Archives of Medical Research最新文献_第2页

Metabolic Dysfunction-Associated Steatohepatitis in Focus: Pathogenesis, Non-Invasive Diagnostics, and Future Approaches 代谢功能障碍相关脂肪性肝炎的焦点：发病机制，非侵入性诊断和未来的方法

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-12-01 DOI: 10.1016/j.arcmed.2025.103350

Abdulrahman Ismaiel , Mhd Bashir Almonajjed , Cristina Sorina Catana , Stefan-Lucian Popa , Dan L. Dumitrascu

Metabolic dysfunction-associated steatohepatitis (MASH) has become a critical public health concern, representing the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD). MASH is characterized by hepatic steatosis, inflammation, hepatocyte ballooning, and fibrosis, which increase the risk of cirrhosis and hepatocellular carcinoma. Closely linked to obesity, insulin resistance, and metabolic syndrome, MASH affects a significant proportion of the global population, requiring accurate diagnostic tools and tailored interventions. This manuscript delves into the current understanding of MASH, focusing on its pathophysiology, diagnostic challenges, and innovative non-invasive strategies. While liver biopsy remains the gold standard for diagnosis, its invasiveness and limitations have prompted the search for alternative approaches. Promising non-invasive techniques, such as elastography, MRI-based techniques, and serum biomarkers like cytokeratin-18, NIS4, and FAST scores, provide new ways to detect MASH and evaluate fibrosis severity. The updated MASLD criteria refine risk stratification further, capturing a broader range of at-risk individuals, including lean phenotypes. As MASH continues to strain healthcare systems worldwide, this review underscores the importance of advancing non-invasive diagnostics and integrating multi-omics approaches. Future research should focus on developing personalized strategies to halt disease progression, enhance early detection, and optimize patient outcomes.

代谢功能障碍相关脂肪性肝炎（MASH）已成为一个重要的公共卫生问题，代表了代谢功能障碍相关脂肪性肝病（MASLD）的进行性形式。MASH的特点是肝脂肪变性、炎症、肝细胞球囊化和纤维化，这些都增加了肝硬化和肝细胞癌的风险。MASH与肥胖、胰岛素抵抗和代谢综合征密切相关，影响着全球很大一部分人口，需要准确的诊断工具和量身定制的干预措施。这份手稿深入到目前对MASH的理解，侧重于其病理生理学，诊断挑战和创新的非侵入性策略。虽然肝活检仍然是诊断的金标准，但其侵入性和局限性促使人们寻找替代方法。有前途的非侵入性技术，如弹性成像、基于mri的技术和血清生物标志物，如细胞角蛋白-18、NIS4和FAST评分，提供了检测MASH和评估纤维化严重程度的新方法。更新的MASLD标准进一步细化了风险分层，捕获了更广泛的高危个体，包括瘦表型。随着MASH继续给全球医疗保健系统带来压力，本综述强调了推进非侵入性诊断和整合多组学方法的重要性。未来的研究应侧重于制定个性化的策略，以阻止疾病的进展，加强早期发现，并优化患者的预后。

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引用次数: 0

Protein Restriction During Pregnancy and Lactation Triggers Steatohepatitis and Adrenal Disorders in Rat Dams: Insights into Maternal Metabolic Health 妊娠和哺乳期蛋白质限制引发大鼠脂肪性肝炎和肾上腺疾病：对母体代谢健康的见解。

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-11-24 DOI: 10.1016/j.arcmed.2025.103334

Luísa Annibal Barata , Matheus Naia Fioretto , Vinícius Alexandre de Andrade Felipe , Patrick Vieira de Souza , Isabelle Tenori Ribeiro , Flávia Alessandra Maciel , Luiz Marcos Frediani Portela , Mirella Franco Moreira , Gustavo Monezzi Cordeiro , Ana Lívia Silvério Vieira , Wellerson Rodrigo Scarano , Elena Zambrano , Luis Antonio Justulin

Background

The Developmental Origins of Health and Disease (DOHaD) concept is strongly supported by epidemiological and experimental data demonstrating that exposure to adverse conditions early in life can impact offspring health. Despite numerous studies showing the early and long-term impacts of maternal malnutrition on offspring, little research has been conducted on its effects on mothers.

