Nano Energy
·
2024
·
IF 16.8
Zhongrong Chen,Yulin Lai,Siyu Xu,Mengfei Zhu,Yue Sun,Yue Cheng,Gang Zhao
Hypertensive emergency is a clinical syndrome characterized by abrupt and substantial elevation of blood pressure in hypertensive patients due to specific triggers, leading to potentially life-threatening consequences. Intravenous injection of sodium nitroprusside is commonly used to rapidly lower blood pressure. However, its specialized nature limits its applicability for first aid or self-help in emergency situations. To address this issue, we have developed a self-powered and controllable microneedle drug delivery system that is easy to use and effective for lowering blood pressure. The system mainly consists of two parts: a piezoelectric thin film self-powered module made of polyvinylidene fluoride and carbon nanotubes, and a drug delivery module composed of polylactic acid-Au microneedles and polylactic acid-Au-polypyrrole microneedles. The results show that different pressures applied to the self-powered module generate different voltages, thereby controlling the drug release efficiency of the microneedles. Compared with conventional active devices, it exhibits a higher drug release rate and effectiveness. Furthermore, the system was successfully utilized to reduce and control blood pressure in spontaneously hypertensive rats. Compared with the injection of sodium nitroprusside, this system can more effectively lower and control blood pressure levels, and its biological safety has been verified. This study presents a controllable and user-friendly rapid blood pressure lowering system suitable for hypertensive emergencies, which has important clinical application prospects.
研究领域:
医学工程
·
药理学
·
生物医学材料
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL DAIRY JOURNAL
·
2025
·
IF 3.4
Ruikai Zhu,Hong Zhang,Yulong Wu,Huanhuan Li,Honggang Tang,Xianrong Xu,Ke Zhao
Hypertension poses a significant threat to human health, and the efficient exploration of food-derived ACEI peptides as milder and safer alternatives to ACEI drugs has garnered increasing attention. Therefore, a combined in silico and in vitro study was performed to investigate novel ACEI peptides from goat milk proteins. First, the papain plus proteinase K was identified as the best enzymatic combination for generating ACEI peptides using BIOPEP. Then the enzymatic conditions of the papain/proteinase, the input order of the enzymes, and the molecular weight (MW) of the hydrolysate were further optimized to obtain the hydrolysate with the highest ACEI activity. Under the optimized condition described, 698 peptides (<25 AA) were successfully identified from the milk hydrolysate of goat (MW < 3 KDa). Among them, six potential novel ACEI peptides were efficiently screened virtually. Verification studies using synthesized peptides partially confirmed the in silico results, with four out of the six selected peptides (FKF, FRY, RWL, and WKP) exhibiting ACEI activity. Additionally, the blood pressure-lowering effects of the top two ACEI peptides (FRY and FKF) were further validated in spontaneously hypertensive rats (SHRs), and FRY treatment significantly lowered the blood pressure of SHRs. To summarize, this study established a rapid enzymatic hydrolysis system for screening novel ACEI peptides and identified a novel antihypertensive peptide, FRY, which provides a new method for research on bioactive peptides research and high-value utilization of goat milk.
研究领域:
食品科学
·
分子生物学
·
医学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Shibo Zhang,Bing Dong,Yao Shuai,Shuyue Deng,Jun Luo,Caixia Sun,Xing Ge,Lilin Chen,Hai Qian,Jianjun Dai,Yanmin Ju
Hypertension is a major risk factor for cardiovascular diseases and needs effective blood pressure reduction. Current antihypertensive drugs, such as captopril, face challenges, including the enzymatic degradation and the liver first-pass effect. Here, we developed a dissolving microneedle (MN) loaded with a peptide-based enzyme-responsive prodrug peptide-captopril (PC) to enhance the stability of captopril and enable efficient transdermal delivery. Kinetic studies revealed that PC exhibited a lower Km value (1.1 × 10–5 M) for esterase-mediated hydrolysis compared to free captopril (2.1 × 10–5 M), indicating improved enzymatic stability. Meanwhile, PC was encapsulated stably in microneedle tips to form the PC MN, achieving approximately 90% transdermal drug delivery. In spontaneously hypertensive rat models, PC MN elicited a rapid and potent blood-pressure-lowering effect, outperforming oral captopril administration. This study presents a promising self-administering strategy to enhance hypertension treatment through efficient transdermal drug delivery.
