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Gut-joint axis: Oral Probiotic ameliorates Osteoarthritis 肠关节轴:口服益生菌改善骨关节炎
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-01 DOI: 10.1016/j.jtcme.2023.06.002
Uzma Amin , Rong Jiang , Shahid Masood Raza , Mengtian Fan , Li Liang , Naibo Feng , Xiaoli Li , Yuyou Yang , Fengjin Guo

Osteoarthritis (OA) etiology is multifactorial, and its prevalence is growing globally. The Gut microbiota shapes our immune system and impacts all aspects of health and disease. The idea of utilizing probiotics to treat different conditions prevails. Concerning musculoskeletal illness and health, current data lack the link to understand the interactions between the host and microbiome. We report that S. thermophilus, L. pentosus (as probiotics), and γ-aminobutyric acid (GABA) harbour against osteoarthritis in vivo and alleviate IL-1β induced changes in chondrocytes in vitro. We examined the increased GABA concentration in mice's serum and small intestine content followed by bacterial treatment. The treatment inhibited the catabolism of cartilage and rescued mice joints from degradation. Furthermore, the anabolic markers upregulated and decreased inflammatory markers in mice knee joints and chondrocytes. This study is the first to represent GABA's chondrogenic and chondroprotective effects on joints and human chondrocytes. This data provides a foundation for future studies to elucidate the role of GABA in regulating chondrocyte cell proliferation. These findings opened future horizons to understanding the gut-joint axis and OA treatment. Thus, probiotic/GABA therapy shields OA joints in mice and could at least serve as adjuvant therapy to treat osteoarthritis.

骨关节炎(OA)的病因是多因素的,其发病率在全球范围内不断增长。肠道微生物群塑造了我们的免疫系统,影响着健康和疾病的方方面面。利用益生菌治疗不同病症的想法十分普遍。关于肌肉骨骼疾病和健康,目前的数据缺乏了解宿主和微生物组之间相互作用的联系。我们报告说,嗜热菌、五味子乳杆菌(益生菌)和γ-氨基丁酸(GABA)在体内可预防骨关节炎,在体外可缓解 IL-1β 诱导的软骨细胞变化。我们研究了细菌处理后小鼠血清和小肠中 GABA 浓度的增加。治疗抑制了软骨的分解,使小鼠关节免于退化。此外,合成代谢标志物上调并减少了小鼠膝关节和软骨细胞中的炎症标志物。这项研究首次体现了 GABA 对关节和人类软骨细胞的软骨生成和软骨保护作用。这些数据为今后研究阐明 GABA 在调节软骨细胞增殖中的作用奠定了基础。这些发现为了解肠道-关节轴和 OA 治疗开辟了未来的视野。因此,益生菌/GABA疗法可以保护小鼠的OA关节,至少可以作为治疗骨关节炎的辅助疗法。
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引用次数: 0
Zhoushi Qi Ling decoction inhibits the progression of castration-resistant prostate cancer in vivo by regulating macrophage infiltration via IL6-STAT3 signaling 周石气灵汤通过IL6-STAT3信号调节巨噬细胞浸润抑制去势耐药前列腺癌症的体内发展
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-01 DOI: 10.1016/j.jtcme.2023.05.005
Hongwen Cao , Dan Wang , Renjie Gao , Lei Chen, Yigeng Feng, Peng Sun

Background and aim

Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits.

Experimental procedure

CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot.

Results and conclusion

Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.

背景和目的前列腺癌是男性的主要恶性肿瘤,死亡率很高。雄激素剥夺疗法是治疗前列腺癌的常用方法,它导致了阉割抗性前列腺癌(CRPC)的进展。目前的疗法对 CRPC 患者的生存率较低。实验过程用表达荧光素酶的CRPC细胞系PC-3-Luc和稳定过表达IL-6的CRPC细胞系PC-3-IL6-Luc建立异种移植肿瘤小鼠模型。利用生物发光成像技术每周对肿瘤进行监测。通过流式细胞仪进行荧光激活细胞分选,对浸润的巨噬细胞进行量化。IL6 mRNA水平采用实时定量 PCR 法测定。结果和结论与生理盐水治疗相比,浙贝母芪苓汤治疗能显著降低 PC3 异种移植肿瘤的进展和浸润巨噬细胞的数量。ZQD治疗明显抑制了IL6 mRNA水平。值得注意的是,与生理盐水治疗相比,ZQD治疗PC3异种移植瘤后磷酸化STAT3的蛋白水平明显下降。我们的研究结果表明,ZQD治疗能显著降低前列腺癌的进展,这体现在浸润巨噬细胞数量的减少和对IL6/STAT3通路的抑制上。
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引用次数: 0
Electroacupuncture on Baihui (DU20) and Xuehai (SP10) acupoints alleviates psoriatic inflammation by regulating neurotransmitter substance P- Neurokinin-1 receptor signaling 电针百会(DU20)和雪海(SP10)穴通过调节神经递质P-神经激肽-1受体信号通路减轻银屑病炎症
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-01 DOI: 10.1016/j.jtcme.2023.07.005
Cong Qi , Fang Feng , JianNing Guo , Yu Liu , XiaoYao Guo , YuJiao Meng , TingTing Di , XueQing Hu , Yazhuo Wang , Ning Zhao , XiaWei Zhang , Yan Wang , Jingxia Zhao , Ping Li

Background

At present, acupuncture-related practices have been widely used to treat psoriasis. In our study, we investigated the effect and explored the mechanism of electroacupuncture (EA) on acupoints Baihui (DU20) and Xuehai (SP10) for the treatment of psoriasis.

