.
几项研究评估了间质瞬时血糖(IFG)监测仪在危重患者中的应用。IFG比毛细管血糖(CBG)测量具有潜在的优势。本研究检查了多器官衰竭(MOF)患者IFG和CBG值之间的一致性,这些患者需要血管加压药物并被送入重症监护病房(ICU)。方法本横断面研究包括11例icu住院患者的394对CBG和IFG测定。所有患者都有MOF,需要静脉输注血管加压素。使用Bland-Altman方法和计算中位数绝对相对差(MARD)来评估IFG对CBG的准确性。临床准确性评估使用克拉克共识误差网格(CEG)。结果IFG与CBG的MARD值为-4.90 (IQR值为-18.05 ~ 9.75)mg/dL。只有76(19.3%)对葡萄糖的MARD高于14%的推荐值。累积平衡阳性和静脉注射胰岛素与MARD增加有关。Bland-Altman分析显示平均差异为4.79% (SD = 24.06%, 95% CI 2.34-7.24%),一致性上限和下限分别为51.93% (95% CI 47.0-55.56%)和-42.36% (95% CI -46.7 -37.9%)。与CBG参考值相比,共有186例(49.9%)IFG高于推荐阈值12.5%。只有246例(62.6%)处于CEG的危险区。结论:ifg在需要血管加压剂输注的MOF患者中没有显示出与CBG相当的分析或临床准确性。
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引用次数: 0
Pirfenidone as a Pleiotropic Antifibrotic Agent in Metabolic Steatohepatitis: From Mechanisms to Clinical Evidence 吡非尼酮作为代谢性脂肪性肝炎的多效抗纤维化药物:从机制到临床证据
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-30 DOI: 10.1016/j.arcmed.2026.103387
Mariana M. Ramírez-Mejía , Guadalupe Ponciano-Rodríguez , Jorge L. Poo , Nahum Méndez-Sánchez
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive phenotype of steatotic liver disease that can lead to advanced fibrosis, cirrhosis and liver-related complications. Pirfenidone is a small synthetic molecule that was originally approved for idiopathic pulmonary fibrosis. It has pleiotropic antifibrotic, anti-inflammatory, antioxidant, and immunomodulatory properties. In preclinical liver models, pirfenidone reduces hepatic stellate cell activation, collagen deposition, oxidative stress and proinflammatory cytokine expression, largely through the modulation of transforming growth factor β (TGF-β), platelet-derived growth factor (PDGF), mitogen-activated protein kinases, and the Nrf2 axis. Early clinical trials, including the large prospective cohort PROMETEO, the randomized controlled trial in compensated cirrhosis ODISEA, and the translational trial in post-sustained viral response fibrosis MINERVA, show improvements in noninvasive fibrosis markers, liver function tests, quality of life, and parallel epigenetic remodeling. These data suggest that pirfenidone acts on central fibrogenic biology and may contribute to histological regression in advanced disease. Larger and longer trials, as well as rational combinations with metabolic agents, are needed to define its therapeutic role in MASH.
代谢功能障碍相关脂肪性肝炎(MASH)是一种进行性脂肪性肝病,可导致晚期纤维化、肝硬化和肝脏相关并发症。吡非尼酮是一种小合成分子,最初被批准用于特发性肺纤维化。它具有多种抗纤维化、抗炎、抗氧化和免疫调节特性。在临床前肝脏模型中,吡非尼酮主要通过调节转化生长因子β (TGF-β)、血小板衍生生长因子(PDGF)、丝裂原活化蛋白激酶和Nrf2轴,降低肝星状细胞活化、胶原沉积、氧化应激和促炎细胞因子的表达。早期临床试验,包括大型前瞻性队列PROMETEO、代偿性肝硬化ODISEA的随机对照试验和持续后病毒反应性纤维化MINERVA的转化试验,均显示无创纤维化标志物、肝功能测试、生活质量和平行表观遗传重塑方面的改善。这些数据表明吡非尼酮对中心纤维化生物学起作用,并可能促进晚期疾病的组织学退化。需要更大规模和更长时间的试验,以及与代谢药物的合理联合,以确定其在MASH中的治疗作用。
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引用次数: 0
Mechanisms of Chemoresistance in Malignant Pleural Mesothelioma: The Regulatory Role of miRNAs 恶性胸膜间皮瘤化疗耐药机制:mirna的调控作用
