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Chinese herbal medicine may reduce major adverse cardiovascular events in patients with dialysis hypotension: A taiwan nationwide cohort study 中药可减少透析低血压患者的主要心血管不良事件:一项台湾全国性队列研究
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-06 DOI: 10.1016/j.jtcme.2024.03.009

Background

The association between Chinese herbal medicine (CHM) and the risk of developing major adverse cardiovascular events (MACEs) in patients with dialysis hypotension is unclear and has not yet been investigated. This study aimed to determine whether CMH intervention could reduce the risk of MACEs in patients with dialysis hypotension.

Methods

The study data from the Taiwan National Health Insurance Research Database were analyzed to clarify this association. For this study, a case-control design with a cohort of patients who received hemodialysis (HD) from 2008 to 2018, 20 295 HD patients who had received blood pressure (BP) raising drugs were identified. After 1:1 frequency-matching, 730 patients were identified as CHM users and CHM non-users. Vascular access revision/reconstruction and MACEs were observed as the main outcomes during the follow-up period.

Results

The occurrence of vascular access revision/reconstruction in HD patients receiving BP raising drugs was associated with a 0.34-fold lower risk in CHM users than in CHM non-users [adjusted hazard ratio (aHR) = 0.34, 95% confidence interval (CI) = 0.26, 0.45]. The occurrences of MACEs in HD patients receiving BP raising drugs was associated with a 0.41-fold lower risk in CHM users than in CHM non-users (aHR = 0.41, 95% CI = 0.33, 0.51). A markedly predominant effect was observed in those receiving CHM for more than 180 days (aHR = 0.32; 95% CI = 0.22, 0.45).

Conclusion

The findings revealed lower vascular access dysfunction and MACEs risk correlated with the use of CHM treatment among HD patients who received BP raising drugs.

背景中药与透析低血压患者发生主要不良心血管事件(MACEs)风险之间的关系尚不明确,也尚未进行过研究。本研究旨在确定中药干预是否能降低透析低血压患者的 MACE 风险。本研究采用病例对照设计,以2008年至2018年接受血液透析(HD)的患者为队列,共确定了20 295名接受过升压药物治疗的HD患者。经过1:1频率匹配后,730名患者被确定为CHM使用者和非CHM使用者。结果在接受升压药物治疗的 HD 患者中,使用 CHM 的患者发生血管通路修正/重建的风险比未使用 CHM 的患者低 0.34 倍[调整后危险比 (aHR) = 0.34,95% 置信区间 (CI) = 0.26,0.45]。在接受升压药物治疗的 HD 患者中,使用 CHM 的患者发生 MACE 的风险比未使用 CHM 的患者低 0.41 倍(aHR = 0.41,95% CI = 0.33,0.51)。结论研究结果表明,在接受降压药治疗的 HD 患者中,血管通路功能障碍和 MACEs 风险的降低与使用 CHM 治疗相关。
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引用次数: 0
Exploring hepatic fibrosis screening via deep learning analysis of tongue images 通过舌头图像的深度学习分析探索肝纤维化筛查
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-06 DOI: 10.1016/j.jtcme.2024.03.010

Background

Tongue inspection, an essential diagnostic method in Traditional Chinese Medicine (TCM), has the potential for early-stage disease screening. This study aimed to evaluate the effectiveness of deep learning-based analysis of tongue images for hepatic fibrosis screening.

Methods

A total of 1083 tongue images were collected from 741 patients and divided into training, validation, and test sets. DenseNet-201, a convolutional neural network, was employed to train the AI model using these tongue images. The predictive performance of AI was assessed and compared with that of FIB-4, using real-time two-dimensional shear wave elastography as the reference standard.

Results

The proposed AI model achieved an accuracy of 0.845 (95% CI: 0.79–0.90) and 0.814 (95% CI: 0.76–0.87) in the validation and test sets, respectively, with negative predictive values (NPVs) exceeding 90% in both sets. The AI model outperformed FIB-4 in all aspects, and when combined with FIB-4, the NPV reached 94.4%.

Conclusion

Tongue inspection, with the assistance of AI, could serve as a first-line screening method for hepatic fibrosis.