Methods

Imiquimod-induced psoriasis-like mouse model was used in this study. Mice were treated with electroacupuncture at DU20 and SP10 (depth of 2–3 mm, frequency of 2/15 Hz, intensity of 0.5–1.0 mA, 10 min/day). The severity of psoriasis-like lesions for each group was assessed. In addition, histological analysis of the lesions were performed. The levels of inflammatory cytokines were determined using Elisa. The expression levels of Substance P (SP) and NK1R were measured using Western blotting. In addition, NK1R inhibitor was administrated to evaluate the target of electroacupuncture in our mouse model.

Results

Electroacupuncture significantly alleviated IMQ-induced skin lesions and epidermal thickness, accompanied with reduced keratinocyte proliferation, CD3+, CD4+, and CD8+ T cells infiltration. The reduced levels of inflammatory cytokines was observed after electroacupuncture treatment. In addition, electroacupuncture inhibited the expression levels of SP and NK1R. NK1R inhibitor could ameliorate lesional symptoms and suppress epidermal thickening and CD3+, CD4+, and CD8 + T cell infiltration.

Conclusions

Electroacupuncture relieved psoriasis-like inflammation and T cell infiltration. This therapeutic action was likely mediated by the modulation of Substance P and its receptor NK1R.

背景目前,针灸相关疗法已被广泛用于治疗银屑病。本研究采用咪喹莫特诱导的银屑病样小鼠模型。小鼠接受电针 DU20 和 SP10(深度 2-3 mm,频率 2/15 Hz,强度 0.5-1.0 mA,10 分钟/天)治疗。对各组银屑病样皮损的严重程度进行评估。此外,还对皮损进行了组织学分析。使用 Elisa 检测炎症细胞因子的水平。用 Western 印迹法测定物质 P(SP)和 NK1R 的表达水平。结果电针显著减轻了 IMQ 诱导的皮损和表皮厚度,同时减少了角质细胞增殖、CD3+、CD4+ 和 CD8+ T 细胞浸润。电针治疗后,炎症细胞因子水平降低。此外,电针还抑制了 SP 和 NK1R 的表达水平。NK1R 抑制剂可改善皮损症状,抑制表皮增厚和 CD3+、CD4+、CD8 + T 细胞浸润。这种治疗作用可能是通过调节物质 P 及其受体 NK1R 实现的。
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引用次数: 0
Gracilaria chorda subcritical-water extracts as ameliorant of insulin resistance induced by high-glucose in zebrafish and dexamethasone in L6 myotubes 芡实亚临界水提取物可改善高糖诱导的斑马鱼胰岛素抵抗和地塞米松诱导的 L6 肌管胰岛素抵抗
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-01-01 DOI: 10.1016/j.jtcme.2023.07.006
Laxmi Sen Thakuri , Chul Min Park , Jin Woo Park , Dong Young Rhyu

Background and aim

Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. Loss of insulin sensitivity disrupts glucose homeostasis and elevates the risk of developing the metabolic syndrome that includes Type 2 diabetes. This study assesses the effect on subcritical-water extract of Gracilaria chorda (GC) at 210 °C (GCSW210) in IR induction models of high glucose (HG)-induced zebrafish larvae and dexamethasone (DEX)-induced L6 myotubes.

Experimental procedure

The dose of HG and DEX for IR induction in zebrafish larvae and L6 myotubes was 130 mM or 0.5 μM. The capacity of glucose uptake was quantified by fluorescence staining or intensity. In addition, the activation of protein and mRNA expressions for insulin signaling (insulin-dependent or independent pathways) was measured.

Results and conclusion

Exposure of zebrafish larvae to HG significantly reduced the intracellular glucose uptake with dose-dependnet manner compared to control. However, the group treated with GCSW210 significantly averted HG levels like the insulin-treated group, and significantly up- or down-regulated the mRNA expressions related to insulin production (insα) and insulin signaling pathways. Moreover, the treatment with GCSW210 effectively regulated the protein expression of PI3K/AKT, AMPK, and GLUT4 involved in the action of insulin in IR models of L6 myotubes compared to DEX-treated control. Our data indicate that GCSW210 stimulates activation of PI3K/AKT and AMPK pathways to attenuate the development of IR induced by HG in zebrafish and DEX in L6 myotubes. In conclusion, GCSW210 is a potential agent for alleviating various diseases associated with the insulin resistance.

