Journal of Clinical Medicine
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2022
·Vol. 11
·期 9
·2573
·
IF 4.964
Rocío Redondo-Rodriguez,Natalia Mena-Vázquez,Alba María Cabezas-Lucena,Sara Manrique-Arija,Arkaitz Mucientes,Antonio Fernández-Nebro
Objective: In this study, we aimed to evaluate the worldwide incidence and prevalence of ANCA-associated vasculitis (AAV). Methods: A systematic search of Medline and Embase was conducted until June 2020 for studies that analyzed the incidence and prevalence of patients aged >16 years diagnosed with AAV in different geographical areas. A meta-analysis was undertaken to estimate the pooled incidence per million person-years and prevalence per million persons in AAV overall and for each subtype of AAV: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The 95% confidence interval (CI) and I2for heterogeneity were calculated. Results: The meta-analysis included 25 studies that met the inclusion criteria and covered a total of 4547 patients with AAV. Frequency increased over time. The global pooled incidence (95% CI) was 17.2 per million person-years (13.3–21.6) and the global pooled prevalence (95% CI) was 198.0 per million persons (187.0–210.0). The pooled incidence per million person-years for each AAV subtype varied from highest to lowest, as follows: GPA, 9.0; MPA, 5.9; and EGPA, 1.7. The individual pooled prevalence per million persons was, as follows: GPA, 96.8; MPA, 39.2; and EGPA, 15.6. AAV was more predominant in the northern hemisphere. By continent, a higher incidence in America and pooled prevalence of AAV was observed in America and Europe. Conclusion: The pooled incidence and prevalence of AAV seem to be increasing over time and are higher in the case of GPA. AAV was generally more frequent (incidence and prevalence) in the northern hemisphere.
研究领域:
风湿病学
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免疫学
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流行病学
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血管炎
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自身免疫性疾病
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临床流行病学
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转化医学
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DOI
高影响因子
Journal of Pharmaceutical Analysis
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2025
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IF 8.9
Lingyan Li,Xingjie Wu,Qianqian Guo,Yu'e Wang,Zhiyong He,Guangqiong Zhang,Shaobo Liu,Liping Shu,Babu Gajendran,Ying Chen,Xiangchun Shen,Ling Tao
Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma expression in vascular endothelial cells and estrogen receptor alpha protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with cholesterol metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.
研究领域:
药剂学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-19
·
IF 16.6
Da Xingwen,Li Ziyan,Huang Xiaofan,He Zuhan,Yu Yubing,Tian Tongtong,Xu Chengqi,Yao Yufeng,Wang Qing K.
Thoracic aortic aneurysm (TAA) is a localized or diffuse dilatation of the thoracic aortas, and causes many sudden deaths each year worldwide. However, there is no effective pharmacologic therapy. Here, we show that AGGF1 effectively blocks TAA-associated arterial inflammation and remodeling in three different mouse models (mice with transverse aortic constriction, Fbn1 C1041G/+ mice, and β-aminopropionitrile-treated mice). AGGF1 expression is reduced in the ascending aortas from the three models and human TAA patients. Aggf1 +/- mice and vascular smooth muscle cell (VSMC)-specific Aggf1 smcKO knockout mice show aggravated TAA phenotypes. Mechanistically, AGGF1 enhances the interaction between its receptor integrin α7 and latency-associated peptide (LAP)-TGF-β1, blocks the cleavage of LAP-TGF-β1 to form mature TGF-β1, and inhibits Smad2/3 and ERK1/2 phosphorylation in VSMCs. Pirfenidone, a treatment agent for idiopathic pulmonary fibrosis, inhibits TAA-associated vascular inflammation and remodeling in wild type mice, but not in Aggf1 +/- mice. In conclusion, we identify an innovative AGGF1 protein therapeutic strategy to block TAA-associated vascular inflammation and remodeling, and show that efficacy of TGF-β inhibition therapies require AGGF1.
