ε2 allele and ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) may confer the association of APOE genetic polymorphism with risks of nephropathy in type 2 diabetes: a meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) contributes to end-stage renal failure. Microvascular injury resulted from reactive oxygen species is implicated in the pathogenesis of DN. Genetic polymorphism of Apolipoprotein E (APOE) influences the antioxidative properties of the protein. The relationship of APOE polymorphism with the risks of nephropathy in type 2 diabetes (T2DN) remains elusive. METHODS: An up-to-date meta-analysis was conducted on the basis of studies selected from PubMed, WanFang database, Embase, Vip database, Web of Science, Scopus, and CNKI database. RESULTS: A total of 33 studies conferring 3266 cases and 3259 controls were selected on the basis of criteria of inclusion and exclusion in this meta-analysis. For APOE alleles, the pooled odds ratio (OR) of ε2 vs. ε3 was 1.89 (95% confidence intervals [95% CI]: 1.49-2.38, P < 0.0001). With regard to APOE genotypes, ε2/ε2, ε2/ε3, and ε2/ε4 increased the risk of T2DN (ε2/ε2 vs. ε3/ε3: OR = 2.32, 95% CI: 1.52-3.56, P = 0.0001; ε2/ε3 vs. ε3/ε3: OR = 1.97, 95% CI: 1.50-2.59, P<0.0001; ε2/ε4 vs. ε3/ε3: OR = 1.69, 95% CI: 1.18-2.44, P = 0.0046). CONCLUSIONS: This meta-analysis found that the APOE ε2 allele and the ε2-involved genotypes (ε2/ε2, ε2/ε3, and ε2/ε4) are the risk factors of T2DN.

Self-compassion and family cohesion moderate the association between suicide ideation and suicide attempts in Chinese adolescents.

BACKGROUND: In recent years, many studies have examined risks factors that facilitated the transition from suicide ideation to suicide attempts. Few studies, however, have examined protective factors against this transition. The current study thus assessed two protective factors, self-compassion and family cohesion, in buffering the transition from suicide ideation to suicide attempts. METHOD: A number of 520 Chinese adolescents (43.46% females, mean age = 12.96 years) completed questionnaires assessing self-compassion, family cohesion, suicide ideation, and suicide attempts two times with a 12-month interval. RESULTS: Self-compassion significantly moderated the association between Wave 1 SI and later SA. The positive dimension of self-compassion thwarted the transition from SI and SA, and the negative dimension of self-compassion strengthened the associations. In addition, family cohesion also significantly moderated the transition from SI to SA. CONCLUSION: Increasing the levels of self-compassion and family cohesion may be the targets for treating adolescents with suicide ideation to prevent them from attempting suicide.

MiRNAs Expression Profiling of Bovine (Bos taurus) Testes and Effect of bta-miR-146b on Proliferation and Apoptosis in Bovine Male Germline Stem Cells.

Spermatogenesis is a complex biological process regulated by well-coordinated gene regulation, including MicroRNAs (miRNAs). miRNAs are endogenous non-coding ribonucleic acids (ncRNAs) that mainly regulate the gene expression at post-transcriptional levels. Several studies have reported miRNAs expression in bull sperm and the process of spermatogenic arrest in cattle and yak. However, studies for the identification of differential miRNA expression and its mechanisms during the developmental stages of testis still remain uncertain. In the current study, we comprehensively analyzed the expression of miRNA in bovine testes at neonatal (3 days after birth, n = 3) and mature (13 months, n = 3) stages by RNA-seq. Moreover, the role of bta-miR-146b was also investigated in regulating the proliferation and apoptosis of bovine male germline stem cells (mGSCs) followed by a series of experiments. A total of 652 miRNAs (566 known and 86 novel miRNAs) were identified, whereas 223 miRNAs were differentially expressed between the two stages. Moreover, an elevated expression level of bta-miR-146b was found in bovine testis among nine tissues, and the functional studies indicated that the overexpression of bta-miR-146b inhibited the proliferation of bovine mGSCs and promoted apoptosis. Conversely, regulation of bta-miR-146b inhibitor promoted bovine mGSCs proliferation. This study provides a basis for understanding the regulation roles of miRNAs in bovine testis development and spermatogenesis.