背景舌象检查是中医(TCM)的一种重要诊断方法,具有早期疾病筛查的潜力。本研究旨在评估基于深度学习的舌象分析在肝纤维化筛查中的有效性。方法从 741 名患者身上共收集了 1083 张舌象,并将其分为训练集、验证集和测试集。采用卷积神经网络 DenseNet-201 利用这些舌头图像训练人工智能模型。结果所提出的人工智能模型在验证集和测试集中的准确率分别达到了 0.845(95% CI:0.79-0.90)和 0.814(95% CI:0.76-0.87),负预测值(NPV)均超过了 90%。人工智能模型在所有方面都优于 FIB-4,当与 FIB-4 结合使用时,NPV 达到 94.4%。
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引用次数: 0
Rosmarinic acid Ameliorates neuronal regeneration in the bridging silicone rubber conduits of the sciatic nerve in taxol‐treated rats 迷迭香酸可改善经紫杉醇处理的大鼠坐骨神经硅橡胶桥接导管中神经元的再生能力
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-05 DOI: 10.1016/j.jtcme.2024.03.004
Ping-Ling Chiu , Mei-Chen Lin , Shih-Tien Hsu , Tin-Yun Ho , Yung-Hsiang Chen , Chung-Chia Chen , Yueh-Sheng Chen

Background and aim

Taxol modulates local inflammatory conditions in peripheral nerves, which may impair their regeneration and recovery when injured. This study aimed to determine the effects of rosmarinic acid (RA, a polyphenol constituent of many culinary herbs) on the regeneration of the sciatic nerves in the bridging conduits.

Experimental procedure

In the cell study, RA decreased nuclear factor (NF)-κB activity induced by taxol in a dose dependency. In the animal model, taxol-treated rats were divided into 3 groups (n = 10/group): taxol (2 mg/kg body weight for 4 times) and taxol + RA (3 times/week for 4 weeks at 20 and 40 mg/kg body weight) groups. Macrophage infiltration, calcitonin gene-related peptide (CGRP) expression levels, neuronal connectivity, animal behavior, and neuronal electrophysiology were evaluated.

Results and conclusion

At the end of 4 weeks, macrophage density, CGRP expression level, and axon number significantly increased in the RA group compared with the taxol group. The RA administration unaffected heat, cold plate licking latencies, and motor coordination. Moreover, the 40 mg/kg RA group had significantly larger nerve conduction velocity and less latency compared to the taxol group. This study suggested that RA could ameliorate local inflammatory conditions to augment the recovery of regenerating nerves by accelerating their regrowth and improving electrophysiological function in taxol-treated peripheral nerve injury repaired with the silicone rubber conduit.

背景和目的他克酚能调节周围神经的局部炎症状况,这可能会影响神经在受伤时的再生和恢复。本研究旨在确定迷迭香酸(RA,许多烹饪草药中的一种多酚成分)对桥接导管中坐骨神经再生的影响。实验过程在细胞研究中,RA 可降低由紫杉醇诱导的核因子(NF)-κB 活性,且与剂量相关。在动物模型中,经紫杉醇处理的大鼠分为 3 组(n = 10/组):紫杉醇组(2 毫克/千克体重,共 4 次)和紫杉醇 + RA 组(20 毫克/千克体重和 40 毫克/千克体重,每周 3 次,共 4 周)。对巨噬细胞浸润、降钙素基因相关肽(CGRP)表达水平、神经元连通性、动物行为和神经元电生理学进行了评估。结果与结论4周结束时,RA组的巨噬细胞密度、CGRP表达水平和轴突数量与紫杉醇组相比显著增加。RA给药不影响热、冷板舔潜伏期和运动协调性。此外,与紫杉醇组相比,40 毫克/千克 RA 组的神经传导速度明显增大,潜伏期明显缩短。这项研究表明,对于经硅橡胶导管修复的经紫杉醇处理的周围神经损伤,RA 可改善局部炎症状况,通过加速再生神经的生长和改善其电生理功能来促进再生神经的恢复。
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引用次数: 0
Soybean oil induces neuroinflammatory response through brain-gut axis under high-fat diet 高脂饮食下大豆油通过脑-肠轴诱导神经炎症反应
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-02-29 DOI: 10.1016/j.jtcme.2024.02.002