Methods

We investigated the effects of protein restriction (6 %) during gestation and lactation on the metabolism, as well as the structural and molecular parameters of the livers and adrenals of dams.

Results

A decrease in food and water consumption was observed in gestational and lactational low-protein (GLLP) mothers during lactation, in addition to systemic changes with a decrease in aspartate aminotransferase (AST) and an increase in creatinine. The adrenal glands of GLLP mothers demonstrated cortical vacuolization and reduced collagen deposition. The liver of GLLP mothers showed a decrease in collagen and an increase in fibrotic areas, macro- and microvesicular steatosis, and hypertrophy, indicating nonalcoholic steatohepatitis (NASH). We observed decreased gene expression of Cyp11b2 and increased expression in Sts and Por in the adrenals of the GLLP group. In the liver, there was a decrease in Ppar g and Hsd3b1, in addition to increased gene expression of Pdh1, Cs, and Pklr in the GLLP group.

Conclusions

Maternal protein restriction (MPR) leads to systemic and structural disorders on the adrenal-liver axis, affecting important molecular processes that indicate hepatic and adrenal stress, as well as disorders in energy metabolism. This could potentially affect the fetal and postnatal health of the offspring, increasing the risk of diseases.

背景：健康和疾病的发育起源（DOHaD）概念得到流行病学和实验数据的有力支持，这些数据表明，生命早期暴露于不利条件会影响后代的健康。尽管有大量研究显示了母亲营养不良对后代的早期和长期影响，但很少有研究表明其对母亲的影响。方法：研究妊娠和哺乳期限制蛋白（6%）对公鼠肝脏和肾上腺代谢及结构和分子参数的影响。结果：在妊娠期和哺乳期低蛋白（GLLP）母亲中，除了天冬氨酸转氨酶（AST）降低和肌酐升高的全身性变化外，还观察到哺乳期间食物和水的消耗减少。GLLP母鼠肾上腺皮质空泡化，胶原沉积减少。GLLP母亲的肝脏显示胶原蛋白减少，纤维化区域增加，大泡和微泡脂肪变性和肥厚，提示非酒精性脂肪性肝炎（NASH）。我们观察到GLLP组肾上腺中Cyp11b2基因表达降低，Sts和Por基因表达升高。在肝脏中，GLLP组Ppar g和Hsd3b1降低，Pdh1、Cs和plklr基因表达增加。结论：母体蛋白限制（MPR）导致肾上腺-肝轴的全身性和结构性紊乱，影响指示肝脏和肾上腺应激的重要分子过程，以及能量代谢紊乱。这可能会影响胎儿和后代的产后健康，增加患病的风险。

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引用次数: 0

Challenges in Expanding the Donor Pool and Improving Long-Term Outcomes for Liver Transplantation 扩大供体池和改善肝移植长期预后的挑战。

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-11-20 DOI: 10.1016/j.arcmed.2025.103348

Alberto Ferrarese , Sara Battistella , Francesca D’Arcangelo , Giuseppe Feltrin , Stefania Barbieri , Domenico Bassi , Alberto Zanetto , Giacomo Germani , Francesco Paolo Russo , Patrizia Burra

Liver transplantation is a curative treatment for many patients with end-stage liver disease, acute liver failure, and primary liver cancer when certain criteria are met. The persistent imbalance between organ availability and the number of patients on the waiting list presents both ethical and medical challenges in everyday clinical practice. Expanding the donor pool—and consequently increasing the number of retrieved grafts—requires action on multiple levels. These include raising awareness about organ donation, promoting willingness to donate, and increasing knowledge of post-transplant outcomes among the general population and healthcare professionals. In addition, organ acceptance criteria should be refined by incorporating recent advances in transplant hepatology and surgery. The survival benefit achieved through liver transplantation is well established for many conditions. To further improve long-term outcomes, more tailored and refined surveillance protocols are needed for the metabolic and neoplastic comorbidities that commonly develop after transplantation. In this updated literature review, we aim to highlight the main advances in these two crucial areas of liver transplantation.

