LncRNA Gm15834 Aggravates Cardiac Hypertrophy by Interacting with Sam68 and Activating NF-κB Mediated Inflammation.

BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

Genomic epidemiology reveals multiple mechanisms of linezolid resistance in clinical enterococci in China.

BACKGROUND: Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. METHODS: Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. RESULTS: The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. CONCLUSIONS: Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.

Immobilization of Perylenetetracarboxylic Dianhydride on Al2O3 for Efficiently Photocatalytic Sulfide Oxidation.

Perylenetetracarboxylic dianhydride (PTCDA) derivatives have received significant attention as molecule photocatalysts. However, the poor recyclability of molecule-type photocatalysts hinders their widespread applications. Herein, immobilization of PTCDA on Al2O3 was achieved by simply physical mixing, which not only dramatically improved their recyclability, but also surprisingly improved the reactivity. A mechanism study suggested that the photo-exited state (PTCDA*) of PTCDA could promote the oxidation of thioanisole to generate PTCDA•-, which sequentially reduces oxygen to furnish superoxide radicals to achieve the catalytic cycle. Herein, the immobilization support Al2O3 was able to facilitate the strong adsorption of thioanisole, thereby boosting the photocatalytic activity. This work provides a new insight that the immobilization of organic molecular photocatalysts on those supports with proper adsorption sites could furnish highly efficient, stable, and recyclable molecular-based heterogeneous photocatalysts.

Exploring microRNAs in craniofacial regenerative medicine.

microRNAs (miRs) have been reported over the decades as important regulators in bone development and bone regeneration. They play important roles in maintaining the stem cell signature as well as regulating stem cell fate decisions. Thus, delivering miRs and miR inhibitors to the defect site is a potential treatment towards craniofacial bone defects. However, there are challenges in translation of basic research to clinics, including the efficiency, specificity, and efficacy of miR manipulation methods and the safety of miR delivery systems. In this review, we will compare miR oligonucleotides, mimics and antagomirs as therapeutic reagents to treat disease and regenerate tissues. Newer technology will be discussed as well as the efficiency and efficacy of using these technologies to express or inhibit miRs in treating and repairing oral tissues. Delivery of these molecules using extracellular vesicles and nanoparticles can achieve different results and depending on their composition will elicit specific effects. We will highlight the specificity, toxicity, stability, and effectiveness of several miR systems in regenerative medicine.

Comparative Phosphoproteomic Profiling in the Prefrontal Cortex of Prenatally Stressed Male Offspring Rats.

Many investigations have indicated that prenatal stress (PS) causes depressive-like disturbances in offspring rats. However, the underlying pathogenic mechanisms have not yet been fully elucidated. The prefrontal cortex (PFC) has been shown to play a role in susceptibility to stress during fetal development; thus, we focused our attention on differential protein phosphorylation in this region of PS-S (susceptibility to PS) offspring rats. The sucrose preference test was used to screen for susceptibility to PS. The validity of the prenatally stressed model was verified by other common depression-like behaviors. We used MS-based TMT quantitative proteomics in combination with the phosphopeptide enrichment method to compare phosphoproteomic profiling in the PFC of PS-S and control male offspring rats. In total, 3,418 phosphoproteins, 8,404 phosphopeptides, and 12,175 phosphosites were identified in this analysis. According to the screening criteria, 902 phosphopeptides increased and 609 decreased in the PFC of the PS-S group compared to the control rats. Gene ontology enrichment analysis indicated that the main enriched terms in the cellular component category were "synapse part," "myelin sheath," "synapse," "neuron part," and "axon." The phosphoproteins enriched in the molecular function and biological process categories were mainly related to cytoskeleton- and projection morphogenesis-associated proteins. KEGG pathway enrichment analyses identified 30 significant KEGG pathways; the top five pathways included salivary secretion, endocrine and other factor-regulated calcium reabsorption, pancreatic secretion, and insulin secretion. Motifs such as ……_S_P…RR, ……S_PE……, ……_S_PV……, ……_S_P.H……, and …S…_S_PT…. were the top five motifs enriched in phosphorylated sites. PS may induce depressive-like behaviors in male offspring rats by regulating the phosphorylation of proteins mainly related to synapses, myelin sheaths, neurons, and the cytoskeleton. The phosphorylation of related proteins may act as key pathogenic hits. Data are available via ProteomeXchange with identifier PXD026563.

