Advances in medical sciences最新文献_第2页

The role of sclerostin in the development and progression of cardiovascular diseases- a potential biomarker? 硬化蛋白在心血管疾病发生发展中的作用——一个潜在的生物标志物？

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.advms.2025.10.003

Sebastian Stelmaszek, Ewa Tarasiuk, Małgorzata Knapp, Remigiusz Kazimierczyk, Anna Lisowska

Sclerostin, a glycoprotein primarily synthesized by osteocytes, is a key regulator of bone remodeling through its inhibition of the Wnt/β-catenin signaling pathway. Beyond its established role in bone metabolism, sclerostin has been identified in vascular tissues, including smooth muscle cells of blood vessels, suggesting a potential role in cardiovascular diseases (CVD). Research on sclerostin's role in CVD has yielded conflicting results, highlighting its complex involvement in vascular calcification and atherosclerosis.

Some studies associate elevated sclerostin levels with a reduced risk of cardiovascular events, potentially due to its inhibition of pathways driving vascular calcification and osteogenic transformation of vascular cells. Conversely, other research links higher sclerostin levels with increased cardiovascular risk, including atherosclerosis, myocardial infarction, and stroke, possibly reflecting a compensatory response to vascular damage or inflammation.

Discrepancies in findings may stem from differences in study populations, methodologies, and confounding factors such as age, renal function, and medication use. Furthermore, sclerostin's dual effects may depend on specific pathological contexts, complicating its interpretation as a biomarker.

This review examines the evidence for sclerostin's role in CVD and its potential utility as a biomarker for cardiovascular risk stratification. While emerging data suggest diagnostic and therapeutic relevance, particularly in populations with chronic kidney disease or metabolic disorders, further research is necessary to elucidate its mechanisms, identify modulating factors, and assess its clinical value. A clearer understanding of sclerostin's vascular effects could pave the way for novel approaches to cardiovascular disease prevention and management.

硬化蛋白（Sclerostin）是一种主要由骨细胞合成的糖蛋白，通过抑制Wnt/β-catenin信号通路，是骨重塑的关键调节因子。除了在骨代谢中已确定的作用外，还在血管组织（包括血管平滑肌细胞）中发现了硬化蛋白，这表明它在心血管疾病（CVD）中具有潜在作用。关于硬化蛋白在心血管疾病中的作用的研究产生了相互矛盾的结果，强调了它在血管钙化和动脉粥样硬化中的复杂参与。一些研究将升高的硬化蛋白水平与降低心血管事件的风险联系起来，这可能是由于它抑制了驱动血管钙化和血管细胞成骨转化的途径。相反，其他研究将较高的硬化蛋白水平与心血管风险增加联系起来，包括动脉粥样硬化、心肌梗死和中风，这可能反映了对血管损伤或炎症的代偿反应。结果的差异可能源于研究人群、方法和混杂因素（如年龄、肾功能和药物使用）的差异。此外，硬化蛋白的双重作用可能取决于特定的病理背景，使其作为生物标志物的解释复杂化。这篇综述探讨了硬化蛋白在心血管疾病中的作用及其作为心血管风险分层生物标志物的潜在用途。虽然新出现的数据表明诊断和治疗的相关性，特别是在慢性肾脏疾病或代谢紊乱人群中，但需要进一步的研究来阐明其机制，确定调节因素，并评估其临床价值。更清楚地了解硬化蛋白的血管作用可以为心血管疾病预防和管理的新方法铺平道路。

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引用次数: 0

Response to Letter to the Editor on “Structured team response and sex-based mortality gaps in acute pulmonary embolism: Conflicting evidence and future directions” 对致编辑的关于“急性肺栓塞的结构化团队反应和基于性别的死亡率差距：相互矛盾的证据和未来方向”的回复。

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.advms.2025.10.005

Grzegorz Procyk , Arkadiusz Pietrasik

引用次数: 0

Intensification of diuretic therapy in pulmonary hypertension – a retrospective evaluation of hemodynamic and functional changes 加强利尿剂治疗肺动脉高压-血流动力学和功能改变的回顾性评估。

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.advms.2025.09.006

Adam Rafałowicz, Jakub Mierzejewski, Łukasz Czuba, Anna Lisowska, Małgorzata Knapp, Karol Kamiński, Katarzyna Ptaszyńska

Purpose

Diuretics are first-line medication in the management of volume overload in pulmonary hypertension (PH). Their impact on the hemodynamic and functional parameters has not been studied. This study analyzes the impact of intensified diuretic therapy on patients deterioration.