Neuroinflammation is considered the principal pathogenic mechanism underlying neurodegenerative diseases, and the incidence of brain disorders is closely linked to dietary fat consumption and intestinal health. To investigate this relationship, 60 8-week-old C57BL/6J mice were subjected to a 20-week dietary intervention, wherein they were fed lard and soybean oil, each at 15% and 35% fat energy. At a dietary fat energy level of 35%, inflammation was observed in both the soybean oil and lard groups. Nevertheless, inflammation was more pronounced in the mice that were administered soybean oil. The process by which nerve cell structure is compromised, inflammatory factors are upregulated, brain antioxidant capacity is diminished, and the TLR4/MyD88/NF-κB p65 inflammatory pathway is activated resulting in damage to the brain-gut barrier. This, in turn, leads to a reduction in the abundance of Akkermansia and unclassified_f_Lachnospiraceae, as well as an increase in Dubosiella abundance, ultimately resulting in brain inflammation and damage. These results suggested that soybean oil induces more severe neuroinflammation compared to lard. Our study demonstrated that, at a dietary fat energy level of 35%, compared to soybean oil, lard could be the healthier option, the outcomes would help provide a reference basis for the selection of residents’ daily dietary oil.

神经炎症被认为是神经退行性疾病的主要致病机制,而脑部疾病的发病率与膳食脂肪摄入量和肠道健康密切相关。为了研究这种关系,我们对 60 只 8 周大的 C57BL/6J 小鼠进行了为期 20 周的饮食干预,分别喂食脂肪能量为 15% 和 35% 的猪油和大豆油。当膳食脂肪能量水平为 35% 时,大豆油组和猪油组都出现了炎症。不过,食用大豆油的小鼠炎症更为明显。神经细胞结构受损、炎症因子上调、大脑抗氧化能力降低、TLR4/MyD88/NF-κB p65 炎症通路被激活导致脑肠屏障受损的过程。这反过来又导致 Akkermansia 和未分类_f_Lachnospiraceae 数量减少,以及 Dubosiella 数量增加,最终导致脑部炎症和损伤。这些结果表明,与猪油相比,大豆油会诱发更严重的神经炎症。我们的研究表明,在膳食脂肪能量水平为 35% 的情况下,与大豆油相比,猪油可能是更健康的选择,其结果将有助于为居民日常膳食油的选择提供参考依据。
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引用次数: 0
Bazi Bushen mitigates age-related muscular atrophy by alleviating cellular senescence of skeletal muscle 八子布神通过缓解骨骼肌的细胞衰老,减轻与年龄有关的肌肉萎缩
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-02-03 DOI: 10.1016/j.jtcme.2024.01.009

Background and aim

Muscular atrophy is one of the most common age-related conditions characterized by the deterioration of skeletal muscle structures and impaired functions. It is associated with cellular senescence and chronic inflammation, which impair the function of muscle stem cells. Bazi Bushen (BZBS) is a patent compound Chinese medicine that has been shown to have anti-aging effects in various animal models. In this study, we investigated the effects and mechanisms of BZBS on muscular atrophy in naturally aged mice.

Experimental procedure

A muscular atrophy model of naturally aged mice (18 months) was employed with administration of BZBS (2 g/kg/d, 1 g/kg/d) and nicotinamide mononucleotide (NMN, 200 mg/kg/d). After six months of drug administration, muscle weight loss, muscle function and muscle histopathology were measured to evaluate the therapeutic effect of BZBS. The expression of cellular senescence, inflammatory and satellite cell-related factors were used to assess the effects of BZBS in inhibiting cellular senescence, reducing inflammation and improving muscle atrophy.

Results and conclusion

Compared with age matched natural aging mice, we found that BZBS improved muscle strength, mass, and morphology by reducing senescent cells, inflammatory cytokines, and intermyofiber fibrosis in aged muscle tissues. We also found that BZBS prevented the reduction of Pax7 positive stem cells and stimulated the activation and differentiation into myocytes. Our results suggest that BZBS might be a promising intervention in senile muscular atrophy.

