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Prevalence of thyroid dysfunction among pregnant women in the horn of Africa: A systematic review and Meta-analysis 非洲之角孕妇甲状腺功能障碍的患病率:系统回顾与元分析
Q3 Medicine Pub Date : 2024-09-30 DOI: 10.1016/j.endmts.2024.100200
Marye Nigatie , Getinet Kumie , Abdu Jemal , Solomon Gedfie , Woldeteklehaymanot Kassahun , Muluken Gashaw , Agenagnew Ashagre , Tadesse Misganaw , Wagaw Abebe , Ermias Getachew , Selamyhun Tadesse , Zelalem Dejazmach , Sisay Ayana , Yalewayker Gashaw , Zelalem Asmare , Assefa Sisay , Atitegeb Abera , Biruk Beletew Abate , Melese Abate Reta

Background

Thyroid dysfunction ranks among the most prevalent endocrine disorders. This disorder during pregnancy has been linked to adverse effects on both the mother and the baby. However, there is a scarcity of data and inconsistent documentation regarding thyroid issues in pregnant women in low-income nations.

Objective

The aim of this systematic review and meta-analysis was to determine the general prevalence of thyroid disorders in pregnant women.

Methods

To identify relevant studies, a comprehensive search was conducted across Scopus, PubMed, Science Direct databases, and Google Scholar and repository registers from January 1, 2000 to December 31, 2023. Ten pertinent publications were chosen for the final meta-analysis. Relevant data was extracted using Microsoft Excel and analyzed using STATA software version 17, employing a random-effect model. Sensitivity analysis was conducted to evaluate each study's impact on the outcome, and Egger's test was utilized to detect publication bias. A trim-and-fill analysis was executed to adjust for bias in the effect estimate. Heterogeneity across studies was assessed using Cochran's Q statistic and I2 statistics. Subgroup analysis was carried by study design, country and publication year.

Results

In this systematic review and meta-analysis, the prevalence of thyroid dysfunction among 2538 pregnant women was 12.0 % (95 % CI: 8.00 %–17.00 %). To account for the significant heterogeneity observed, a random effect model was utilized. Specifically, the prevalence of hypothyroidism in pregnant women was determined to be 10.00 % (95 % CI: 4.00–16.00 %) with a high level of heterogeneity (I2 = 94.27 %, p < 0.001). Notably, the sensitivity analysis conducted did not reveal any substantial impact on the overall pooled prevalence of thyroid dysfunction.

Conclusion

The meta-analysis revealed a significantly higher rate of thyroid disorders among pregnant women compared to global estimates. To assess the effects of treating thyroid conditions on pregnancy outcomes and inform clinical decisions, it is recommended to implement cost-effective thyroid-stimulating hormone screening during pregnancy.
背景甲状腺功能障碍是最常见的内分泌疾病之一。妊娠期甲状腺功能紊乱会对母婴造成不良影响。为了确定相关研究,我们在 Scopus、PubMed、Science Direct 数据库、Google Scholar 和文献库登记中进行了全面搜索,搜索时间为 2000 年 1 月 1 日至 2023 年 12 月 31 日。最终选择了 10 篇相关出版物进行荟萃分析。使用 Microsoft Excel 提取相关数据,并使用 STATA 软件 17 版进行分析,采用随机效应模型。进行了敏感性分析以评估每项研究对结果的影响,并利用 Egger 检验来检测发表偏倚。此外,还进行了修剪填充分析,以调整效应估计值的偏差。使用 Cochran's Q 统计量和 I2 统计量评估了各研究之间的异质性。根据研究设计、国家和发表年份进行了分组分析。结果 在这项系统回顾和荟萃分析中,2538 名孕妇的甲状腺功能障碍患病率为 12.0 %(95 % CI:8.00 %-17.00 %)。为了解释所观察到的显著异质性,我们采用了随机效应模型。具体而言,孕妇甲减患病率被确定为 10.00 %(95 % CI:4.00-16.00 %),异质性很高(I2 = 94.27 %,p < 0.001)。值得注意的是,所进行的敏感性分析并未显示出对甲状腺功能障碍总患病率的实质性影响。为了评估治疗甲状腺疾病对妊娠结局的影响并为临床决策提供依据,建议在孕期开展具有成本效益的促甲状腺激素筛查。
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引用次数: 0
Platelet activation and inflammation in transgender women using hormone therapy 使用激素疗法的变性妇女的血小板活化和炎症反应
Q3 Medicine Pub Date : 2024-09-30 DOI: 10.1016/j.endmts.2024.100201
Lieve Mees van Zijverden , Moya Henriëtte Schutte , Marieke Tebbens , Milou Cecilia Madsen , Jeske Joanna Katarina van Diemen , Chantal Maria Wiepjes , Martin den Heijer , Abel Thijs

Objective

The pathophysiological process behind the increased risk of cardiovascular disease (CVD) in transgender women remains to be elucidated. This exploratory study aimed to investigate whether changes in platelet activation and inflammation after the start of feminizing gender-affirming hormone therapy (GAHT) could be a contributing mechanism.