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-27 DOI: 10.1016/j.arcmed.2025.103326
Andrea Martinez-Marroquin , Javier Gaytán-Cervantes , Haydeé Rosas-Vargas , Constantino López-Macías , Itzel Peralta-Salguero , Miguel Cid-Soto , Violeta Castro Leyva , Marlon De Ita , Carolina González-Torres
Malignant pleural mesothelioma (MPM), is a rare and aggressive cancer that originates in the mesothelium lining the lungs. It is considered an occupational disease associated with exposure to asbestos in the workplace. MPM is often diagnosed in the late stages and has a poor response to treatment. Since the cause of the limited response to therapy in patients with MPM is unknown, it is necessary to establish the mechanisms related to chemoresistance, such as microRNAs (miRNAs), which play a specific role. Several studies have demonstrated that the downregulation of miR-15 and miR-16 in MPM cell lines is associated with chemoresistance, and that their overexpression contributes to sensitizing cells to chemotherapy. In addition, some miRNAs have been shown to be associated with epithelial-mesenchymal transition (EMT) in MPM cells. EMT has been linked to the acquisition of a chemoresistant phenotype; moreover, the release of miRNAs into circulating exosomes from patients with MPM could also impact the resistance to conventional treatments. This review aims to summarize the current knowledge on the role of miRNAs in MPM and their relationship with chemoresistance, as well as to establish new knowledge to support the development of improved treatment for patients with MPM.
恶性胸膜间皮瘤(MPM)是一种罕见的侵袭性癌症,起源于肺部的间皮层。它被认为是一种职业病,与在工作场所接触石棉有关。MPM通常在晚期被诊断出来,对治疗的反应很差。由于MPM患者对治疗反应有限的原因尚不清楚,因此有必要建立与化疗耐药相关的机制,例如发挥特定作用的microRNAs (miRNAs)。一些研究表明,MPM细胞系中miR-15和miR-16的下调与化疗耐药有关,并且它们的过表达有助于细胞对化疗敏感。此外,一些mirna已被证明与MPM细胞的上皮-间质转化(EMT)有关。EMT与化学耐药表型的获得有关;此外,MPM患者将mirna释放到循环外泌体中也可能影响对常规治疗的耐药性。本文旨在总结mirna在MPM中的作用及其与化疗耐药的关系的现有知识,并建立新的知识,以支持MPM患者改进治疗的发展。
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引用次数: 0
Viewpoint: Beyond Glycated Hemoglobin—The Frontier of Novel Biomarkers in Diabetes Care 观点:超越糖化血红蛋白——糖尿病治疗新生物标志物的前沿
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-24 DOI: 10.1016/j.arcmed.2025.103331
Yashendra Sethi , Inderbir Padda , Siddharth Gosavi , Saurabh Singhal , Arsalan Moinuddin
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引用次数: 0
Cardiomyopathy in Northwestern Mexico: Clinical Spectrum, Morphological Variants, and Sarcomere Gene Mutations 墨西哥西北部的心肌病:临床谱、形态变异和肌瘤基因突变
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-24 DOI: 10.1016/j.arcmed.2025.103362
Cyntia Zulema Machain-Leyva , Cuitláhuac Arroyo-Rodríguez , Luis Alejandro Padilla-Islas , Francisco A. Martínez Hernández , Sergio Ramón Figueroa-Sauceda , Verónica Zazueta-Armenta