Methods

The retrospective analysis included 38 patients who were divided into Group 1 (n = 24, no change in the equivalent diuretic dose or treatment without diuretics) and Group 2 (n = 14, increase in the equivalent diuretic dose). Measurements at baseline and after 6 months included echocardiographic parameters, 6-min walk test distance (6MWTd), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP).

Results

In the initial assessment of the studied parameters, Group 2 had a significantly greater inferior vena cava diameter (IVCd) and right ventricle internal diameter in diastole (RVIDd), trends towards greater right atrium area (RAA), lower tricuspid annular plane systolic excursion (TAPSE), and greater NT-proBNP values compared to Group 1. Over the 6-month follow-up period, Group 1 had a significant increase in IVCd, systolic pulmonary artery pressure (sPAP), significant decrease in TAPSE/sPAP ratio and trends towards increased mean pulmonary artery pressure (mPAP) and 6MWTd values. Group 2, on the other hand, had no significant worsening, which reflects a stabilizing impact of intensified diuretic therapy.

Conclusion

Intensified diuretic therapy in patients with PH and fluid overload appears to stabilize exercise capacity and prevent deterioration of cardiac function over a 6-month period.

目的：利尿剂是治疗肺动脉高压（PH）容量超载的一线药物。它们对血流动力学和功能参数的影响尚未研究。本研究分析强化利尿剂治疗对患者病情恶化的影响。方法：回顾性分析38例患者，分为1组（n=24，等效利尿剂剂量不变或不使用利尿剂治疗）和2组（n=14，等效利尿剂剂量增加）。基线和6个月后的测量包括超声心动图参数、6分钟步行测试距离（6MWTd）和脑利钠肽n端原激素（NT-proBNP）。结果：在研究参数的初步评估中，与1组相比，2组下腔静脉直径（IVCd）和右心室舒张内径（RVIDd）显著增加，右心房面积（RAA）增加，三尖瓣下环面收缩偏移（TAPSE）增加，NT-proBNP值增加。在6个月的随访期间，1组IVCd、收缩期肺动脉压（sPAP）显著升高，TAPSE/sPAP比值显著降低，平均肺动脉压（mPAP）和6MWTd值有升高趋势。另一方面，组2没有明显恶化，这反映了利尿剂强化治疗的稳定作用。结论：在6个月的时间里，强化利尿剂治疗PH和液体超载患者可以稳定运动能力，防止心功能恶化。

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引用次数: 0

SGLT2 inhibitors attenuate cholesterol accumulation in Human Aortic Smooth Muscle Cells SGLT2抑制剂可降低人主动脉平滑肌细胞中的胆固醇积累。

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.advms.2025.10.006

Agnieszka Pawlos , Ewelina Woźniak , Marlena Broncel , Aleksandra Piechota-Polańczyk , Paulina Gorzelak-Pabiś

Purpose

The influence of SGLT2 inhibitors (SGLT2i) on cholesterol accumulation in Human Aortic Smooth Muscle Cells (HAoSMCs) has not yet been evaluated. This study aimed to assess the effect of SGLT2 inhibitors on cholesterol accumulation in HAoSMCs.

Materials and methods

HAoSMCs were treated with empagliflozin (1 and 10 μM), dapagliflozin (1 and 10 μM), and canagliflozin (1 and 10 μM), with or without cholesterol–methyl-β-cyclodextrin complex (cholesterol complex), for 144 h. Lipid accumulation was assessed using Oil Red O staining, and absorbance at 492 nm was measured to quantify lipid content. Relative absorbance values were calculated against a medium control.