Social-biological influences on sleep duration among adult residents of Northeastern China.

BACKGROUND: Cold climates traditionally have conferred long sleep duration in the residents in northeast China; however, modern lifestyle reduces sleep duration. In this study, we investigated social-biological factors influencing sleep duration in the adult residents in northeast China. METHODS: This study was performed using data from the Investigation of Chronic Disease Morbidity Rate and Risk Factors of Adults in Jilin Province, China. Associations between sleep duration and indices of demographic characteristics, health-related behaviors, and disease history in adult residents were analyzed using univariate analysis and multivariate logistic regression analysis. RESULTS: The mean sleep duration was 7.24 h. Of the 21,435 participants, approximately 53.4% had short sleep duration (sleep duration per day < 7 h), and 10.5% had long sleep duration (sleep duration per day > 9 h). There were associations between short sleep duration and indices, including age, place of residence, marital status, educational level, alcohol drinking, dietary, obesity, and history of coronary heart disease (CHD) or myocardial infarction (MI). There existed associations of long sleep duration with indices, such as age, place of residence, occupation, educational level, average monthly earnings, and physical exercise. CONCLUSION: Short sleep duration is common among residents in northeast China. Age, place of residence, and educational level are implicated in both short sleep duration and long sleep duration. Short sleep duration inclines to link with the indices (marital status, alcohol drinking, dietary, obesity, and history of CHD or MI). However, long sleep duration is relevant to the indices (occupation, average monthly earnings, and physical exercise).

The associations among self-criticism, hopelessness, rumination, and NSSI in adolescents: A moderated mediation model.

INTRODUCTION: Nonsuicidal self-injury (NSSI) is a pervasive public health problem among adolescents. Self-criticism has been identified as an important risk factor for NSSI. Potential mediators of the relationship between self-criticism and NSSI and potential moderators that may exacerbate or buffer this association, however, have seldom been explored. The current study tested the mediating effect of hopelessness and the moderating effect of rumination. METHODS: 915 Chinese participants (405 girls; mean age = 15.85, SD = 1.47) were recruited from junior and senior high schools. They completed questionnaires regarding self-criticism, hopelessness, rumination, and NSSI. RESULTS: Self-criticism was significantly associated with NSSI, and this association was mediated by hopelessness. Rumination strengthened the association between self-criticism and hopelessness, as well as the association between hopelessness and NSSI. CONCLUSIONS: Although this study is a cross-sectional design, these findings can help researchers and practitioners understand the relationship among self-criticism, hopelessness, rumination, and NSSI. Moreover, implications for preventions and interventions of NSSI were discussed.

A longitudinal study testing the role of psychache in the association between emotional abuse and suicidal ideation.

OBJECTIVE: Research suggests that emotional abuse is associated with adolescent suicidal ideation. But how they are related is still unclear. The present study tested the temporal relationship between emotional abuse and suicidal ideation, with psychache as the potential mediator. We also examined the reciprocal relationship between psychache and suicidal ideation. METHOD: A number of 2,259 Chinese high school students (53.8% females, mean age = 15.11, SD = 1.57) in Hong Kong completed questionnaires assessing emotional abuse, psychache, and suicidal ideation three times at 6-month intervals. RESULTS: The results supported the mediating effect of psychache in the path from emotional abuse to suicidal ideation. In addition, psychache and suicidal ideation were related reciprocally over time. CONCLUSION: The findings of this study may help researchers and practitioners understand the pathways by which emotional abuse impacts adolescent suicidal ideation. Implications for preventions and interventions of suicidal ideation were discussed.

Low self-esteem, entrapment, and reason for living: A moderated mediation model of suicidal ideation.

Adolescent suicidal ideation has become a top public health concern. It is thus significant to explore both risk and protective factors of adolescent suicidal ideation. The present study tested a moderated mediation model of suicidal ideation in a sample of Chinese adolescents. Chinese adolescents of 1074 (54.2% females, aged between 11 and 18 years) completed questionnaires assessing self-esteem, entrapment, reason for living, and suicidal ideation. We found that entrapment mediated the association between low self-esteem and suicidal ideation. The association between entrapment and suicidal ideation was moderated by reason for living. Findings of this study may expand our understanding of the development of suicidal ideation, and facilitate future research exploring the interplay of risk and protective factors of suicidality. Clinical implications of these findings were also discussed.