研究领域:
药剂学
·
生物化学
·
生物医学工程
·
心血管医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 4
·e70208
·
IF 3.4
Wenpu Yao,Junyi Li,Xiaoyan Zhu,Ruiyang Ma,Yunpeng Xu,Ruida Ma,Zihao Guo,Guangqing Mu,Xuemei Zhu
Hypertension is a common chronic disease driven by multiple physiological mechanisms, primarily the overactivation of the renin–angiotensin system (RAS). Gamma-aminobutyric acid (GABA), a nonprotein amino acid, has well-documented health benefits, including antihypertensive and calming effects. This study evaluates the blood pressure-lowering effects of Lactiplantibacillus plantarum DPUL-F233 bacterial powder in spontaneously hypertensive rats (SHRs). The bacterial powder was produced using optimized fermentation and freeze-drying techniques. In the oral administration experiment on SHRs, the group treated with a high dose of bacterial powder via long-term gavage showed a significant reduction in blood pressure compared to the untreated group. Specifically, the final measurements of diastolic and systolic blood pressure were reduced to 206.0 ± 2.35 mm Hg and 145.0 ± 6.78 mm Hg, respectively. The angiotensin-converting enzyme I/Angiotensin II/AT1R axis was downregulated, while the angiotensin-converting enzyme II/Angiotensin 1–7/MasR axis was upregulated, rebalancing the RAS signaling pathway. The high-dose group also demonstrated protective effects on the heart and kidneys, with significant improvements observed in reducing cardiac hypertrophy and kidney damage. Additionally, molecular simulation studies indicated potential inhibition of ACE I by GABA. The results suggest that GABA-rich L. plantarum DPUL-F233 powder has significant potential as a natural antihypertensive supplement, particularly for use in functional food development.
研究领域:
微生物学
·
医学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2021
·
IF 6.922
Tiantian Wang,Lei Gao,Zejun Yang,Feifei Wang,Yuexin Guo,Boya Wang,Rongxuan Hua,Hongwei Shang,Jingdong Xu
Purpose Hypertension (HTN) is a major risk factor for cardiovascular disease. In recent years, there were numerous studies on the function of stress in HTN. However, the gut dysbiosis linked to hypertension in animal models under stress is still incompletely understood. Purpose of this study is to use multiple determination method to determine the juvenile stage intestinal bacteria, cytokines and changes in hormone levels. Methods Four groups of juvenile male spontaneously hypertensive rats (SHRs) and age-matched male Wistar-Kyoto (WKY) rats were randomly selected as control and experimental groups. Rats in the two stress groups were exposed to restraint stress for 3 hours per day for 7 consecutive days. In one day three times in the method of non-invasive type tail-cuff monitoring blood pressure. The detailed mechanism was illuminated based on the intestinal change using immunohistochemical and immunofluorescence staining and the stress-related hormone and inflammation factors were analyzed via ELISA method. The integrity of the epithelial barrier was assessed using FITC/HRP and the expression levels of proteins associated with the tight junction was detected by Western blot. The alteration of stress-related intestinal flora from ileocecal junction and distal colon were also analyzed using its 16S rDNA sequencing. Results The results indicate that acute stress rapidly increases mean arterial pressure which is positive correlation to hormone concentration, especially in SHR-stress group. Meanwhile, stress promoted the enhancement of epithelial permeability accompanied with a reduced expression of the tight junction-related protein and the macrophages (Mφ) aggregation to the lamina propria. There were remarkable significant increase of stress-related hormones and pro-inflammatory factor interleukin (IL)-6 along with a decrease in the diversity of intestinal flora and an imbalance in the F/B ratio. Conclusion Our results reveal that stress accompanied with HTN could significantly disrupt the domino effect between intestinal flora and homeostasis.
