Archives of Medical Research最新文献

英文中文

Establishment of High-Altitude Reference Values for the Pan-Immune-Inflammation Value in Healthy Adults Living in Mexico City 墨西哥城健康成人泛免疫炎症值高海拔参考值的建立

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-08-20 DOI: 10.1016/j.arcmed.2025.103281

Luis M Amezcua-Guerra , Malinalli Brianza-Padilla , Mireya Martínez-García , Guadalupe Gutiérrez-Esparza

Background

The Pan-Immune-Inflammation Value (PIV) is a novel composite biomarker that combines neutrophil, monocyte, platelet, and lymphocyte counts. It is useful for prognostic stratification across various clinical conditions. However, reference values for PIV have predominantly been established in populations living below 1000 m, which limits its applicability in high-altitude regions.

Aim

To establish reference values for PIV and its hematological components in healthy adults living in Mexico City.

Methods

Data from the Tlalpan 2020 cohort, a prospective study of healthy adults aged 20–50 from Mexico City, were analyzed. Reference values were determined following the Clinical and Laboratory Standards Institute guidelines, with stratification by sex.

Results

A total of 2290 participants (63% women) with a mean age of 37.0 ± 9.1 years were included. The mean PIV was 249.6 ± 416.9, which decreased to 221.9 ± 332.2 after excluding outliers. Significant sex differences were observed, with women exhibiting higher PIV values. The reference ranges for the total cohort were 65.8–491.6, with sex-specific ranges of 66.7–519.1 for women and 62.8–441.3 for men. Women also had higher reference values for neutrophils and platelets, while monocytes and lymphocytes were similar between sexes.

Conclusions

This study provides high-altitude-specific reference values for PIV and its components in Mexico City’s population, which are notably lower than those in low-altitude regions. The observed sex differences highlight the importance of considering sex as a biological variable when interpreting immunoinflammatory biomarkers.

泛免疫炎症值（PIV）是一种结合中性粒细胞、单核细胞、血小板和淋巴细胞计数的新型复合生物标志物。它对不同临床状况的预后分层是有用的。然而，PIV的参考值主要是在1000米以下的人群中建立的，这限制了其在高海拔地区的适用性。目的建立墨西哥城健康成人PIV及其血液学指标的参考值。方法分析来自Tlalpan 2020队列的数据，这是一项来自墨西哥城的20-50岁健康成年人的前瞻性研究。参考值是根据临床和实验室标准协会的指南确定的，并按性别分层。结果共纳入2290例受试者，其中女性63%，平均年龄37.0±9.1岁。平均PIV为249.6±416.9，剔除异常值后降至221.9±332.2。观察到显著的性别差异，女性表现出更高的PIV值。整个队列的参考范围为65.8-491.6，女性为66.7-519.1，男性为62.8-441.3。女性中性粒细胞和血小板的参考值也更高，而单核细胞和淋巴细胞的参考值在两性之间相似。结论本研究提供了墨西哥城人口PIV及其成分的高海拔特异性参考值，该参考值明显低于低海拔地区。观察到的性别差异强调了在解释免疫炎症生物标志物时将性别作为生物学变量考虑的重要性。

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引用次数: 0

Unveiling Longitudinal Weight Dynamics in Type 2 Diabetes: Insights From a Comprehensive Care Program 揭示2型糖尿病纵向体重动态：来自综合护理计划的见解

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-08-20 DOI: 10.1016/j.arcmed.2025.103271

Ana C. García-Ulloa , Liliana Pérez-Peralta , Luz E. Urbina-Arronte , José L. Cárdenas-Fragoso , Maria V. Landa-Anell , Marco A. Melgarejo-Hernández , Valeria Miranda Gil , Sergio Ponce-de-León , Sergio Hernández-Jiménez , Group of Study CAIPaDi

Background and Aims

Overweight and obesity are prevalent conditions that contribute to significant health problems, including type two diabetes (T2D). Moderate weight loss improves metabolic control and cardiovascular risk. We aimed to identify the demographic and clinical characteristics of patients with T2D who experienced weight changes after a multidisciplinary intervention.

Methods

We analyzed 622 patients with complete 3-year follow-up information. Inclusion criteria were less than 5-years since diabetes diagnosis and an absence of disabling chronic complications. Descriptive statistics, ANOVA or Kruskal-Wallis tests were used for group comparisons, and logistic regression to identify predictors of weight change.