Exploring craniofacial and dental development with microRNAs.

microRNAs (miRs) are small RNA molecules that regulate many cellular and developmental processes. They control gene expression pathways during specific developmental time points and are required for tissue homeostasis and stem cell maintenance. miRs as therapeutic reagents in tissue regeneration and repair hold great promise and new technologies are currently being designed to facilitate their expression or inhibition. Due to the large amount of miR research in cells and cancer many cellular processes and gene networks have been delineated however, their in vivo response can be different in complex tissues and organs. Specifically, this report will discuss animal developmental models to understand the role of miRs as well as xenograft, disease, and injury models. We will discuss the role of miRs in clinical studies including their diagnostic function, as well as their potential ability to correct craniofacial diseases.

High Molecular Weight Poly(glutamic acid) to Improve BMP2-Induced Osteogenic Differentiation.

FDA-approved bone morphogenetic protein 2 (BMP2) has serious side effects due to the super high dose requirement. Heparin is one of the most well-studied sulfated polymers to stabilize BMP2 and improve its functionality. However, the clinical use of heparin is questionable because of its undesired anticoagulant activity. Recent studies suggest that poly(glutamic acid) (pGlu) has the potential to improve BMP2 bioactivity with less safety concerns; however, the knowledge on pGlu's contribution remains largely unknown. Therefore, we aimed to study the role of pGlu in BMP2-induced osteogenesis and its potential application in bone tissue engineering. Our data, for the first time, indicated that both low (L-pGlu) and high molecular weight pGlu (H-pGlu) were able to significantly improve the BMP2-induced early osteoblastic differentiation marker (ALP) in MC3T3-E1 preosteoblasts. Importantly, the matrix mineralization was more rapidly enhanced by H-pGlu compared to L-pGlu. Additionally, our data indicated that only α-H-pGlu could significantly improve BMP2's activity, whereas γ-H-pGlu failed to do so. Moreover, both gene expression and mineralization data demonstrated that α-H-pGlu enabled a single dose of BMP2 to induce a high level of osteoblastic differentiation without multiple doses of BMP2. To study the potential application of pGlu in tissue engineering, we incorporated the H-pGlu+BMP2 nanocomplexes into the collagen hydrogel with significantly elevated osteoblastic differentiation. Furthermore, H-pGlu-coated 3D porous gelatin and chitosan scaffolds significantly enhanced osteogenic differentiation through enabling sustained release of BMP2. Thus, our findings suggest that H-pGlu is a promising new alternative with great potential for bone tissue engineering applications.

Inhibition of lncRNA Gm15834 Attenuates Autophagy-Mediated Myocardial Hypertrophy via the miR-30b-3p/ULK1 Axis in Mice.

Emerging evidence reveals that autophagy plays crucial roles in cardiac hypertrophy. Long noncoding RNAs (lncRNAs) are novel transcripts that function as gene regulators. However, it is unclear whether lncRNAs regulate autophagy in cardiac hypertrophy. Here, we identified a novel transcript named lncRNA Gm15834, which was upregulated in the transverse aortic constriction (TAC) model in vivo and the angiotensin-II (Ang-II)-induced cardiac hypertrophy model in vitro and was regulated by nuclear factor kappa B (NF-κB). Importantly, forced expression of lncRNA Gm15834 enhanced autophagic activity of cardiomyocytes and promoted myocardial hypertrophy, whereas silencing of lncRNA Gm15834 attenuated autophagy-induced myocardial hypertrophy. Mechanistically, we found that lncRNA Gm15834 could function as an endogenous sponge RNA of microRNA (miR)-30b-3p, which was downregulated in cardiac hypertrophy. Inhibition of miR-30b-3p enhanced cardiomyocyte autophagic activity and aggravated myocardial hypertrophy, whereas overexpression of miR-30b-3p suppressed autophagy-induced myocardial hypertrophy by targeting the downstream autophagy factor of unc-51-like kinase 1 (ULK1). Moreover, inhibition of lncRNA Gm15834 by adeno-associated virus carrying short hairpin RNA (shRNA) suppressed cardiomyocyte autophagic activity, improved cardiac function, and mitigated cardiac hypertrophy. Taken together, our study identified a novel regulatory axis encompassing lncRNA Gm15834/miR-30b-3p/ULK1/autophagy in cardiac hypertrophy, which may provide a potential therapy target for cardiac hypertrophy.

