LncRNA SNHG12 suppresses adipocyte inflammation and insulin resistance by regulating the HDAC9/Nrf2 axis.

Obesity is often associated with low-grade inflammation. The incidence of obesity has increased annually worldwide, which seriously affects human health. A previous study indicated that long noncoding RNA SNHG12 was downregulated in obesity. Nevertheless, the role of SNHG12 in obesity remains to be elucidated. In this study, qRT-PCR, western blot, and ELISA were utilized to examine the gene and protein expression. Flow cytometry was employed to investigate the M2 macrophage markers. RNA pull-down assay and RIP were utilized to confirm the interactions of SNHG12, hnRNPA1, and HDAC9. Eventually, a high-fat diet-fed mouse model was established for in vivo studies. SNHG12 overexpression suppressed adipocyte inflammation and insulin resistance and promoted M2 polarization of macrophages that was caused by TNF-α treatment. SNHG12 interacted with hnRNPA1 to downregulate HDAC9 expression, which activated the Nrf2 signaling pathway. HDAC9 overexpression reversed the effect of SNHG12 overexpression on inflammatory response, insulin resistance, and M2 phenotype polarization. Overexpression of SNHG12 improved high-fat diet-fed mouse tissue inflammation. This study revealed the protective effect of SNHG12 against adipocyte inflammation and insulin resistance. This result further provides a new therapeutic target for preventing inflammation and insulin resistance in obesity.

Gut microbiome combined with metabolomics reveals biomarkers and pathways in central precocious puberty.

BACKGROUND: Central precocious puberty (CPP) is a common disease in prepubertal children and results mainly from disorders in the endocrine system. Emerging evidence has highlighted the involvement of gut microbes in hormone secretion, but their roles and downstream metabolic pathways in CPP remain unknown. METHODS: To explore the gut microbes and metabolism alterations in CPP, we performed the 16S rRNA sequencing and untargeted metabolomics profiling for 91 CPP patients and 59 healthy controls. Bioinformatics and statistical analyses, including the comparisons of alpha and beta diversity, abundances of microbes, were undertaken on the 16S rRNA gene sequences and metabolism profiling. Classifiers were constructed based on the microorganisms and metabolites. Functional and pathway enrichment analyses were performed for identification of the altered microorganisms and metabolites in CPP. RESULTS: We integrated a multi-omics approach to investigate the alterations and functional characteristics of gut microbes and metabolites in CPP patients. The fecal microbiome profiles and fecal and blood metabolite profiles for 91 CPP patients and 59 healthy controls were generated and compared. We identified the altered microorganisms and metabolites during the development of CPP and constructed a machine learning-based classifier for distinguishing CPP. The Area Under Curves (AUCs) of the classifies were ranged from 0.832 to 1.00. In addition, functional analysis of the gut microbiota revealed that the nitric oxide synthesis was closely associated with the progression of CPP. Finally, we investigated the metabolic potential of gut microbes and discovered the genus Streptococcus could be a candidate molecular marker for CPP treatment. CONCLUSIONS: Overall, we utilized multi-omics data from microorganisms and metabolites to build a classifier for discriminating CPP patients from the common populations and recognized potential therapeutic molecular markers for CPP through comprehensive analyses.

Evolutionary coexistence in a metacommunity: Competition-colonization trade-off, ownership effects, environmental fluctuations.

We study the adaptive dynamics of the colonization rate of species living in a patchy habitat when there is a trade-off with the competitive strength for individual patches. To that end, we formulate a continuous-time competition-colonization model that also includes ownership effects as well as random disturbance affecting the mortality rate. We find that intermediate disturbance (as measured by the fluctuation intensity of the mortality rate), a strong competition-colonization trade-off, and a weak ownership effect are necessary conditions for evolutionary branching and hence for the emergence of polymorphisms (i.e., coexistence) by small evolutionary steps. Specifically, concerning ownership we find that with low-intermediate disturbance, a weak ownership advantage favours evolutionary branching while ownership disadvantage does not. This asymmetry disappears at the higher-intermediate disturbance. Moreover, at a low-intermediate disturbance, the effect of the strength of the competition-colonization trade-off on evolutionary branching is non-monotonic disappears because the possibility of branching disappears again when the trade-off is too strong. We also find that there can be multiple evolutionary attractors for polymorphic populations, each with its own basin of attraction. With small but non-zero random evolutionary steps and depending on the initial polymorphic condition just after branching, a coevolutionary trajectory may come arbitrarily close to the shared boundary of two such basins and may even jump from one side to the other, which can lead to various kinds of long-term evolutionary dynamics, including evolutionary branching-extinction cycles.