背景和目的肌肉萎缩是最常见的与年龄有关的疾病之一,其特征是骨骼肌结构退化和功能受损。它与细胞衰老和慢性炎症有关,而细胞衰老和慢性炎症会损害肌肉干细胞的功能。八子布参(BZBS)是一种专利复方中药,已被证明在多种动物模型中具有抗衰老作用。实验过程采用自然衰老小鼠(18 个月)肌肉萎缩模型,给予 BZBS(2 克/千克/天,1 克/千克/天)和烟酰胺单核苷酸(NMN,200 毫克/千克/天)。用药 6 个月后,测量肌肉重量损失、肌肉功能和肌肉组织病理学,以评估 BZBS 的治疗效果。结果和结论与年龄匹配的自然衰老小鼠相比,我们发现 BZBS 通过减少衰老细胞、炎症细胞因子和衰老肌肉组织中的肌纤维间纤维化,改善了肌肉的强度、质量和形态。我们还发现,BZBS 可防止 Pax7 阳性干细胞的减少,并刺激其活化和分化为肌细胞。我们的研究结果表明,BZBS可能是治疗老年性肌肉萎缩的一种有前景的干预措施。
{"title":"Bazi Bushen mitigates age-related muscular atrophy by alleviating cellular senescence of skeletal muscle","authors":"","doi":"10.1016/j.jtcme.2024.01.009","DOIUrl":"10.1016/j.jtcme.2024.01.009","url":null,"abstract":"<div><h3>Background and aim</h3><p>Muscular atrophy is one of the most common age-related conditions characterized by the deterioration of skeletal muscle structures and impaired functions. It is associated with cellular senescence and chronic inflammation, which impair the function of muscle stem cells. Bazi Bushen (BZBS) is a patent compound Chinese medicine that has been shown to have anti-aging effects in various animal models. In this study, we investigated the effects and mechanisms of BZBS on muscular atrophy in naturally aged mice.</p></div><div><h3>Experimental procedure</h3><p>A muscular atrophy model of naturally aged mice (18 months) was employed with administration of BZBS (2 g/kg/d, 1 g/kg/d) and nicotinamide mononucleotide (NMN, 200 mg/kg/d). After six months of drug administration, muscle weight loss, muscle function and muscle histopathology were measured to evaluate the therapeutic effect of BZBS. The expression of cellular senescence, inflammatory and satellite cell-related factors were used to assess the effects of BZBS in inhibiting cellular senescence, reducing inflammation and improving muscle atrophy.</p></div><div><h3>Results and conclusion</h3><p>Compared with age matched natural aging mice, we found that BZBS improved muscle strength, mass, and morphology by reducing senescent cells, inflammatory cytokines, and intermyofiber fibrosis in aged muscle tissues. We also found that BZBS prevented the reduction of Pax7 positive stem cells and stimulated the activation and differentiation into myocytes. Our results suggest that BZBS might be a promising intervention in senile muscular atrophy.</p></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"14 5","pages":"Pages 510-521"},"PeriodicalIF":3.3,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2225411024000099/pdfft?md5=bf532ec2822075732006712c249ba855&pid=1-s2.0-S2225411024000099-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139875037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mulberry leaf extract inhibits obesity and protects against diethylnitrosamine-induced hepatocellular carcinoma in rats 桑叶提取物可抑制肥胖,并保护大鼠免受亚硝胺诱发的肝细胞癌的危害
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-22 DOI: 10.1016/j.jtcme.2024.01.007
Yun-Ching Chang , Meng-Hsun Yu , Hui-Pei Huang , Dong-Hui Chen , Mon-Yuan Yang , Chau-Jong Wang

Mulberry leaf has been recognized as a traditional Chinese medicinal plant, which was distributed throughout the Asia. The aqueous extract of mulberry leaf extract (MLE) has various biologically active components such as polyphenols and flavonoids. However, the inhibitory effect of MLE in hepatocarcinogenesis is poorly understood. In this study, we determined the role of MLE supplementation in preventing hepatocarcinogenesis in a carcinogen-initiated high-fat diet (HFD)-promoted Sprague-Dawley (SD) rat model. The rats were fed an HFD to induce obesity and spontaneous hepatomas by administering 0.01% diethylnitrosamine (DEN) in their drinking water for 12 weeks (HD group), and also to fed MLE through oral ingestion at daily doses of 0.5%, 1%, or 2%. At the end of the 12-week experimental period, the liver tumors were analyzed to identify markers of oxidative stress and antioxidant enzyme activities, and their serum was analyzed to determine their nutritional status and liver function. Histopathological analysis revealed that MLE supplementation significantly suppressed the severity and incidence of hepatic tumors. Furthermore, compared with the HFD + DEN groups, the expression of protein kinase C (PKC)-α and Rac family small GTPase 1 (Rac1) was lower in the MLE groups. These findings suggest that MLE prevents obesity-enhanced, carcinogen-induced hepatocellular carcinoma development, potentially through the protein kinase C (PKC)α/Rac1 signaling pathway. MLE might be an effective chemoprevention modality for nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH)-related hepatocarcinogenesis.