肝移植是许多终末期肝病、急性肝衰竭和原发性肝癌患者在满足一定标准时的根治性治疗方法。器官供应和等待名单上的患者数量之间的持续不平衡在日常临床实践中提出了伦理和医学挑战。扩大供体池，从而增加移植的数量，需要在多个层面上采取行动。这些措施包括提高对器官捐赠的认识，促进捐赠意愿，增加普通人群和医疗保健专业人员对移植后结果的了解。此外，器官接受标准应结合移植肝病学和外科的最新进展加以完善。通过肝移植获得的生存益处在许多情况下都是公认的。为了进一步改善长期预后，需要针对移植后常见的代谢和肿瘤合并症制定更有针对性和更精细的监测方案。在这篇最新的文献综述中，我们旨在强调肝移植这两个关键领域的主要进展。

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引用次数: 0

In Vitro Evaluation of the Impact of Oxygen Concentrations on Thrombomodulin Expression in a First-Trimester Trophoblast Cell Line 体外评价氧浓度对孕早期滋养细胞血栓调节蛋白表达的影响。

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-11-15 DOI: 10.1016/j.arcmed.2025.103332

Paula Cardona , Daniel Palacios , Anny Alvarez , Alicia E. Damiano , Reggie García-Robles , Paola Ayala-Ramírez

Introduction

The placenta is a transient organ essential for fetal development. Abnormal placental development can lead to obstetric syndromes, such as preeclampsia (PE) and fetal growth restriction (FGR). Physiological hypoxia activates intracellular pathways via hypoxia-inducible transcription factors (HIFs), which are crucial for placentation. This study uses an in vitro model to investigate the role of oxygen concentration in the expression of thrombomodulin (THBD), a protein involved in placental hemostasis.

Methods

Swan 71, a first-trimester trophoblast cell line, was cultured under normoxic (21 % O₂) and physiological hypoxic (2 and 8 % O₂) conditions. Hypoxia/reoxygenation assays were also performed. To assess potential modulation of THBD expression by HIF-1α, cobalt chloride (CoCl₂) was used to stabilize HIF-1α, while zinc chloride (ZnCl₂) inhibited its expression. RT-qPCR and Western blot analyses were performed to quantify THBD and KLF4 expression.

Results

Significant increases in THBD mRNA and protein levels were observed under 2 % O₂ conditions (p = 0.03). CoCl₂ treatment further enhanced THBD and KLF4 expression (p < 0.01 in both experiments), while ZnCl₂ inhibited these effects (p < 0.01). This suggests a key role for HIF-1α in THBD regulation. However, in silico analysis did not identify any direct hypoxia response elements within the human THBD gene, suggesting the presence of an indirect regulatory mechanism potentially involving KLF4.

Discussion

These results suggest that physiological hypoxia positively regulates THBD expression through HIF-1α stabilization and KLF4-mediation. These findings provide insight into the molecular mechanisms of placental adaptation to hypoxia and are relevant for understanding pregnancy complications like PE and intrauterine growth restriction (IUGR).

胎盘是胎儿发育所必需的一个短暂器官。胎盘发育异常可导致产科综合征，如先兆子痫（PE）和胎儿生长受限（FGR）。生理性缺氧通过缺氧诱导的转录因子（hif）激活细胞内通路，这对胎盘至关重要。本研究采用体外模型研究氧浓度在血栓调节素（THBD）表达中的作用，THBD是一种参与胎盘止血的蛋白。方法：在常氧（21% O2）和生理性缺氧（2% O2和8% O2）条件下培养早期妊娠滋养细胞Swan 71。还进行了缺氧/再氧化试验。为了评估HIF-1α对THBD表达的潜在调节作用，用氯化钴（CoCl₂）稳定HIF-1α，而氯化锌（ZnCl₂）抑制其表达。RT-qPCR和Western blot分析定量THBD和KLF4的表达。结果：2% O2条件下大鼠THBD mRNA和蛋白水平显著升高（p = 0.03）。CoCl2进一步增强了THBD和KLF4的表达（p < 0.01），而ZnCl2抑制了这些作用（p < 0.01）。这表明HIF-1α在THBD调控中起关键作用。然而，在硅分析中没有发现人类THBD基因中任何直接的缺氧反应元件，这表明存在可能涉及KLF4的间接调节机制。讨论：这些结果提示生理性缺氧通过HIF-1α稳定和klf4介导正向调节THBD的表达。这些发现为胎盘适应缺氧的分子机制提供了见解，并有助于理解妊娠并发症，如PE和宫内生长限制（IUGR）。