Background

Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease characterized by left ventricular (LV) hypertrophy that cannot be fully explained by abnormal loading conditions.

Aim

To describe the clinical spectrum, morphological variants and sarcomere gene mutations in patients with HCM from northwestern Mexico.

Materials and Methods

We conducted a prospective, cross-sectional study of patients diagnosed with HCM by echocardiography. Morphological variants were classified as: asymmetric septal, concentric, mid-cavity, lateral, and apical according to the location of the greatest LV thickening. Next-generation sequencing was performed with a predesigned panel of 19 genes associated with HCM.

Results

A total of 110 patients (47.3% women; median age 58) were enrolled. Apical HCM was the most frequent morphological variant (42%), followed by asymmetric septal HCM (35%). Patients with apical HCM were older than those with other variants (p = 0.002). Patients with asymmetric septal hypertrophy had a higher septal/posterior wall thickness ratio (1.85 ± 0.6, p = 0.0001) and a larger left atrial anteroposterior diameter (48 ± 9, p = 0.0001). LV outflow obstruction, systolic anterior motion, and severe mitral regurgitation were more prevalent in patients with asymmetric septal HCM (p = 0.0001). Patients with concentric HCM had the greatest E/e’ ratio (16.3 ± 8, p = 0.01). Among genotyped patients, 44% had a sarcomeric gene mutation, most commonly MYBPC3 (24%) and MYH7 (7%), with no significant differences across morphological variants.

Conclusions

Apical HCM was the most frequent morphological variant of HCM in the studied population. Consistent with global reports, MYBPC3 and MYH7 were the most commonly identified gene mutations.
背景肥厚性心肌病(HCM)是一种常见的遗传性心脏病,其特征是左心室(LV)肥大,不能完全用异常负荷条件来解释。目的描述墨西哥西北部HCM患者的临床谱、形态学变异和肌瘤基因突变。材料和方法我们对超声心动图诊断为HCM的患者进行了前瞻性横断面研究。根据左室最大增厚的位置,形态学变异分为:不对称间隔型、同心型、中腔型、外侧型和顶端型。使用预先设计的19个与HCM相关的基因进行下一代测序。结果共纳入110例患者(女性47.3%,中位年龄58岁)。顶端HCM是最常见的形态变异(42%),其次是不对称的间隔HCM(35%)。根尖HCM患者比其他变异患者年龄大(p = 0.002)。不对称间隔肥厚患者的间隔/后壁厚度比较高(1.85±0.6,p = 0.0001),左房前后径较大(48±9,p = 0.0001)。左室流出梗阻、收缩期前运动和严重二尖瓣反流在不对称室间隔HCM患者中更为普遍(p = 0.0001)。同心型HCM患者E/ E′比值最高(16.3±8,p = 0.01)。在基因分型的患者中,44%的患者有肉瘤基因突变,最常见的是MYBPC3(24%)和MYH7(7%),在形态变异之间没有显著差异。结论鼻尖型HCM是研究人群中最常见的HCM形态变异。与全球报告一致,MYBPC3和MYH7是最常见的基因突变。
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引用次数: 0
First 1,000 Days of Life Have a Direct Impact on Health: A Mexican Strategy 生命最初1000天对健康有直接影响:墨西哥战略。
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-19 DOI: 10.1016/j.arcmed.2025.103369
Victoria Ramirez , Itzel Kim , Regina J. Bautista , Claudia J. Bautista
Chronic non-communicable degenerative diseases are the leading cause of mortality, morbidity, and disability in Mexico and worldwide, negatively impacting national economies by consuming health and social resources. These diseases include hypertension, obesity, and cardiovascular diseases resulting from inadequate dietary conditions and current lifestyles. It is undeniable that nutrition and healthy habits are prerequisites for a healthy life. However, the significance of nutrition and health habits is amplified during the initial 1,000 days of life, when an individual is unable to select their food or environment. This is due to the fact that this is a period of organ and system development, when the body is particularly vulnerable to inadequate nutrition and a toxic environment, especially during pregnancy. The present review has two objectives. First, it aims to describe the importance of maintaining a healthy, balanced diet from conception through the first two years of life. Second, it will explore current Mexican nutritional recommendations, public strategies, and innovations to improve in each stage of development. This review will also help formulate targeted health strategies for this population, fostering the comprehensive approach essential for establishing lifelong healthy habits with long-term benefits for children, adolescents, and adults.
慢性非传染性退行性疾病是墨西哥和全世界死亡、发病和残疾的主要原因,通过消耗卫生和社会资源对国民经济产生负面影响。这些疾病包括高血压、肥胖和心血管疾病,这些疾病是由不适当的饮食条件和目前的生活方式造成的。不可否认,营养和健康的习惯是健康生活的先决条件。然而,营养和健康习惯的重要性在生命的最初1 000天中被放大,因为那时一个人无法选择食物或环境。这是因为这是一个器官和系统发育的时期,当身体特别容易受到营养不足和有毒环境的影响,特别是在怀孕期间。本次审查有两个目的。首先,它旨在描述从怀孕到生命最初两年保持健康、均衡饮食的重要性。其次,它将探讨墨西哥目前的营养建议、公共战略和创新,以改善每个发展阶段。这项审查还将有助于为这一人群制定有针对性的健康战略,促进对建立终身健康习惯至关重要的综合方法,并为儿童、青少年和成人带来长期利益。
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引用次数: 0
Decoding the Mutational Hierarchy of Thyroid Cancer and Associated Signaling Pathways 解码甲状腺癌的突变层次和相关的信号通路。
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-05 DOI: 10.1016/j.arcmed.2025.103366
Disha Nashier , Gowrang Kasaba Manjunath , Alisha Parveen , Sumira Malik , Tamoghna Mitra , Chandan Goswami , Muniasamy Neerathilingam , Ankit Watts , Abhishek Kumar