桑叶是一种传统的中药植物,分布于亚洲各地。桑叶水提取物(MLE)具有多种生物活性成分,如多酚和类黄酮。然而,桑叶提取物对肝癌发生的抑制作用却鲜为人知。在这项研究中,我们确定了补充 MLE 在致癌物质引发的高脂饮食(HFD)促进的 Sprague-Dawley (SD)大鼠模型中预防肝癌发生的作用。通过在饮用水中添加 0.01% 的二乙基亚硝胺 (DEN),给大鼠喂食高脂饮食诱发肥胖和自发性肝癌,为期 12 周(HD 组),同时通过口服 MLE,每日剂量为 0.5%、1% 或 2%。12 周实验结束时,对肝脏肿瘤进行分析,以确定氧化应激和抗氧化酶活性的标记物,并对血清进行分析,以确定其营养状况和肝功能。组织病理学分析表明,补充 MLE 能明显抑制肝肿瘤的严重程度和发病率。此外,与高纤维食物组+ DEN组相比,MLE组中蛋白激酶C(PKC)-α和Rac家族小GTP酶1(Rac1)的表达较低。这些研究结果表明,MLE可通过蛋白激酶C(PKC)α/Rac1信号通路阻止肥胖增强的、由致癌物质诱发的肝细胞癌的发展。MLE可能是一种有效的化学预防非酒精性脂肪肝(NAFLD)/非酒精性脂肪性肝炎(NASH)相关肝癌发生的方法。
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引用次数: 0
Natural 7,8-secolignans from Schisandra sphenanthera fruit potently inhibit SARS-CoV-2 3CLpro and inflammation 五味子果实中的天然 7,8-secolignans 可有效抑制 SARS-CoV-2 3CLpro 和炎症反应
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-16 DOI: 10.1016/j.jtcme.2024.01.005

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), turned into a global pandemic, and there remains an urgent demand for specific/targeted drugs for the disease. The 3C-like protease (3CLpro) is a promising target for developing anti-coronavirus drugs. Schisandra sphenanthera fruit is a well-known traditional Chinese medicine (TCM) with good antiviral activity. This study found that the ethanolic extract displayed a significant inhibitory effect against SARS-CoV-2 3CLpro. Forty-four compounds were identified in this extract using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Combining molecular docking and in vitro experiments, we found that two epimeric 7,8-secolignans, rel-(1S,2R)-1-(3,4-dimethoxyphenyl)-2-methyl-3-oxobutyl-3,4-dimethoxybenzoate (2) and rel-(1S,2S)-1-(3,4-dimethoxyphenyl)-2-methyl-3-oxobutyl-3,4-dimethoxybenzoate (4), potently inhibited 3CLpro with IC50 values of 4.88 ± 0.60 μM and 4.75 ± 0.34 μM, respectively. Moreover, in vivo and in vitro experiments indicated that compounds 2 and 4 were potent in regulating the inflammatory response and preventing lung injury. Our findings indicate that compounds 2 and 4 may emerge as promising SARS-CoV-2 inhibitors via 3CLpro inhibition and anti-inflammatory mechanisms.

由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)已演变成全球大流行病,对该疾病的特异性/靶向药物仍有迫切需求。3C 样蛋白酶(3CLpro)是开发抗冠状病毒药物的一个很有前景的靶点。五味子是一种著名的传统中药,具有良好的抗病毒活性。本研究发现,五味子乙醇提取物对 SARS-CoV-2 3CLpro 有明显的抑制作用。利用超高效液相色谱-四极杆飞行时间质谱法(UPLC-Q-TOF/MS)鉴定了该提取物中的 44 种化合物。结合分子对接和体外实验,我们发现了两种7,8-仲木质素的外嵌体,即rel-(1S,2R)-1-(3,4-二甲氧基苯基)-2-甲基-3-氧代丁基-3、(2)和 rel-(1S,2S)-1-(3,4-二甲氧基苯基)-2-甲基-3-氧代丁基-3,4-二甲氧基苯甲酸酯(4)能有效抑制 3CLpro 的 IC50 值为 4.88 ± 0.60 μM 和 4.75 ± 0.34 μM。此外,体内和体外实验表明,化合物 2 和 4 能有效调节炎症反应并防止肺损伤。我们的研究结果表明,化合物 2 和 4 可通过抑制 3CLpro 和抗炎机制成为有前途的 SARS-CoV-2 抑制剂。
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引用次数: 0
Molecular study of the KCNJ11 gene and its correlation with Prakriti to preventing and managing type 2 diabetes KCNJ11 基因的分子研究及其与 Prakriti 在预防和控制 2 型糖尿病方面的相关性
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-11 DOI: 10.1016/j.jtcme.2024.01.004