Results

Participants were 56.2 % women, with an average age of 55.8 ± 10.5 years. 53 % were overweight and 47 % were obese at baseline. At 3-years, 35.5 % lost weight, 33.9 % maintained weight, and 30.5 % gained weight; 16.6 % achieved a normal weight. Patients who gained weight were younger than those who lost or maintained it (60 vs. 61 years, p = 0.04). Higher baseline HbA1c (OR 1.14, 95 % CI 1.03–1.26, p = 0.008) and lower quality of life at three months (OR 1.48, 95 % CI 0.95–2.28, p = 0.07) were associated with weight gain. Higher baseline BMI (OR 0.90, 95 % CI 0.85–0.95, p < 0.001), longer diabetes duration (OR 0.81, 95 % CI 0.70–0.94, p = 0.005), and iSGLT2 treatment were linked to weight loss.

Conclusion

Only 16 % of patients achieved normal weight after 3-years: 35.5 % lost weight, 33.9 % maintained their weight, and 30.5 % gained weight. Identifying predictors of weight change may guide targeted interventions in diabetes care.

背景和目的超重和肥胖是导致包括2型糖尿病（T2D）在内的重大健康问题的普遍状况。适度减肥可以改善代谢控制和心血管风险。我们的目的是确定在多学科干预后经历体重变化的T2D患者的人口学和临床特征。方法对622例患者进行完整的3年随访资料分析。纳入标准为糖尿病诊断后不到5年，无致残性慢性并发症。描述性统计、方差分析或Kruskal-Wallis检验用于组间比较，logistic回归用于确定体重变化的预测因子。结果女性占56.2%，平均年龄（55.8±10.5）岁。53%的人超重，47%的人肥胖。3年后，35.5%的人体重减轻，33.9%的人保持体重，30.5%的人体重增加；16.6%达到正常体重。体重增加的患者比体重减轻或保持不变的患者更年轻（60岁对61岁，p = 0.04）。较高的基线HbA1c （OR 1.14, 95% CI 1.03-1.26, p = 0.008）和较低的3个月生活质量（OR 1.48, 95% CI 0.95-2.28, p = 0.07）与体重增加有关。较高的基线BMI （OR 0.90, 95% CI 0.85-0.95, p < 0.001）、较长的糖尿病病程（OR 0.81, 95% CI 0.70-0.94, p = 0.005）和iSGLT2治疗与体重减轻有关。结论3年后只有16%的患者体重恢复正常，35.5%的患者体重减轻，33.9%的患者体重保持不变，30.5%的患者体重增加。确定体重变化的预测因素可以指导有针对性的糖尿病治疗干预。

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引用次数: 0

A Primer on Monkeypox Infection: An Emerging Threat to Global Public Health 猴痘感染入门：对全球公共卫生的新威胁

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-08-20 DOI: 10.1016/j.arcmed.2025.103279

Rasanpreet Kaur , Saurabh Gupta , Shreya Pathak , Manish Sharma , Deepak Parashar , Bhuvnesh Prasad Sharma , Vivek Kashyap , Jitendra Singh , Chakresh Jain , Prem Shankar

Monkeypox (mpox) is caused by a poxvirus closely related to the smallpox virus. It spreads by intimate contact between humans and animals. Prior immunization against smallpox only provides partial protection against mpox. Recently, the WHO declared mpox as a global public health emergency. Mpox is characterized by a brief febrile illness with lymphadenopathy, followed by a rash that develops in phases of macules, papules, vesicles, and pustules, spreading centrifugally. Most patients recover within two to four weeks. Children, pregnant women, and immunocompromised individuals are more likely to experience complications. A precise laboratory diagnosis can be made by using a molecular method, such as polymerase chain reaction (PCR) to detect viral DNA in the tested sample. Most of the treatment is symptomatic, and supportive care is usually sufficient for moderate, self-limited cases of mpox. However, antiviral medications, such as tecovirimat, brincidofovir, and cidofovir, as well as vaccinia immune globulin intravenous (VIGIV), are available as therapeutic options. For high-risk groups, such as healthcare professionals and close contacts, vaccination with currently available smallpox vaccines is advised. This review emphasizes an overview of the history, etiology, epidemiology, structure, reservoirs, transmission, virus phylogeny, genome organization, clinical cases and symptoms, diagnosis, treatment, and prevention of mpox with recent updates. Therefore, a multifaceted approach is essential and includes improved surveillance, early diagnosis, isolation of index cases, immunization, and adoption of a “One Health” approach to prevent an mpox outbreak.