Background

Thyroid cancer (TC) is the most prevalent endocrine malignancy, and its development is influenced by various genomic abnormalities. Activating mutations in oncogenes such as BRAF and RAS significantly contribute to tumorigenesis. Nevertheless, the overall mutational landscape of TC remains unclear.

Methods

We conducted a systematic analysis of genomic data from 1,629 TC samples across four independent studies (including TCGA and MSKCC) available on the cBioPortal platform. We calculated mutation frequencies for all genes and categorized those exceeding a 3% threshold as high-frequency driver genes (Tier I) and genes with moderate mutation rates (Tier II).

Results

A total of 1,363 genes exhibited mutation frequencies above 3% within the TC cohort. Tier I genes included BRAF (56.9%), NRAS (9.3%), TERT promoter (4.6%), HRAS (3.5%), and TTN (3.2%), with BRAFV600E. Tier II featured 19 genes, such as TG (2.9%), linked to follicular carcinogenesis, and TP53 (2.7%), associated with poorly differentiated subtypes. Pathway analysis revealed enrichment in MAPK/ERK signaling, PI3K-AKT activation, and telomerase maintenance. PPI networks identified lesser-studied interactors involved in DNA repair and cell cycle regulation, suggesting new therapeutic targets. Among the 1,620 patients with TC, females predominated and the peak incidence occurred in middle adulthood. This study illustrates a strong mutual exclusivity between BRAF and RET alterations, with minimal co-occurrence, indicating functional redundancy through shared MAPK/ERK and PI3K/AKT signaling pathways.

Conclusions

The present study clarifies the mutation hierarchy and cooperative pathways in TC, underscoring the significance of BRAF- and RAS-driven oncogenesis. The discovery of under-explored genes within DNA damage response and cell cycle networks paves the way for targeted therapy development. Furthermore, the high frequency of TERT promoter mutations emphasizes their role in disease progression.
背景:甲状腺癌(TC)是最常见的内分泌恶性肿瘤,其发展受多种基因组异常的影响。致癌基因如BRAF和RAS的激活突变显著促进肿瘤的发生。然而,TC的整体突变情况仍不清楚。方法:我们对cbiopportal平台上提供的四个独立研究(包括TCGA和MSKCC)的1,629个TC样本的基因组数据进行了系统分析。我们计算了所有基因的突变频率,并将超过3%阈值的基因分类为高频驱动基因(第一级)和中等突变率基因(第二级)。结果:在TC队列中,共有1363个基因的突变频率高于3%。一级基因包括BRAF(56.9%)、NRAS(9.3%)、TERT启动子(4.6%)、HRAS(3.5%)和TTN(3.2%),以及BRAFV600E。第二类有19个基因,如TG(2.9%),与滤泡癌发生有关,TP53(2.7%),与低分化亚型相关。通路分析显示MAPK/ERK信号、PI3K-AKT激活和端粒酶维持富集。PPI网络确定了参与DNA修复和细胞周期调节的较少研究的相互作用,提出了新的治疗靶点。1620例TC患者中,女性居多,发病高峰出现在成年中期。该研究表明,BRAF和RET改变之间具有很强的互斥性,且很少共存,表明通过共享的MAPK/ERK和PI3K/AKT信号通路存在功能冗余。结论:本研究阐明了TC的突变层次和协同途径,强调了BRAF和ras驱动的肿瘤发生的意义。DNA损伤反应和细胞周期网络中未被探索的基因的发现为靶向治疗的发展铺平了道路。此外,TERT启动子突变的高频率强调了它们在疾病进展中的作用。
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引用次数: 0
Symbiotic (L. acidophilus and Agave Inulin) Prevents Cognitive Impairment in High-Fat Diet/STZ Rats 共生菌(嗜酸乳杆菌和龙舌兰菊粉)预防高脂饮食/STZ大鼠的认知障碍。
IF 3.4 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2026-01-05 DOI: 10.1016/j.arcmed.2025.103368
Alejandra Romo-Araiza , Luis A. Márquez , Gabriela Rocha-Botello , Emilio J. Galván , Teresa Ponce-Lopez , Ana María Fernández-Presas , Ricardo Jasso-Chávez , Macarena Fuentes-Fernández Cueto , Diego Bustamante-Laguna , Andrés Alfaro-González , Aranza Pérez-Arreola , Carlos Aguirre-Rivera , Iván Ignacio Mejía , Andrea P. Ibarra-Garcia , Elisa García-Vences , Roxana Rodriguez-Barrera , Yolanda Cruz-Martinez , Exsal Manuel Albores-Méndez , Marco Antonio Vargas , Luis Miguel Rodriguez-Serrano , Antonio Ibarra