Results

Incubation of HAoSMCs with 10 μg/ml cholesterol complex resulted in a significant increase (31.8 %) in absorbance compared to untreated cells (p < 0.0001). The presence of SGLT2 inhibitors significantly reduced the absorbance to 9.8–18.2 % in comparison to 31.8 % cholesterol complex alone. This effect was statistically significant for empagliflozin at 1 μM and 10 μM (p = 0.0497 and p = 0.0026, respectively) and dapagliflozin at 1 μM and 10 μM (p = 0.0286 and p = 0.0009, respectively). Interestingly, for canagliflozin, statistical significance was observed only at the higher concentration of 10 μM (p = 0.0057).

Conclusion

SGLT2 inhibitors may have a protective effect against cholesterol complex accumulation in HAoSMCs. There were no significant differences between the doses and types of SGLT2 inhibitors; however, dapagliflozin and empagliflozin showed a significant effect regardless of the concentration, while canagliflozin only at higher concentration.

目的：SGLT2抑制剂（SGLT2i）对人主动脉平滑肌细胞（HAoSMCs）胆固醇积累的影响尚未被评估。本研究旨在评估SGLT2抑制剂对HAoSMCs中胆固醇积累的影响。材料与方法：采用依帕格列净（1和10μM）、达格列净（1和10μM）和卡格列净（1和10μM），加或不加胆固醇-甲基-β-环糊精配合物（胆固醇配合物）处理HAoSMCs 144小时。使用Oil Red O染色评估脂质积累，并测量492nm吸光度以定量脂质含量。相对吸光度值与介质对照进行计算。结果：含10 μg/ml胆固醇复合物的HAoSMCs与未处理的细胞相比，吸光度显著增加（31.8%）(p结论：SGLT2抑制剂可能对HAoSMCs中胆固醇复合物的积累具有保护作用。SGLT2抑制剂的剂量和类型之间无显著差异；但无论浓度如何，达格列净和恩格列净均表现出显著效果，而卡格列净仅在较高浓度下才表现出显著效果。

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引用次数: 0

Impact of anti-HLA antibodies on the immunological status of patients with cardiac allograft vasculopathy (CAV) after heart transplantation. hla抗体对心脏移植后同种异体移植物血管病变（CAV）患者免疫状态的影响

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-10-01 Epub Date: 2025-07-23 DOI: 10.1016/j.advms.2025.07.001

Katarzyna Kowalik, Joanna Was, Katarzyna Kozar-Kaminska, Ilona Minota, Krzysztof Komuda, Aneta Rekawek, Tomasz Zielinski

Purpose: Heart transplantation (HTx) is an established method of treating patients with end-stage heart failure. Properly selected immunosuppression effectively reduces the risk of acute transplant rejection; however, it may also lead to various side effects including cardiac allograft vasculopathy (CAV), which is one of the most common causes of death in patients during the first year after HTx. There is an urgent need to develop new strategies for monitoring a patient's immune system to modify the immunosuppressive therapy, if needed. The purpose of this study is to compare the immune status of patients with diagnosed CAV + to that of patients without CAV-.

Material and methods: We collected blood samples from patients long-term after transplantation: 19 clinically stable patients CAV+ and 19 CAV-. Immunological parameters were assessed by analyzing lymphocyte subpopulations with flow cytometry and detecting the presence of alloantibodies with the use of Luminex technology.

Results: Statistical analysis demonstrated significant differences between CAV+ and CAV- patients only within the group of patients with detected alloantibodies (AlloAb+). The most notable observation is that a significantly higher proportion of CAV + AlloAb + patients demonstrated the CD4⁺ T lymphocyte population expressing IL2 compared to CAV-AlloAb + patients. Similarly, in these groups, we observed a prevalence of CD8⁺ lymphocytes expressing IFNγ+ and IL2+TNFα+IFNγ+.

