Hibernation is an adaptive behavior for some small animals to survive cold winter. Hibernating mammals usually down-regulate their body temperature from ~37℃ 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.

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.

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.

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 antiapoptosis 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.

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℃), 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℃). 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.

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 (1^st 75.2%, 2^nd 62.3%, 3^rd 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 1^st 16.5%, 2^nd 23.8%, 3^rd 29.6%, P = 0.016; bronchopulmonary dysplasia BPD 1^st 15.5%, 2^nd 26.7%, 3^rd 33.8%, P < 0.0001; intraventricular hemorrhage IVH 1^st 20.4%, 2^nd 32.4%, 3^rd 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.