The evolution of the irreversible transition from a free-swimming state to an immobile sessile state in aquatic invertebrates modelled in a chemostat.

To better understand the environmental factors and ecological processes underlying the evolution of the irreversible transition from a free-swimming state to an immobile sessile state as seen in many aquatic invertebrates, we study the adaptive dynamics of the settling rate of a hypothetical microorganism onto the wall of a chemostat. The two states, floating or settled, differ in their nutrient ingestion, reproduction and death rate. We consider three different settling mechanisms involving competition for space on the wall: (i) purely exploitative competition where free-swimming individuals settle in vacant space only, (ii) mixed exploitative and interference competition where individuals attempt to settle in any place but fail and die if the space is already occupied, and (iii) mixed exploitative and interference competition, but now settling in occupied space is successful and the former occupant dies. In the simplified environment of the chemostat, the input concentration of nutrients and the dilution rate of the tank are the main environmental control variables. Using the theory of adaptive dynamics, we find that the settling mechanisms and environmental control variables have qualitatively different effects on the evolution of the settling rate in terms of the direction of evolution as well as on species diversity. In the case of purely exploitative competition a small change in the settings of the environmental control variables can lead to an abrupt reversal of the direction of evolution, while in the case of mixed exploitative and interference competition the effect is gradual. For all three settling mechanisms, periodic fluctuations in the nutrient input open the possibility of evolutionary branching leading to the long-term coexistence of an intermediate and an infinitely high settling rates (in the case of low-frequency fluctuations), and an intermediate and a zero settling rates (in the case of high-frequency fluctuations).

Resident-invader dynamics of similar strategies in fluctuating environments.

We study resident-invader dynamics in fluctuating environments when the invader and the resident have close but distinct strategies. First we focus on a class of continuous-time models of unstructured populations of multi-dimensional strategies, which incorporates environmental feedback and environmental stochasticity. Then we generalize our results to a class of structured population models. We classify the generic population dynamical outcomes of an invasion event when the resident population in a given environment is non-growing on the long-run and stochastically persistent. Our approach is based on the series expansion of a model with respect to the small strategy difference, and on the analysis of a stochastic fast-slow system induced by time-scale separation. Theoretical and numerical analyses show that the total size of the resident and invader population varies stochastically and dramatically in time, while the relative size of the invader population changes slowly and asymptotically in time. Thereby the classification is based on the asymptotic behavior of the relative population size, and which is shown to be fully determined by invasion criteria (i.e., without having to study the full generic dynamical system). Our results extend and generalize previous results for a stable resident equilibrium (particularly, Geritz in J Math Biol 50(1):67-82, 2005; Dercole and Geritz in J Theor Biol 394:231-254, 2016) to non-equilibrium resident population dynamics as well as resident dynamics with stochastic (or deterministic) drivers.

Protective Effect of Sciadopitysin against Isoproternol-Induced Myocardial Infarction in Rats.

The current study enumerates the beneficial role of sciadopitysin (SDN) against isoproternol (ISO)-induced myocardial infarction (MI) in rats. The MI was experimentally induced via subcutaneous injection of ISO in experimental rats. SDN showed to prevent myocardial necrosis via reducing the levels of creatine kinase-MB and lactate dehydrogenase activities. It also showed to improve myocardial ability and decrease infarct volume. The level of cardiac-specific troponin-T (Tn-T), tumor necrosis factor-α and interleukin-6 were showed to be declined in SDN-treated group as determined by ELISA analysis. At the tested dose, SDN causes reduction in oxidative stress via enhancing the levels of glutathione peroxidase and superoxide dismutase, while reducing the level of myeloperoxidase and malondialdehyde. Cardiac histological changes were observed via hematoxylin and eosin staining along with cardiac function after pre- and post administration of SDN. In western blot analysis, SDN showed significant downregulation of cleaved caspase-3 and Bax, whereas Bcl-2 expression was found to be significantly elevated in dose-dependent manner.