研究领域:
心血管疾病
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ANNALS OF THE RHEUMATIC DISEASES
·
2022
·Vol. 81
·期 12
·1647-1653
·
IF 27.973
Cristina Ponte,Peter C Grayson,Joanna C Robson,Ravi Suppiah,Katherine Bates Gribbons,Andrew Judge,Anthea Craven,Sara Khalid,Andrew Hutchings,Richard A Watts,Peter A Merkel,Raashid A Luqmani
Objective To develop and validate updated classification criteria for giant cell arteritis (GCA). Methods Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate items, (2) prospective collection of candidate items present at the time of diagnosis, (3) expert panel review of cases, (4) data‐driven reduction of candidate items, (5) derivation of a points‐based risk classification score in a development data set and (6) validation in an independent data set. Results The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C reactive protein ≥10 mg/L (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging and fluorodeoxyglucose–positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% CI 0.88 to 0.94) with a sensitivity of 87.0% (95% CI 82.0% to 91.0%) and specificity of 94.8% (95% CI 91.0% to 97.4%). Conclusion The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.
研究领域:
风湿病学
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血管炎
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临床免疫学
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诊断学
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流行病学
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医学影像学
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转化医学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
wenwen Li,Zeyuan Deng,Shuang Xiao,qian Du,Mengru Zhang,Hailing Song,Caidong Zhao,Liufeng Zheng
The high-fat diet (HFD) is a major risk factor for cardiovascular disease. However, the specific effects of HFD on vascular inflammation and the protective role of vitexin, a bioactive small-molecule compound derived from food, require further research. This study investigated the protective effects of vitexin intervention against HFD-induced vascular inflammation and its underlying mechanism. The results demonstrated that vitexin intervention significantly reduced body weight, serum total cholesterol, and low-density lipoprotein cholesterol levels in HFD-fed mice. Vitexin also improved vascular pathological changes and inflammatory status in the mice. Furthermore, vitexin intervention reduced serum TMAO levels in HFD-fed mice and achieved this effect by altering gut microbiota composition. HFD significantly increased N6-methyladenosine (m6A) levels in aorta tissues, while vitexin intervention reversed this abnormal m6A level. Vitexin could directly bind to fat mass and obesity-associated protein (FTO), potentially promoting m6A demethylation. The dose-response relationship between TMAO and inflammation/m6A was further validated in HUVEC cell and in vivo mouse experiments. Specifically, TMAO increased m6A levels and inflammation, while vitexin inhibited TMAO-mediated m6A modification, exhibiting anti-inflammatory effects. In conclusion, this study demonstrates the protective role of vitexin against HFD-induced vascular inflammation by inhibiting TMAO-mediated RNA m6A modification and laying the foundation for the development of functional foods.
研究领域:
药理学
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心脏病学
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Wenjing Huang,Zhujun Zeng,Yan Lang,Xia Xiang,Gaofu Qi,Gan Lu,Xiangliang Yang
In recent decades, epidemiological, clinical, and experimental studies have demonstrated that a diet with antioxidant or anti-inflammatory function plays a central role in the prevention of atherosclerosis (AS). The purpose of this study was to explore the effects of Cannabis seed oil (CO) administration on in vitro antioxidant capacity as well as blood lipid profiles, lipid peroxidation, inflammatory response, and endothelial cell integrity. Female ApoE–/– mice were fed a high-cholesterol diet and administrated with CO or phosphate-buffered saline (PBS) and seal oil by gavage for 8 weeks. The results show that CO administration reduced the levels of serum triglycerides and low-density lipoprotein cholesterol at week 6. Additionally, a decrease in serum tumor necrosis factor α and nitric oxide was also observed. Moreover, results from CD31 staining and scanning electron microscopy revealed that CO treatment alleviated the endothelial cell damage and lipid deposition induced by a high-cholesterol diet. The ratio of lesion area to the total aorta area was 19.57% for the CO group, which was lower than the PBS control group (24.67%). Collectively, CO exerted anti-atherosclerotic effects by modulating serum lipid profiles and inflammatory responses and improving endothelial cell integrity and arterial lipid deposition. The results provide a promising preventive strategy for the early progression of AS.