研究领域:
心血管疾病
·
药理学
·
免疫学
·
微生物学
·
病理生理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2025
·Vol. 56
·期 3
·1-15
·
IF 2.2
Bai Jing,Yang Yujuan
The Hippo/YAP signaling pathway is closely related to the occurrence and development of cardiovascular diseases. However, it’s still unclear whether this pathway plays a certain role in hypertension. In this study, aortic morphology and function in spontaneously hypertensive rats (SHR) were comprehensively evaluated using Wistar-Kyoto rats (WKY) as controls. Results indicated that the aorta of SHRs have distinct changes in pathological structure. Furthermore, the proliferative activity of vascular smooth muscle cells (VSMCs) was enhanced, with vascular fibrosis being aggravated. Immunohistochemical analysis revealed that SHRs exhibited high expression of Yes-Associated Protein (YAP). Western Blot analysis showed that cytoplasmic YAP and TAZ expression decreased in hypertensive rats, indicating that YAP/TAZ nuclear transfer increased and Hippo/YAP signaling pathway had been activated. The cell function experiments of VSMCs extracted from rat aorta showed that the cell viability and proliferation ability of VSMCs in SHRs were enhanced, the expression of Fibronectin and collagen I was increased, and vascular fibrosis was aggravated. siRNA-YAP (si-YAP) can reverse the above phenomenon in VSMCs. Knockdown of YAP can inhibit Foxm1 expression. As an inhibitor of large tumor suppressor kinases LAST1/2, GA-107 can inhibit the phosphorylation level of YAP, increase blood pressure, aggravate aortic pathomorphological changes, promote VSMCs proliferation and vascular fibrosis, and thus aggravate hypertension symptoms in SHRs. However, these effects of GA-107 can be antagonized by inhibiting Foxm1 with thiosulfathiazole (Thio). Conclusively, Hippo/YAP signaling pathway promotes vascular remodeling through the regulation of Foxm1 and causes hypertension.
研究领域:
心血管疾病
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 4
·1-7
·
IF 2.447
Yiyuan Zhou,Fang Zhang,Huijiao Jiang,Di Xu,Dongyang Deng
The present study hypothesized that fumaric acid and succinic acid may exhibit therapeutic effects on gestational hypertension. During pregnancy, estrogen upregulates ten‑eleven translocation 1 (TET1) expression, which subsequently increases calcium‑activated potassium channel subunit β1 (KCNMB1) expression. KCNMB1 is associated with hypertension. Fumaric acid and succinic acid are understood to inhibit TET. Therefore, the present study investigated whether fumaric acid and succinic acid exhibit therapeutic effects on gestational hypertension and whether these effects are mediated by TET1 and KCNMB1. Nω‑Nitro‑L‑arginine methyl ester hydrochloride was injected into rats to establish a gestational hypertension model. Dimethyl fumarate (DMF) and succinic acid were administrated into rats to treat gestational hypertension. Rats were divided into five groups: i) Control; ii) model; iii) DMF; iv) succinic acid; and v) DMF + succinic acid. Blood pressure was monitored by a noninvasive meter and urinary protein was determined using a urinary protein kit. Placenta pathology was examined by hematoxylin‑eosin staining. Compared with the control group, urinary protein and blood pressure in the model group increased significantly. The placental cells in the control group were arranged orderly. However, in the model group, decidual cellular edema of placenta and vacuolar degeneration were observed, and the intervascular membrane was markedly thicker with plenty of fibrin deposition. These results indicate successful establishment of a gestational hypertension model. However, compared with the model group, urinary protein, blood pressure, edema, vacuoles and fibrin deposition were markedly reduced in the DMF, succinic acid and DMF + succinic acid groups. mRNA and protein levels of TET1 and KCNMB1 in placenta were evaluated by immunohistochemical analysis, reverse transcription‑quantitative polymerase chain reaction and western blotting. The TET1 and KCNMB1 levels in the model group were markedly increased compared with those in the control group. However, compared with the model group, the expression levels were markedly downregulated in the DMF, succinic acid and DMF + succinic acid groups. In conclusion, fumaric acid and succinic acid may treat gestational hypertension by downregulating the expression of KCNMB1 and TET1.