Design

Longitudinal cohort study.

Methods

Venous blood was collected from 17 transgender women at 0, 12 and 52 weeks after GAHT initiation, consisting of estradiol and testosterone suppression. Platelet activation markers plasma thromboxane B2, Closure Time, CD63, CD62p, platelet-leukocyte complexes and immature platelet fraction were measured. CRP and 11 cytokines were measured as inflammation markers.

Results

CD63, CD62p and platelet-leukocyte complexes tended to increase after 12 weeks of GAHT. After 52 weeks, all platelet activation markers showed anti-aggregatory changes. Eight out twelve inflammation markers exhibited a decreasing tendency at week 12. Equivalently, after 52 weeks, eight inflammation markers tended to decrease, seven of which had also exhibited a decrease at week 12.

Conclusions

The collective findings suggest that platelet activation fluctuates during feminizing GAHT, exhibiting an initial increase followed by a decrease. Additionally, inflammation markers tend to decrease. Within the scope of this study, we could not identify GAHT induced platelet activation as a definite contributing factor in the increased risk of CVD in transgender women. Studies with larger numbers of participants and longer follow-up duration are needed to further investigate the effect of feminizing gender-affirming hormone therapy on platelet activation and inflammation.

Trial registration

EudraCT #2017-003072-31.
目的变性女性罹患心血管疾病(CVD)的风险增加背后的病理生理过程仍有待阐明。这项探索性研究旨在探讨女性化性别确认激素疗法(GAHT)开始后,血小板活化和炎症的变化是否可能是一个促成机制。测量血小板活化标志物血浆血栓素 B2、闭合时间、CD63、CD62p、血小板-白细胞复合物和未成熟血小板部分。结果CD63、CD62p和血小板-白细胞复合物在GAHT 12周后呈上升趋势。52 周后,所有血小板活化标志物都出现了抗聚集变化。在第 12 周时,12 种炎症标志物中有 8 种呈下降趋势。结论 这些研究结果表明,在女性化 GAHT 期间,血小板活化会发生波动,最初会增加,随后会减少。此外,炎症标志物也呈下降趋势。在本研究的范围内,我们无法确定 GAHT 诱导的血小板活化是导致变性女性心血管疾病风险增加的明确因素。要进一步研究女性化性别肯定激素疗法对血小板活化和炎症的影响,还需要进行参与者人数更多和随访时间更长的研究。
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引用次数: 0
Long-term diabetic hyperglycaemia modifies social behaviour in rats 长期糖尿病高血糖改变大鼠的社会行为
Q3 Medicine Pub Date : 2024-09-30 DOI: 10.1016/j.endmts.2024.100197
Justine Renaud , Alexandre Clouet , Giulia Costa , Jimmy Beaulieu , Domenico Sergi , Maria-Grazia Martinoli
Diabetes is a known risk factor for cognitive decline and mood disorders. However, the effects of long-term diabetic hyperglycaemia on the various dimensions of social behaviours, such as play or aggression, remains to be fully elucidated. In this study, we evaluated the social behaviour in a nicotinamide-streptozotocin rat model of long-term diabetic hyperglycaemia, in the absence of glucose-lowering treatments. Five months following induction of hyperglycaemia, we scored affiliative/exploratory or aggressive social interactions between pairs of unacquainted rats in a neutral arena. Our results demonstrate alterations in the behaviour of long-term diabetic rats faced with social novelties. Specifically, diabetic hyperglycaemic rats engaged in hyper-sociable and hyper-aggressive encounters. Interestingly, social interactivity was not associated with the degree of hyperglycaemia in affiliative/exploratory or in aggressive social interactions, in our long-term diabetic rat model. Altogether, our data suggest a lack of social appropriateness in long-term diabetic hyperglycaemic rats which is independent of the degree of hyperglycaemia. These findings support the importance of a tight glycaemic control in the management of diabetes at every stage of the disease and enlighten the importance of impaired glycaemic control as a novel metabolic player impacting the neural networks of social behaviours.
众所周知,糖尿病是认知能力下降和情绪障碍的危险因素。然而,长期糖尿病高血糖对玩耍或攻击等各种社会行为的影响仍有待全面阐明。在这项研究中,我们评估了烟酰胺-链脲佐菌素大鼠长期糖尿病高血糖模型在没有降糖治疗的情况下的社会行为。在诱导高血糖五个月后,我们对一对不相识的大鼠在中性场中的从属/探索性或攻击性社会互动进行了评分。我们的研究结果表明,长期糖尿病大鼠面对社会新事物时的行为发生了改变。具体地说,糖尿病高血糖大鼠参与了高社交性和高攻击性的接触。有趣的是,在我们的长期糖尿病大鼠模型中,在从属/探索性或攻击性社会互动中,社会互动性与高血糖程度无关。总之,我们的数据表明,长期糖尿病高血糖大鼠缺乏社交适当性,这与高血糖程度无关。这些研究结果支持了在糖尿病的各个阶段严格控制血糖的重要性,并揭示了血糖控制受损作为影响社会行为神经网络的新型代谢参与者的重要性。
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引用次数: 0
Increase of serum vitamin D levels in the COVID-19 pandemic: Report of a Mexican reference clinical laboratory COVID-19 大流行中血清维生素 D 水平的升高:墨西哥参考临床实验室的报告
Q3 Medicine Pub Date : 2024-09-30 DOI: 10.1016/j.endmts.2024.100199
García-Alcalá Héctor , Minutti-Zanella Claudia , Orta-Flores Verónica , López-Martínez Briceida