Conclusion: Our study provides new evidence that the presence of alloantibodies in the bloodstream of patients after HTx impacts T cells activation and subsequent cytokine production. These data may facilitate establishing parameters that could help identify patients with a higher risk of CAV progression.

目的：心脏移植（HTx）是治疗终末期心力衰竭的一种成熟方法。正确选择免疫抑制可有效降低急性移植排斥反应的风险；然而，它也可能导致各种副作用，包括同种异体心脏移植血管病变（CAV），这是HTx术后第一年患者死亡的最常见原因之一。迫切需要开发新的策略来监测患者的免疫系统，以修改免疫抑制治疗，如果需要的话。本研究的目的是比较诊断为CAV+的患者与未诊断为CAV-的患者的免疫状况。材料和方法：我们收集移植后长期患者的血液样本：临床稳定的CAV+患者19例，CAV-患者19例。通过流式细胞术分析淋巴细胞亚群和使用Luminex技术检测同种异体抗体的存在来评估免疫学参数。结果：统计分析显示，仅在检测到同种异体抗体（AlloAb+）的患者组中，CAV+和CAV-患者之间存在显著差异。最值得注意的观察结果是，与CAV-AlloAb+患者相比，CAV+AlloAb+患者的CD4+ T淋巴细胞群表达IL2的比例明显更高。同样，在这些组中，我们观察到CD8+淋巴细胞表达IFNγ+和IL2+TNFα+IFNγ+的患病率。结论：我们的研究提供了新的证据，证明HTx患者血液中同种抗体的存在影响T细胞的活化和随后的细胞因子的产生。这些数据可能有助于建立有助于识别CAV进展风险较高的患者的参数。

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引用次数: 0

In vitro effects of transient receptor potential channel modulators on human tuba smooth muscle 瞬时受体电位通道调节剂对人大号平滑肌的体外作用。

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-10-01 DOI: 10.1016/j.advms.2025.11.001

Ozan Ozturk , Selin Acar-Sahan , Baris Karadas , Mustafa Sengul , Huseyin Yilmaz , Selen Bahceci , Tijen Kaya-Temiz

Purpose

There is relatively little data on the presence of Transient Receptor Potential (TRP) channels in human tubal tissue. Our study aimed to evaluate the contraction-relaxation responses of TRPV1 channel modulators in human tuba uterina tissue. We also aimed to investigate the presence of TRPV1 channel proteins by immunohistochemical staining with TRPV1 antibodies in tuba tissue.

Material and method

Ten patients with a mean age of 37.7 years who underwent tubal ligation for sterilization were included. Tissue samples were evaluated for in vitro contractility in a tissue bath. Changes in tuba smooth muscle isometric tension were measured in mg contraction. The basal mean tension was considered as 100 and capsaicin responses in the presence or absence of antagonist were expressed as a percentage of the basal mean tension.

Results

Concentrations of capsaicin 10⁻⁷, 10⁻⁶, 10⁻⁵, and 10⁻⁴ M; AMG 9810 10⁻⁵ M and 3x10⁻⁵ M; ruthenium red 10⁻⁵ M and 3x10⁻⁵ M were used. Relaxation response was obtained after cumulative capsaicin administration (maximum relaxation by 20 %). This relaxation was partially reversed when capsaicin was applied in the presence of AMG 9810. When capsaicin was applied in the presence of ruthenium red, a complete reversal of relaxation was observed. Immunohistochemical examination of tuba tissue using TRPV1 antibodies revealed moderate to high staining.

Conclusion

The presence of TRPV1 channel in human tuba tissue and its relaxant effect were demonstrated for the first time in this study.