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引用次数: 0

Hot Topics in Gastroenterology and Hepatology 胃肠病学和肝病学热点话题。

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-11-12 DOI: 10.1016/j.arcmed.2025.103347

Ludovico Abenavoli , Nahum Méndez-Sánchez

引用次数: 0

A Combination of Whey Protein and Vitamin D Reduces Sarcopenia in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial 乳清蛋白和维生素D的组合可减少慢性阻塞性肺疾病患者的肌肉减少症。随机对照试验

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-11-12 DOI: 10.1016/j.arcmed.2025.103330

Rizwan Qaisar , Imran Ullah Khan , Firdos Ahmad , Asima Karim

Background and aims

Patients with chronic obstructive pulmonary disease (COPD) experience an accelerated decline in muscle strength, mass, and functional capacity, known as sarcopenia. The effects and relevant mechanisms of supplementing whey protein and vitamin D (whey-D) on sarcopenia are unclear.

Methods

We conducted a randomized, controlled, double-blind, single-center trial in patients with COPD, categorized as placebo (n = 83) and whey-D (n = 80), along with age-matched controls (n = 75) for 16 weeks. Handgrip strength (HGS), gait speed (GS), the short physical performance battery (SPPB), and plasma levels of c-terminal agrin-fragment-22 (CAF22, a marker of neuromuscular junction [NMJ] integrity), and neurofilament light chain (NfL, a marker of neurodegeneration) were measured before and after whey-D supplementation.

Results

At baseline, patients with COPD had lower HGS, GS, and SPPB scores, and higher plasma CAF22 and NfL levels than controls (all p < 0.05). Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all p < 0.05), unlike the placebo group. Whey-D also reduced plasma CAF22 levels (p < 0.05), suggesting NMJ repair, but did not alter plasma NfL. We also observed dynamic correlations of plasma CAF22 with HGS, GS, and total SPPB scores in the whey-D group. Lastly, whey-D also reduced plasma C-reactive protein and increased 25-OH vitamin D levels (both p < 0.05).

Conclusion

Sixteen weeks of whey-D supplement improved muscle strength and functional capacity in patients with COPD, partly through NMJ repair. Our data show that targeted nutritional supplements may be relevant to treating sarcopenia and functional disability in patients with COPD.

背景和目的慢性阻塞性肺疾病（COPD）患者经历肌肉力量、质量和功能能力的加速下降，称为肌肉减少症。补充乳清蛋白和维生素D（乳清-D）对肌肉减少症的影响及其相关机制尚不清楚。方法：我们在COPD患者中进行了一项随机、对照、双盲、单中心试验，这些患者分为安慰剂组（n = 83）和乳清- d组（n = 80），以及年龄匹配的对照组（n = 75），为期16周。测定补充乳清d前后的握力（HGS）、步态速度（GS）、短时物理性能电池（SPPB）和血浆c-末端agrin-fragment-22 （CAF22，神经肌肉连接处[NMJ]完整性的标志）和神经丝轻链（NfL，神经变性的标志）水平。结果基线时，COPD患者HGS、GS和SPPB评分低于对照组，血浆CAF22和NfL水平高于对照组（p < 0.05）。与安慰剂组不同，乳清- d补充剂改善了COPD患者的HGS、GS和总SPPB评分（均p <； 0.05）。乳清- d还降低了血浆CAF22水平（p < 0.05），提示NMJ修复，但未改变血浆NfL。我们还观察到乳清d组血浆CAF22与HGS、GS和总SPPB评分的动态相关性。最后，乳清-D还降低了血浆c反应蛋白，增加了25-OH维生素D水平（p < 0.05）。结论：16周的乳清- d补充可部分通过NMJ修复改善COPD患者的肌肉力量和功能能力。我们的数据显示，有针对性的营养补充可能与治疗慢性阻塞性肺病患者的肌肉减少症和功能残疾有关。