Background

The COVID-19 pandemic prompted health professionals to look for prevention and treatment options to improve outcomes. Vitamin D3 (VitD) is a sun dependent, immunomodulatory hormone that was widely used approaching COVID-19 because of previous experience with other RTIs. Its use was recommended in clinical practice guidelines and mainstream media, motivating supplement consumption. This increased the demand for serum VitD determinations, as well as the progressive increase of serum VitD levels.

Objective

Study the change in mean VitD serum levels in the population of one reference clinical laboratory before and during pandemic years.

Methods

We analyzed 65,481 results (78% female, mean age of 53.47 (M = 55, IQR = 25)).

Results

The median Vitamin D level was higher in all seasons in the pandemic years compared to previous years: spring 24 ng/dL (IQR 13.7) vs 25.4 ng/dL (IQR 17), summer 23.5 ng/dL (IQR 13.4) vs 24.2 ng/dL (IQR 16.3), autumn 23.7 ng/dL (IQR 14.3) vs 27 ng/dL (IQR 18.7), winter 22.4 ng/dL (IQR 14.9) vs 23.4 ng/dL (IQR 17.8).

Conclusions

The increase in serum VitD during the pandemic years is probably due to the recommendations of its use in guidelines of clinical practice. Although up to date the CDC and NIH have deemed there is not enough information in favor or against VitD use, epidemiology studies should be done to observe the impact of widespread VitD use in COVID-19 and other illnesses.
背景 COVID-19 大流行促使卫生专业人员寻找预防和治疗方案,以改善治疗效果。维生素 D3(VitD)是一种依赖阳光的免疫调节激素,由于之前在其他 RTIs 中的经验,它在 COVID-19 中被广泛使用。临床实践指南和主流媒体都推荐使用维生素 D3,从而促进了补充剂的消费。研究方法我们分析了 65,481 份结果(78% 为女性,平均年龄为 53.47 岁(M = 55 岁,IQR = 25 岁))。结果与往年相比,大流行年各季的维生素 D 水平中位数均较高:春季为 24 ng/dL (IQR 13.7) vs 25.4 ng/dL (IQR 17),夏季为 23.5 ng/dL (IQR 13.4) vs 24.2 ng/dL (IQR 16.3),秋季为 23.7 ng/dL (IQR 14.3) vs 27 ng/dL (IQR 14.3) 。结论大流行期间血清 VitD 的增加可能是由于临床实践指南建议使用 VitD。尽管到目前为止,美国疾病预防控制中心(CDC)和美国国立卫生研究院(NIH)认为没有足够的信息支持或反对使用 VitD,但仍应开展流行病学研究,以观察广泛使用 VitD 对 COVID-19 和其他疾病的影响。
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引用次数: 0
Hypoalbuminemia on admission in diabetic patients correlates with severity of illness in COVID-19: A retrospective clinical study and literature review 糖尿病患者入院时的低白蛋白血症与 COVID-19 的病情严重程度相关:回顾性临床研究和文献综述
Q3 Medicine Pub Date : 2024-09-03 DOI: 10.1016/j.endmts.2024.100196
Mayumi Shoji , Naoya Teramoto , Takahiro Ishikawa , Aiko Hayashi , Ai Matsumoto , Hidetoshi Ochiai , Ayano Yamaguchi , Yukari Maeda , Atsushi Takasaki , Chihiro Hiraga , Shintaro Ide , Kana Ide , Masashi Yamamoto , Yoshiro Maezawa , Ayako Shigeta , Seiichiro Sakao , Takuji Suzuki , Misuzu Yahaba , Toshihumi Taniguchi , Hidetoshi Igari , Masaya Koshizaka