The reciprocal associations between identity disturbance, relationship disturbance, and suicidal ideation among Chinese adolescents: A three-wave cross-lag study.

OBJECTIVE: Adolescence is a developmental period associated with a heightened risk for suicidal ideation. During this phase of life, individuals tend to focus on both intrapersonal self and interpersonal relationships. Thus, it is of much significance to understand the roles of intrapersonal and interpersonal factors in the development of suicidal ideation among adolescents. The present study examined the reciprocal associations between identity disturbance, relationship disturbance, and suicidal ideation by using a three-wave cross-lag model in a sample of adolescents. METHOD: A number of 3,600 Chinese adolescents (56.6% females, mean age = 14.58 years) completed questionnaires assessing the three main study variables as well as depressive symptoms, anxiety, and suicidal attempts three times at 6-month intervals. RESULTS: After controlling for gender, age, depressive symptoms, anxiety, and suicidal attempts, relationship disturbance significantly predicted suicidal ideation over time, and vice versa. Suicidal ideation significantly predicted identity disturbance over time, but not vice versa. We also found the mediating effect of relationship disturbance in the path from identity disturbance to suicidal ideation. CONCLUSION: The results suggested the important role of previous relationship disturbance in predicting later suicidal ideation. Theoretical and clinical implications of these findings were discussed.

The mediating role of coping strategy in the association between family functioning and nonsuicidal self-injury among Taiwanese adolescents.

OBJECTIVE: Nock's (2009) integrated theoretical model suggests that both intrapersonal and interpersonal factors contribute to the development of nonsuicidal self-injury (NSSI). Based on this model, the present study examined the roles of family functioning and coping strategy in predicting NSSI, as well as the mediating effect of coping strategy in the relationship between family functioning and NSSI. Gender differences on the associations of these variables were also examined. METHOD: A sample of 1,989 secondary school students (52.0% females) in Taiwan was assessed by self-report measures of perceived family functioning, coping strategy, and NSSI. RESULTS: Results showed that both family functioning and avoidance/emotion-focused coping strategy predicted NSSI. Additionally, the association between family functioning and NSSI was mediated by avoidance/emotion-focused coping strategy. Gender differences were not found on the associations among these study variables. CONCLUSIONS: These data provided evidences that the Nock's (2009) integrated theoretical model may help to explain how coping strategy mediates the effect of family functioning on NSSI. The implications of the findings for future research and intervention were discussed.

Distress Intolerance Mediates the Relationship between Child Maltreatment and Nonsuicidal Self-Injury among Chinese Adolescents: A Three-Wave Longitudinal Study.

Nonsuicidal self-injury (NSSI) is a serious public health concern among adolescents. Identifying risk factors of NSSI is important to effectively prevent or reduce such behavior. Child maltreatment is one of the most widely recognized risk factors for NSSI. How child maltreatment and NSSI is related, however, is still unclear. The present study tested the temporal relationship between physical and emotional abuse and NSSI, with distress intolerance as the potential mediator. Potential gender differences on these associations were also tested. We assessed all study variables among 2259 Chinese adolescents (53.8% females; Mage = 15.11 years, SD = 1.57) for three times at 6-month intervals. The results showed that distress intolerance only mediated the relationship between emotional abuse and NSSI, but not between physical abuse and NSSI. In addition, this mediation effect of distress intolerance was significant only for females. The findings of this study can help researchers and practitioners understand pathways by which child maltreatment impacts adolescent NSSI. Implications for preventions and interventions of NSSI were discussed.

Brief report: A preliminary comparison of self-compassion between adolescents with nonsuicidal self-injury thoughts and actions.

Despite the public health significance of nonsuicidal self-injury (NSSI) among adolescents, little is known about the possible overlaps or differences between individuals with NSSI thoughts and those with NSSI actions. The present study compared between individuals with different NSSI status on self-compassion. With a sample of 606 Chinese adolescents (38.8% females; Mage = 13.58, SD = 1.04), we investigated differences on the six subscales of the Self-Compassion Scale (i.e., self-kindness/self-judgment, common humanity/isolation, and mindfulness/over-identification) across three groups: NSSI-action group (n = 86), NSSI-thought group (n = 98), and no-NSSI group (n = 422). Results revealed that individuals with NSSI thoughts and NSSI actions shared greater self-judgment, isolation, and over-identification than those without NSSI, but differed from each other on self-kindness and common humanity, with individuals with NSSI thoughts reporting more self-kindness and common humanity than those with NSSI actions. Further empirical investigations into the influence of self-compassion on NSSI will benefit the development of interventions for adolescent NSSI.