In Ayurveda, every individual is believed to possess a unique entity known as Prakriti, which distinguishes them from others physically, physiologically, and psychologically. This entity also determines an individual's response to a particular stimulus, and it is believed that such responses are not solely determined by genetics. The present research aims to validate the Ayurvedic concept of Prakriti from a modern molecular perspective to strengthen the personalized and precise treatment approach. A study was conducted to investigate the role of the KCNJ11gene in the susceptibility of individuals to type 2 diabetes mellitus (T2DM) with their metabolic status. The research involved allele mining on three major Prakriti groups - Vata, Pitta, and Kapha - in 112 patients with T2DM and 112 healthy individuals. The KCNJ11 gene, responsible for insulin secretion membrane pore formation, was analyzed to determine the susceptibility of different Prakriti types to T2DM. The MutPred tool predicted the molecular cause of disease-related amino acid substitution. According to the study, only Pitta and Kapha Prakriti were diagnosed with diabetes, while all three Prakriti types were present in the control group of healthy individuals. A protein model was prepared, and the changes resulting from mutations were observed for each group in their protein sequence, both as synonymous and non-synonymous mutations. Ultimately, these changes contributed to the manifestation of T2DM. Based on the findings, it appears that Prakriti groups may experience changes in protein function due to nonsynonymous mutations and differences in amino acids at the protein level.

阿育吠陀认为,每个人都拥有一个被称为 "普拉克里提"(Prakriti)的独特实体,它使每个人在身体、生理和心理上都与众不同。这一实体还决定了个体对特定刺激的反应,而且据信这种反应并非完全由遗传决定。本研究旨在从现代分子角度验证阿育吠陀的 "普拉克里提"(Prakriti)概念,以加强个性化和精确的治疗方法。本研究旨在调查 KCNJ11 基因在 2 型糖尿病(T2DM)易感性中的作用。研究涉及对 112 名 T2DM 患者和 112 名健康人的三个主要普拉克里蒂组别(Vata、Pitta 和 Kapha)进行等位基因挖掘。研究分析了负责胰岛素分泌膜孔形成的 KCNJ11 基因,以确定不同般若类型对 T2DM 的易感性。MutPred工具预测了与疾病相关的氨基酸置换的分子原因。研究结果表明,只有 Pitta 和 Kapha 般若体被诊断为糖尿病,而在健康人对照组中,所有三种般若体都存在。研究人员制作了一个蛋白质模型,并观察了每个组别的蛋白质序列因同义和非同义突变而发生的变化。这些变化最终导致了 T2DM 的出现。根据研究结果,Prakriti 组的蛋白质功能可能会因为非同义突变和蛋白质水平上氨基酸的差异而发生变化。
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引用次数: 0
Curcumin in treatment of hematological cancers: Promises and challenges 姜黄素治疗血液肿瘤:前景与挑战
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-05 DOI: 10.1016/j.jtcme.2023.10.004
Maliheh Entezari , Armita Tayari , Mahshid Deldar Abad Paskeh , Simin Khorsand Kheirabad , Sahar Naeemi , Afshin Taheriazam , Hossein Dehghani , Shokooh Salimimoghadam , Mehrdad Hashemi , Sepideh Mirzaei , Saeed Samarghandian