Introduction

To elucidate factors associated with severe disease in patients with coronavirus disease 2019 (COVID-19) pneumonia complicated with diabetes mellitus.

Methods

Among patients with COVID-19 pneumonia hospitalized from January to September 2021, 100 patients with diabetes were included in the study. Patients in the intensive care unit admission or in-hospital death category were defined as the severe group (26 patients), and the other patients as the moderate group (74 patients). Comparisons were made between the two groups. Medical histories were extracted from the medical records, and statistical analysis was performed.

Results

Patients were 62.1 ± 13.0 years of age, 70 % male, 48 % aged 65 years and more, and HbA1c was 7.72 ± 1.51 %. The severe group had significantly higher blood glucose level, CRP, WBC, and LDH on admission. Serum albumin level was significantly lower in the severe group and was significantly negatively correlated with number of days on oxygen administration (r = 0.447) and maximal oxygen concentration (r = 0.561). Multiple logistic regression analysis with severity of illness as the objective variable showed that high CRP and low albumin levels on admission, and older age were independently associated.

Conclusions

Low albumin levels on admission may be an indicator of severe disease in patients with diabetes.

导言:目的:阐明冠状病毒病2019(COVID-19)肺炎并发糖尿病患者的重症相关因素。 方法:在2021年1月至9月住院的COVID-19肺炎患者中,纳入100名糖尿病患者。将入住重症监护室或院内死亡的患者定义为重度组(26 例),其他患者定义为中度组(74 例)。对两组患者进行比较。从病历中提取病史,并进行统计分析。 结果 患者年龄为(62.1 ± 13.0)岁,男性占 70%,65 岁及以上占 48%,HbA1c 为(7.72 ± 1.51)%。重症组患者入院时的血糖水平、CRP、白细胞和 LDH 明显较高。严重组的血清白蛋白水平明显较低,且与吸氧天数(r = 0.447)和最大氧浓度(r = 0.561)呈显著负相关。以病情严重程度为客观变量的多元逻辑回归分析表明,入院时的高 CRP 和低白蛋白水平与年龄较大有独立关联。
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引用次数: 0
Influence of the increase in intestinal permeability and microbiota change in the development of Hashimoto's thyroiditis - Systematic review 肠道渗透性增加和微生物群变化对桥本氏甲状腺炎发病的影响 - 系统综述
Q3 Medicine Pub Date : 2024-08-31 DOI: 10.1016/j.endmts.2024.100195
Desislav G. Tomov , Boryana A. Levterova , Valentina N. Mihailova , Dimitar M. Troev , Maria Z. Miteva , Yordanka I. Uzunova , Maria M. Orbetzova

The etiology of Hashimoto's thyroiditis is still unclear. Genetic predisposition and the effects of various environmental factors are discussed. The present article is a systematic review of publications on the occurrence and development of this disease in the presence of impaired functions of the gastrointestinal tract and changes in the microbiota. Increased intestinal permeability, as well as changes in the microbiota, can disrupt the normal functioning of the immune system and can lead to the development of an autoimmune disease. Normalization of the diversity of the microbiota before an autoimmune process occurs can be achieved both with the use of pro-biotic strains and with appropriate dietary changes.

桥本氏甲状腺炎的病因尚不清楚。本文讨论了遗传易感性和各种环境因素的影响。本文系统回顾了有关在胃肠道功能受损和微生物群发生变化的情况下该疾病发生和发展的文献。肠道渗透性增加以及微生物群的变化会破坏免疫系统的正常功能,并导致自身免疫性疾病的发生。通过使用益生菌株和适当改变饮食习惯,可以在自身免疫过程发生之前使微生物群的多样性恢复正常。
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引用次数: 0
Depression in type 2 diabetes mellitus: Prevalence, characteristics, associated factors, and treatment outcomes 2 型糖尿病患者中的抑郁症:患病率、特征、相关因素和治疗效果
Q3 Medicine Pub Date : 2024-08-17 DOI: 10.1016/j.endmts.2024.100194
Hoa Van Tran , Hiep Ngo Buu Tran , Toan Hoang Ngo , Kien Trung Nguyen

Background

Previous studies have demonstrated that sertraline has a positive impact on improving depression; however, data on the prevalence and treatment outcomes of sertraline among patients with comorbid Type 2 diabetes mellitus and depression remain limited.