Disseminated nontuberculous mycobacterial infection with cryptic immunodeficiency mimicking malignancy: a case report.

BACKGROUND: Nontuberculous mycobacteria (NTM) usually invades vulnerable hosts. Disseminated NTM (dNTM) infection can affect nearly all organs and be easily misdiagnosed as metastatic carcinoma or other systemic diseases, especially in seemingly immunocompetent hosts. Identification of underlying immunodeficiency is critical for the diagnosis and treatment of dNTM. Adult-onset immunodeficiency (AOID) with anti-IFN-γ autoantibodies has recently been recognized as a crucial but frequently neglected risk factor for dNTM infection. Frequent relapses of infection are common in AOID patients despite appropriate anti-infective treatment and B-cell-depleting therapy has shown some promising results. Herein, we report a case of dNTM infection mimicking malignancy in an AOID patient who was successfully treated with rituximab. CASE PRESENTATION: A middle-aged male presented with fever, productive cough, multifocal skin abscesses and multiple osteolytic lesions with pathological fractures. Chest CT revealed consolidation of the lingula while bronchoscopy showed a mass completely blocking the airway opening of the inferior lingual segment. Metagenomic next-generation sequencing and mycobacterial culture of skin pus and bronchoalveolar lavage fluid reported Mycobacterium Colombiense, confirming the diagnosis of dNTM infection. However, anti-NTM antibiotics alone failed to prevent disease relapse and progression. Further evaluation indicated undetectable serum IFN-γ concentration and high-titer autoantibodies against IFN-γ, suggesting that AOID was the underlying reason for dNTM. Rituximab was added to treatment and successfully controlled the infection without relapse at one-year follow-up. CONCLUSION: We reported a rare case of disseminated Mycobacterium Colombiense infection manifested with pulmonary mass, pathological fracture and dermapostasis in a host with AOID. Our case demonstrated that AOID should be screened when patients get the episode of disseminated NTM infection particularly when other risk factors are excluded. Besides prolonged anti-NTM therapy, AOID-associated NTM infection should be treated with B-cell-depleting therapy to prevent recurrence.

The combination of initial markers to predict refractory Mycoplasma pneumoniae pneumonia in Chinese children: a case control study.

OBJECTIVE: Thise study is aimed to identify the biomarkers for predicting refractory Mycoplasma pneumoniae pneumonia in Chinese children at the time of the hospital admission. METHODS: The case control study retrospectively analyzed the clinical characteristics and laboratory results of Chinese pediatric patients presenting with common and refractory Mycoplasma pneumoniae pneumonia (CMPP and RMPP). Overall, there were 216 cases in the CMPP group and 88 cases in the RMPP group. Venous blood was collected, and serum ferritin (SF), lactate dehydrogenase (LDH), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte count (NLR), and other indexes were measured. A single factor analysis, an ROC curve analysis, and a logistic regression analysis were used to determine the independent risk factors of RMPP and find combination of initial markers for RMPP. RESULTS: There were significant differences between the RMPP group and the CMPP group in mean SF (529.82 [357.86] vs. 147.22 [122.68] ng/mL), LDH (522.08 [389.08] vs. 286.85 [101.02] U/L), D-dimer (6.65 [5.66] vs. 1.46 [2.45] µg/mL), CRP (62.80 [52.15] vs. 19.03 [24.50] mg/L), PCT (0.80 [2.61] vs. 0.16 [0.44]) ng/mL, and NLR (4.14 [2.52] vs. 2.62 [1.55]), with P < 0.05 for each comparison. ROC cut-off values of the above indexes were 329.01 ng/mL, 375.50 U/L, 2.10 µg/mL, 43.08 mg/L, 0.08 ng/mL, and 2.96, respectively. The logistic regression analysis showed that SF, D-dimer, and CRP are independent risk factors to predict RMPP. CONCLUSION: SF, D-dimer, and CRP are statistically significant biomarkers to predict RMPP in Chinese children patients in the settings of pediatric emergency department.

Genotypic differences in CC224, CC363, CC449 and CC446 of Moraxella catarrhalis isolates based on whole genome SNP, MLST and PFGE typing.