背景和目的胰岛素抵抗(IR)是细胞不能对胰岛素做出正常反应的一种病理状态。胰岛素敏感性的丧失会破坏葡萄糖稳态,并增加患代谢综合征(包括 2 型糖尿病)的风险。本研究评估了210 °C下雏菊亚临界水提取物(GCSW210)对高葡萄糖(HG)诱导的斑马鱼幼体和地塞米松(DEX)诱导的L6肌细胞管IR诱导模型的影响。葡萄糖摄取能力通过荧光染色或强度进行量化。结果和结论与对照组相比,暴露于 HG 的斑马鱼幼体以剂量依赖网络的方式显著降低了细胞内葡萄糖摄取量。然而,用 GCSW210 处理的斑马鱼组与胰岛素处理的斑马鱼组一样,能显著避免 HG 水平,并能显著上调或下调与胰岛素分泌(insα)和胰岛素信号通路相关的 mRNA 表达。此外,与DEX处理的对照组相比,GCSW210能有效调节IR模型L6肌管中参与胰岛素作用的PI3K/AKT、AMPK和GLUT4的蛋白表达。我们的数据表明,GCSW210能刺激PI3K/AKT和AMPK通路的活化,从而减轻HG诱导的斑马鱼IR和DEX诱导的L6肌管IR的发展。总之,GCSW210 是一种缓解与胰岛素抵抗相关的各种疾病的潜在药物。
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引用次数: 0
The characterization of traditional Chinese medicine natures and flavors using network pharmacology integrated strategy 利用网络药理学综合策略分析中药性味特征
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2023-12-25 DOI: 10.1016/j.jtcme.2023.12.004
Hong Wang, Wenfeng Wei, Jing Liu, Shuang Zhang, Yunli Zhao, Zhiguo Yu

Background and aim

Due to the complexity of TCM ingredients and medication compatibility, TCM cannot be used like chemical medicines. The theory of “Four Natures and five Flavors” provides a theoretical basis for the use of TCM. “Four Natures and five Flavors” are originated from pharmacological rules based on clinical practices. Whereas, How to describe and characterize “Natures”(Warm, Hot, Cold and Cool) and “Flavors” (Pungent, Sour, Sweet, Bitter and Salty) scientifically remain the issue that needs to be solved. The aim of this study is to establish the TCM characterization models based on the integrated pharmacology network strategy and provide a deeper understanding of TCM theory.

Experimental procedure

Five “Pungent-Neutral”, nine “Sweet-Neutral and nine “Bitter-Neutral” TCMs were selected to characterize the “Flavors” (Pungent, Sweet and Bitter). Nine “Pungent-Warm” and nine “Bitter-Cold” TCMs were selected to characterize the “Natures” (Warm and Cold). The screened chemical ingredients were analyzed by classification and the screened characteristics targets were analyzed by GO and KEGG enrichment analysis.

Results and conclusion

In the “Pungent” group, flavonoids are the most. “Pungent” may have immune-regulatory effects and potential anticancer activity. In the “Sweet” group, isoflavones are the most. “Sweet” are related to effectively invigorate health. Fatty acids in the “Warm” group are the most. Flavonoids in the “Cold’ group are far more than other components. “Warm” and “Cold” are both related to fatty acid and energy metabolism.