Objectives

Determine the prevalence and associated factors of depression, and evaluate the treatment outcomes of sertraline intervention at two dosage levels (50 mg per day and 100 mg per day) in patients with comorbid depression and type 2 diabetes mellitus in Vietnam.

Materials and methods

The study included type 2 diabetes mellitus patients receiving outpatient treatment at Bac Lieu General Hospital from March 2023 to March 2024. Following the assessment of depression prevalence and associated factors, a randomized, single-blind clinical trial was conducted. Patients were randomly assigned to two groups: odd-numbered patients received treatment with 50 mg/day sertraline dosage, while even-numbered patients received treatment with 100 mg/day sertraline dosage. The criteria for success included improvement in symptoms and severity of depression after 6 months of treatment.

Results

A total of 225 type 2 diabetes mellitus patients with a mean age of 63.8 ± 10.7 years were included, among whom 72 were diagnosed with depression, accounting for a prevalence rate of 32 %. Among these patients, 51 were female (70.8 %) and 21 were male (29.2 %). Female gender, overweight, obesity, diabetes duration over 36 months, and a history of cardiovascular disease were found to be associated with depression. However, in the multivariate model, only overweight, obesity, HbA1c ≥ 6.5 %, and a history of cardiovascular disease were identified as independent factors contributing to depression in type 2 diabetes mellitus patients, with odds ratios of 4.12 (95 % CI: 1.78–9.56; p = 0.001), 0.37 (95 % CI: 0.15–0.95; p = 0.038) and 25.90 (95 % CI: 9.05–74.12; p < 0.001), respectively. Following 6 months of treatment, in the 50 mg/day dosage group, the proportion of patients with moderate to severe depression decreased from 77.8 % to 33.3 % (p < 0.001). Similarly, in the 100 mg/day dosage group, the proportion of patients with moderate to severe depression decreased from 94.4 % to 52.8 % (p < 0.001).

Conclusion

Depression accounts for approximately one-third of type 2 diabetes mellitus cases. Overweight, obesity, HbA1c levels, and cardiovascular disease are independent factors associated with depression. Intervention with sertraline for depression treatment at both 50 mg/day and 100 mg/day dosages demonstrates significant improvements in depression severity after 6 months of treatment.

背景以往的研究表明,舍曲林对改善抑郁症有积极影响;然而,有关舍曲林在合并 2 型糖尿病和抑郁症患者中的流行率和治疗效果的数据仍然有限。研究对象包括 2023 年 3 月至 2024 年 3 月期间在越南北略总医院接受门诊治疗的 2 型糖尿病患者。在对抑郁症患病率和相关因素进行评估后,开展了一项随机、单盲临床试验。患者被随机分配到两组:奇数患者接受每天 50 毫克舍曲林剂量的治疗,偶数患者接受每天 100 毫克舍曲林剂量的治疗。结果 共纳入 225 名 2 型糖尿病患者,平均年龄为(63.8 ± 10.7)岁,其中 72 人被确诊患有抑郁症,患病率为 32%。这些患者中有 51 名女性(70.8%)和 21 名男性(29.2%)。研究发现,女性性别、超重、肥胖、糖尿病病程超过 36 个月以及心血管疾病史与抑郁症有关。然而,在多变量模型中,只有超重、肥胖、HbA1c ≥ 6.5 % 和心血管疾病史被确定为导致 2 型糖尿病患者抑郁的独立因素,其几率比为 4.12 (95 % CI: 1.78-9.56; p = 0.001)、0.37 (95 % CI: 0.15-0.95; p = 0.038) 和 25.90 (95 % CI: 9.05-74.12; p <0.001)。治疗 6 个月后,50 毫克/天剂量组的中度至重度抑郁症患者比例从 77.8% 降至 33.3% (p <0.001)。同样,在 100 毫克/天剂量组中,中重度抑郁症患者的比例从 94.4% 降至 52.8%(p <0.001)。超重、肥胖、HbA1c 水平和心血管疾病是与抑郁症相关的独立因素。使用舍曲林治疗抑郁症,剂量为 50 毫克/天和 100 毫克/天,治疗 6 个月后,抑郁症的严重程度明显改善。
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引用次数: 0
Portulaca oleracea (purslane) aqueous extract reduced the adverse metabolic outcomes and favored liraglutide activities in streptozotocin-induced cardiometabolic disorders of male Wistar rats 马齿苋水提取物降低了链脲佐菌素诱导的雄性 Wistar 大鼠心脏代谢紊乱的不良代谢结果,并提高了利拉鲁肽的活性
Q3 Medicine Pub Date : 2024-08-14 DOI: 10.1016/j.endmts.2024.100191
Adewumi O. Oyabambi , Blessing B. Aindero , Adeoba M. Awolola , Aisha Y. Adebayo , Ifeoluwa B. Iluromi , Kehinde S. Olorunniyi