{"title":"A Combination of Whey Protein and Vitamin D Reduces Sarcopenia in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial","authors":"Rizwan Qaisar , Imran Ullah Khan , Firdos Ahmad , Asima Karim","doi":"10.1016/j.arcmed.2025.103330","DOIUrl":"10.1016/j.arcmed.2025.103330","url":null,"abstract":"<div><h3>Background and aims</h3><div>Patients with chronic obstructive pulmonary disease (COPD) experience an accelerated decline in muscle strength, mass, and functional capacity, known as sarcopenia. The effects and relevant mechanisms of supplementing whey protein and vitamin D (whey-D) on sarcopenia are unclear.</div></div><div><h3>Methods</h3><div>We conducted a randomized, controlled, double-blind, single-center trial in patients with COPD, categorized as placebo (<em>n</em> = 83) and whey-D (<em>n</em> = 80), along with age-matched controls (<em>n</em> = 75) for 16 weeks. Handgrip strength (HGS), gait speed (GS), the short physical performance battery (SPPB), and plasma levels of c-terminal agrin-fragment-22 (CAF22, a marker of neuromuscular junction [NMJ] integrity), and neurofilament light chain (NfL, a marker of neurodegeneration) were measured before and after whey-D supplementation.</div></div><div><h3>Results</h3><div>At baseline, patients with COPD had lower HGS, GS, and SPPB scores, and higher plasma CAF22 and NfL levels than controls (all <em>p</em> < 0.05). Whey-D supplements improved HGS, GS, and total SPPB scores in patients with COPD (all <em>p</em> < 0.05), unlike the placebo group. Whey-D also reduced plasma CAF22 levels (<em>p</em> < 0.05), suggesting NMJ repair, but did not alter plasma NfL. We also observed dynamic correlations of plasma CAF22 with HGS, GS, and total SPPB scores in the whey-D group. Lastly, whey-D also reduced plasma C-reactive protein and increased 25-OH vitamin D levels (both <em>p</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>Sixteen weeks of whey-D supplement improved muscle strength and functional capacity in patients with COPD, partly through NMJ repair. Our data show that targeted nutritional supplements may be relevant to treating sarcopenia and functional disability in patients with COPD.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":"57 4","pages":"Article 103330"},"PeriodicalIF":3.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486487","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

Impact of Desloratadine on Treatment Response and Inflammation During Neoadjuvant Chemotherapy in Stage II–III Breast Cancer: A Randomized Pilot Study 地氯雷他定对II-III期乳腺癌新辅助化疗期间治疗反应和炎症的影响：一项随机试点研究

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-11-11 DOI: 10.1016/j.arcmed.2025.103333

Hossein Azimi , Afifeh Jafari , Seyed Reza Khandozi , Yasser Bagheri , Marie Saghaeian Jazi , Somayeh Ghorbani , Gholamreza Roshandel , Homa Davoodi

Background

Desloratadine, commonly used for allergy symptoms, has demonstrated its potential to increase survival rates in patients with breast cancer. This trial aimed to assess the efficacy of desloratadine in improving treatment response and inflammation markers during neoadjuvant chemotherapy.

Methods

In this single-blind, pilot phase II trial, 49 patients with newly diagnosed breast cancer were randomized into two groups: an intervention group (n = 23), and a control group (n = 26). The intervention group received desloratadine in addition to anthracycline-based chemotherapy, while the control group received standard anthracycline-based chemotherapy alone. The primary endpoint was the treatment response, which was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints included plasma histamine, IL-6, TNF-α levels, and PBMC biomarkers (H1R, NF-κB, TLR-4).

Results

Data from 20 patients in the intervention group and 22 patients in the control group were analyzed (patients in stages II and III were enrolled; no stage I cases were observed, and two stage IV patients [one per group] were excluded due to insufficient subgroup size). The intervention group showed a higher overall response rate (65 %) than the control group (45.5 %), though the difference was not statistically significant (p = 0.232). Stage III patients in the intervention group had a significantly higher response rate (90.91 % [intervention] vs. 11.11 % [control], p = 0.001). No adverse effects were reported.