Background

Type 2 diabetes has been linked to oxidative stress, inflammation, and an imbalance in the gut microbiota, all of which contribute to neuroinflammation and cognitive decline. Gut microbiota influence inflammation and produce various substances, including butyrate, a short-chain fatty acid that promotes brain-derived neurotrophic factor (BDNF), which is essential for memory. This study investigated whether prebiotics, probiotics, or a combination of both (symbiotics) could improve memory in diabetic rats.

Methods

Male Wistar rats were divided into five groups: control; diabetic and obese (induced by a high-fat diet and streptozotocin); diabetic and obese with prebiotics (inulin); diabetic and obese with probiotics (Lactobacillus acidophilus); and diabetic and obese with symbiotics (inulin + L. acidophilus). Treatments lasted 42 d. Memory performance was evaluated using the Morris water maze (spatial memory) and the Eight-arm radial maze (working memory). After testing, hippocampal tissue was analyzed for inflammatory markers (TNF-α, IL-10), BDNF, and butyric acid.

Results

Diabetes impaired memory and increased neuroinflammatory markers. All supplemented groups showed improved memory. The symbiotic group exhibited the most pronounced benefits, with higher levels of BDNF, IL-10, and butyric acid, and reduced TNF-α. Electrophysiological recordings revealed that diabetes reduced the firing frequency of CA1 pyramidal cells and decreased the synaptic strength in the hippocampus. Symbiotic supplementation preserved these neuronal and synaptic functions.

Conclusion

Symbiotic treatment effectively countered diabetes-induced cognitive deficits by reducing neuroinflammation, increasing neurotrophic support, and maintaining synaptic plasticity. These results imply that altering the gut microbiota through symbiotic supplementation may be an effective approach to prevent or mitigate diabetes-associated cognitive decline.
背景:2型糖尿病与氧化应激、炎症和肠道微生物群失衡有关,所有这些都会导致神经炎症和认知能力下降。肠道微生物群影响炎症并产生各种物质,包括丁酸盐,一种促进脑源性神经营养因子(BDNF)的短链脂肪酸,对记忆至关重要。本研究调查了益生元、益生菌或两者的组合(共生)是否能改善糖尿病大鼠的记忆。方法:雄性Wistar大鼠分为5组:对照组;糖尿病和肥胖(由高脂肪饮食和链脲佐菌素引起);糖尿病和肥胖与益生元(菊粉);糖尿病和肥胖与益生菌(嗜酸乳杆菌);糖尿病和肥胖与共生菌(菊粉+嗜酸乳杆菌)。处理42 d。采用Morris水迷宫(空间记忆)和八臂径向迷宫(工作记忆)评价记忆性能。测试后,分析海马组织的炎症标志物(TNF-α, IL-10), BDNF和丁酸。结果:糖尿病患者记忆受损,神经炎症标志物升高。所有补充组的记忆力都有所改善。共生组表现出最明显的益处,BDNF、IL-10和丁酸水平较高,TNF-α水平降低。电生理记录显示,糖尿病降低了CA1锥体细胞的放电频率,降低了海马的突触强度。共生补充保存了这些神经元和突触的功能。结论:共生治疗通过减少神经炎症、增加神经营养支持和维持突触可塑性,有效对抗糖尿病诱导的认知功能障碍。这些结果表明,通过补充共生菌来改变肠道微生物群可能是预防或减轻糖尿病相关认知能力下降的有效方法。
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