Understanding the evolutionary path of M. catarrhalis from macrolide-susceptible to macrolide-resistant organism, is important for hindering macrolide resistance from propagation. Multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole genome SNP typing (WGST), as useful and practical typing tools, have both advantages and disadvantages. We studied the utility of these 3 typing methods, including the level of agreement, consistency and drawbacks, in characterizing M. catarrhalis clones and clonal complexes. We focused on four clonal complexes [CC224, CC363, CC449 (CCN10) and CC446 (CCN08)] and found that PFGE and WGST had a high level of agreement and a proper consistency of the same clone or very closely related clones, while MLST is less discriminatory for different clones. Furthermore, we also established an evolutionary distance cut-off value for "The same clone". Moreover, we detected macrolide-resistant M. catarrhalis in CC224, which had previously been considered as a macrolide-susceptible clonal complex. A higher number of isolates belonged to ST215 compared to ST446, implying that ST215 is more likely to be the primary founder. Our study also demonstrated that all the four clonal complexes belong to the M. catarrhalis lineage 1, which is considered to be related to increased virulence potential and serum resistance. We also observed that copB II was highly related to CC449 and LOS type B was mainly confined in CC224. In conclusion, these findings provide further insight into the evolutionary characteristics of M. catarrhalis.

Photocatalytic Bacterial Inactivation by a Rape Pollen-MoS2 Biohybrid Catalyst: Synergetic Effects and Inactivation Mechanisms.

A novel and efficient 3D biohybrid photocatalyst, defective MoS2 nanosheets encapsulated carbonized rape pollen, was fabricated and applied to water disinfection. The rape pollen-MoS2 (PM) biohybrid showed excellent dispersibility, high stability, and efficient charge-carrier separation and migration ability, resulting in the highly enhanced photocatalytic inactivation performance toward various waterborne bacteria under different light sources. The inactivation mechanisms were systematically investigated. Reactive species (RSs), including electrons, holes, and reactive oxygen species (•O2- and •OH), played major roles in inactivating bacteria. The antioxidant system of bacteria exhibited a self-protection capacity by eliminating the photogenerated RSs from PM biohybrid at the early stage of inactivation. With the accumulation of RSs, the cell membrane and membrane-associated functions were destroyed, as suggested by the collapse of cell envelope and subsequent loss of cell respiration and ATP synthesis capacity. The microscopic images further confirmed the destruction of the bacterial membrane. After losing the membrane barrier, the oxidation of cytoplasmic proteins and lipids caused by invaded RSs occurred readily. Finally, the leakage of DNA and RNA announced the irreversible death of bacteria. These results indicated that the bacterial inactivation began with the membrane rupture, followed by the oxidation and leakage of intracellular substances. This work not only provided a new insight into the combination of semiconductors with earth-abundant biomaterials for fabricating high-performance photocatalysts, but also revealed the underlying mechanisms of photocatalytic bacterial inactivation in depth.

Prevalence and risk factors of nocturnal enuresis among children ages 5-12 years in Xi'an, China: a cross-sectional study.

BACKGROUND: Nocturnal enuresis (NE) has a negative impact on children's health and imposes a long-term burden on families. With economic development and cultural improvements, parents and medical professionals pay more attention to NE. The aim of this study was to investigate the prevalence and risk factors of NE among children ages 5-12 years in Xi'an, China. METHODS: A stratified cluster sampling method was used to conduct a cross-sectional study of NE in 10 kindergartens and 20 primary schools in Xi'an. We used univariate analysis to compare the prevalences of characteristics such as gender, duration of disposable diaper (DD) use, toilet training onset time, daily living habits, academic performance, and family history of NE. Logistic regression analysis was used to calculate odds ratio and to determine risk factors of NE. RESULTS: The study included 6568 children ages 5-12 years, of which 262 (3.99%) had NE. The prevalence rates of NE decreased with age, with the highest prevalence at age 5 (9.09% for boys; 6.03% for girls). However, the prevalence increased with duration of DD use. Children experienced more NE if they never accepted toilet training (7.83%) or if they drank sugary beverages during the day (5.36%). Sleep disorders, sweets intake, drinking low amounts of plain water during the day, and family history of NE, were statistically associated with NE. CONCLUSION: NE was closely associated with a family history of NE, being male, long-term use of DD, delayed toilet training, drinking sugary beverages and/or consuming little plain water, and sleep disorders. A supportive parental attitude towards NE and timely medical treatment can improve the quality of life of enuretic children.