目的：关于人类输卵管组织中瞬时受体电位（TRP）通道存在的数据相对较少。我们的研究旨在评估TRPV1通道调节剂在人子宫大管组织中的收缩-松弛反应。我们还旨在通过免疫组织化学染色，用TRPV1抗体在大号组织中研究TRPV1通道蛋白的存在。材料与方法：选取10例平均年龄37.7岁行输卵管结扎绝育术的患者。组织样品在组织浴中评估体外收缩性。在mg收缩时测量了大号平滑肌等距张力的变化。基础平均张力被认为是100，在存在或不存在拮抗剂的情况下，辣椒素反应以基础平均张力的百分比表示。结果：辣椒素浓度为10-7、10-6、10-5、10-4 M；AMG 9810 10- 5m和3x10- 5m；采用钌红10- 5m和3x10- 5m。累积辣椒素给药后获得松弛反应（最大松弛20%）。当在AMG 9810存在的情况下使用辣椒素时，这种松弛被部分逆转。当在钌红存在的情况下应用辣椒素时，观察到松弛的完全逆转。使用TRPV1抗体对大号组织进行免疫组化检查，显示中高染色。结论：本研究首次证实了人大号组织中TRPV1通道的存在及其松弛作用。

{"title":"In vitro effects of transient receptor potential channel modulators on human tuba smooth muscle","authors":"Ozan Ozturk , Selin Acar-Sahan , Baris Karadas , Mustafa Sengul , Huseyin Yilmaz , Selen Bahceci , Tijen Kaya-Temiz","doi":"10.1016/j.advms.2025.11.001","DOIUrl":"10.1016/j.advms.2025.11.001","url":null,"abstract":"<div><h3>Purpose</h3><div>There is relatively little data on the presence of Transient Receptor Potential (TRP) channels in human tubal tissue. Our study aimed to evaluate the contraction-relaxation responses of TRPV1 channel modulators in human tuba uterina tissue. We also aimed to investigate the presence of TRPV1 channel proteins by immunohistochemical staining with TRPV1 antibodies in tuba tissue.</div></div><div><h3>Material and method</h3><div>Ten patients with a mean age of 37.7 years who underwent tubal ligation for sterilization were included. Tissue samples were evaluated for <em>in vitro</em> contractility in a tissue bath. Changes in tuba smooth muscle isometric tension were measured in mg contraction. The basal mean tension was considered as 100 and capsaicin responses in the presence or absence of antagonist were expressed as a percentage of the basal mean tension.</div></div><div><h3>Results</h3><div>Concentrations of capsaicin 10<sup>−7</sup>, 10<sup>−6</sup>, 10<sup>−5</sup>, and 10<sup>−4</sup> M; AMG 9810 10<sup>−5</sup> M and 3x10<sup>−5</sup> M; ruthenium red 10<sup>−5</sup> M and 3x10<sup>−5</sup> M were used. Relaxation response was obtained after cumulative capsaicin administration (maximum relaxation by 20 %). This relaxation was partially reversed when capsaicin was applied in the presence of AMG 9810. When capsaicin was applied in the presence of ruthenium red, a complete reversal of relaxation was observed. Immunohistochemical examination of tuba tissue using TRPV1 antibodies revealed moderate to high staining.</div></div><div><h3>Conclusion</h3><div>The presence of TRPV1 channel in human tuba tissue and its relaxant effect were demonstrated for the first time in this study.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 2","pages":"Pages 427-435"},"PeriodicalIF":2.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Sex-based differences in patients with acute pulmonary embolism managed by a pulmonary embolism response team: a multicenter, retrospective cohort study 肺栓塞反应小组处理急性肺栓塞患者的性别差异：一项多中心、回顾性队列研究。

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-09-11 DOI: 10.1016/j.advms.2025.09.003

Grzegorz Procyk , Paweł Kurzyna , Karolina Jasińska-Gniadzik , Julia Maria Smyk , Marcin Wasilewski , Rafał Wolański , Piotr Szwed , Dominika Rymaszewska , Dominika Zajkowska , Katarzyna Wrona , Szymon Darocha , Marta Banaszkiewicz , Michał Florczyk , Dariusz Zieliński , Krzysztof Wróbel , Marcin Grabowski , Grzegorz Opolski , Adam Torbicki , Marcin Kurzyna , Aleksandra Gąsecka , Arkadiusz Pietrasik

Purpose

Pulmonary embolism (PE) is the third most frequent acute cardiovascular condition worldwide. PE response teams (PERTs) were proposed recently to facilitate treatment implementation in PE patients. There is limited data regarding the characteristics of patients consulted by PERTs. We aimed to analyze sex-related differences in baseline characteristics, applied treatment, and prognosis of acute PE patients consulted by a local PERT. We did not seek to assess the influence of PERT on potential differences.