背景和目的由于中药成分的复杂性和药物相容性,中药不能像化学药那样使用。四性五味 "理论为中药的使用提供了理论依据。"四性五味 "源于临床实践的药理规律。然而,如何科学地描述和表征 "性"(温、热、寒、凉)和 "味"(辛、酸、甘、苦、咸)仍是亟待解决的问题。本研究旨在建立基于整合药理学网络策略的中药表征模型,加深对中药理论的理解。实验过程选取 5 味 "辛中性 "中药、9 味 "甘中性 "中药和 9 味 "苦中性 "中药来表征 "味"(辛、甘、苦)。九种 "辛温 "和九种 "苦寒 "中药被筛选出来,以表征 "性"(温和寒)。对筛选出的化学成分进行分类分析,对筛选出的特征靶标进行 GO 和 KEGG 富集分析。"辛味 "可能具有免疫调节作用和潜在的抗癌活性。在 "甜味 "组中,异黄酮最多。甜 "与有效促进健康有关。温 "组中脂肪酸最多。寒 "组中的类黄酮远高于其他成分。温 "和 "寒 "都与脂肪酸和能量代谢有关。
{"title":"The characterization of traditional Chinese medicine natures and flavors using network pharmacology integrated strategy","authors":"Hong Wang,&nbsp;Wenfeng Wei,&nbsp;Jing Liu,&nbsp;Shuang Zhang,&nbsp;Yunli Zhao,&nbsp;Zhiguo Yu","doi":"10.1016/j.jtcme.2023.12.004","DOIUrl":"10.1016/j.jtcme.2023.12.004","url":null,"abstract":"<div><h3>Background and aim</h3><p>Due to the complexity of TCM ingredients and medication compatibility, TCM cannot be used like chemical medicines. The theory of “Four Natures and five Flavors” provides a theoretical basis for the use of TCM. “Four Natures and five Flavors” are originated from pharmacological rules based on clinical practices. Whereas, How to describe and characterize “Natures”(Warm, Hot, Cold and Cool) and “Flavors” (Pungent, Sour, Sweet, Bitter and Salty) scientifically remain the issue that needs to be solved. The aim of this study is to establish the TCM characterization models based on the integrated pharmacology network strategy and provide a deeper understanding of TCM theory.</p></div><div><h3>Experimental procedure</h3><p>Five “Pungent-Neutral”, nine “Sweet-Neutral and nine “Bitter-Neutral” TCMs were selected to characterize the “Flavors” (Pungent, Sweet and Bitter). Nine “Pungent-Warm” and nine “Bitter-Cold” TCMs were selected to characterize the “Natures” (Warm and Cold). The screened chemical ingredients were analyzed by classification and the screened characteristics targets were analyzed by GO and KEGG enrichment analysis.</p></div><div><h3>Results and conclusion</h3><p>In the “Pungent” group, flavonoids are the most. “Pungent” may have immune-regulatory effects and potential anticancer activity. In the “Sweet” group, isoflavones are the most. “Sweet” are related to effectively invigorate health. Fatty acids in the “Warm” group are the most. Flavonoids in the “Cold’ group are far more than other components. “Warm” and “Cold” are both related to fatty acid and energy metabolism.</p></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"14 3","pages":"Pages 343-349"},"PeriodicalIF":4.5,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2225411023001384/pdfft?md5=9062875cd7de154665e6dc5e2908a99b&pid=1-s2.0-S2225411023001384-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139194919","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
Curcuma longa alone and in combination with pioglitazone attenuates paraquat-induced lung injury in rats through improving inflammation, oxidative stress and fibrosis 莪术单独或与吡格列酮联用可通过改善炎症、氧化应激和纤维化减轻百草枯诱导的大鼠肺损伤
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2023-12-01 DOI: 10.1016/j.jtcme.2023.12.001
Seyedeh Zahra Ghasemi, Sima Beigoli, S. Behrouz, Z. Gholamnezhad, Nema Mohammadian Roshan, M. Boskabady
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引用次数: 0
A diet enriched with Pistacia atlantica fruits improves the female rats' reproductive system 富含楷果的饮食可改善雌性大鼠的生殖系统
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2023-11-28 DOI: 10.1016/j.jtcme.2023.09.004
Manijeh Dogani , Nayere Askari , Ali Kalantari Hesari

Background and aim

Baneh (Pistacia atlantica) is a plant species that is commonly consumed as food and has a long-standing traditional use as a sexual enhancer. Despite its widespread use, a limited amount of academic and scientific literature is available regarding its potential impact on the reproductive system. The present research aimed to study the effect of a diet enriched with Baneh on the female rats’ reproductive system.

Experimental procedure

Three groups of rats (n = 8) were subjected to the intended diet for six weeks. Subsequently, their histomorphometric parameters, sex hormone levels, as well as the expression of oxytocin (OXT) and oxytocin receptor (OXTR) genes were measured. The rats’ serum vitamin D, zinc, and lipid profiles were also evaluated.

Results and conclusion

Results revealed that compared to the normal food, the diet containing 20 % Baneh significantly increased the progesterone and estradiol levels three and two times, respectively. It decreased the total body weight while increasing the ratio of ovary weight to the body weight. Furthermore, the Baneh-enriched diet raised HDL, zinc, and vitamin D levels, though it reduced the LDL and TG levels by 15 μg/dl and 24 μg/dl, respectively, and the concentration of ovary malondialdehyde decreased by 50 % in the treated group. Also, the diet increased the follicle graph, corpus luteum, the thickness of the epithelium, the number of endometrial glands, and the expression of both OXT and OXTR genes. Our findings suggested that P. atlantica could considerably improve the female sex hormone levels and their reproductive system.

背景和目的巴戟天(Pistacia atlantica)是一种通常作为食物食用的植物物种,长期以来在传统上被用作增强性能力的药物。尽管其用途广泛,但有关其对生殖系统潜在影响的学术和科学文献数量有限。本研究旨在研究富含 Baneh 的饮食对雌性大鼠生殖系统的影响。随后,测量了它们的组织形态参数、性激素水平以及催产素(OXT)和催产素受体(OXTR)基因的表达。结果和结论结果显示,与普通食物相比,含有 20% Baneh 的食物能显著提高孕酮和雌二醇水平,分别是普通食物的三倍和两倍。它降低了总重量,同时提高了卵巢重量与体重之比。此外,富含 Baneh 的膳食提高了高密度脂蛋白、锌和维生素 D 的水平,但低密度脂蛋白和总胆固醇水平分别降低了 15 μg/dl 和 24 μg/dl,而且处理组的卵巢丙二醛浓度降低了 50%。此外,饮食还增加了卵泡图、黄体、上皮厚度、子宫内膜腺体数量以及 OXT 和 OXTR 基因的表达。我们的研究结果表明,P. atlantica 能显著改善女性的性激素水平和生殖系统。
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引用次数: 0
Integrating single-cell and spatial transcriptomics to elucidate the crosstalk between cancer-associated fibroblasts and cancer cells in hepatocellular carcinoma with spleen-deficiency syndrome 整合单细胞和空间转录组学,阐明肝细胞癌伴脾脏缺失综合征中癌症相关成纤维细胞与癌细胞之间的串联关系
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2023-11-22 DOI: 10.1016/j.jtcme.2023.11.008
Qiuxia Chen , Jin Luo , Jiahui Liu , He Yu , Meiling Zhou , Ling Yu , Yan Chen , Shijun Zhang , Zhuomao Mo

Background and aim

Most patients with hepatocellular carcinoma (HCC) in China have been diagnosed with spleen deficiency syndrome (SDS), which accelerates the progression of HCC by disrupting the tumor microenvironment homeostasis. This study aimed to investigate the intercellular crosstalk in HCC with SDS.