猴痘是由一种与天花病毒密切相关的痘病毒引起的。它通过人与动物的亲密接触传播。事先接种天花疫苗只能提供部分预防m痘的保护。最近，世界卫生组织宣布麻疹为全球突发公共卫生事件。麻疹的特点是短暂的发热性疾病，伴有淋巴结病变，随后出现分阶段的皮疹，有斑疹、丘疹、囊泡和脓疱，呈离心扩散。大多数患者在两到四周内康复。儿童、孕妇和免疫功能低下的人更容易出现并发症。精确的实验室诊断可以通过使用分子方法，如聚合酶链反应（PCR）来检测检测样本中的病毒DNA。大多数治疗是对症的，支持性护理通常对中度、自限性m痘病例就足够了。然而，抗病毒药物，如替科维莫、brincidofovir和西多福韦，以及牛痘免疫球蛋白静脉注射（VIGIV），都是可用的治疗选择。对于高危人群，如卫生保健专业人员和密切接触者，建议接种目前可用的天花疫苗。本文综述了麻疹的历史、病因学、流行病学、结构、宿主、传播、病毒系统发育、基因组组织、临床病例和症状、诊断、治疗和预防的最新进展。因此，必须采取多方面的方法，包括改进监测、早期诊断、隔离指示病例、免疫接种和采用“同一个健康”方法来预防痘暴发。

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引用次数: 0

Comment on “Loneliness and Cognitive Function in Older Adults Living in Latin America: A Systematic Review” “拉丁美洲老年人孤独感与认知功能：一项系统综述”评论

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-08-20 DOI: 10.1016/j.arcmed.2025.103277

ARUNSUNDAR MOHANASUNDARAM , JEREMIAH OLUWATOMI ITODO DANIEL , BHUSHAN PATIL

引用次数: 0

Neuromodulation and Exercise Therapy: A Synergistic Approach to Improve Physical Mobility 神经调节和运动疗法：一种提高身体活动能力的协同方法

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-08-20 DOI: 10.1016/j.arcmed.2025.103282

JIA DONG JAMES WANG , LING-LING CHAN , YEW LONG LO , ENG KING TAN

引用次数: 0

Monocarboxylate Transporter 4 Inhibition Reduces Synovial Hyperproliferation and Metabolic Reprogramming Under Hypoxia in Rheumatoid Arthritis 单羧酸转运蛋白4抑制可减少类风湿关节炎缺氧下滑膜增生和代谢重编程

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-08-18 DOI: 10.1016/j.arcmed.2025.103283

Meican Ma, Ting Liu, Haifeng Chen, Zhao Wang, Jie Zhou, Yu Zhou, Fenghong Yuan

Objectives

In hypoxic conditions, the acidic environment characteristic of rheumatoid arthritis (RA) induces metabolic changes in fibroblast-like synoviocytes (FLS), markedly promoting the synovial proliferation. Monocarboxylate transporter 4 (MCT4) plays a crucial role in cellular pH regulation and synovial fibroblast activation by regulating lactate export. This study investigates the impact of MCT4 inhibition on RA and elucidates its underlying mechanisms.

Method

RA-FLS cells were treated with siMCT4 and VB124 (a selective MCT4 inhibitor), significantly affecting glucose and glutamine uptake and altering lactate efflux. Metabolite analysis using liquid chromatography-mass spectrometry (LC-MS) revealed the mechanisms of carbon metabolism reprogramming. ChIP-qPCR analysis demonstrated changes in hypoxia-inducible factor-1α (HIF1-α) binding to the MCT4 promoter. The therapeutic effects of siMCT4 and VB124 were validated in a collagen-induced arthritis (CIA) model, and their efficacy was assessed through arthritis scores and histological examination.

