Apoptosis is an important mechanism for the development of heart failure. Mitochondria are central to the execution of apoptosis in the intrinsic pathway. The main regulator of mitochondrial pathway of apoptosis is Bcl-2 family which includes pro- and anti-apoptotic proteins. MicroRNAs are small noncoding RNA molecules that regulate gene expression by inhibiting mRNA translation and/or inducing mRNA degradation. It has been proposed that microRNAs play critical roles in the cardiovascular physiology and pathogenesis of cardiovascular diseases. Our previous study has found that microRNA-181c, a miRNA expressed in the myocardial cells, plays an important role in the development of heart failure. With bioinformatics analysis, we predicted that miR-181c could target the 3' untranslated region of Bcl-2, one of the anti-apoptotic members of the Bcl-2 family. Thus, we have suggested that miR-181c was involved in regulation of Bcl-2. In this study, we investigated this hypothesis using the Dual-Luciferase Reporter Assay System. Cultured myocardial cells were transfected with the mimic or inhibitor of miR-181c. We found that the level of miR-181c was inversely correlated with the Bcl-2 protein level and that transfection of myocardial cells with the mimic or inhibitor of miR-181c resulted in significant changes in the levels of caspases, Bcl-2 and cytochrome C in these cells. The increased level of Bcl-2 caused by the decrease in miR-181c protected mitochondrial morphology from the tumour necrosis factor alpha-induced apoptosis.

Mutations in the transcription factor TBX20 (T-box 20) are associated with congenital heart disease. Germline ablation of Tbx20 results in abnormal heart development and embryonic lethality by embryonic day 9.5. Because Tbx20 is expressed in multiple cell lineages required for myocardial development, including pharyngeal endoderm, cardiogenic mesoderm, endocardium, and myocardium, the cell type-specific requirement for TBX20 in early myocardial development remains to be explored.

Obesity has become the most common metabolic disorder worldwide. Promoting brown adipose tissue (BAT) and beige adipose tissue formation, and therefore, a functional increase in energy expenditure, may counteract obesity. Mice lacking type IIβ regulatory subunit of adenosine 3',5' cyclic monophosphate (cAMP)-dependent protein kinase A (PKA-RIIB) display reduced adiposity and resistance to diet-induced obesity. PKA-RIIB, encoded by the Prkar2b gene, is most abundant in BAT and white adipose tissue (WAT) and in the brain. In this study, we show that mice lacking PKA-RIIB have increased energy expenditure, limited weight gain, and improved glucose metabolism. PKA-RIIB deficiency induces brownlike adipocyte in inguinal WAT (iWAT). PKA-RIIB deficiency also increases the expression of uncoupling protein 1 and other thermogenic genes in iWAT and primary preadipocytes from iWAT through a mechanism involving increased PKA activity, which is represented by increased phosphorylation of PKA substrate, cAMP response element binding protein, and P38 mitogen-activated protein kinase. Our study provides evidence for the role of PKA-RIIB deficiency in regulating thermogenesis in WAT, which may potentially have therapeutic implications for the treatment of obesity and related metabolic disorders.

Human heart failure is a complex syndrome and a primary cause of morbidity and mortality in the world. However, the molecular pathways involved in the remodelling process are poorly understood. In this study, we performed exhaustive global proteomic surveys of cardiac ventricle isolated from failing and non-failing human hearts, and determined the regulatory pathway to uncover the mechanism underlying heart failure. Two-dimensional gel electrophoresis (2-DE) coupled with tandem mass spectrometry was used to identify differentially expressed proteins in specimens from failing (n = 9) and non-failing (n = 6) human hearts. A total of 25 proteins with at least 1.5-fold change in the failing heart were identified; 15 proteins were up-regulated and 10 proteins were down-regulated. The altered proteins belong to three broad functional categories: (i) metabolic [e.g. NADH dehydrogenase (ubiquinone), dihydrolipoamide dehydrogenase, and the cytochrome c oxidase subunit]; (ii) cytoskeletal (e.g. myosin light chain proteins, troponin I type 3 and transthyretin) and (iii) stress response (e.g. αB-crystallin, HSP27 and HSP20). The marked differences in the expression of selected proteins, including HSP27 and HSP20, were further confirmed by Western blot. Thus, we carried out full-scale screening of the protein changes in human heart failure and profiled proteins that may be critical in cardiac dysfunction for future mapping.