Biology of MarR family transcription factors and implications for targets of antibiotics against tuberculosis.

The emergence of multidrug resistant (MDR) Mycobacterium tuberculosis strains and increased incidence of HIV coinfection fueled the difficulty in controlling tuberculosis (TB). MarR (multiple antibiotic resistance regulator) family transcription factors can regulate marRAB operon and are involved in resistance to multiple environmental stresses. We have summarized the structure, function, distribution, and regulation of the MarR family proteins, as well as their implications for novel targets for antibiotics, especially for tuberculosis.

Upregulation of miR-29b-3p protects cardiomyocytes from hypoxia-induced apoptosis by targeting TRAF5.

BACKGROUND: MicroRNAs (miRNAs) are pivotal regulators in regulating hypoxia-induced cardiomyocyte injury. This study was designed to evaluate the effects of miR-29b-3p on hypoxic cardiomyocytes. METHODS: Human AC16 cells were cultured under normoxic or hypoxic conditions. Hypoxic injury was confirmed based on alterations in cell viability using CCK-8 assay and apoptosis using flow cytometry and Hoechst staining. Bioinformatics analyses and the dual-luciferase reporter assay were performed to predict and validate the target gene of miR-29b-3p. RESULTS: We found that hypoxia suppressed cell viability and promoted apoptosis. TNF receptor-associated factor 5 (TRAF5) was a potential target gene of miR-29b-3p. Our in vitro experiments revealed that miR-29b-3p overexpression or TRAF6 knockdown significantly protected cardiomyocytes against hypoxia-induced injury. Moreover, knockdown of TRAF5 knockdown potentiated the protective effects of miR-29b-3p against hypoxia-induced cell injury. CONCLUSION: These findings suggest that upregulation of miR-29b-3p could protect cardiomyocytes against hypoxia-induced injury through downregulation of TRAF5. Targeting TRAF5 with miR-29b-3p might be a potential therapeutic method for AMI.

LncRNA Gm43843 Promotes Cardiac Hypertrophy via miR-153-3p/Cacna1c Axis.

Long noncoding RNAs (lncRNAs) have been reported to engage in many human diseases, including cardiac hypertrophy. Cardiac hypertrophy was mainly caused by excessive pressure load, which can eventually lead to a decline in myocardial contractility. Gm43843, a novel lncRNA, has not been well explored in cardiac hypertrophy so far. Herein, we are going to search the function and the underlying molecular mechanism of Gm43843 in cardiac hypertrophy. Gm43843 levels were measured via qRT-PCR in mouse myocardial cells when they are treated with angiogenin II (Ang II) or transfected with different plasmids. Western blot assay was implemented to detect the cardiac hypertrophy-related protein markers, while the cell was analyzed via immunofluorescence (IF) assay to evaluate the hypertrophy. Meanwhile, the binding of Gm43843 and the putative targets was examined based on mechanistic assay results. We found that Gm43843 expression was increased with the elevated concentration of Ang II. Inhibited Gm43843 was detected to reduce the hypertrophy of mouse myocardial cells. Meanwhile, Gm43843/miR-153-3p/Cacna1c axis was found to modulate cardiac hypertrophy. In short, Gm43843 promotes cardiac hypertrophy via miR-153-3p/Cacna1c axis.

Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway.