Results

In patients with RA, MCT4 levels are significantly elevated. Inhibition of MCT4 effectively reduces synovial hyperproliferation and impacts metabolic reprogramming. Specifically, blocking MCT4 in RA-FLS reduces glucose consumption and lactate production while remodeling the metabolic landscape by increasing fumarate, citrate, and malate levels, and decreasing glucose-6-phosphate and aspartate levels. This metabolic shift is accompanied by improvements in mitochondrial structure and function, reduced mitochondrial swelling, and decreased oxidative stress, underscoring the relationship between MCT4 inhibition and cellular energetics. Furthermore, our investigations reveal that HIF1-α directly regulates MCT4 activation, providing a molecular mechanism by which hypoxia promotes MCT4-mediated metabolic reprogramming.

Conclusion

These findings highlight MCT4 as a central regulator of RA proliferation and a promising therapeutic target.

目的：在缺氧条件下，类风湿关节炎（RA）的酸性环境特征诱导成纤维细胞样滑膜细胞（FLS）代谢变化，显著促进滑膜增殖。单羧酸转运蛋白4 （MCT4）通过调节乳酸输出在细胞pH调节和滑膜成纤维细胞活化中起关键作用。本研究探讨MCT4抑制对RA的影响，并阐明其潜在机制。方法用siMCT4和VB124（一种选择性MCT4抑制剂）处理ra - fls细胞，显著影响葡萄糖和谷氨酰胺摄取并改变乳酸外排。液相色谱-质谱联用分析揭示了碳代谢重编程的机制。ChIP-qPCR分析显示缺氧诱导因子-1α (HIF1-α)与MCT4启动子结合的变化。在胶原诱导关节炎（CIA）模型中验证siMCT4和VB124的治疗效果，并通过关节炎评分和组织学检查评估其疗效。结果RA患者MCT4水平明显升高。抑制MCT4有效地减少滑膜过度增生和影响代谢重编程。具体而言，在RA-FLS中阻断MCT4可减少葡萄糖消耗和乳酸生成，同时通过增加富马酸盐、柠檬酸盐和苹果酸盐水平以及降低葡萄糖-6-磷酸和天冬氨酸水平重塑代谢景观。这种代谢转变伴随着线粒体结构和功能的改善、线粒体肿胀的减少和氧化应激的降低，强调了MCT4抑制与细胞能量学之间的关系。此外，我们的研究表明，HIF1-α直接调节MCT4的激活，提供了缺氧促进MCT4介导的代谢重编程的分子机制。结论这些发现表明MCT4是RA增殖的中心调节因子，是一个有希望的治疗靶点。

{"title":"Monocarboxylate Transporter 4 Inhibition Reduces Synovial Hyperproliferation and Metabolic Reprogramming Under Hypoxia in Rheumatoid Arthritis","authors":"Meican Ma, Ting Liu, Haifeng Chen, Zhao Wang, Jie Zhou, Yu Zhou, Fenghong Yuan","doi":"10.1016/j.arcmed.2025.103283","DOIUrl":"10.1016/j.arcmed.2025.103283","url":null,"abstract":"<div><h3>Objectives</h3><div>In hypoxic conditions, the acidic environment characteristic of rheumatoid arthritis (RA) induces metabolic changes in fibroblast-like synoviocytes (FLS), markedly promoting the synovial proliferation. Monocarboxylate transporter 4 (MCT4) plays a crucial role in cellular pH regulation and synovial fibroblast activation by regulating lactate export. This study investigates the impact of MCT4 inhibition on RA and elucidates its underlying mechanisms.</div></div><div><h3>Method</h3><div>RA-FLS cells were treated with siMCT4 and VB124 (a selective MCT4 inhibitor), significantly affecting glucose and glutamine uptake and altering lactate efflux. Metabolite analysis using liquid chromatography-mass spectrometry (LC-MS) revealed the mechanisms of carbon metabolism reprogramming. ChIP-qPCR analysis demonstrated changes in hypoxia-inducible factor-1α (HIF1-α) binding to the MCT4 promoter. The therapeutic effects of siMCT4 and VB124 were validated in a collagen-induced arthritis (CIA) model, and their efficacy was assessed through arthritis scores and histological examination.</div></div><div><h3>Results</h3><div>In patients with RA, MCT4 levels are significantly elevated. Inhibition of MCT4 effectively reduces synovial hyperproliferation and impacts metabolic reprogramming. Specifically, blocking MCT4 in RA-FLS reduces glucose consumption and lactate production while remodeling the metabolic landscape by increasing fumarate, citrate, and malate levels, and decreasing glucose-6-phosphate and aspartate levels. This metabolic shift is accompanied by improvements in mitochondrial structure and function, reduced mitochondrial swelling, and decreased oxidative stress, underscoring the relationship between MCT4 inhibition and cellular energetics. Furthermore, our investigations reveal that HIF1-α directly regulates MCT4 activation, providing a molecular mechanism by which hypoxia promotes MCT4-mediated metabolic reprogramming.</div></div><div><h3>Conclusion</h3><div>These findings highlight MCT4 as a central regulator of RA proliferation and a promising therapeutic target.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"57 1","pages":"Article 103283"},"PeriodicalIF":3.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866484","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