Micro-RNAs regulate gene expression by directly binding to the target mRNAs. The goal of the study was to examine the expression profiling of miRNAs in human failing hearts and identify the key miRNAs that regulate molecular signalling networks and thus contribute to this pathological process. The levels of miRNAs and expressed genes were analysed in myocardial biopsy samples from patients with end-stage heart failure (n = 14) and those from normal heart samples (n = 8). Four networks were built including the Gene regulatory network, Signal-Network, miRNA-GO-Network and miRNA-Gene-Network. According to the fold change in the network and probability values in the microarray cohort, RT-PCR was performed to measure the expression of five of the 72 differentially regulated miRNAs. miR-340 achieved statistically significant. miR-340 was identified for the first time in cardiac pathophysiological condition. We overexpressed miR-340 in cultured neonatal rat cardiomyocytes to identify whether miR-340 plays a determining role in the progression of heart failure. ANP, BNP and caspase-3 were significantly elevated in the miR-340 transfected cells compared with controls (P < 0.05). The cross-sectional area of overexpressing miR-340 cardiomyocytes (1952.22 ± 106.59) was greater (P < 0.0001) than controls (1059.99 ± 45.59) documented by Laser Confocal Microscopy. The changes of cellular structure and the volume were statistical significance. Our study provided a comprehensive miRNA expression profiling in the end-stage heart failure and identified miR-340 as a key miRNA contributing to the occurrence and progression of heart failure. Our discoveries provide novel therapeutic targets for patients with heart failure.

Circulating tumor DNA (ctDNA) served as a noninvasive method with less side effects using peripheral blood. Given the studies on concordance rate between liquid and solid biopsies in Chinese breast cancer (BC) patients were limited, we sought to examine the concordance rate of different kinds of genomic alterations between paired tissue biopsies and ctDNA samples in Chinese BC cohorts.

Gestational trophoblastic diseases (GTDs) are characterized by vascular abnormalities of the trophoblast, but their pathogenesis is unknown. Angiogenin (ANG) and matrix metalloproteinase (MMP)-2, which are molecules implicated in the angiogenic process, may play some role in this process.

Normally, fish will decrease food intake or even stop feeding during the winter. In previous studies, two widely cultured gibel carp strains (strain A and strain F) showed differences in lipid and glucose metabolism. Therefore, we hypothesized that the physiological changes during the overwintering period would be different between the two strains. Thus, the two strains were starved for 77 days, after which the levels of glucose and lipid metabolism, ER stress, autophagy, and apoptosis were determined. The starvation increased hepatic glycogenolysis and fatty acid β-oxidation but suppressed lipogenesis in both strains overwintering. Considering the effects of genotype, strain F had higher levels of ER stress and autophagy but lower levels of apoptosis than strain A, suggesting that strain F might be more resistant to overwintering starvation. The interactions between strains and starvation periods were observed in plasma triglyceride contents and the mRNA levels of pyruvate kinase (pk), sterol regulatory element binding protein 1 (srebp1), activating transcription factor 4 (atf4), and autophagy protein 12 (atg12). In conclusion, long-term starvation during winter could induce hepatic glycogenolysis and fatty acid β-oxidation but suppress lipogenesis, ER stress, autophagy, and apoptosis in gibel carp, and strain F may be more resistant to starvation during winter. Taken together, these results discovered the responses to prolonged starvation stress during winter in two strains of gibel carp and could provide information for genotype selection, especially for selecting strains better adapted to winter.

The activation of brown adipose tissue (BAT) is considered as a promising therapeutic target for obesity. APPL1 (Adaptor protein containing the Pleckstrin homology domain, Phosphotyrosine binding domain and Leucine zipper motif) is an intracellular adaptor protein and its genetic variation is correlated with BMI and body fat distribution in diabetic patients. However, little is known about the roles of APPL1 in BAT thermogenesis.

To explore the mechanism of levonorgestrel (LNG)-ameliorating adenomyosis through long non-coding RNA H19 (lncRNA H19)/miR-17/Toll-like receptor 4 (TLR4) pathway.

Neoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little possibility for organ preservation. Immunotherapy has been shown to have significant survival benefits in microsatellite instability-high patients but poor response in microsatellite stable (MSS) patients. Studies have demonstrated that radiotherapy and immunotherapy have synergistic effects in cancer treatment. There is no existing evidence about the clinical efficacy of immunotherapy combined with nCRT for patients with MSS ultra-low rectal cancer.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary.