研究领域:
药理学
·
妇产科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Tingting Zhou,Zhiwei Wang,Xiaowang Lv,Mengting Guo,Ning Zhang,Liangju Liu,Li Geng,Jing Shao,Ka Zhang,Mengru Gao,Aiqin Mao,Yifei Zhu,Fan Yu,Lei Feng,Xiaoyan Wang,Qixiao Zhai,Wei Chen,Xin Ma
Currently, the regulation of specific gut microbial metabolism for the development and/or treatment of hypertension remains largely unexplored. Here, we show that α-lipomycin, produced by Streptomyces aureofaciens ( S. aureofaciens ) Tü117, is upregulated in the serum of high-salt diet (HSD) mice and patients with essential hypertension. α-lipomycin causes vasodilation impairment involving transient receptor potential vanilloid 4 (TRPV4)-mediated nitric oxide and endothelium-derived hyperpolarizing factor pathways in mice. We also find that Lactobacillus plantarum ( L. plantarum ) CCFM639 attenuates the increase in blood pressure (BP) potentially through inhibiting the proliferation of S. aureofaciens Tü117 in mice. An exploratory intervention trial indicates that L. plantarum CCFM639 supplementation reduces BPs in subjects newly diagnosed with pre-hypertension or stage 1 hypertension without antihypertensive medication. Our findings provide evidence for a role of S. aureofaciens Tü117-associated α-lipomycin elevation in the pathogenesis of HSD-induced hypertension, highlighting that targeting gut bacteria serves as a new therapeutic intervention for hypertension.
研究领域:
微生物学
·
药理学
·
心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2018
·
IF 3.47
Hong Ding,Xiaofei Li,Jian Li,Zhike Li,Yunhui Niu,Wanying Ren,Jianyang Tan,Shanye Yin
The present study examined the effects of procyanidin B2 (PB2) on L-NAME (nitric oxide synthase inhibitor)-induced hypertensive nephropathy. After 4 weeks of treatment with daily PB2 supplementation, lower blood pressure levels were observed in rats. The potential mechanisms were combined with amelioration of renal function impairment. The L-NAME–induced renal histological damage were reduced by PB2 treatment, which showed similar protective tendency in kidney injury molecule–1, nephrin, fibronectin and α–smooth muscle actin protein expression. This appears to be due to PB2 inducing a less pronounced generation of renal reactive oxygen species and inflammatory mediators than in the model group. Downregulation of Ang II type 1 receptor and NADPH oxidase subunit (NOX4, gp91phox and p47phox) played a critical role in the effect of PB2 reducing oxidative stress production. These activities could further support the use of PB2 commercially in food for the prevention of hypertension and its complications.
研究领域:
药理学
·
肾病学
·
高血压研究
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Foods
·
2025
·Vol. 14
·期 5
·835
·
IF 5.1
Chuling Liu,Li Cheng,Mingtian Yang,Zhengli He,Yanan Jia,Li Xu,Yuansong Zhang
Monascusis a fungus widely used in food fermentation. This study employed microbial technology, combined with microscopic morphological observations and ITS sequence analysis, to isolate, purify, and identify 10 strains of red yeast mold from variousMonascusproducts. After the HPLC detection of metabolic products, the M8 strain containing the toxic substance citrinin was excluded. Using the EWM-TOPSIS model, the remaining nine safeMonascusstrains were evaluated for their inhibitory activities against pancreatic lipase, α-glucosidase, α-amylase, and the angiotensin-converting enzyme. The M2 strain with the highest comprehensive scores for lowering blood sugar, blood lipids, and blood pressure was selected. Its fermentation product at a concentration of 3 mg/mL had inhibition rates of 96.938%, 81.903%, and 72.215%, respectively. The contents of the blood lipid-lowering active substance Monacolin K and the blood sugar and blood pressure-lowering active substance GABA were 18.078 mg/g and 5.137 mg/g, respectively. This strain can be utilized for the biosynthesis of important active substances such as Monacolin K and GABA, as well as for the fermentation production of safe and effective functional foods to address health issues like high blood lipids, high blood sugar, and high blood pressure in people. This study also provides insights into the use of natural fungi to produce healthy foods for combating chronic diseases in humans.