A Risk Stratification Score for Predicting First Episode of Upper Gastrointestinal Bleeding in Patients With Cirrhosis 预测肝硬化患者首次上消化道出血的风险分层评分

IF 4.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-07-17 DOI: 10.1016/j.arcmed.2025.103253

Nasser Mousa , Sherif Elbaz , Alaa Elmetwalli , Marwa Mansour , Mostafa Abdelsalam , Mohammed Abdelaziz , Manal Hashem , Ola El-Emam , Niveen El-wakeel , Ayman Elgamal , Mohamed Wahba , Mohamed Selim , Muhammad Diasty , Wesam Elderiny , Adel El-Assmy , Eman Abdelkader

Background and Aims

Although endoscopy is the standard method for diagnosing esophageal varices (EV), it is only available in developed countries. This study aims to identify predictors of the initial variceal bleeding (VB) occurrence and to develop a scoring system to predict the VB in patients with cirrhosis.

Methods

This study analyzed 236 patients with cirrhosis who experienced their first upper gastrointestinal bleeding (UGIB) episode. A logistic regression model was used to identify independent risk factors for VB and create a scoring system. We assessed the predictive ability of the scoring system using the area under the receiver operating characteristic curve (AUC-ROC).

Results

Of the included patients, 154 had EV as the bleeding source. The following were identified as independent risk factors for the first VB episode: age over 60 years, diabetes mellitus (DM), absence of ischemic heart disease, platelets below 130,000/uL, albumin >2.9 g/dL, bilirubin level >1.4 mg/dL, and Child-Pugh score B. A score was developed by assigning points to each risk factor and summing the total score (maximum 7 points). This score was categorized into three risk groups: low risk <3 points; intermediate risk 3–4 points; and high risk ≥5 points. The performance score was assessed using AUC-ROC analysis. Both the low- and high-risk categories had high sensitivity but low specificity, while the intermediate-risk group had balanced sensitivity and specificity.

Conclusion

Our score is a valuable noninvasive tool for predicting the first VB episode. It helps determine the urgency of endoscopy and the need for aggressive management strategies.

背景与目的虽然内窥镜检查是诊断食管静脉曲张（EV）的标准方法，但它仅在发达国家可用。本研究旨在确定肝硬化患者初始静脉曲张出血（VB）发生的预测因素，并建立一个预测VB的评分系统。方法本研究分析了236例首次上消化道出血（UGIB）发作的肝硬化患者。采用logistic回归模型识别VB的独立危险因素并建立评分系统。我们使用受试者工作特征曲线下面积（AUC-ROC）评估评分系统的预测能力。结果本组154例患者出血源为EV。以下被确定为首次VB发作的独立危险因素：年龄超过60岁，糖尿病（DM），无缺血性心脏病，血小板低于130,000/uL，白蛋白2.9 g/dL，胆红素水平1.4 mg/dL， Child-Pugh评分b。通过对每个危险因素进行评分并将总分相加（最高7分）得出评分。这个分数被分为三个风险组：低风险<；3分；中级风险3-4分；高危≥5分。采用AUC-ROC分析评定疗效评分。低危组和高危组敏感性高，特异度低；中危组敏感性和特异度平衡。结论我们的评分是一种有价值的无创预测VB首次发作的工具。它有助于确定内窥镜检查的紧迫性和积极的管理策略的需要。