Cardiometabolic diseases including Diabetes mellitus accounts >400 million deaths globally. Portulaca oleracea (Purslane) noted for its rich antioxidants, is a perennial herbaceous plant widely cultivated across countries. This study aimed to determine the ameliorative effect of ethanolic extract of Portulaca oleracea (EPO) on cardiometabolic diseases of streptozotocin (STZ)-induced diabetic male Wistar rats. Twenty-five male Wistar rats weighing between 120 and 150 g were randomly distributed into five groups and treated respectively as; Control (CTR): normal chow + vehicle (normal saline; orally), EPO; 400 mg/kg orally, STZ; 60 mg/kg intraperitoneally + vehicle, (STZ; 60 mg/kg + EPO; 400 mg/kg orally), STZ+ EPO+ Liraglutide (LG); 0.2 mg/kg subcutaneously. After four weeks, animals were anesthetized by 1 % chloroform inhalation for 5 min (5.0 ppm) and blood was collected by cardiac puncture. Plasma, cardiac and adipose tissue homogenate were analyzed, and data expressed as mean ± SEM; p < 0.05 were accepted as significant. The diabetic rats showed decreased body weight, reduced blood glucose and AMP-activated protein kinase (AMPK), adipose mass, insulin (p < 0.05). Portulaca oleracea resulted in reduced plasma fasting blood glucose (FBG), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF- α) and increased pancreatic beta cell functions (HOMA-B) compared to the diabetic rats (p < 0.05). Also, plasma AMPK, insulin and glutathione (GSH) increased in the purslane, and liraglutide treated (p < 0.05), which is a known glucagon-like peptide-1 receptor (GLP-1R) agonist. In conclusion, purslane possess GLP-1R agonist activities and improved glucometabolic activities and this presents a great advantage in the management of cardiovascular risks associated with diabetes.

包括糖尿病在内的心血管代谢疾病导致全球 4 亿人死亡。马齿苋因富含抗氧化剂而闻名,是一种多年生草本植物,在各国广泛种植。本研究旨在确定马齿苋乙醇提取物(EPO)对链脲佐菌素(STZ)诱导的糖尿病雄性 Wistar 大鼠心脏代谢疾病的改善作用。25 只体重在 120 至 150 克之间的雄性 Wistar 大鼠被随机分为 5 组,分别接受以下治疗:对照组(CTR):正常饲料 + 载体(生理盐水;口服)、EPO;400 毫克/千克口服、STZ;60 毫克/千克腹腔注射 + 载体、(STZ;60 毫克/千克 + EPO;400 毫克/千克口服)、STZ+ EPO+ 利拉鲁肽(LG);0.2 毫克/千克皮下注射。四周后,动物吸入1%氯仿5分钟(5.0 ppm)麻醉,心脏穿刺采血。对血浆、心脏和脂肪组织匀浆进行分析,数据以平均值 ± SEM 表示;以 p < 0.05 为差异有显著性。结果表明,糖尿病大鼠体重减轻,血糖降低,AMPK(AMP-activated protein kinase)、脂肪量和胰岛素减少(p < 0.05)。与糖尿病大鼠相比,马齿苋降低了血浆空腹血糖(FBG)、白细胞介素 6(IL-6)、肿瘤坏死因子-α(TNF- α),增加了胰腺β细胞功能(HOMA-B)(p < 0.05)。此外,马齿苋和利拉鲁肽(一种已知的胰高血糖素样肽-1受体(GLP-1R)激动剂)治疗大鼠的血浆 AMPK、胰岛素和谷胱甘肽(GSH)均有所增加(p < 0.05)。总之,马齿苋具有 GLP-1R 激动剂活性和改善糖代谢的活性,这在控制与糖尿病相关的心血管风险方面具有极大的优势。
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引用次数: 0
Exploring the recent advancements and future prospects of personalized medicine in type 2 diabetes 探索 2 型糖尿病个性化医疗的最新进展和未来前景
Q3 Medicine Pub Date : 2024-08-13 DOI: 10.1016/j.endmts.2024.100193
Shahrzad Manavi Nameghi