Experimental procedure

An HCC-SDS mouse model was established using orthotopic HCC transplantation based on reserpine-induced SDS. Single-cell data analysis and cancer cell prediction were conducted using Seurat and CopyKAT package, respectively. Intercellular interactions were explored using CellPhoneDB and CellChat and subsequently validated using co-culture assays, ELISA and histological staining. We performed pathway activity analysis using gene set variation analysis and the Seurat package. The extracellular matrix (ECM) remodeling was assessed using a gel contraction assay, atomic force microscopy, and Sirius red staining. The deconvolution of the spatial transcriptomics data using the “CARD” package based on single-cell data.

Results and conclusion

We successfully established the HCC-SDS mouse model. Twenty-nine clusters were identified. The interactions between cancer cells and cancer-associated fibroblasts (CAFs) were significantly enhanced via platelet-derived growth factor (PDGF) signaling in HCC-SDS. CAFs recruited in HCC-SDS lead to ECM remodeling and the activation of TGF-β signaling pathway. Deconvolution of the spatial transcriptome data revealed that CAFs physically surround cancer cells in HCC-SDS. This study reveals that the crosstalk of CAFs-cancer cells is crucial for the tumor-promoting effect of SDS. CAFs recruited by HCC via PDGFA may lead to ECM remodeling through activation of the TGF-β pathway, thereby forming a physical barrier to block immune cell infiltration under SDS.

背景和目的在中国,大多数肝细胞癌(HCC)患者被诊断为脾虚综合征(SDS),SDS通过破坏肿瘤微环境稳态而加速HCC的进展。本研究旨在探讨SDS合并HCC的细胞间串扰。实验过程在利血平诱导的SDS基础上,利用正位HCC移植建立了HCC-SDS小鼠模型。分别使用 Seurat 和 CopyKAT 软件包进行单细胞数据分析和癌细胞预测。使用 CellPhoneDB 和 CellChat 探索了细胞间的相互作用,随后使用共培养试验、ELISA 和组织学染色进行了验证。我们使用基因组变异分析和 Seurat 软件包进行了通路活性分析。细胞外基质(ECM)重塑是通过凝胶收缩试验、原子力显微镜和天狼星红染色进行评估的。使用基于单细胞数据的 "CARD "软件包对空间转录组学数据进行解卷积。共鉴定出 29 个集群。在 HCC-SDS 中,癌细胞与癌相关成纤维细胞(CAFs)之间的相互作用通过血小板衍生生长因子(PDGF)信号传导显著增强。HCC-SDS中招募的CAFs导致了ECM重塑和TGF-β信号通路的激活。空间转录组数据的解卷积显示,CAFs 在 HCC-SDS 中物理性地包围着癌细胞。这项研究揭示了CAFs-癌细胞的串联对于SDS的肿瘤促进作用至关重要。HCC通过PDGFA招募的CAFs可能会通过激活TGF-β途径导致ECM重塑,从而形成物理屏障,阻止免疫细胞在SDS下浸润。
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引用次数: 0
Qufeng tongluo decoction decreased proteinuria in diabetic mice by protecting podocytes via promoting autophagy 曲风通络汤通过促进自噬保护荚膜细胞,从而减少糖尿病小鼠的蛋白尿
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2023-11-21 DOI: 10.1016/j.jtcme.2023.11.007
Boran Ni , Yao Xiao , Ruojun Wei , Weijing Liu , Liwei Zhu , Yifan Liu , Zhichao Ruan , Jiamu Li , Shidong Wang , Jinxi Zhao , Weijun Huang

Background

Diabetic kidney disease (DKD) is one of diabetic complications, which has become the leading cause of end-stage kidney disease. In addition to angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker(ACEI/ARB) and sodium-glucose cotransporter-2 inhibitor (SGLT2i), traditional Chinese medicine (TCM) is an effective alternative treatment for DKD. In this study, the effect of Qufeng Tongluo (QFTL) decoction in decreasing proteinuria has been observed and its mechanism has been explored based on autophagy regulation in podocyte.