MCM2 is involved in subtyping and tamoxifen resistance of ERα-positive breast cancer by acting as the downstream factor of ERα.

Tamoxifen (TAM) resistance is finally developed in over 40% of patients with estrogen receptor α-positive breast cancer (ERα+ -BC), documenting that discovering new molecular subtype is needed to confer perception to the heterogeneity of ERα+ -BC. We obtained representative gene sets subtyping ERα+ -BC using gene set variation analysis (GSVA), non-negative matrix factorization (NMF), and COX regression methods on the basis of METABRIC, TCGA, and GEO databases. Furthermore, the risk score of ERα+ -BC subtyping was established using least absolute shrinkage and selection operator (LASSO) regression on the basis of genes in the representative gene sets, thereby generating the two subtypes of ERα+ -BC. We further found that minichromosome maintenance complex component 2 (MCM2) functioned as the hub gene subtyping ERα+ -BC using GO, KEGG, and MCODE. MCM2 expression was capable for specifically predicting 1-year overall survival (OS) of ERα+ -BC and correlated with T stage, AJCC stage, and tamoxifen (TAM) sensitivity of ERα+ -BC. The downregulation of MCM2 expression inhibited proliferation, migration, and invasion of TAM-resistant cells and promoted G0/G1 arrest. Altogether, tamoxifen resistance entails that MCM2 is a hub gene subtyping ERα+ -BC, providing a novel dimension for discovering a potential target of TAM-resistant BC.

Meta-Analysis of the Effectiveness and Safety of Shugan Jieyu Capsules for the Treatment of Insomnia.

A systematic review and meta-analysis were conducted to evaluate the clinical effectiveness and safety of Shugan Jieyu capsules for treating insomnia by searching seven databases up to February 21, 2022. The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the studies was assessed using the risk of bias assessment tool. This article describes in detail how to retrieve and screen the literature. The detailed steps for conducting the meta-analysis are also included in the protocol. Fourteen studies were found to be eligible, including 1,283 insomnia patients (644 with and 639 without Shugan Jieyu capsules at baseline). The meta-analysis showed a better total clinical effectiveness (odds ratio [OR]: 5.71, 95% confidence interval [CI]: 3.56 to 9.15) and a lower Pittsburgh Sleep Quality Index (PSQI) score (mean difference [MD]: -2.95, 95% CI: -4.97 to -0.93) with combined Shugan Jieyu capsules and Western medicine compared to Western medicine alone. The secondary outcomes showed that the Shugan Jieyu capsule group had significantly reduced adverse reactions and improvements in sleep duration, night awakening, nightmares with excessive dreaming, daytime sleepiness, and low energy. Further multicenter randomized trials must be encouraged to provide more concrete evidence on whether Shugan Jieyu capsules are beneficial in routine clinical practice.

Local ancestry and selection in admixed Sanjiang cattle.

The majority of native cattle are taurine × indicine cattle of diverse phenotypes in the central region of China. Sanjiang cattle, a typical breed in the central region, play a central role in human livelihood and have good adaptability, including resistance to dampness, heat, roughage, and disease, and are thus regarded as an important genetic resource. However, the genetic history of the successful breed remains unknown. Here, we sequenced 10 Sanjiang cattle genomes and compared them to the 70 genomes of 5 representative populations worldwide. We characterized the genomic diversity and breed formation process of Sanjiang cattle and found that Sanjiang cattle have a mixed ancestry of indicine (55.6%) and taurine (33.2%) dating to approximately 30 generations ago, which has shaped the genome of Sanjiang cattle. Through ancestral fragment inference, selective sweep and transcriptomic analysis, we identified several genes linked to lipid metabolism, immune regulation, and stress reactions across the mosaic genome of Sanjiang cattle showing an excess of taurine or indicine ancestry. Taurine ancestry might contribute to meat quality, and indicine ancestry is more conducive to adaptation to hot climate conditions, making Sanjiang cattle a valuable genetic resource for the central region of China. Our results will help us understand the evolutionary history and ancestry components of Sanjiang cattle, which will provide a reference for resource conservation and selective breeding of Chinese native cattle.