The pathophysiology of Type 2 Diabetes (T2D) is intricate, involving three main processes that lead to elevated glucose levels. Insulin resistance hinders glucose utilization in muscles, adipose tissue, and the liver. Additionally, pancreatic dysfunction results in excessive glucose release and disrupts insulin and glucagon levels, contributing to hyperglycemia. Tailoring management strategies to individual needs and stages of the disease is crucial. Genetic factors play a significant role in the development of T2D and must be considered in treatment planning. Genome-Wide Association Studies (GWAS) have identified numerous genetic loci and Single Nucleotide Polymorphisms (SNPs) associated with T2D. A personalized approach considers a wide range of factors, such as patient characteristics, medical history, complications, and genetic makeup. By customizing treatment plans to suit each patient's unique needs, it may be possible to improve outcomes and reduce the impact of T2D on overall health. While some may argue that personalized diabetes care has been utilized for a long time, integrating it into the standard treatment of T2D remains a challenging task with numerous obstacles.

The current review aims to describe the vision of personalized medicine in diabetes and offers helpful suggestions for a better understanding of this issue, as well as disseminating information about novel treatment approaches like Next Generation Sequencing (NGS) and pharmacotherapy.

2 型糖尿病(T2D)的病理生理学错综复杂,涉及导致血糖水平升高的三个主要过程。胰岛素抵抗阻碍了肌肉、脂肪组织和肝脏对葡萄糖的利用。此外,胰腺功能障碍会导致葡萄糖释放过多,并扰乱胰岛素和胰高血糖素水平,从而引发高血糖。根据个人需求和疾病的不同阶段制定相应的管理策略至关重要。遗传因素在 T2D 的发病过程中起着重要作用,在制定治疗计划时必须予以考虑。全基因组关联研究(GWAS)发现了许多与 T2D 相关的基因位点和单核苷酸多态性(SNPs)。个性化治疗方法考虑了患者特征、病史、并发症和基因构成等多种因素。通过定制适合每位患者独特需求的治疗方案,也许可以改善治疗效果,减少 T2D 对整体健康的影响。本综述旨在描述糖尿病个性化医疗的愿景,为更好地理解这一问题提供有益的建议,并传播有关下一代测序(NGS)和药物疗法等新型治疗方法的信息。
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引用次数: 0
Influence of O-GlcNAcylation on KGN cell function O-GlcNAcylation 对 KGN 细胞功能的影响
Q3 Medicine Pub Date : 2024-08-13 DOI: 10.1016/j.endmts.2024.100192
Abigail M. Maucieri , David H. Townson
<div><p>O-GlcNAcylation is a unique form of post-translational glycosylation that affects a variety of cytoplasmic and nuclear proteins of cells. Aberrant O-GlcNAcylation is characteristic of many cancers, and impacts cell proliferation, tumorigenicity and metabolism. O-GlcNAcylation occurs in granulosa cells of ovarian follicles, its expression differs between small (3-5 mm) and large (>8.5 mm) antral follicles, and its manipulation in vitro alters granulosa cell proliferation and metabolism. Here, the aim was to assess whether O-GlcNAcylation similarly occurs in cells from a type of granulosa cell tumor, specifically KGN cells, knowing these cells share functional features of granulosa cells of mature, preovulatory follicles (e.g., FSH-responsiveness and estradiol production). The immortal KGN cell line was utilized to conduct cell culture experiments for the detection and manipulation of O-GlcNAcylation. The cells were grown to confluency in serum containing medium and then sub-cultured in serum-free conditions for immunodetection of O-GlcNAcylation (<em>n</em> = 