Materials and methods

The study included 235 patients diagnosed with PE in the three participating hospitals between September 2017 and December 2021. Clinical and treatment data were obtained from medical records.

Results

We found that women were older than men (median [IQR]: 66.0 [49.5–77.0] vs. 58.5 [49.0–69.3] years, P = 0.02). Cough was more prevalent in men (23.0 % vs. 7.3 %, P = 0.001). Smoking was more frequent in men (32.5 % vs. 15.6 %, P = 0.004), whereas hormonal therapy was more frequent in women (11.0 % vs. 0.8 %, P = 0.001). Hospitalized women required intubation more often than men (16.5 % vs. 6.3 %, P = 0.02). Proximal deep vein thrombosis was more common in men (46.8 % vs. 33.9 %, P = 0.047). Low molecular weight heparins were more often used in men (82.5 % vs. 66.1 %, P = 0.004).

Conclusions

Most analyzed parameters did not differ between the sexes in acute PE patients treated by a PERT. Differences in risk factors are associated with well-established sex-related differences, with smoking more often reported in men and hormonal therapy more common in women. Notably, the survival rate was comparable for women and men.

目的：肺栓塞（PE）是全球第三大最常见的急性心血管疾病。最近提出了PE反应小组（PERTs），以促进PE患者的治疗实施。关于pert咨询的患者特征的数据有限。我们的目的是分析在当地PERT咨询的急性PE患者的基线特征、应用治疗和预后方面的性别相关差异。我们没有试图评估PERT对潜在差异的影响。材料与方法：研究纳入了2017年9月至2021年12月在三家参与医院诊断为PE的235例患者。临床和治疗资料来源于医疗记录。结果：我们发现女性比男性年龄大（中位[IQR]: 66.0[49.5-77.0]比58.5[49.0-69.3]岁，P=0.02）。咳嗽在男性中更为普遍（23.0%比7.3%，P=0.001）。吸烟在男性中更常见（32.5%比15.6%，P=0.004），而激素治疗在女性中更常见（11.0%比0.8%，P=0.001）。住院女性比男性更需要插管（16.5%比6.3%，P=0.02）。近端深静脉血栓在男性中更为常见（46.8%比33.9%，P=0.047）。低分子量肝素在男性中使用较多（82.5%比66.1%，P=0.004）。结论：在接受PERT治疗的急性PE患者中，大多数分析参数在性别之间没有差异。危险因素的差异与已确立的性别差异有关，吸烟在男性中更为常见，激素治疗在女性中更为常见。值得注意的是，女性和男性的存活率相当。

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引用次数: 0

Association of FKBP5 gene polymorphism with insomnia symptoms in the depressive episodes of stress-related bipolar disorder FKBP5基因多态性与压力相关性双相情感障碍抑郁发作失眠症状的关系

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-09-10 DOI: 10.1016/j.advms.2025.09.004

Ovinuchi Ejiohuo , Karolina Bilska , Karolina Gattner , Łukasz Mech , Dominik Spalek , Maria Skibińska , Monika Dmitrzak-Węglarz , Paweł Kapelski , Beata Narożna , Bartłomiej Budziński , Aleksandra Szczepankiewicz , Joanna Pawlak

Purpose

Stress-related bipolar disorder (BP) arises from complex genetic, environmental, and clinical interactions. While FKBP5(key stress response regulator) is linked to mood disorders, its role in insomnia during depressive episodes remains unclear. This study explores the association between FKBP5 polymorphisms and insomnia symptoms occurring during the depressive episodes of BP.