Methods

In vivo study, db/db mice were used as diabetes model and db/m mice as blank control. Db/db mice were treated with QFTL decoction, rapamycin, QFTL + 3-Methyladenine (3-MA), trehalose, chloroquine (CQ) and QFTL + CQ. Mice urinary albumin/creatinine (UACR), nephrin and autophagy related proteins (LC3 and p62) in kidney tissue were detected after intervention of 9 weeks. Transcriptomics was operated with the kidney tissue from model group and QFTL group. In vitro study, mouse podocyte clone-5 (MPC-5) cells were stimulated with hyperglycemic media (30 mmol/L glucose) or cultured with normal media. High-glucose-stimulated MPC-5 cells were treated with QFTL freeze-drying powder, rapamycin, CQ, trehalose, QFTL+3-MA and QFTL + CQ. Cytoskeletal actin, nephrin, ATG-5, ATG-7, Beclin-1, cathepsin L and cathepsin B were assessed. mRFP-GFP-LC3 was established by stubRFP-sensGFP-LC3 lentivirus transfection.

Results

QFTL decoction decreased the UACR and increased the nephrin level in kidney tissue and high-glucose-stimulated podocytes. Autophagy inhibitors, including 3-MA and chloroquine blocked the effects of QFTL decoction. Further study showed that QFTL decoction increased the LC3 expression and relieved p62 accumulation in podocytes of db/db mice. In high-glucose-stimulated MPC-5 cells, QFTL decoction rescued the inhibited LC3 and promoted the expression of ATG-5, ATG-7, and Beclin-1, while had no effect on the activity of cathepsin L and cathepsin B. Results of transcriptomics also showed that 51 autophagy related genes were regulated by QFTL decoction, including the genes of ATG10, SCOC, ATG4C, AMPK catalytic subunit, PI3K catalytic subunit, ATG3 and DRAM2.

Conclusion

QFTL decoction decreased proteinuria and protected podocytes in db/db mice by regulating autophagy.