研究领域:
营养学
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心脏病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2025
·
IF 5.4
Hailing Song,Yun Ma,qian Du,Zeyuan Deng,Yalun Zou,Yadong Miao,Jing Li,Liufeng Zheng
Methionine-containing cyclolinopeptide ([1–9-NαC]-linusorb B2, CLB) and α-linolenic acid (ALA), two anti-inflammatory flaxseed constituents, were investigated for their combined vascular benefits. CLB-enriched orbitides were prepared for long-term high-fat diet (HFD)-fed mouse studies, while high-purity CLB monomer (>97%) was isolated via preparative chromatography for acute in vivo and cell-based assays. Structural confirmation and purity validation were achieved via mass spectrometry and liquid chromatography. CLB-enriched orbitides co-administered with ALA in HFD-fed mice reduced body weight gain, serum trimethylamine N-oxide (TMAO), dyslipidemia, and vascular inflammation, histologically confirmed by reduced pro-inflammatory mediators and endothelial repair. Purified CLB combined with ALA further demonstrated efficacy in alleviating TMAO-induced acute vascular inflammation in mice. Mechanistically, CLB enhanced ALA metabolism by upregulating key enzymes (lipoxygenases and cytochrome P450) and directly binding to their catalytic pockets. Combined effect loss upon enzyme inhibition confirmed ALA metabolic modulation as the key mechanism. These findings highlight CLB's role in amplifying ALA's efficacy to combat vascular inflammation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2020
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IF 4.352
Jinfu Qian,Wu Luo,Chengyi Dai,Jun Wang,Xinfu Guan,Chunpeng Zou,Nipon Chattipakorn,Gaojun Wu,Weijian Huang,Guang Liang
Angiotensin II (Ang II)-induced vascular inflammation and injury entails endothelial to mesenchymal transition (EndMT). Recent studies have shown that Ang II engages toll-like receptor 4 (TLR4) in the vasculature to mediate adverse effects. Here, we aimed to investigate whether myeloid differentiation protein 2 (MD2), an extracellular molecule indispensable for TLR4 activation, mediates Ang II-induced vascular injury and EndMT. We utilized MD2 knockout mice and wildtype mice treated with a specific MD2 inhibitor to decipher its role in aortas of Ang II-challenged mice. To confirm our results and to provide mechanistic insights, we exposed cultured endothelial cells to Ang II, with or without MD2 silencing. We show that Ang II causes deleterious remodeling and EndMT in aortas of mice within two weeks. These Ang II effects were largely absent in MD2 knockout mice and in wildtype mice treated with a MD2 inhibitor. MD2 silencing in cultured endothelial cells confirmed the essential role of MD2 in Ang II-induced inflammatory factor induction, and EndMT-associated phenotypic change. We also found that Ang II-MD2-EndMT axis involves the activation of nuclear factor-κB. Our studies highlight an essential role of MD2 in Ang II-induced vascular inflammation and EndMT contributing to vascular injury. These results also imply that MD2 may be targeted to dampen inflammatory cardiovascular and EndMT-associated diseases.
研究领域:
心血管疾病
·
分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2020
·
IF 7.097
Chao Teng,Chenshi Lin,Feifei Huang,Xuyang Xing,Shenyu Chen,Ling Ye,Helena S. Azevedo,Chenjie Xu,Zhengfeng Wu,Zhongjian Chen,Wei He
Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein, targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy (drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals, named as baicalein nanorods (BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo . In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.
研究领域:
药理学
·
纳米技术
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心血管疾病
·
分子生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Meng Ding,Yuan Zhu,Xiaoting Xu,Hui He,Tianyu Jiang,Xiaochuan Mo,Zhuting Wang,Wenfeng Yu,Hailong Ou
Macrophage inflammation and oxidative stress promote atherosclerosis progression. Naringenin is a naturally occurring flavonoid with antiatherosclerotic properties. Here, we elucidated the effects of naringenin on monocyte/macrophage endothelial infiltration and vascular inflammation. We found naringenin inhibited oxidized low-density lipoprotein (oxLDL)-induced pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α toward an M2 macrophage phenotype and inhibited oxLDL-induced TLR4 (Toll-like receptor 4) membrane translocation and downstream NF-κB transcriptional activity. Results from flow cytometric analysis showed that naringenin reduced monocyte/macrophage infiltration in the aorta of high-fat-diet-treated ApoE-deficient mice. The aortic cytokine levels were also inhibited in naringenin-treated mice. Further, we found that naringenin reduced lipid raft clustering and acid sphingomyelinase (ASMase) membrane gathering and inhibited the TLR4 and NADPH oxidase subunit p47phox membrane recruitment, which reduced the inflammatory response. Recombinant ASMase treatment or overexpression of ASMase abolished the naringenin function and activated macrophage and vascular inflammation. We conclude that naringenin inhibits ASMase-mediated lipid raft redox signaling to attenuate macrophage activation and vascular inflammation.
