A novel missense mutation Smad4 V354L enhances the efficacy of docetaxel in non-small cell lung cancer.

NSCLC is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients. The different mutations in tumor oncogene and suppressors might be associated with the response to therapy. However, little is known about how Smad4 genomic alterations cause the therapeutic effect of docetaxel.

MSC-derived exosomes attenuates pulmonary hypertension via inhibiting pulmonary vascular remodeling.

Pulmonary hypertension (PH) is a serious cardiopulmonary disease with significant morbidity and mortality. Vascular obstruction leads to a continuous increase in pulmonary vascular resistance, vascular remodeling, and right ventricular hypertrophy and failure, which are the main pathological features of PH. Currently, the treatments for PH are very limited, so new methods are urgently needed.

Effect of Oridonin on Experimental Animal Model of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious disease that occurs in premature and low-birth-weight infants. In recent years, the incidence of BPD has not decreased, and there is no effective treatment for it. Oridonin (Ori) is a traditional Chinese medicine with a wide range of biological activities, especially pharmacological and anti-inflammatory.

Effective therapy of advanced breast cancer through synergistic anticancer by paclitaxel and P-glycoprotein inhibitor.

Multi-drug resistance (MDR) in advanced breast cancer (ABC) is triggered by the high expression of P-glycoprotein (P-gp), which reduces intracellular concentration of anti-tumor drugs, in turn preventing oxidative stress damage to cytoplasmic and mitochondrial membranes. It is therefore of clinical relevance to develop P-gp-specific targeted nanocarriers for the treatment of drug resistant ABC. Herein, a drug carrier targeting CD44 and mitochondria was synthesised for the delivery of encequidar (ER, P-gp inhibitor) and paclitaxel (PTX).

Quantifying carotid stiffness in chronic kidney disease using ultrafast ultrasound imaging.

Background: The mortality and disability of chronic kidney disease (CKD) are highly linked to the incidence of atherosclerotic cardiovascular events. Numerous clinical biochemical indicators of renal function often only increase in advanced stages of CKD, driving an urgent need for reliable indicators of atherosclerosis in early CKD. Ultrafast pulse wave velocity (ufPWV) can evaluate the stiffness of the straight carotid and quantitatively reflect the degree of early atherosclerosis.

Serum protein profile analysis via label-free quantitation proteomics in patients with early-onset preeclampsia.

Background: Preeclampsia (PE) is a serious pregnancy complication, resulting in potentially life-threatening conditions for both mother and foetus. It is worth noting that early-onset PE has become a great challenge for clinicians due to its complex manifestation, rapid progression and serious complications. This study aims to investigate differential serum proteome profiles in patients with early-onset PE.

Development of novel palbociclib-based CDK4/6 inhibitors exploring the back pocket behind the gatekeeper.

CDK4/6 inhibitors plus endocrine therapy is a standard therapy for HR+/HER2- breast cancer. Herein, using structure-based drug design strategy, a novel series of palbociclib derivatives were designed and synthesized as CDK4/6 inhibitors, among which compound 17m exhibited more potent CDK4/6 inhibitory activity and in vitro antiproliferative activity against the phosphorylated Rb-positive cell line MDA-MB-453 than the approved drug palbociclib. Moreover, compound 17m possessed remarkable CDK4/6 selectivity over other CDK family members including CDK1, CDK2, CDK3, CDK5, CDK7 and CDK9.

AhR agonist tapinarof ameliorates lupus autoimmunity by suppressing Tfh cell differentiation via regulation of the JAK2-STAT3 signaling pathway.

Background: The aryl hydrocarbon receptor (AhR) is a critical regulator of the pathogenesis of autoimmune disorders. We aimed to investigate the therapeutic effect of the AhR agonist tapinarof during the development of systemic lupus erythematosus (SLE).

Methods: MRL/lpr mice were intraperitoneally injected with 1 or 5 mg/kg tapinarof for 6 weeks.

Ligustrazine Inhibits the Migration and Invasion of Renal Cell Carcinoma.