Transcription factor AP-2 gamma/Krüppel-like factor 10 axis is involved in miR-3656-related dysfunction of endothelial cells in hypertension.

BACKGROUND: Dysfunction of endothelial cells links to microvascular rarefaction, reflecting the pathogenesis of hypertension. Our previous studies found that miR-3656 reduces nitric oxide generation and von Willebrand factor (vWF) cleavage, thereby retarding blood flow and potentially increasing blood pressure. In this paper, we investigated mechanism of transcription regulation contributing to miR-3656-damaged endothelial cells in hypertension. METHODS: The effects of miR-3656 on function of endothelial cells were analyzed on the basis of proliferation, migration, tube formation, and apoptosis. The mRNA level and protein level of genes were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Dual-luciferase reporter assay was performed to confirm the binding between miR-3656 and 3' untranslated region (UTR) of transcription factor AP-2 gamma ( TFAP2C ). The binding between TFAP2C and the promoter region of Krüppel-like factor 10 ( KLF10 ) was confirmed by chromatin immunoprecipitation-qPCR assay. RESULTS: miR-3656 impaired the cell proliferation, migration, tube formation, and apoptosis of endothelial cells. miR-3656 inhibited the expression of TFAP2C by directly targeting 3'UTR of TFAP2C ; moreover, miR-3656-induced injury of endothelial cells was rescued by TFAP2C overexpression. Furthermore, downregulated TFAP2C decreased KLF10 expression by binding to KLF10 promoter region, and upregulated KLF10 reversed the effects of silencing TFAP2C on endothelial cells. These inhibitory processes led to interference of miR-3656 to KLF10-promoted function of endothelial cells. CONCLUSION: TFAP2C/KLF10 axis is involved in miR-3656-related dysfunction of endothelial cells in hypertension. The 3'UTR of TFAP2C and KLF10 promoter region are the hubs of the TFAP2C/KLF10 axis.

MiR-204-5p-targeted AP1S2 is necessary for papillary thyroid carcinoma.

MiR-204-5p, as a tumour suppressor, has been found in several cancers. However, whether miR-204-5p is involved in papillary thyroid carcinoma (PTC) has not yet been investigated. In this study, we identified miR-204-5p as a down-regulated miRNA in PTC tissues, unveiling that the levels of miR-204-5p in serum of patients with PTC were linked to PTC risk, and that the expression in patients concomitant with both PTC and benign lesions was much lower than that in patients only with PTC. Furthermore, we documented that miR-204-5p inhibited proliferation, migration, invasion, and cell cycle progression and triggered apoptosis of PTC cells via cell biology experiments. Finally, we identified that AP1S2 was a target of miR-204-5p using RNA-seq, iTRAQ, and bioinformatics prediction. Overall, miR-204-5p functions as a suppressor for PTC pathogenesis via the miR-204-5p/AP1S2 axis.

Association between KCNJ11 E23K polymorphism and the risk of type 2 diabetes mellitus: A global meta-analysis.

BACKGROUND: Potassium inwardly rectifying channel, subfamily J member 11(KCNJ11) is considered to be a potential susceptible gene of type 2 diabetes mellitus (T2DM), and the association between KCNJ11 E23K polymorphism and T2DM risk is still controversial worldwide. This meta-analysis was performed to assess the association more accurately between KCNJ11 E23K polymorphism and T2DM risk. METHODS: The up-to-data meta-analysis was conducted based on studies selected from eight databases (PubMed, Web of Science, Medline, Scopus, Embase, CNKI, WanFang, and Vip). Five gene models were included in our study: allele model (K-allele vs. E-allele), heterozygous model (EK vs. EE), homozygous model (KK vs. EE), dominant genetic model (EK + KK vs. EE), and recessive genetic model (EK + EE vs. KK). Association strength was evaluated by odds ratio (OR) and 95% confidence interval (CI), publication bias was evaluated by Begg's funnel plot and Egger's test, sensitivity analysis and trial sequential analysis (TSA) were used to evaluate the stability of the results. RESULTS: According to the inclusion and exclusion criteria, 31 eligible articles were finally selected in our meta-analysis, including 8754 T2DM cases and 7587 controls. We found that allelic model (OR = 1.25, 95%CI: 1.15-1.35, P < 0.01), heterozygous model (OR = 1.31, 95% CI: 1.18-1.44, P < 0.01), homozygous model (OR = 1.48, 95% CI: 1.24-1.76, P < 0.01), and dominant genetic model (OR = 1.35, 95% CI: 1.22-1.50, P < 0.01) were significantly associated with increased risk of T2DM, but recessive genetic model (OR = 0.78, 95% CI: 0.67-0.91, P < 0.01) was considered as a protective factor for T2DM. No significant evidence of publication bias was found. CONCLUSION: Our meta-analysis confirms the association between KCNJ11 E23K polymorphism and the risk of T2DM, highlighting that gene-gene interaction and gene-environment interaction should be investigated in future.