{"title":"A Risk Stratification Score for Predicting First Episode of Upper Gastrointestinal Bleeding in Patients With Cirrhosis","authors":"Nasser Mousa , Sherif Elbaz , Alaa Elmetwalli , Marwa Mansour , Mostafa Abdelsalam , Mohammed Abdelaziz , Manal Hashem , Ola El-Emam , Niveen El-wakeel , Ayman Elgamal , Mohamed Wahba , Mohamed Selim , Muhammad Diasty , Wesam Elderiny , Adel El-Assmy , Eman Abdelkader","doi":"10.1016/j.arcmed.2025.103253","DOIUrl":"10.1016/j.arcmed.2025.103253","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Although endoscopy is the standard method for diagnosing esophageal varices (EV), it is only available in developed countries. This study aims to identify predictors of the initial variceal bleeding (VB) occurrence and to develop a scoring system to predict the VB in patients with cirrhosis.</div></div><div><h3>Methods</h3><div>This study analyzed 236 patients with cirrhosis who experienced their first upper gastrointestinal bleeding (UGIB) episode. A logistic regression model was used to identify independent risk factors for VB and create a scoring system. We assessed the predictive ability of the scoring system using the area under the receiver operating characteristic curve (AUC-ROC).</div></div><div><h3>Results</h3><div>Of the included patients, 154 had EV as the bleeding source. The following were identified as independent risk factors for the first VB episode: age over 60 years, diabetes mellitus (DM), absence of ischemic heart disease, platelets below 130,000/uL, albumin >2.9 g/dL, bilirubin level >1.4 mg/dL, and Child-Pugh score B. A score was developed by assigning points to each risk factor and summing the total score (maximum 7 points). This score was categorized into three risk groups: low risk <3 points; intermediate risk 3–4 points; and high risk ≥5 points. The performance score was assessed using AUC-ROC analysis. Both the low- and high-risk categories had high sensitivity but low specificity, while the intermediate-risk group had balanced sensitivity and specificity.</div></div><div><h3>Conclusion</h3><div>Our score is a valuable noninvasive tool for predicting the first VB episode. It helps determine the urgency of endoscopy and the need for aggressive management strategies.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 7","pages":"Article 103253"},"PeriodicalIF":4.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653397","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

Response to: Loneliness and Cognitive Function in Older Adults Living in Latin America: A Systematic Review 拉丁美洲老年人的孤独感与认知功能：一项系统综述

IF 4.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-07-17 DOI: 10.1016/j.arcmed.2025.103278

DAVID CAMACHO , PAMELA TELLA-VEGA , FERNANDO A. WAGNER , CAROLINA SANTAMARÍA-ULLOA , AMANDA LEHNING , JOSEPH J. GALLO , CARMEN GARCIA-PEÑA

引用次数: 0

Strengthening Access to Post-Pandemic Mental Health Care: An Action Proposal 加强获得大流行后精神卫生保健：一项行动建议

IF 4.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-07-10 DOI: 10.1016/j.arcmed.2025.103255

Nicole Lobos-Villatoro, Carlos Güida, Osvaldo Artaza

引用次数: 0

Spironolactone Partially Reverses Autism-Like Behaviors Linked to ErbB4 and mTOR Phosphorylation in the Mouse Prefrontal Cortex and Striatum 螺内酯部分逆转小鼠前额皮质和纹状体中与ErbB4和mTOR磷酸化相关的自闭症样行为

IF 4.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-07-10 DOI: 10.1016/j.arcmed.2025.103254

David Zarate-Lopez , Rosendo García-Carrillo , Luis Castro-Sánchez , Alma Y. Galvez-Contreras , Oscar Gonzalez-Perez

Background and Aims

Autism spectrum disorder (ASD) is a condition resulting from a combination of genetic and environmental influences that lead to atypical brain development, particularly in regions such as the striatum and prefrontal cortex. There is increasing evidence linking the epidermal growth factor (EGF) and its receptor (EGFR or ErbB1) to the etiopathogenesis of ASD. However, ErbB4, another ErbB member, has also been implicated in this process. To investigate whether dysregulation of ErbB4 and its downstream mTOR signaling pathway in the striatum and prefrontal cortex contributes to stereotypical behaviors and social deficits in an autism-like rodent model.

Methods

We analyzed the phosphorylation levels of ErbB4and mTOR in the prefrontal cortex and striatum of 31 d old mice that were prenatally exposed to valproate (VPA; 500 mg/kg) or the control vehicle (0.9 % NaCl). Social and stereotypic behaviors were assessed using the three-chamber social test and the marble burying test, respectively. Then, the VPA groups were treated with 50 mg/kg of spironolactone, a selective ErbB4 antagonist.