Materials and methods

A total of 347 individuals with BP (42 % male, 58 % female; 78 % insomnia symptoms) were assessed using the SCID, OPCRIT, and TaqMan genotyping for eight FKBP5 polymorphisms. Participants were grouped based on the presence/absence of a stressor before the first episode. Statistical analyses (ANCOVA and Chi-square with pairwise post hoc tests) were performed using Statistica 13.3 and R. Functional annotation of significantly associated variants was conducted using Ensembl VEP, RegulomeDB, HaploReg, and SNPnexus.

Results

FKBP5 rs755658 polymorphism may be associated with insomnia symptoms in individuals with stressors, with CT/CC genotypes showing a higher likelihood of symptoms (p = 0.03; BH-adjusted p = 0.22, below the 0.25 threshold) compared to the TT. Seven polymorphisms were significantly associated with BP subtypes in those without stressors, suggesting genetic influence. The rs755658 variant is predicted to affect gene expression, transcription factor binding, and post-transcriptional regulation.

Conclusions

These findings suggest that FKBP5 genetic variants may affect sleep disturbances with a stressor present, highlighting their role in stress regulation and insomnia during depressive episodes in BP. Given the study's exploratory nature, findings should be interpreted cautiously and validated in larger, independent samples. Future studies should investigate the underlying mechanisms and therapeutic implications.

目的：应激相关性双相情感障碍（BP）是由复杂的遗传、环境和临床相互作用引起的。虽然FKBP5（关键应激反应调节因子）与情绪障碍有关，但它在抑郁症发作期间失眠中的作用尚不清楚。本研究探讨了FKBP5多态性与BP抑郁发作期间失眠症状之间的关系。材料和方法：使用SCID、OPCRIT和TaqMan基因分型对8个FKBP5多态性进行评估，共347例BP患者（42%为男性，58%为女性，78%为失眠症状）。参与者根据首次发作前压力源的存在与否进行分组。使用Statistica 13.3和r进行统计分析（ANCOVA和卡方结合两两事后检验）。使用Ensembl VEP、RegulomeDB、HaploReg和SNPnexus对显著相关变异进行功能注释。结果：FKBP5 rs755658多态性可能与压力源个体的失眠症状有关，与TT相比，CT/CC基因型显示出更高的症状可能性（p = 0.03； bh调整p = 0.22，低于0.25阈值）。在没有应激源的受试者中，有7个多态性与BP亚型显著相关，提示遗传影响。预计rs755658变异会影响基因表达、转录因子结合和转录后调控。结论：这些研究结果表明，FKBP5基因变异可能影响存在压力源的睡眠障碍，突出了它们在BP抑郁发作期间的压力调节和失眠中的作用。鉴于该研究的探索性，研究结果应谨慎解释，并在更大的独立样本中进行验证。未来的研究应探讨其潜在的机制和治疗意义。

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引用次数: 0

Atherosclerosis in the context of hemostasis and neovascularization – Current state of knowledge 动脉粥样硬化在止血和新生血管的背景下-目前的知识状况。

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-09-08 DOI: 10.1016/j.advms.2025.09.002

Urszula Jakobsche-Policht , Agnieszka Bronowicka-Szydełko , Rajmund Adamiec , Dorota Bednarska-Chabowska , Emilia Królewicz , Łukasz Lewandowski , Kinga Gostomska-Pampuch , Arkadiusz Derkacz , Katarzyna Budrewicz , Ewa Grzebyk , Maciej Nowak , Daria Dolińska , Paulina Matlak , Julia Sobczyńska , Maciej Ziomek , Maciej Tota , Wojciech Stach , Dominik Fidorowicz , Katarzyna Madziarska

Atherosclerosis is a progressive process resulting from endothelial dysfunction, primarily caused by damage to the integrity of the glycocalyx. Its pathogenesis is complex and involves numerous biomechanical and biochemical factors, such as blood pressure, shear forces, lipid metabolism disorders, monocyte migration and their transformation into macrophages, immune response, lipid accumulation, neovascularization, and activation of coagulation. Recently, the possibility of atherosclerosis regression has been confirmed, although the mechanisms behind the reversal of changes remain unknown. This review presents current knowledge on the pathogenesis of atherosclerosis, with particular emphasis on pro-atherogenic processes in the glycocalyx and endothelium, especially those related to hemostasis, neovascularization, and epigenetic changes.