Ligustrazine is a Chinese herb ( approved for use as a medical drug in China. Recent evidence suggests that ligustrazine has promising antitumor properties. Our preliminary results showed that ligustrazine could inhibit the growth of human renal cell carcinoma (RCC) cell lines.

Quantifying carotid stiffness in a pre-hypertensive population with ultrafast ultrasound imaging.

Purpose: The aim of this study was to assess carotid stiffening in a pre-hypertensive (PHT) population using ultrafast pulse wave velocity (ufPWV).

Methods: This study retrospectively enrolled 626 individuals who underwent clinical interviews, serum tests, and assessments of the systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS), and pulse wave velocity-end of systole (PWV-ES) between January 2017 and December 2021. The patients were divided into three groups according to their blood pressure (BP)-normal BP (NBP): SBP <130 mmHg and DBP <80 mmHg (n=215); PHT: 130 mmHg≤SBP<140 mmHg and/or 80 mmHg≤DBP<90 mmHg (n=119); hypertensive (HT): SBP ≥140 mmHg and/or DBP ≥90 mmHg (n=292).

Individualized References of Carotid Stiffening Quantified With Ultrafast Ultrasound Imaging: Model Construction and Preliminary Validation.

To establish and preliminarily validate an individualized reference of carotid stiffness quantified by ultrafast pulse wave velocity (ufPWV), our study included 225 healthy individuals in the modeling cohort and 628 individuals in the validation cohort. All participants underwent assessment of carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole and pulse wave velocity-end of systole (PWV-ES). A threshold equation of estimated PWV-ES was obtained by multiple linear regression analysis in the modeling cohort as follows: estimated PWV-ES (m/s) = 0.

Carotid stiffening predicts cardiovascular risk stratification in mid-life: non-invasive quantification with ultrafast ultrasound imaging.

Purpose: The present study investigated the association between Systematic COronary Risk Evaluation (SCORE)-estimated cardiovascular risk and carotid stiffening in a middle-aged population using ultrafast pulse wave velocity (ufPWV).

Methods: This study enrolled 683 participants without known cardiovascular disease or diabetes mellitus who underwent ufPWV measurements. Clinical interviews, physical examinations, laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity (PWV) at the beginning of systole (PWV-BS), and PWV at the end of systole (PWV-ES) were assessed.

Genetic susceptibility analysis of FGF5 polymorphism to preeclampsia in Chinese Han population.

Fibroblast growth factor 5 (FGF5), which is a well-established causative factor for blood pressure, has been identified as a susceptibility gene for preeclampsia (PE) in European and Central Asian women. Here, we examined whether polymorphism rs16998073 in FGF5 confer a significant risk to PE in Chinese Han population by case-control association analysis. FGF5 rs16998073 was genotyped by Sanger sequencing in women with preeclampsia (n = 187) and healthy controls (n = 229) of Han Chinese.

A review of BMP and Wnt signaling pathway in the pathogenesis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells.

Design, synthesis and biological evaluation of dual HDAC and VEGFR inhibitors as multitargeted anticancer agents.

Herein, a novel series of dual histone deacetylase (HDAC) and vascular endothelial growth factor receptor (VEGFR) inhibitors were designed, synthesized and biologically evaluated based on previously reported pazopanib-based HDAC and VEGFR dual inhibitors. Most target compounds showed significant HDAC1, HDAC6 and VEGFR2 inhibition, which contributed to their potent antiproliferative activities against multiple cancer cell lines and significant antiangiogenic potencies in both human umbilical vein endothelial cell (HUVEC) tube formation assays and rat thoracic aorta ring assays. Further HDAC selectivity evaluations indicated that hydroxamic acids 5 and 9e possessed HDAC isoform selectivity profiles similar to that of the approved HDAC inhibitor suberoylanilide hydroxamic acid(SAHA), while hydrazide12 presented an HDAC isoform selectivity profilesimilar to that of the clinical HDAC inhibitor MS-275.