Conclusion

Desloratadine may improve treatment response in stage III breast cancer, supporting its potential role as a complementary agent in neoadjuvant chemotherapy.

Ethical code

This study was registered with the Iranian Registry of Clinical Trials (IRCT) under the registration number IRCT20230221057485N1.

地氯雷他定，通常用于过敏症状，已被证明具有提高乳腺癌患者生存率的潜力。本试验旨在评估地氯雷他定在新辅助化疗期间改善治疗反应和炎症标志物的疗效。方法将49例新诊断的乳腺癌患者随机分为干预组（n = 23）和对照组（n = 26）。干预组在蒽环类药物化疗的基础上给予地氯雷他定治疗，对照组单独给予标准蒽环类药物化疗。主要终点是治疗反应，根据实体肿瘤反应评价标准（RECIST）进行评估。次要终点包括血浆组胺、IL-6、TNF-α水平和PBMC生物标志物（H1R、NF-κB、TLR-4）。结果对干预组20例患者和对照组22例患者的数据进行分析（纳入II期和III期患者，未观察到I期病例，因亚组规模不足而排除2例IV期患者[每组1例]）。干预组总有效率（65%）高于对照组（45.5%），但差异无统计学意义（p = 0.232）。干预组III期患者有效率显著高于对照组（干预组90.91%，对照组11.11%,p = 0.001）。无不良反应报告。结论地氯雷他定可改善III期乳腺癌的治疗反应，支持其作为新辅助化疗补充药物的潜在作用。本研究已在伊朗临床试验登记处（IRCT）注册，注册号为IRCT20230221057485N1。

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引用次数: 0

Implications of the Liver-Gut Axis in Liver Disease: From Mechanisms to Therapeutic Targets 肝肠轴在肝病中的意义：从机制到治疗靶点。

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-11-03 DOI: 10.1016/j.arcmed.2025.103335

Mariana M. Ramírez-Mejía , Guadalupe Ponciano-Rodríguez , Nahum Méndez-Sánchez

The liver-gut axis is a bidirectional communication system that integrates metabolic, immune, microbial, and nutritional signals which are critical to hepatic homeostasis. Disruption of this axis, through dysbiosis, altered intestinal barrier integrity, microbial translocation, and maladaptive immune activation, has become a central mechanism in the onset and progression of chronic liver diseases. Common pathways include changes in microbial composition and altered production of metabolites such as short-chain fatty acids, bile acids, ethanol, and trimethylamine N-oxide and activation of proinflammatory cascades via Toll-like receptors, NOD receptors, and inflammasomes. These alterations lead to steatosis, oxidative stress, fibrogenesis, and carcinogenesis. Notably, each liver disease presents distinct alterations. Beyond pathogenesis, modulation of the liver-gut axis has been shown to have therapeutic potential. Microbiota-targeted interventions, bile acid signaling modulators, and dietary and lifestyle strategies can restore microbial balance, strengthen the intestinal barrier, and attenuate liver injury. However, long-term safety, disease-specific efficacy, and integration with standard treatments remain key challenges. This review aims to provide an overview of the liver-gut axis. First, it describes its general regulatory mechanisms, then analyzes the specific alterations in the main chronic liver diseases and finally, it discusses the therapeutic implications of acting on this axis.

肝肠轴是一个双向通讯系统，整合了代谢、免疫、微生物和营养信号，这些信号对肝脏稳态至关重要。通过生态失调、肠道屏障完整性改变、微生物易位和不适应的免疫激活，这条轴的破坏已成为慢性肝病发生和发展的中心机制。常见的途径包括微生物组成的改变和代谢物如短链脂肪酸、胆胆酸、乙醇和三甲胺n -氧化物产生的改变，以及通过toll样受体、NOD受体和炎症小体激活促炎级联反应。这些改变导致脂肪变性、氧化应激、纤维生成和癌变。值得注意的是，每种肝脏疾病都有明显的变化。除了发病机制外，肝肠轴的调节已被证明具有治疗潜力。针对微生物群的干预、胆汁酸信号调节剂以及饮食和生活方式策略可以恢复微生物平衡，加强肠道屏障，减轻肝损伤。然而，长期安全性、疾病特异性疗效和与标准治疗的整合仍然是关键的挑战。这篇综述旨在提供肝-肠轴的概述。首先介绍其一般调控机制，然后分析其在主要慢性肝病中的具体改变，最后讨论作用于该轴的治疗意义。