Results

Prenatal exposure to VPA induced deficits in social interaction and an increase in repetitive behaviors. These behaviors coexist with dysregulation of the ErbB4 phosphorylation and modifications in the mTOR signaling pathway in both brain regions. Treatment with spironolactone reduced repetitive behaviors, which was consistent with reduced ErbB4 phosphorylation and mTOR signaling.

Conclusions

These results support the idea that ErbB4 has abnormal expression and activity levels in the striatum and prefrontal cortex. Antagonizing ErbB4 with spironolactone improves repetitive behavioral patterns associated with ASD.

背景和自闭症谱系障碍（ASD）是一种由遗传和环境影响共同导致非典型大脑发育的疾病，特别是在纹状体和前额皮质等区域。越来越多的证据表明，表皮生长因子（EGF）及其受体（EGFR或ErbB1）与ASD的发病有关。然而，ErbB4，另一个ErbB成员，也参与了这一过程。研究纹状体和前额叶皮层ErbB4及其下游mTOR信号通路的失调是否与自闭症样啮齿动物模型的刻板行为和社交缺陷有关。方法分析了产前暴露于丙戊酸（VPA）的31日龄小鼠前额皮质和纹状体erbb4和mTOR磷酸化水平。500 mg/kg)或对照（0.9% NaCl）。社会行为和刻板印象行为分别采用三室社会测验和弹珠掩埋测验进行评估。然后，VPA组给予50 mg/kg选择性ErbB4拮抗剂螺内酯。结果胎儿期暴露于VPA可导致社会交往缺陷和重复行为增加。这些行为与ErbB4磷酸化的失调和两个脑区mTOR信号通路的修饰共存。螺内酯治疗减少了重复行为，这与ErbB4磷酸化和mTOR信号传导的减少是一致的。结论ErbB4在纹状体和前额叶皮层中表达和活性异常。用螺内酯拮抗ErbB4可改善与ASD相关的重复性行为模式。

{"title":"Spironolactone Partially Reverses Autism-Like Behaviors Linked to ErbB4 and mTOR Phosphorylation in the Mouse Prefrontal Cortex and Striatum","authors":"David Zarate-Lopez , Rosendo García-Carrillo , Luis Castro-Sánchez , Alma Y. Galvez-Contreras , Oscar Gonzalez-Perez","doi":"10.1016/j.arcmed.2025.103254","DOIUrl":"10.1016/j.arcmed.2025.103254","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Autism spectrum disorder (ASD) is a condition resulting from a combination of genetic and environmental influences that lead to atypical brain development, particularly in regions such as the striatum and prefrontal cortex. There is increasing evidence linking the epidermal growth factor (EGF) and its receptor (EGFR or ErbB1) to the etiopathogenesis of ASD. However, ErbB4, another ErbB member, has also been implicated in this process. To investigate whether dysregulation of ErbB4 and its downstream mTOR signaling pathway in the striatum and prefrontal cortex contributes to stereotypical behaviors and social deficits in an autism-like rodent model.</div></div><div><h3>Methods</h3><div>We analyzed the phosphorylation levels of ErbB4and mTOR in the prefrontal cortex and striatum of 31 d old mice that were prenatally exposed to valproate (VPA; 500 mg/kg) or the control vehicle (0.9 % NaCl). Social and stereotypic behaviors were assessed using the three-chamber social test and the marble burying test, respectively. Then, the VPA groups were treated with 50 mg/kg of spironolactone, a selective ErbB4 antagonist.</div></div><div><h3>Results</h3><div>Prenatal exposure to VPA induced deficits in social interaction and an increase in repetitive behaviors. These behaviors coexist with dysregulation of the ErbB4 phosphorylation and modifications in the mTOR signaling pathway in both brain regions. Treatment with spironolactone reduced repetitive behaviors, which was consistent with reduced ErbB4 phosphorylation and mTOR signaling.</div></div><div><h3>Conclusions</h3><div>These results support the idea that ErbB4 has abnormal expression and activity levels in the striatum and prefrontal cortex. Antagonizing ErbB4 with spironolactone improves repetitive behavioral patterns associated with ASD.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"56 7","pages":"Article 103254"},"PeriodicalIF":4.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589100","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}

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