背景糖尿病肾病(DKD)是糖尿病并发症之一,已成为终末期肾病的主要病因。除了血管紧张素转换酶抑制剂/血管紧张素 II 受体阻滞剂(ACEI/ARB)和钠-葡萄糖共转运体-2 抑制剂(SGLT2i)外,中药也是治疗 DKD 的有效替代疗法。本研究观察了曲风通络汤(QFTL)降低蛋白尿的作用,并基于荚膜细胞的自噬调节探讨了其作用机制。Db/db 小鼠分别接受 QFTL 煎剂、雷帕霉素、QFTL + 3-甲基腺嘌呤(3-MA)、曲哈糖、氯喹(CQ)和 QFTL + CQ 治疗。干预 9 周后,检测了肾组织中的小鼠尿白蛋白/肌酐(UACR)、肾素和自噬相关蛋白(LC3 和 p62)。对模型组和 QFTL 组的肾组织进行了转录组学研究。在体外研究中,小鼠荚膜细胞克隆-5(MPC-5)细胞用高血糖培养基(30 mmol/L葡萄糖)刺激或用正常培养基培养。用 QFTL 冻干粉、雷帕霉素、CQ、妥哈糖、QFTL+3-MA 和 QFTL + CQ 处理高血糖刺激的 MPC-5 细胞。结果QFTL煎剂降低了肾组织和高葡萄糖刺激的荚膜细胞中的UACR,提高了肾素水平。3-MA和氯喹等自噬抑制剂阻断了QFTL煎剂的作用。进一步的研究表明,蟾酥煎剂可增加 LC3 的表达,并缓解 p62 在 db/db 小鼠荚膜细胞中的积累。在高葡萄糖刺激的 MPC-5 细胞中,芪苈强心煎剂能挽救被抑制的 LC3,促进 ATG-5、ATG-7 和 Beclin-1 的表达,但对 cathepsin L 和 cathepsin B 的活性没有影响。转录组学研究结果表明,51个自噬相关基因受QFTL煎剂调控,包括ATG10、SCOC、ATG4C、AMPK催化亚基、PI3K催化亚基、ATG3和DRAM2。
{"title":"Qufeng tongluo decoction decreased proteinuria in diabetic mice by protecting podocytes via promoting autophagy","authors":"Boran Ni ,&nbsp;Yao Xiao ,&nbsp;Ruojun Wei ,&nbsp;Weijing Liu ,&nbsp;Liwei Zhu ,&nbsp;Yifan Liu ,&nbsp;Zhichao Ruan ,&nbsp;Jiamu Li ,&nbsp;Shidong Wang ,&nbsp;Jinxi Zhao ,&nbsp;Weijun Huang","doi":"10.1016/j.jtcme.2023.11.007","DOIUrl":"10.1016/j.jtcme.2023.11.007","url":null,"abstract":"<div><h3>Background</h3><p>Diabetic kidney disease (DKD) is one of diabetic complications, which has become the leading cause of end-stage kidney disease. In addition to angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker(ACEI/ARB) and sodium-glucose cotransporter-2 inhibitor (SGLT2i), traditional Chinese medicine (TCM) is an effective alternative treatment for DKD. In this study, the effect of Qufeng Tongluo (QFTL) decoction in decreasing proteinuria has been observed and its mechanism has been explored based on autophagy regulation in podocyte.</p></div><div><h3>Methods</h3><p>In vivo study, db/db mice were used as diabetes model and db/m mice as blank control. Db/db mice were treated with QFTL decoction, rapamycin, QFTL + 3-Methyladenine (3-MA), trehalose, chloroquine (CQ) and QFTL + CQ. Mice urinary albumin/creatinine (UACR), nephrin and autophagy related proteins (LC3 and p62) in kidney tissue were detected after intervention of 9 weeks. Transcriptomics was operated with the kidney tissue from model group and QFTL group. In vitro study, mouse podocyte clone-5 (MPC-5) cells were stimulated with hyperglycemic media (30 mmol/L glucose) or cultured with normal media. High-glucose-stimulated MPC-5 cells were treated with QFTL freeze-drying powder, rapamycin, CQ, trehalose, QFTL+3-MA and QFTL + CQ. Cytoskeletal actin, nephrin, ATG-5, ATG-7, Beclin-1, cathepsin L and cathepsin B were assessed. mRFP-GFP-LC3 was established by stubRFP-sensGFP-LC3 lentivirus transfection.</p></div><div><h3>Results</h3><p>QFTL decoction decreased the UACR and increased the nephrin level in kidney tissue and high-glucose-stimulated podocytes. Autophagy inhibitors, including 3-MA and chloroquine blocked the effects of QFTL decoction. Further study showed that QFTL decoction increased the LC3 expression and relieved p62 accumulation in podocytes of db/db mice. In high-glucose-stimulated MPC-5 cells, QFTL decoction rescued the inhibited LC3 and promoted the expression of ATG-5, ATG-7, and Beclin-1, while had no effect on the activity of cathepsin L and cathepsin B. Results of transcriptomics also showed that 51 autophagy related genes were regulated by QFTL decoction, including the genes of ATG10, SCOC, ATG4C, AMPK catalytic subunit, PI3K catalytic subunit, ATG3 and DRAM2.</p></div><div><h3>Conclusion</h3><p>QFTL decoction decreased proteinuria and protected podocytes in db/db mice by regulating autophagy.</p></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"14 3","pages":"Pages 312-320"},"PeriodicalIF":4.5,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2225411023001219/pdfft?md5=d07f00c2512f8ebe69e9f4c1b19adf52&pid=1-s2.0-S2225411023001219-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139299659","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
Peripheral pulse harmonic analysis and its clinical application: A systematic review 外周脉搏谐波分析及其临床应用:系统综述
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2023-11-20 DOI: 10.1016/j.jtcme.2023.11.006
Kun-Yuan Hsiao , Jiunn-Horng Kang , Yeong-Shing Wu , Hen-Hong Chang , Cheng-Ta Yang
<div><h3>Introduction</h3><p>Pulse harmonic analysis is a quantitative and objective methodology within traditional Chinese medicine (TCM) used to evaluate pulse characteristics. However, interpreting pulse wave data is challenging due to its inherent complexity. This study aims to provide a comprehensive review and comparison of existing human pulse wave harmonic analysis methods to elucidate their patterns and characteristics.</p></div><div><h3>Methods</h3><p>A systematic review of clinical research reports published from 1990 to 2021 was conducted, focusing on variations in harmonic characteristics across different medical conditions and physiological states. Keyword searches included terms related to analysis methods (e.g., "Pulse Spectrum," "harmonic analysis," "harmonic index") and measured indicators (e.g., "vascular response," "PPG," "Photoplethysmography," "aortic," "arterial," "blood pressure"). Supplementary research using PubMed's Mesh terms specifically targeted "Pulse wave analysis" within the methods and statistical analysis domain. Articles were filtered based on predefined criteria, including human participants and research related to pulse pressure or vascular volume changes. Conference papers, animal studies, and irrelevant research were excluded, with literature evaluation scales selected based on the retrieved research reports.