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

血液肿瘤包括白血病、骨髓瘤和淋巴瘤,每年新确诊的血液肿瘤病例多达 17.8 万例。治疗血液肿瘤的方法多种多样,包括放疗、化疗、免疫疗法和干细胞移植。然而,这些疗法仍会导致患者死亡。另一方面,姜黄素作为一种抑制人类癌症的抗癌剂已经问世。使用姜黄素治疗血液癌症的研究一直在进行。姜黄素能降低白血病、骨髓瘤和淋巴瘤细胞的活力和存活率。姜黄素能刺激细胞凋亡和 G2/M 停滞,从而阻碍肿瘤的发展。姜黄素能降低基质金属蛋白酶的水平,从而抑制癌症转移。姜黄素能抑制血管内皮生长因子、Akt 和 STAT3 等多个下游靶点,从而抑制血液肿瘤的进展。姜黄素会刺激 DNA 损伤,降低癌细胞对照射的抵抗力。此外,姜黄素还能提高血液肿瘤,尤其是骨髓瘤的药物敏感性。为了靶向输送姜黄素并改善其药代动力学和抗癌特性,人们开发了含有姜黄素和其他抗癌剂的纳米结构。
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引用次数: 0
In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation – Targeting Mpro and pan-coronavirus post-fusion Spike protein 传统(悉达医学)多草药配方中植物成分的计算机抗病毒评估——靶向Mpro和泛冠状病毒融合后刺突蛋白
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-01 DOI: 10.1016/j.jtcme.2023.07.004
Sumit Kumar Mandal , MD Muzaffar-Ur Rehman , Ashish Katyal , Kanishk Rajvanshi , Manoj Kannan , Mohit Garg , Sankaranarayanan Murugesan , P.R. Deepa

Background and aim

Novel nature of the viral pathogen SARS-CoV-2 and the absence of standard drugs for treatment, have been a major challenge to combat this deadly infection. Natural products offer safe and effective remedy, for which traditional ethnic medicine can provide leads. An indigenous poly-herbal formulation, Kabasura Kudineer from Siddha system of medicine was evaluated here using a combination of computational approaches, to identify potential inhibitors against two anti-SARS-CoV-2 targets – post-fusion Spike protein (structural protein) and main protease (Mpro, non-structural protein).

Experimental procedure

We docked 32 phytochemicals from the poly-herbal formulation against viral post-fusion Spike glycoprotein and Mpro followed by molecular dynamics using Schrodinger software. Drug-likeness analysis was performed using machine learning (ML) approach and pkCSM.

Results

The binding affinity of the phytochemicals in Kabasura Kudineer revealed the following top-five bioactives: Quercetin > Luteolin > Chrysoeriol > 5-Hydroxy-7,8-Dimethoxyflavone > Scutellarein against Mpro target, and Gallic acid > Piperlonguminine > Chrysoeriol > Elemol > Piperine against post-fusion Spike protein target. Quercetin and Gallic acid exhibited binding stability in complexation with their respective viral-targets and favourable free energy change as revealed by the molecular dynamics simulations and MM-PBSA analysis. In silico predicted pharmacokinetic profiling of these ligands revealed appropriate drug-likeness properties.

Conclusion

These outcomes provide: (a) potential mechanism for the anti-viral efficacy of the indigenous Siddha formulation, targeting Mpro and post-fusion Spike protein (b) top bioactive lead-molecules that may be developed as natural product-based anti-viral pharmacotherapy and their pleiotropic protective effects may be leveraged to manage co-morbidities associated with COVID-19.

背景和目的SARS-CoV-2 病毒病原体的新颖性和治疗标准药物的缺乏,一直是抗击这种致命感染的主要挑战。天然产品提供了安全有效的治疗方法,而传统民族医药则可以提供这方面的线索。实验过程我们利用 Schrodinger 软件,将 32 种植物化学物质与病毒融合后 Spike 糖蛋白和 Mpro 进行对接,然后进行分子动力学分析。结果Kabasura Kudineer中植物化学物质的结合亲和力显示出以下前五位生物活性物质:槲皮素、木犀草素、5-羟基-7,8-二甲氧基黄酮、黄芩苷与 Mpro 靶标结合,没食子酸、胡椒龙葵碱、樱草酚、榄香酚、胡椒碱与融合后穗状病毒蛋白靶标结合。分子动力学模拟和 MM-PBSA 分析表明,槲皮素和没食子酸在与各自的病毒靶标复合物结合时表现出稳定性和良好的自由能变化。这些配体的硅学药代动力学分析表明,它们具有适当的药物相似性:(这些结果提供了:(a)本土释迦配方抗病毒疗效的潜在机制,其靶点是 Mpro 和融合后 Spike 蛋白(b)顶级生物活性先导分子,可开发为基于天然产品的抗病毒药物疗法,其多生物保护效应可用于控制与 COVID-19 相关的并发症。
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引用次数: 1
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Journal of Traditional and Complementary Medicine
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