Ibuprofen treatment for patent ductus arteriosus in preterm infants: a retrospective cohort study in a leading Chinese center

Objective There is a dilemma of ibuprofen treatment with patent ductus arteriosus (PDA) as to how and when to treat. We aimed to clarify this issue in very preterm infants (VPIs; < 32 weeks). Methods This retrospective study included 1 659 VPIs who were diagnosed with PDA according to echocardiographic examinations and cardiovascular dysfunction scoring system (the CVD scoring). The VPIs were classified into six groups (A1, A2, A3, B1, B2, and B3) based on CVD scores (A, < 3, and B, ≥ 3), and treatment with ibuprofen for PDA (1, conservational management; 2, early ibuprofen treatment; and 3, late ibuprofen treatment). Treatment was stopped when PDA was closed, CVD score was zero or PDA needed ligation. Results VPIs with CVD scores < 3 had most PDA closure without surgery, and early ibuprofen treatment did not significantly affect PDA closure. VPIs with CVD scores ≥ 3 had some PDA closure after 2 courses of treatment, but closure rates decreased linearly with ibuprofen course (1st 75.2%, 2nd 62.3%, 3rd 50.0%, P < 0.0001), and early ibuprofen treatment (group B2) did not increase PDA closure compared to late ibuprofen treatment (group B3). In these same infants, the longer they were in CVD scores ≥ 3, the more the complications of preterm were increased (retinopathy of prematurity ROP 1st 16.5%, 2nd 23.8%, 3rd 29.6%, P = 0.016; bronchopulmonary dysplasia BPD 1st 15.5%, 2nd 26.7%, 3rd 33.8%, P < 0.0001; intraventricular hemorrhage IVH 1st 20.4%, 2nd 32.4%, 3rd 23.8%, P = 0.015). Conclusion Ibuprofen is suggested for PDA closure when the PDA reopens or has developed into the stage when the CVD score ≥ 3.

Chinese herbal medicines with beneficial effects

Among the vast resources of traditional Chinese medicine (TCM) herbal species, only a handful of Chinese herbs are growing in frigid regions or extreme environment but they have a unique property. The most recognizable TCM herb falling in this category is Panax ginseng, which is widely considered the representative tonic herb with oceans of beneficial effects on human health. In this article, we will introduce several typical Chinese herbal medicines with beneficial effects aiming to arouse broader attention from the scientific community to expand the exploration and exploitation on this for their potential applications to meet the increasingly demanding medical needs.

Direct evidence of VEGF-mediated neuroregulation and afferent explanation of blood pressure dysregulation during angiogenic therapy

Objective Oncocardiology is increasingly hot research field/topic in the clinical management of cancer with anti-angiogenic therapy of vascular endothelial growth factor (VEGF) that may cause cardiovascular toxicity, such as hypertension via vascular dysfunction and attenuation of eNOS/NO signaling in the baroreflex afferent pathway. The aim of the current study was to evaluate the potential roles of VEGF/VEGF receptors (VEGFRs) expressed in the baroreflex afferent pathway in autonomic control of blood pressure (BP) regulation. Methods The distribution and expression of VEGF/VEGFRs were detected in the nodose ganglia (NG) and nucleus of tractus solitary (NTS) using immunostaining and molecular approaches. The direct role of VEGF was tested by NG microinjection under physiological and hypertensive conditions. Results Immunostaining data showed that either VEGF or VEGFR2/VEGFR3 was clearly detected in the NG and NTS of adult male rats. Microinjection of VEGF directly into the NG reduced the mean blood pressure (MBP) dose-dependently, which was less dramatic in renovascular hypertension (RVH) rats, suggesting the VEGF-mediated depressor response by direct activation of the 1st-order baroreceptor neurons in the NG under both normal and disease conditions. Notably, this reduced depressor response in RVH rats was directly caused by the downregulation of VEGFR2, which compensated the up regulation of VEGF/VEGFR3 in the NG during the development of hypertension. Conclusion It demonstrated for the first time that the BP-lowering property of VEGF/VEGFRs signaling via the activation of baroreflex afferent function may be a common target/pathway leading to BP dysregulation in anti-angiogenic therapy.

Tranilast treats cold-related hypertension by reducing the expression of NLRP3 inflammasome

Objective Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events. Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the development of hypertension. Tranilast (TR), an inhibitor of NLRP3, provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent. This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions. Methods and results Sprague Dawley (SD) rats were exposed to moderate cold temperature (4±1°C), and then were randomized to receive TR or vehicle for 3 weeks, while the control group was raised under rat room temperature (RT, 23±1°C). We found that cold exposure substantially increased blood pressure, NLRP3 inflammasome level, and fibrosis in aorta, which were reversed by TR. Conclusion TR has an anti-hypertensive property in cold environment, and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis. These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.