Association study of hypertension susceptibility genes , and with preeclampsia in Chinese Han population.

Objective: Preeclampsia (PE) is a disorder that occurs during the pregnancy and could affect the maternal and perinatal mortality as well as morbidity. The aim of our study is to investigate the associations between the hypertension susceptibility genes , and with PE in Chinese Han population.

Methods: A case-control study including 178 PE patients and 202 healthy controls was conducted to assess the associations between three loci ( rs155524, rs2932538 and rs4373814) and PE.

Protective effect of baicalin against pulmonary arterial hypertension vascular remodeling through regulation of TNF-α signaling pathway.

Pulmonary arterial hypertension (PAH) is a progressive cardiovascular disease with high mortality. However, there were no efficient medical drugs for PAH to enormously improve the survival and quality of life measures. The present study aimed to explore the protective effect of baicalin against experimental PAH in vivo and vitro.

Mesenchymal Stromal Cell-derived Exosomes Attenuate Experimental Pulmonary Arterial Hypertension.

Background: Pulmonary arterial Hypertension (PH) is a chronic disease that ultimately progresses to right ventricular failure and death. Until now, there is still a lack of effective treatment applied. The purpose of the present study was to observe the protective effect of Mesenchymal Stromal Cell-Derived Exosomes (MSC-EXO) against experimental Pulmonary arterial Hypertension (PH) and right ventricular failure.

The protective effects of MSC-EXO against pulmonary hypertension through regulating Wnt5a/BMP signalling pathway.

The aim of the study was to explore the mechanism of mesenchymal stem cell-derived exosomes (MSC-EXO) to protect against experimentally induced pulmonary hypertension (PH). Monocrotaline (MCT)-induced rat model of PH was successfully established by a single intraperitoneal injection of 50 mg/kg MCT, 3 weeks later the animals were treated with MSC-EXO via tail vein injection. Post-operation, our results showed that MSC-EXO could significantly reduce right ventricular systolic pressure (RVSP) and the right ventricular hypertrophy index, attenuate pulmonary vascular remodelling and lung fibrosis in vivo.

Absent atherosclerotic risk factors are associated with carotid stiffening quantified with ultrafast ultrasound imaging.

Objectives: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV).

Methods: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.

The Protective of Baicalin on Myocardial Ischemia-Reperfusion Injury.

Background: The aim of this study was to explore the inhibitory effect of baicalin on myocardial apoptosis induced by Ischemia-Reperfusion (I/R).

Methods: Sprague Dawley rats' heart and myocardial cells I/R model were established in vivo and vitro, then 100 mg/kg and 10 μmol/l baicalin were administrated, respectively. The experiment was randomly divided into 4 groups (n=10): Control; I/R; IR+DMEM; and I/R+baicalin groups.

Mesenchymal stromal cell-derived exosomes improve pulmonary hypertension through inhibition of pulmonary vascular remodeling.

Background: Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, right ventricular hypertrophy and failure. So far no effective treatment exists for this disease; hence, novel approaches are urgently needed. The aim of the present research was to observe the treatment effect of mesenchymal stromal cell derived exosomes and reveal the mechanism.

STAT1 transcriptionally regulates the expression of S1PR1 by binding its promoter region.

Sphingosine 1-phosphate receptor 1 (S1PR1) plays a pivotal role in mediating trafficking and migration of immune cells. Previous reports also identify S1PR1 as an important susceptibility gene of asthma and other autoimmune disorders. However, little has been known about the regulatory mechanism of S1PR1 expression.

EPO enhances the protective effects of MSCs in experimental hyperoxia-induced neonatal mice by promoting angiogenesis.

Bronchopulmonary dysplasia (BPD) is the most common type of chronic lung disease in infancy; however, there is no effective treatment for it. In the present study, a neonatal mouse BPD model was established by continuous exposure to high oxygen (HO) levels. Mice were divided randomly into 5 groups: control, BPD, EPO, MSCs, and MSCs+EPO.