Epidemiological status quo of hypertension in elderly population in Changchun, China: a cross-sectional study.

OBJECTIVES: To investigate the epidemiological status quo of hypertension in elderly population in Changchun, China, and provide a reference for the prevention and control strategies of hypertension of elderly population in this region. DESIGN: A cross-sectional study, as a part of a comprehensive project in Northeast China, was designed to perform in 10 districts in Changchun. PARTICIPANTS AND SETTING: A total of 6846 participants who were ≥60 years old were selected using a random sampling method. MAIN OUTCOME MEASURES: The epidemiological status quo of hypertension. RESULTS: The prevalence of hypertension in Changchun was 52.6%. Among participants with hypertension enrolled in this study, 87.6% of the participants had been diagnosed with hypertension before the study, 69.1% was taking antihypertensive medications and 66.9% had effective blood pressure control. Obesity, widower/widow, history of diseases and family history of hypertension were risk factors of hypertension (all p<0.05). Participants with obesity, a personal history of heart coronary disease, or a family history of hypertension were susceptible to realising risks of hypertension (all p<0.05). However, participants with diabetes, hyperlipidaemia, or a family history of hypertension were difficult to control blood pressure within the normal range (all p<0.05). In addition, 92.6% participants taking antihypertensive medications used a single medication, and calcium channel blockers was the most commonly used antihypertensive medications in monotherapy. CONCLUSION: The rates of awareness, treatment and control of hypertension are greater in Changchun than those in China, indicating that the prevention and control of hypertension in Changchun are effective. However, the prevalence of hypertension in the elderly population in China is lower than that in Changchun, also rendering Changchun a substantial challenge for the supervision of hypertension.

Circulating miR-3656 induces human umbilical vein endothelial cell injury by targeting eNOS and ADAMTS13: a novel biomarker for hypertension.

BACKGROUND: Hypertension, as one of the most common chronic diseases, is a major public health issue. Previous studies have shown that there are miRNAs differentially expressed in hypertensive patients. In addition, hypertension is closely related to endothelial dysfunction, and miRNAs have been identified as important molecular mediators for endothelial function. Therefore, it is necessary to identify specific miRNAs related to hypertension and explore their molecular mechanism in the progression of hypertension. METHODS: We investigated the association of circulating levels of miR-3656 with hypertension. Furthermore, in-vitro studies were performed to investigate its possible mechanisms for hypertension in that the direct target genes of miR-3656 were confirmed using dual-luciferase reporter assay; moreover, the effects of miR-3656 on proliferation, migration, apoptosis, and microvascular rarefaction of HUVECs were investigated using MTS kit, wound-healing assay, FITC Annexin V apoptosis detection kit, and tube formation assay, correspondingly. RESULTS: Circulating miR-3656 was upregulated in patients with hypertension. MiR-3656 suppressed the proliferation, migration, and angiogenesis of HUVECs, but promoted the apoptosis of HUVECs. In addition, eNOS and ADAMTS13 were direct target genes of miR-3656, and overexpression of eNOS and ADAMTS13 abolished the effect of miR-3656 on HUVECs. CONCLUSION: MiR-3656 is a potential biomarker for hypertension. MiR-3656 is involved in endothelial cellular injury implicated in hypertension by targeting eNOS and ADAMTS13.