</p></div><div><h3>Results</h3><p>Initially, 6487 research reports were identified, and after screening, 50 reports were included in the review. The analysis revealed that low-frequency harmonics increase following vigorous activity or sympathetic excitation but decrease during rest or parasympathetic excitation. Cardiovascular patients exhibited elevated first harmonics associated with the liver meridian, while diabetes patients displayed weakened third harmonics related to the spleen meridian. Liver dysfunction was linked to changes in the first harmonic, and cancer patients showed signs of liver and kidney yin deficiency in the first and second harmonics. These findings underscore the potential of harmonic analysis for TCM disease diagnosis and organ assessment. Moreover, individuals with conditions such as liver dysfunction, cancer, and gynecological disorders displayed distinct intensity patterns across harmonics one through ten compared to healthy controls, albeit with some variations. Heterogeneity in these studies mainly stemmed from differences in measurement methods and study populations. Additionally, research suggested that factors like blood circulation and cognitive activity influenced harmonic intensity.</p></div><div><h3>Conclusions</h3><p>In summary, this report consolidates prior research on pulse wave harmonics analysis, revealing unique patterns associated with various physiological conditions. Despite limitations, such as limited sample sizes in previous studies, the observed associations between physiological states and harmonics hold promise for potential clinical applications. Th
导言脉搏谐波分析是传统中医用于评估脉搏特征的一种定量客观方法。然而,由于其固有的复杂性,解释脉搏波数据具有挑战性。本研究旨在对现有的人体脉搏波谐波分析方法进行全面回顾和比较,以阐明其规律和特点。方法对 1990 年至 2021 年发表的临床研究报告进行了系统回顾,重点关注不同病症和生理状态下谐波特征的变化。关键词搜索包括与分析方法(如 "脉谱"、"谐波分析"、"谐波指数")和测量指标(如 "血管反应"、"PPG"、"Photoplethysmography"、"主动脉"、"动脉"、"血压")相关的术语。使用 PubMed 的 Mesh 术语进行的补充研究特别针对方法和统计分析领域中的 "脉搏波分析"。文章根据预定义标准进行筛选,包括人类参与者和与脉压或血管容积变化相关的研究。会议论文、动物实验和无关研究均被排除在外,并根据检索到的研究报告选择了文献评价量表。结果最初确定了 6487 份研究报告,经过筛选,50 份报告被纳入综述。分析结果显示,低频谐波在剧烈活动或交感神经兴奋时会增加,但在休息或副交感神经兴奋时会减少。心血管疾病患者表现出与肝经相关的第一谐波升高,而糖尿病患者则表现出与脾经相关的第三谐波减弱。肝功能异常与第一谐波的变化有关,癌症患者的第一和第二谐波显示出肝肾阴虚的迹象。这些发现强调了谐波分析在中医疾病诊断和器官评估方面的潜力。此外,与健康对照组相比,患有肝功能异常、癌症和妇科疾病的个体在一至十次谐波中显示出不同的强度模式,尽管存在一些差异。这些研究的异质性主要源于测量方法和研究人群的不同。此外,研究表明血液循环和认知活动等因素也会影响谐波强度。尽管之前的研究存在样本量有限等局限性,但观察到的生理状态与谐波之间的关联为潜在的临床应用带来了希望。这项研究为动脉波谐波分析的未来应用奠定了坚实的基础,促进了这种分析方法的广泛应用。
{"title":"Peripheral pulse harmonic analysis and its clinical application: A systematic review","authors":"Kun-Yuan Hsiao ,&nbsp;Jiunn-Horng Kang ,&nbsp;Yeong-Shing Wu ,&nbsp;Hen-Hong Chang ,&nbsp;Cheng-Ta Yang","doi":"10.1016/j.jtcme.2023.11.006","DOIUrl":"10.1016/j.jtcme.2023.11.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Pulse harmonic analysis is a quantitative and objective methodology within traditional Chinese medicine (TCM) used to evaluate pulse characteristics. However, interpreting pulse wave data is challenging due to its inherent complexity. This study aims to provide a comprehensive review and comparison of existing human pulse wave harmonic analysis methods to elucidate their patterns and characteristics.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;A systematic review of clinical research reports published from 1990 to 2021 was conducted, focusing on variations in harmonic characteristics across different medical conditions and physiological states. Keyword searches included terms related to analysis methods (e.g., \"Pulse Spectrum,\" \"harmonic analysis,\" \"harmonic index\") and measured indicators (e.g., \"vascular response,\" \"PPG,\" \"Photoplethysmography,\" \"aortic,\" \"arterial,\" \"blood pressure\"). Supplementary research using PubMed's Mesh terms specifically targeted \"Pulse wave analysis\" within the methods and statistical analysis domain. Articles were filtered based on predefined criteria, including human participants and research related to pulse pressure or vascular volume changes. Conference papers, animal studies, and irrelevant research were excluded, with literature evaluation scales selected based on the retrieved research reports.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Initially, 6487 research reports were identified, and after screening, 50 reports were included in the review. The analysis revealed that low-frequency harmonics increase following vigorous activity or sympathetic excitation but decrease during rest or parasympathetic excitation. Cardiovascular patients exhibited elevated first harmonics associated with the liver meridian, while diabetes patients displayed weakened third harmonics related to the spleen meridian. Liver dysfunction was linked to changes in the first harmonic, and cancer patients showed signs of liver and kidney yin deficiency in the first and second harmonics. These findings underscore the potential of harmonic analysis for TCM disease diagnosis and organ assessment. Moreover, individuals with conditions such as liver dysfunction, cancer, and gynecological disorders displayed distinct intensity patterns across harmonics one through ten compared to healthy controls, albeit with some variations. Heterogeneity in these studies mainly stemmed from differences in measurement methods and study populations. Additionally, research suggested that factors like blood circulation and cognitive activity influenced harmonic intensity.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;In summary, this report consolidates prior research on pulse wave harmonics analysis, revealing unique patterns associated with various physiological conditions. Despite limitations, such as limited sample sizes in previous studies, the observed associations between physiological states and harmonics hold promise for potential clinical applications. Th","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"14 2","pages":"Pages 223-236"},"PeriodicalIF":4.5,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2225411023001207/pdfft?md5=30babb8588217a198dc1d70c2df3ce04&pid=1-s2.0-S2225411023001207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139296191","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
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Journal of Traditional and Complementary Medicine
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