Piperine (PIP) exerts numerous pharmacological effects and its involvement in endoplasmic reticulum (ER) stress (ERS)-led apoptosis has garnered attention. The present study focused on whether PIP played protective effects on hypoxia/reoxygenation (H/R)-induced cardiomyocytes by repressing ERS-led apoptosis. The potential molecular mechanisms in association with the PI3K/AKT signaling pathway were investigated. Primary neonatal rat cardiomyocytes (NRCMs) were isolated and randomized into four groups: Control + vehicle group, control + PIP group, H/R + vehicle group and H/R + PIP group. The H/R injury model was constructed by 4 h of hypoxia induction followed by 6 h of reoxygenation. A total of 10 µM PI3K/AKT inhibitor LY294002 was supplemented to the cells during the experiments. Cell viability and myocardial enzymes were detected to evaluate myocardial damage. A flow cytometry assay was performed to assess apoptotic response. Western blot analysis was performed to detect the expression of related proteins including PI3K, AKT, CHOP, GRP78 and cleaved caspase-12. The results showed that H/R markedly promoted myocardial damage as shown by the increased release of lactate dehydrogenase and creatine kinase levels, but a reduction in cell viability. In addition, ERS-induced apoptosis was markedly promoted by H/R in NRCMs, as shown by the increased apoptotic rates and expression of C/EBP-homologous protein, endoplasmic reticulum chaperone BiP and caspase-12. PIP administration reversed cell injury and ERS-induced apoptosis in H/R. Mechanistic studies concluded that the apoptosis-inhibitory contributions and cardio-favorable effects of PIP were caused partly by the activation of the PI3K/AKT signaling pathway, which was verified by LY294002 administration. To conclude, PIP can reduce ERS-induced apoptosis by activating the PI3K/AKT signaling pathway during the process of H/R injury, which could be a potential therapeutic target for the treatment of myocardial ischemia/reperfusion injury.

Effects of healthcare failure mode and effect analysis on the prevention of multi-drug resistant organisms infections in oral and maxillofacial surgery.

OBJECTIVE: Care models of Healthcare Failure Mode and Effect Analysis (FMEA) were evaluated for the prevention of multi-drug resistant organisms (MDRO) infections in oral and maxillofacial surgery. METHODS: Two hundred patients who received oral and maxillofacial surgery from January to December 2017 were enrolled as the control group, and another 200 patients who received oral and maxillofacial surgery from January to December 2018 were enrolled as the FMEA group. The incidence of MDRO, the implementation of preventive and control measures, the mastery of preventive and control knowledge, and oral self-care ability were compared between the two groups. Risk Priority Number (RPN) and behavioral changes of health care personnel were observed in FMEA group. RESULTS: The FMEA group had a lower incidence of MDRO (2.00%) than the control group (6.00%) and a higher rate of acquisition of prevention and control knowledge (93.00%) than the control group (84.50%) (P < 0.05). Patients in FMEA group were higher than those in the control group in terms of compliance towards isolation signs and precautions, appropriate use of PPE, implementation of disinfection measures, hand hygiene and exercise of self-care agency (ESCA) scale scores (P < 0.05). The total RPN score of the FMEA group before and after management was 1384 and 180, respectively, and the reduction rate of total RPN scores was 86.99%. Scores with regard to knowledge, attitude, and behavior of health care personnel were increased after FMEA treatment (P < 0.05). CONCLUSION: The nursing model of FMEA for oral and maxillofacial surgery can prevent MDRO infections, reduce RPN, improve the implementation of preventive and control measures as well as oral self-care ability and the acquisition of knowledge.

Hierarchical Assembly of Nanocellulose into Filaments by Flow-Assisted Alignment and Interfacial Complexation: Conquering the Conflicts between Strength and Toughness.

Filaments comprising solely cellulose nanofibrils (CNFs) have been fabricated by flow-assisted assembling, where the strength can be improved greatly with the sacrifice of toughness. Inspired by the architecture of natural nacre and plant cell wall, the combined technique of convergent microfluidic spinning and in situ interfacial complexation between CNF and chitosan molecules was used to construct the filaments with hierarchical assembly of highly oriented CNFs locked by chitosan complexes, showing simultaneous enhancements of strength and toughness. In specific, the best performing filament exhibited a toughness of 88.9 kJ/m3 and a tensile strength of 1289 MPa because of the strong interfacial complexation interactions between CNFs and chitosan molecules. The tensile strength was further raised to 1627 MPa when the filaments were cross-linked synergistically by using Ca2+, surpassing the reported values in the literature. Molecular dynamics simulations revealed the possible fracture mechanism of the filaments under tension. With excellent mechanical performance and biocompatibility, the resulting CNF/chitosan filament system showed a promising application potential as nonabsorbable surgical sutures. The demonstrated spinning technology also offered a new avenue for the fabrication of high-performance filaments.