研究领域:
心血管疾病
·
药理学
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免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Quan Wang,Yi Duan,Hongshu Jing,Zhihua Wu,Yu Tian,Ke Gong,Qianqian Guo,Jiali Zhang,Ying Sun,Zhaojun Li,Yourong Duan
Atherosclerosis is a chronic disease initiated by lipid-mediated vascular inflammation . From the perspective of conventional treatment, it is difficult to achieve good therapeutic effects via regulation of a single lipid or anti-inflammatory effects. Herein, we designed an amphiphilic low molecular weight heparin-unsaturated fatty acid conjugate (LMWH-uFA) that acted as both an antiatherosclerotic agent and a nanocarrier with self-delivery properties. Structurally, LMWH-uFA self-assembled to form micelles with LMWH as the shell and uFA as the core, without any additives, which guaranteed their biosafety. Functionally, the hydrophilic segment, LMWH, prevented monocyte adhesion to inhibit early vascular inflammation, and the hydrophobic segment, uFA, could participate in the regulation of blood lipids. The anti-inflammatory drug rapamycin (RAP) was encapsulated in the micellar core, which improved its water solubility, and cooperated with LMWH to achieve targeted blockade of the vascular inflammation cascade at P-selectin. The three treatment modules, LMWH, uFA and RAP, were integrated into one system for different therapeutic targets in anticipation of better efficacy. In an atherosclerosis mouse model, RAP-loaded NPs significantly reduced the plaque area and showed satisfactory curative effects, which were related to the targeting of lipid regulation and inflammation. Thus, these modular micellar nanoparticles offer a promising approach for the clinical treatment of atherosclerosis.
研究领域:
药理学
·
纳米医学
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Fanxing Xu,Jingxian Wu,Yumei Hu,Chun Chu,Wenjun Liu,Xiang Li,Wen Zheng,Weishuo Yang,Boyan Zhao,Jiangxue Guo,Zhenzhong Wang,Ying Jia,Wei Xiao
Ethnopharmacological relevance Tongsaimai (TSM) is a traditional Chinese medicine that has several therapeutic qualities, including anti-inflammatory, anti-oxidative, and anti-vasculitis effects. However, its impacts and underlying mechanisms on wound healing remain unclear. Aim of the study The aim of our study was to evaluate TSM for its pro-healing effect and the relevant mechanisms using both experimental validation and network pharmacology analysis. Materials and methods The components of TSM were detected by high-performance liquid chromatography combined with diode array detector (HPLC-DAD). Skin wounds with a diameter of 4 mm were created on the backs of mice, after which, topical treatments of 2.5–10% TSM were applied onto the lesions once daily for either 2 or 7 days. Then, the wound tissues were collected to determine the impacts of TSM on collagen deposition, epithelial cell proliferation , oxidative stress, inflammation, and angiogenesis. Moreover, the effects of TSM (0.5–2 mg/mL) on the cell viability of HUVECs and HaCaT cells were evaluated. Results A total of 11 components in TSM were identified by HPLC-DAD. TSM was found to enhance the rate of wound contraction and increase epithelial thickness and collagen deposition during the healing process. In addition, TSM increased SOD activity and downregulated MDA and IL-1β levels in the wound tissues. Immunofluorescence analysis further indicated an increased expression of Ki67, CD31, and VEGF in wound tissues following TSM administration. Results of the network pharmacology analysis revealed that multiple pathways including VEGF, PI3K/Akt, and MAPK pathways were involved in the pharmacological actions of TSM on wound healing. Accordantly, in vitro experiments revealed that TSM promoted the proliferation of HUVECs and HaCaT cells while activating the PI3K/Akt pathway. Conclusions Our results suggest that TSM may serve as a therapeutic medication to improve wound healing by employing multiple regulatory mechanisms that affect proliferation, angiogenesis, collagen deposition, oxidative stress, and inflammation.
研究领域:
药理学
·
民族药理学
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传统中药
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伤口愈合
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）