MiR-103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts.

Cardiac hypertrophy is a common pathological change frequently accompanied by chronic hypertension and myocardial infarction. Nevertheless, the pathophysiological mechanisms of cardiac hypertrophy have never been elucidated. Recent studies indicated that miR-103 expression was significantly decreased in heart failure patients. However, less is known about the role of miR-103 in cardiac hypertrophy. The present study was designed to investigate the relationship between miR-103 and the mechanism of pressure overload-induced cardiac hypertrophy. TRPV3 protein, cardiac hypertrophy marker proteins (BNP and ß-MHC) and autophagy associated proteins (Beclin-1 and LC3-II) were up-regulated, as well as, miR-103 expression and autophagy associated proteins (p62) were down-regulated in cardiac hypertrophy models in vivo and in vitro respectively. Further results indicated that silencing TRPV3 or forcing overexpression of miR-103 could dramatically inhibit cell surface area, relative fluorescence intensity of Ca2+ signal and the expressions of BNP, ß-MHC, Beclin-1 and LC3-II, but promote p62 expression. Moreover, TRPV3 protein was decreased in neonatal rat ventricular myocyte transfected with miR-103, but increased by AMO-103. Co-transfection of the miR-103 with the luciferase reporter vector into HEK293 cells caused a sharp decrease in luciferase activity compared with transfection of the luciferase vector alone. The miR-103-induced depression of luciferase activity was rescued by an AMO-103. These findings suggested that TRPV3 was a direct target of miR-103. In conclusion, miR-103 could attenuate cardiomyocyte hypertrophy partly by reducing cardiac autophagy activity through the targeted inhibition of TRPV3 signalling in the pressure-overloaded rat hearts.

Analysis of the SNP rs3747333 and rs3747334 in NLGN4X gene in autism spectrum disorder: a meta-analysis.

BACKGROUND: The SNP rs3747333 and rs3747334 in Neuroligin 4X (NLGN4X) gene have been demonstrated to be associated with the susceptibility to Autism spectrum disorder (ASDs; MIM 209850), but the results are inconsistent. Therefore, a meta-analysis of eligible studies reporting the association between rs3747333 and rs3747334 and ASD was carried out to enhance the reliability of published results. METHODS: A systematic literature search was performed using PubMed, Web of Science, Cochrane Library to search English articles concerning the relation between rs3747333, rs3747334 and ASD up to Sep. 21th, 2017. Summary odds ratios (OR) and 95% confidence interval (CI) were used to evaluate the risk of rs3747333, rs3747334 in the ASD. The heterogeneity and publication bias of the eligible studies were also evaluated. RESULTS: Six eligible studies involving 1284 subjects (735 patients and 549 healthy controls) were included in this meta-analysis. Overall, the results indicated that there was no significant risk elevation between rs3747333, rs3747334 variants and ASD (OR = 0.39, 95% CI 0.10-1.60). Furthermore, sensitivity analysis and publication bias analysis confirmed this result. CONCLUSIONS: In conclusion, our meta-analysis suggests that the rs3747333, rs3747334 in NLGN4X gene are not frequent causes of ASD.

Activation of transient receptor potential vanilloid 3 channel (TRPV3) aggravated pathological cardiac hypertrophy via calcineurin/NFATc3 pathway in rats.

Cardiac hypertrophy is a compensatory response to mechanical stimuli and neurohormonal factors, ultimately progresses to heart failure. The proteins of some transient receptor potential (TRP) channels, Ca2+ -permeable nonselective cation channel, are highly expressed in cardiomyocytes, and associated with the occurrence of cardiac hypertrophy. Transient receptor potential vanilloid 3 (TRPV3) is a member of TRP, however, the functional role of TRPV3 in cardiac hypertrophy remains unclear. TRPV3 was elevated in pathological cardiac hypertrophy, but not in swimming exercise-induced physiological cardiac hypertrophy in rats. TRPV3 expression was also increased in Ang II-induced cardiomyocyte hypertrophy in vitro, which was remarkably increased by carvacrol (a nonselective TRPV channel agonist), and reduced by ruthenium red (a nonselective TRPV channel antagonist). Interestingly, we found that activated TRPV3 in Ang II-induced cardiomyocyte hypertrophy was accompanied with increasing intracellular calcium concentration, promoting calcineurin, and phosphorylated CaMKII protein expression, and enhancing NFATc3 nuclear translocation. However, blocking or knockdown of TRPV3 could inhibit the expressions of calcineurin, phosphorylated CaMKII and NFATc3 protein by Western blot. In conclusion, the activation of TRPV3 aggravated pathological cardiac hypertrophy through calcineurin/NFATc3 signalling pathway and correlated with the protein expression levels of calcineurin, phosphorylated CaMKII and NFATc3, revealing that TRPV3 might be a potential therapeutic target for cardiac hypertrophy.

Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling.

Metformin recently gained traction as potential anti-endometrial cancer agent for its new applications. However, the underlying mechanisms of the anti-cancer effect of metformin in the endometrial cancer have not yet been fully elucidated. Sixty-five patients diagnosed as endometrial carcinoma were grouped into (n = 33) and non-treatment mixed (n = 32) for analysis. Thirty healthy donors were recruited as controls. We attempt to investigate the effect of metformin on Ki-67, PI3K, p-AKT, p-S6K1, and p-4EBP1 staining in human endometrial cancer by immunohistochemical staining. We found that increased Ki-67 expression in women with endometrial cancer, which were reversed by conventional anti-diabetic doses of metformin in present work. In parallel, the reduced PI3K, p-AKT, p-S6K1, and p-4EBP1 staining induced by metformin appeared to play an important role for the anti-proliferative effects of metformin in endometrial cancer patients. Metformin significantly decreased proliferation in human endometrial cancer may by inhibiting PI3K/AKT/mTOR signaling. Our present results add to the growing body of evidence supporting metformin as a potential anti-cancer agent in endometrial cancer.

[Analysis of clinical characteristics and genetic mutation in a pedigree affected with Chediak-Higashi syndrome].

OBJECTIVE: To explore the genetic basis for a pedigree affected with Chediak-Higashi syndrome (CHS). METHODS: Clinical data of two CHS patients from the pedigree was collected and analyzed. Targeted next generation sequencing and Sanger sequencing were conducted to detect potential mutation of the LYST gene. RESULTS: Both patients presented immunodeficiency, oculocutaneous albinism, and acidophilic inclusion body on bone marrow and blood smears. A homozygous c.6077_6078insA (p.Tyr2026Terfs) mutation was detected in the LYST gene in both patients. CONCLUSION: Genetic testing can play an important role in the diagnosis of CHS.

Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus.

Prenatal stress (PS) results in various behavioral and emotional alterations observed in later life. In particular, PS impairs spatial learning and memory processes but the underlying mechanism involved in this pathogenesis still remains unknown. Here, we reported that PS lowered the body weight in offspring rats, particularly in female rats, and impaired spatial learning and memory of female offspring rats in the Morris water maze. Correspondingly, the decreased CaMKII and CREB mRNA in the hippocampus were detected in prenatally stressed female offspring, which partially explained the effect of PS on the spatial learning and memory. Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring.

Hippocampal Acetylation may Improve Prenatal-Stress-Induced Depression-Like Behavior of Male Offspring Rats Through Regulating AMPARs Expression.

This study is to determine the role and mechanism of hippocampal acetylation in prenatal stress (PS) induced depression-like behavior of male offspring rats. PS-induced depression rat model was established. Sucrose preference and forced swim test were used to observe the behavior changes of male offspring rats. Hippocampal acetylation was induced by Trichostatin A injection. Quantitative real-time PCR and Western blot were used to determine the changes of AMPARs in acetylated hippocampus. The behavioral tests proved that AMPA was involved in the PS-induced depression-like behavior in offspring rats. Hippocampal acetylation significantly increased the preference to sucrose of PS-induced offspring rats and reduced the immobile time in forced swimming test, suggesting that acetylation could improve PS-induced depression-like behaviors. In addition, PS inhibited the expression levels of GluA1-3 subunits of AMPARs in the offspring hippocampus, while Hippocampal acetylation could reverse this effect by increasing GluA1-3 expression. PS-induced reduction of GluA1-3 subunits of AMPARs may be an important potential mechanism of offspring depression. Hippocampal acetylation may improve PS-induced offspring depression-like behavior through the enhanced expression of AMPARs (GluA1-3 subunits).