8 expts.), for cell proliferation (<em>n</em> = 3 expts) and for metabolism assays (<em>n</em> = 12 expts.). The KGN cells were also treated without or with small molecule inhibitors to directly enhance or impair O-GlcNAcylation. Immunoblotting confirmed O-GlcNAc expression in KGN cells, as well as the efficacy of Thiamet-G and OSMI-1 to augment (<em>P</em> < 0.05) and inhibit O-GlcNAcylation (P < 0.05), respectively. Only the inhibition of O-GlcNAcylation compromised KGN cell proliferation (<em>P</em> < 0.05), resulting in a 25 % reduction in proliferation compared to control conditions over a 72 h culture period. Seahorse XFe96 analysis measured effects of O-GlcNAcylation on cellular respiration in the KGN cells. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) provided indices of glycolysis and oxidative phosphorylation, respectively. During a glycolysis stress test, high glucose increased ECAR and decreased OCR (<em>P</em> < 0.05); oligomycin did not further affect ECAR (<em>P</em> > 0.05), but impaired OCR (<em>P</em> < 0.05); and 2-deoxy-<span>d</span>-glucose decreased ECAR (P < 0.05) without affecting OCR (<em>P</em> > 0.05). Comparatively, a mitochondrial stress test revealed oligomycin increased ECAR (<em>P</em> < 0.05) with a compensatory decrease in OCR (P < 0.05); FCCP increased both ECAR and OCR (<em>P</em> < 0.05); and rotenone + antimycin A decreased both ECAR and OCR (P < 0.05). Manipulation of O-GlcNAcylation in the KGN cells had no effect on ECAR (<em>P</em> > 0.05), but inhibited OCR (<em>P</em> < 0.05). Collectively, the results indicate O-GlcNAcylation occurs in KGN cells, its inhibition impairs cell proliferation, and while KGN cells rely upon both glycolysis and oxidative phosphorylation for cellular respiration, manipulation of O-GlcNAcylation acutely perturbs only oxidative phosphorylation,
O-GlcNAcylation 是一种独特的翻译后糖基化形式,会影响细胞的各种胞质和核蛋白。异常的 O-GlcNAcylation 是许多癌症的特征,会影响细胞增殖、致瘤性和新陈代谢。O-GlcNAcylation发生在卵巢卵泡的颗粒细胞中,其表达在小卵泡(3-5毫米)和大卵泡(8.5毫米)之间存在差异,体外操作会改变颗粒细胞的增殖和新陈代谢。本文旨在评估O-GlcNAcylation是否同样发生在一种颗粒细胞瘤的细胞中,特别是KGN细胞,因为这些细胞具有成熟的排卵前卵泡颗粒细胞的功能特征(如FSH反应性和雌二醇生成)。我们利用永生的KGN细胞系进行细胞培养实验,以检测和处理O-GlcNAcylation。细胞在含血清的培养基中生长至汇合,然后在无血清条件下进行亚培养,用于免疫检测 O-GlcNAcylation(n = 8 例)、细胞增殖(n = 3 例)和代谢测定(n = 12 例)。在不使用或使用小分子抑制剂的情况下,也对 KGN 细胞进行了处理,以直接增强或削弱 O-GlcNAcylation。免疫印迹证实了 KGN 细胞中 O-GlcNAc 的表达,以及 Thiamet-G 和 OSMI-1 分别增强(P < 0.05)和抑制 O-GlcNAcylation (P < 0.05)的功效。只有对 O-GlcNAcylation 的抑制才会影响 KGN 细胞的增殖(P < 0.05),与对照组相比,在 72 小时的培养期内,增殖率降低了 25%。海马 XFe96 分析测试了 O-GlcNAcylation 对 KGN 细胞呼吸的影响。细胞外酸化率(ECAR)和耗氧量(OCR)分别提供了糖酵解和氧化磷酸化的指标。在糖酵解压力测试中,高葡萄糖增加了ECAR,降低了OCR(P < 0.05);低聚霉素没有进一步影响ECAR(P > 0.05),但损害了OCR(P < 0.05);2-脱氧-d-葡萄糖降低了ECAR(P < 0.05),但没有影响OCR(P > 0.05)。相比之下,线粒体应激试验显示,寡霉素增加了 ECAR(P <;0.05),而 OCR 补偿性下降(P <;0.05);FCCP 增加了 ECAR 和 OCR(P <;0.05);鱼藤酮 + 抗霉素 A 降低了 ECAR 和 OCR(P <;0.05)。操纵 KGN 细胞中的 O-GlcNAcylation 对 ECAR 没有影响(P >;0.05),但抑制了 OCR(P <;0.05)。总之,研究结果表明,KGN细胞中存在O-GlcNAcylation,抑制O-GlcNAcylation会影响细胞增殖,虽然KGN细胞依靠糖酵解和氧化磷酸化进行细胞呼吸,但操纵O-GlcNAcylation只会急性干扰氧化磷酸化,这也是之前在大前卵泡颗粒细胞中观察到的效果。
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Endocrine and Metabolic Science
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