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引用次数: 0

Non-Invasive Testing in Metabolic Dysfunction Associated Fatty Liver Disease 代谢功能障碍相关脂肪性肝病的无创检测。

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-10-31 DOI: 10.1016/j.arcmed.2025.103337

Cameron Gofton , Jacob George

Since the introduction of non-alcoholic steatohepatitis into the medical nomenclature, liver biopsy has been the best option for diagnosis, despite multiple limitations. Due to this inaccurate gold standard, there has been a need to develop non invasive testing for this disease to better diagnose and stage this condition. With the development of new terminology in 2020 of metabolic-dysfunction associated fatty liver disease providing a positive diagnostic criterion followed by metabolic-dysfunction associated steatotic liver disease, there has been extensive work to transition existing biomarkers into these new conditions. Despite this, there remains current gaps in biomarker development to meet the needs of this condition, particularly in view of its worldwide increasing prevalence. In this narrative review, we summarise the current concepts of non-invasive testing, review the available biomarkers and their accuracy in steatosis, steatohepatitis, and fibrosis, and discuss future concepts of biomarker development.

自从将非酒精性脂肪性肝炎引入医学术语以来，肝活检一直是诊断的最佳选择，尽管存在多种限制。由于这种不准确的金标准，有必要为这种疾病开发非侵入性测试，以更好地诊断和分期这种疾病。随着2020年代谢功能障碍相关脂肪性肝病新术语的发展，为代谢功能障碍相关脂肪性肝病提供了积极的诊断标准，人们已经开展了广泛的工作，将现有的生物标志物转化为这些新病症。尽管如此，目前在生物标志物开发方面仍存在差距，以满足这种情况的需求，特别是考虑到其在世界范围内日益普遍。在这篇叙述性综述中，我们总结了目前无创检测的概念，回顾了脂肪变性、脂肪性肝炎和纤维化中可用的生物标志物及其准确性，并讨论了生物标志物发展的未来概念。

引用次数: 0

The future of pancreatic cancer therapy: getting better, but not good enough yet 胰腺癌治疗的未来：越来越好，但还不够好。

IF 3.4 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research

Pub Date : 2025-10-30 DOI: 10.1016/j.arcmed.2025.103336

Johannes Klose, Jessica Doebereiner, Yoshiaki Sunami, Artur Rebelo, Ulrich Ronellenfitsch, Jorg Kleeff

Diagnosis of pancreatic cancer is generally regarded as dismal with poor prognosis due to advanced stage at presentation and limited treatment options. In the last years, treatment options for patients with pancreatic cancer, even in advanced stages of disease, improved. Beside tailored-approaches including chemotherapies in neo or adjuvant intention, new targets as well as vaccination has been implemented into therapeutic strategies. Additionally, embedded into individual treatment strategies, surgical approached were refined providing the potential chance for cure even in metastatic disease.

The aim of this review article is to describe current and further treatment options for patients with pancreatic cancer showing promising results. However, more efforts are needed to further improve patients’ prognosis.

胰腺癌的诊断通常被认为是令人沮丧的，预后差，由于晚期的表现和有限的治疗选择。在过去的几年里，胰腺癌患者的治疗选择有所改善，即使是在疾病的晚期。除了量身定制的方法，包括新或辅助目的的化疗，新的靶点以及疫苗接种已被实施到治疗策略中。此外，嵌入到个人治疗策略中，手术方法被改进，甚至在转移性疾病中也提供了治愈的潜在机会。这篇综述文章的目的是描述胰腺癌患者目前和未来的治疗选择，显示出有希望的结果。然而，进一步改善患者预后还需要更多的努力。

引用次数: 0