Exposure to airborne particulate matter with an aerodynamic diameter less than or equivalent to 2.5 microns (PM2.5) easily induces acute myocardial infarction in populations with high-risk cardiovascular diseases such as hyperlipidemia, but its mechanism remains unclear. In this study, hyperlipidemic rats were used to examine the effects of PM2.5 exposure on the cardiovascular system and the mechanism for its induction of cardiovascular events. We found that PM2.5 exposure resulted in bigger changes in the myocardial enzyme profile (cTnI, LDH, CK, CK-MB) in hyperlipidemic rats than that of control rats, as well as a significant increase in the C-reactive protein (CRP) level and a decrease in the superoxide dismutase (SOD) activity. It promoted a hypercoagulable state, significantly increased blood pressure and heart rate, while decreased the variability of heart rate in hyperlipidemic rats. In addition, pathological test showed that PM2.5 exposure more easily deteriorated myocardial injury in hyperlipidemic rats. It upregulated the phosphorylation levels of myocardial c-Jun NH2-terminal kinase (JNK) and P53, resulting in the elevated expression of downstream effector protein Bax and the decreased expression of Bcl-2, and then increased caspase3 level leading to cardiomyocyte apoptosis, while little change of caspase2 was observed. Taken together, PM2.5 exposure induced more serious inflammation and oxidative stress in the circulation system of hyperlipidemic rats, promoted a hypercoagulable state and triggered cardiomyocyte apoptosis, in which JNK/P53 pathway played a key role.

To test the hypothesis that effects of dietary carbohydrate and lipid concentrations on growth performance, feeding utilization, glucose and lipid metabolism in gibel carp A strain may be differ from F strain, these two strain of gibel carp were fed with one of three different isonitrogenous diets: HCLL (45% carbohydrate, 2% lipid), MCML (30% carbohydrate, 8% lipid), or LCHL (15% carbohydrate, 14% lipid). After 8 weeks, the HCLL-fed fish had the highest hepatosomatic index, hepatic crude lipid levels, and triglyceride levels and lipid retention efficiency. Enhanced lipogenesis and lipid uptake potential were observed in fish fed HCLL and MCML diets. Moreover, increases in glucose transport (glut2, P = 0.003) and glycolysis (gk, P = 0.012; 6pfk, P = 0.005) in livers of both strains were induced by the high-carbohydrate diet. Genotype-specific effect was identified on plasma lipid content. Plasma triglyceride levels were also greater in the F strain than in the A strain. Furthermore, the F strain had higher levels of fatty acid β-oxidation and glycolysis compared with the A strain. Nutrient retention was affected (P < 0.05) by the interaction between genotype and diet, implied dietary carbohydrate played a vital role in lipid accumulation in gibel carp. As dietary lipids increased, the F strain exhibited better feed utilization and a higher PRE than the A strain. However, the A strain had better growth performance. Overall, the F strain had better glucose uptake, glycolysis potential, and lipid utilization ability than the A strain.

With the establishment of the heart-gut axis concept, accumulating studies suggest that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Yet, little evidence has been reported in characterizing the gut microbiota shift in atrial fibrillation.

Intracavernous injection (ICI) of adipose-derived stem cells (ADSCs) has been demonstrated promising for neurogenic erectile dysfunction (ED). However, due to the sponge-like structure of corpus cavernosum (CC) with abundant vessels, ICI was indeed like intravenous injection. Thus, the cell escaping may be a concern of safety and limited therapy, but the issue has not been clearly demonstrated yet.

Hearts often undergo abnormal remodelling and hypertrophic growth in response to pathological stress. Long non-coding RNAs (LncRNAs) can change cardiac function and participate in regulation of cardiac hypertrophy. The present study aims to identify the role of AK045171 in cardiac hypertrophy and the underlying mechanism in hypertrophic cascades. Mice with cardiac hypertrophy were established through transverse aortic constriction (TAC). Cardiac hypertrophy in cardiomyocytes was induced by angiotensin II (angII). The expression of AK045171 and its target gene SP1 was examined in cardiomyocytes transfected with miRNA. The AK045171 expression level was downregulated in mice after TAC surgery. Overexpression of AK045171 attenuated cardiac hypertrophy both in vitro and in vivo. The mechanism study indicated that AK045171 binds with SP1, which promotes transcription activation of MEG3. It is suggested that overexpression of AK045171 might have clinical potential to suppress cardiac hypertrophy and heart failure.

Hypothalamic obesity (HO) is a severe complication following craniopharyngioma, but studies regarding the sequelae in adult-onset patients with craniopharyngioma are sparse.

Breast cancer (BC), which is the most common malignant tumor in females, is associated with increasing morbidity and mortality. Effective treatments include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular-targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, an increasing amount of evidence has shown that the infiltration of immune cells into the tumor microenvironment, coupled with the immune phenotype of tumor cells, will significantly affect tumor development and malignancy. Consequently, immunotherapy has become a promising treatment for BC prevention and as a modality that can influence patient prognosis.

Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whether p38/JNK contributed directly to L3MBTL4-induced vascular remodeling and exploring the potential mechanism of L3MBTL4 in vascular smooth muscle cells (VSMCs).