Overexpression of microRNA-135b-5p attenuates acute myocardial infarction injury through its anti-oxidant and anti-apptotic properties

Objective Myocardial infarction (MI) remains the leading cause of morbidity and mortality due partly to the limited regenerative capacity of cardiomyocytes to replace cardiomyocyte lost due to apoptosis. Inhibiting cardiomyocyte apoptosis is recognized as an effective therapeutic approach for MI. MicroRNAs (miRNAs, miRs), which regulate target genes at the post-transcriptional level, play a significant role in the regulation of cardiovascular diseases such as MI. MicroRNA-135b (miR-135b) has a protective effect on cardiomyocytes. However, the role of miR-135b in cardiomyocyte apoptosis in infarct myocardium needs further clarification. Methods We generated α-MHC-miR-135b transgenic mice to investigate the role of miR-135b in myocardial injury after MI. MiR-135b mimic and negative control (NC) were transfected into H2O2-induced cardiomyocytes to evaluate the effect of overexpression of miR-135b on the levels of reactive oxygen species (ROS) and apoptosis. Results Our results showed that overexpression of miR-135b had protective effect on cardiomyocyte injury both in vivo and in vitro. MiR-135b inhibited cardiomyocyte apoptosis and ROS generation, downregulated proapoptosis proteins (cleaved-caspase-3 and Bax), and increased anti-apoptosis protein (Bcl-2). Moreover, miR-135b showed an inhibitory effect on apoptosis-related protein target transient receptor potential vanilloid-type 4 (TRPV4) cation channel. Conclusion MiR-135b might be considered a new molecular target for potential replacement therapy as antiapoptotic cardioprotection in the setting of MI.

Changes of calcitonin gene-related peptide and other serological indicators in vestibular migraine patients

Objective It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine (VM) patients, and to explain the potential pathological effects of these biomarkers. The hypothesis of VM being a variant of migraine was examined. Methods A total of 32 VM patients, 35 migraine patients, and 30 healthy control subjects (HC) were selected for this cross-sectional study. Detailed statistics on demographic data, clinical manifestations, calcitonin gene-related peptide (CGRP) and common clinical laboratory indicators were measured within 24 hours from the onset of the conditions. Receptor operating characteristic (ROC) curve and area under the curve (AUC) were analyzed for biomarkers. The risk factors of VM and migraine were determined through univariate and multivariate analyses. Results Compared with HC, serum CGRP levels (p (VM) = 0.012, p (Migraine) = 0.028) increased and Mg2+ levels (p (VM) < 0.001, p (Migraine) < 0.001) deceased in VM patients and migraine patients. In multiple logistic regression, VM was correlated with CGRP [odds ratio (OR) = 1.07; 95% confidence interval (CI), 1.02–1.12; P = 0.01] and Mg2+ [odds ratio (OR) = 0.03; 95% CI, 0.07–0.15; P < 0.001)]. Migraine was correlated with CGRP [odds ratio (OR) = 1.07; 95% CI, 1.02–1.12; P = 0.01] and Mg2+ [odd ratio (OR = 0.01; 95% CI, 0–0.02; P <0.001)]. Mg2+ discriminated good differentiation between VM and migraine groups, with AUC of 0.649 (95% CI, 0.518 to 0.780). The optimal threshold for Mg2+ to diagnose VM was 0.805. Conclusions This study demonstrated that CGRP and Mg2+ may be promising laboratory indicators to discriminate HC from VM/migraine, while Mg2+ may be uded as a discriminator between VM and migraine.

Role of microRNAs in the process of metformin treating multiple diseases

Metformin as the first-line treatment for type 2 diabetes mellitus has been discovered to exert beneficial effects on many diseases for nearly ten years, but its specific mechanism is still unclear. As a new class of gene expression regulators with pleiotropic properties, microRNAs (miRNAs) participate in multiple physiological processes such as cell differentiation, proliferation, survival, and metabolism, which drive them to play a regulatory role in the occurrence, development and even treatment of various diseases. A substantial body of research has found the relationship between metformin and miRNAs, in which metformin can alter the expression profiles of miRNAs in multiple disease states and on the other hand the signal pathways involving miRNAs may contribute to the pharmacological actions of metformin. This review summarizes the effects of metformin on miRNAs and their relationship in different diseases (like tumor, metabolic diseases, etc.), which should be of a great help for our better understanding of the mechanism of metformin for treating multiple diseases.

Mammalian hibernation: a unique model for medical research

Hibernation is an adaptive behavior for some small animals to survive cold winter. Hibernating mammals usually down-regulate their body temperature from ~37°C to only a few degrees. During the evolution, mammalian hibernators have inherited unique strategies to survive extreme conditions that may lead to disease or death in humans and other non-hibernators. Hibernating mammals can not only tolerant deep hypothermia, hypoxia and anoxia, but also protect them against osteoporosis, muscle atrophy, heart arrhythmia and ischemia-reperfusion injury. Finding the molecular and regulatory mechanisms underlying these adaptations will provide novel ideas for treating related human diseases.