研究领域:
微生物学
·
食品科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2021
·
IF 6.922
Shutian Zhang,Li Hu,Chengzhi Han,Renhui Huang,Kokwin Ooi,Xinyi Qian,Xiaorong Ren,Dechang Chu,Haili Zhang,Dongshu Du,Chunmei Xia
Purpose Oxidative/nitrosative stress, neuroinflammation and their intimate interactions mediate sympathetic overactivation in hypertension. An immoderate inflammatory response is characterized not only by elevated proinflammatory cytokines (PICs) but by increases in mitochondrial dysfunction, reactive oxygen species (ROS), and nitric oxide (NO). Recent data pinpoint that both the phospholipid and lipid droplets (LDs) are potent modulators of microglia physiology. Methods Stress rats underwent compound stressors for 15 days with PLIN2-siRNA or scrambled-siRNA (SC-siRNA) administrated into the rostral ventrolateral medulla (RVLM). Lipids were analyzed by mass spectroscopy-based quantitative lipidomics. The phenotypes and proliferation of microglia, LDs, in the RVLM of rats were detected; blood pressure (BP) and myocardial injury in rats were evaluated. The anti-oxidative/nitrosative stress effect of phosphatidylethanolamine (PE) was explored in cultured primary microglia. Results Lipidomics analysis showed that 75 individual lipids in RVLM were significantly dysregulated by stress [PE was the most one], demonstrating that lipid composition changed with stress. In vitro, prorenin stress induced the accumulation of LDs, increased PICs, which could be blocked by siRNA-PLIN2 in microglia. PLIN2 knockdown upregulated the PE synthesis in microglia. Anti-oxidative/nitrosative stress effect of PE delivery was confirmed by the decrease of ROS and decrease in 3-NT and MDA in prorenin-treated microglia. PLIN2 knockdown in the RVLM blocked the number of iNOS + and PCNA + microglia, decreased BP, alleviated cardiac fibrosis and hypertrophy in stressed rats. Conclusion PLIN2 mediates microglial polarization/proliferation via downregulating PE in the RVLM of stressed rats. Delivery of PE is a promising strategy for combating neuroinflammation and oxidative/nitrosative stress in stress-induced hypertension.
研究领域:
神经科学
·
药理学
·
分子生物学
·
心脏病学
·
生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2025
·
IF 4
Dafa Yi,Jiazong Ye,Zebei Lu,Leilei Lu,Tengfei Qi,Tong Luo,Xiuyun Peng,Abdullah Al Mamun,Quan Zhou,Daqing Chen,Shuanghu Wang
This study investigates the potential drug-drug interactions between commonly prescribed anti-hypertensive drugs and mobocertinib in clinical practice to provide the scientific basis for the appropriate therapeutic application of drugs. The study used UPLC-MS/MS to detect the essential metabolites of mobocertinib in rat liver microsomes. Moreover, several anti-hypertensive drugs were used as inhibitors and the IC 50 values were determined for calcium channel blockers, angiotensin II receptor blockers and α and β receptor blockers against mobocertinib. The inhibitory mechanism of mobocertinib was further investigated for nicardipine, irbesartan, telmisartan, carvedilol, prazosin hydrochloride and spironolactone. Twenty-five Sprague Dawley ( SD) rats were randomly divided into five groups: benidipine, nicardipine, telmisartan, irbesartan and blank control groups. The drugs were administered over a period of 7 days. Mobocertinib was administered once by gavage to five groups and then blood samples were collected for further analysis. UPLC-MS/MS was performed to analyze the concentration of mobocertinib and its metabolites in rat plasma. Most anti-hypertensive drugs were found to inhibit the metabolism of mobocertinib in vitro. Several anti-hypertensive drugs were also found to increase the plasma concentration and decrease the metabolic rate of mobocertinib when administered multiple times. More importantly, we found that benidipine, nicardipine, telmisartan and irbesartan inhibited the metabolism of mobocertinib in vitro and in vivo . In summary, our data reveal that anti-hypertensive drugs interact with mobocertinib and additional attention is needed when co-administering the two drugs.
研究领域:
药理学
·
临床医学
✓ 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）