动脉粥样硬化是由内皮功能障碍引起的进行性过程，主要由糖萼完整性受损引起。其发病机制复杂，涉及众多生物力学和生化因素，如血压、剪切力、脂质代谢紊乱、单核细胞迁移及其向巨噬细胞的转化、免疫反应、脂质积累、新生血管形成和凝血激活等。最近，动脉粥样硬化消退的可能性已被证实，尽管逆转变化背后的机制尚不清楚。本文综述了动脉粥样硬化发病机制的最新知识，特别强调了糖萼和内皮的促动脉粥样硬化过程，特别是与止血、新生血管和表观遗传改变有关的过程。

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引用次数: 0

Ropivacaine and lidocaine at clinically relevant concentrations suppress proliferation and migration of ovarian cancer cells and induce morphological alterations 临床相关浓度的罗哌卡因和利多卡因抑制卵巢癌细胞的增殖和迁移，并引起形态学改变。

IF 2.6 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-09-08 DOI: 10.1016/j.advms.2025.08.003

Jane M. Hayden , Andreas Tinnert , Kersti Alm , Jonatan Oras , Linda Block , Anil Gupta , Sven-Egron Thörn , Stina Oredsson

Purpose

Ovarian cancer ranks as a gynecological malignancy with poor prognosis, specifically if detected late. Primary treatment includes cytoreductive surgery and adjuvant chemotherapy with curative intent. Local anesthetics (LA) administered in the perioperative period may potentially impact patient outcome by several mechanisms. The beneficial impact of LA has been attributed, among other factors, to the drug's inhibitory effect on cancer cells. The primary aim of the study was to evaluate the effect of clinically relevant concentrations of ropivacaine and lidocaine on ovarian cancer cell lines.

Method

Three ovarian cancer cell lines (SKOV-3, SW-626 and CA-OV-3) were treated with 1, 10, 100, or 1000 μM of the two LAs. Cell function and morphology were assessed in the following ways: cell counting, phase-contrast and holographic microscopy, a conventional MTT assay for dose response testing, wound healing assay for migration, and cancer stem cell (CSC) identification by aldehyde dehydrogenase.

Results

Both ropivacaine and lidocaine significantly reduced cell number, altered morphology, suppressed migration, and decreased the population of CSCs in a concentration-dependent manner.

Conclusion

LAs exert a direct inhibitory effect on ovarian cancer cell lines in vitro, suggesting their potential benefits in perioperative management for patients undergoing surgery. Clinical studies using LA during ovarian cancer surgery are needed.

目的：卵巢癌是一种预后较差的妇科恶性肿瘤，尤其是发现较晚。主要治疗包括细胞减少手术和辅助化疗。围手术期局部麻醉（LA）的使用可能会通过几种机制影响患者的预后。除其他因素外，LA的有益作用归因于该药物对癌细胞的抑制作用。该研究的主要目的是评估临床相关浓度的罗哌卡因和利多卡因对卵巢癌细胞系的影响。方法：分别用1、10、100、1000 μM的两种LAs作用于3株卵巢癌细胞系SKOV-3、SW-626和CA-OV-3。通过以下方法评估细胞功能和形态：细胞计数，相对比和全息显微镜，常规MTT试验用于剂量反应测试，伤口愈合试验用于迁移，醛脱氢酶鉴定癌症干细胞（CSC）。结果：罗哌卡因和利多卡因均显著减少细胞数量，改变形态，抑制迁移，并以浓度依赖的方式减少CSC的数量。结论：LAs在体外对卵巢癌细胞系有直接抑制作用，提示其在手术患者围手术期管理中的潜在益处。在卵巢癌手术中使用LA的临床研究是必要的。

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