Long non-coding RNA MEG3 knockdown represses airway smooth muscle cells proliferation and migration via sponging miR-143-3p/FGF9 in asthma.

BACKGROUND: Asthma is a respiratory disease characterized by airway remodeling. We aimed to find out the role and mechanism of lncRNA MEG3 in asthma. METHODS: We established a cellular model of asthma by inducing human airway smooth muscle cells (HASMCs) with PDGF-BB, and detected levels of lncRNA MEG3, miR-143-3p and FGF9 in HASMCs through qRT-PCR. The functions of lncRNA MEG3 or miR-143-3p on HASMCs were explored by cell transfection. The binding sites of miR-143-3p and FGF9 were subsequently analyzed with bioinformatics software, and validated with dual-luciferase reporter assay. MTT, 5-Ethynyl-2'-deoxyuridine (EdU) assay, and Transwell were used to detect the effects of lncRNA MEG3 or miR-143-3p on proliferation and migration of HASMCs. QRT-PCR and western blot assay were used to evaluate the level of proliferation-related marker PCNA in HASMCs. RESULTS: The study found that lncRNA MEG3 negatively correlated with miR-143-3p, and miR-143-3p could directly target with FGF9. Silence of lncRNA MEG3 can suppress migration and proliferation of PDGF-BB-induced HASMCs via increasing miR-143-3p. Further mechanistic studies revealed that miR-143-3p negatively regulated FGF9 expression in HASMCs. MiR-143-3p could inhibit PDGF-BB-induced HASMCs migration and proliferation through downregulating FGF9. CONCLUSION: LncRNA MEG3 silencing could inhibit the migration and proliferation of HASMCs through regulating miR-143-3p/FGF9 signaling axis. These results imply that lncRNA MEG3 plays a protective role against asthma.

Bacterial persisters: molecular mechanisms and therapeutic development.

Persisters refer to genetically drug susceptible quiescent (non-growing or slow growing) bacteria that survive in stress environments such as antibiotic exposure, acidic and starvation conditions. These cells can regrow after stress removal and remain susceptible to the same stress. Persisters are underlying the problems of treating chronic and persistent infections and relapse infections after treatment, drug resistance development, and biofilm infections, and pose significant challenges for effective treatments. Understanding the characteristics and the exact mechanisms of persister formation, especially the key molecules that affect the formation and survival of the persisters is critical to more effective treatment of chronic and persistent infections. Currently, genes related to persister formation and survival are being discovered and confirmed, but the mechanisms by which bacteria form persisters are very complex, and there are still many unanswered questions. This article comprehensively summarizes the historical background of bacterial persisters, details their complex characteristics and their relationship with antibiotic tolerant and resistant bacteria, systematically elucidates the interplay between various bacterial biological processes and the formation of persister cells, as well as consolidates the diverse anti-persister compounds and treatments. We hope to provide theoretical background for in-depth research on mechanisms of persisters and suggest new ideas for choosing strategies for more effective treatment of persistent infections.

Trichoderma guizhouense NJAU4742 augments morphophysiological responses, nutrient availability and photosynthetic efficacy of ornamental Ilex verticillata.

Winterberry holly (Ilex verticillata [L.] A. Gray), a deciduous shrub producing glossy bright red berries, is a valuable ornamental and medicinal plant with good market prospects. However, the growth and development of I. verticillata are significantly affected by various stresses, and environmentally hazardous agrochemicals are often used to mitigate them. Trichoderma spp., ubiquitous soil-borne eco-friendly plant growth-promoting fungi, are potent biostimulants and biofertilizers and viable alternatives to agrochemicals for healthy and sustainable agriculture. In this study, the temporal efficacy of different dosages of the filamentous fungus Trichoderma guizhouense NJAU4742 in promoting morphophysiological responses of I. verticillata and the physicochemical properties and enzymatic activities of the substrate were investigated. Different concentrations of the strain T. guizhouense NJAU4742 spore suspension (C [0%], T1 [5%, v/m], T2 [10%, v/m] and T3 [15%, v/m]) were injected in the substrate contained in a pot in which 1-year-old I. verticillata was planted for temporal treatment (15, 45 and 75 days) under open-air conditions. The beneficial effects of T2 and/or T3 treatment for a long duration (75 days) were evident on the different root, aerial and photosynthetic traits; total contents of nitrogen (N), phosphorus (P) and potassium (K) in different tissues and the physicochemical properties of the substrate and its enzymatic activities (urease and invertase). Overall, the study revealed the potency of strain T. guizhouense NJAU4742 as a sustainable solution to improve the growth and development and ornamental value of I. verticillata.

Lifestyle intervention in children with obesity and nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled trial in Ningbo city (the SCIENT study).

BACKGROUND: The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. METHODS: This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8-10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students' body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. DISCUSSION: The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. TRIAL REGISTRATION: Clinicaltrials.gov NCT05482191. Registered on July 2022.

A feature selection method based on graph theory for cancer classification.

OBJECTIVE: Gene expression profile data is a good data source for people to study tumors, but gene expression data has the characteristics of high dimension and redundancy. Therefore, gene selection is a very important step in microarray data classification. METHOD: In this paper, a feature selection method based on the maximum mutual information coefficient and graph theory is proposed. Each feature of gene expression data is treated as a vertex of the graph, and the maximum mutual information coefficient between genes is used to measure the relationship between the vertices to construct an undirected graph, and then the core and coritivity theory is used to determine the feature subset of gene data. RESULTS: In this work, we used three different classification models and three different evaluation metrics such as accuracy, F1-Score, and AUC to evaluate the classification performance to avoid reliance on any one classifier or evaluation metric. The experimental results on six different types of genetic data show that our proposed algorithm has high accuracy and robustness compared to other advanced feature selection methods. CONCLUSION: In this method, the importance and correlation of features are considered at the same time, and the problem of gene selection in microarray data classification is solved.

Crystal structures, interactions with biomacromolecules and anticancer activities of Mn(II), Ni(II), Cu(II) complexes of demethylcantharate and 2-aminopyridine.

Three novel transition metal complexes (Hapy)(2)[M(DCA)(2)]·6H(2)O (M = Mn(II) (1), Ni(II) (2), Cu(II) (3); DCA = demethylcantharate, 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylate, C(8)H(8)O(5); Hapy = 2-aminopyridine acid, C(5)H(7)N(2)) were synthesized and characterized by elemental analysis, infrared spectra, thermogravimetric analysis and X-ray diffraction. DNA binding properties of the complexes were investigated by electronic absorption spectra, fluorescence spectra and viscosity measurements. Results indicated the complexes could bind to DNA through partial intercalation mode with binding constants K ( b )/(L·mol(-1)) of 1.91 × 10(4) (1), 5.13 × 10(4) (2) and 1.12 × 10(5) (3) at 298 K. Meanwhile, the interactions of the complexes with BSA were also studied by fluorescence spectra. The results suggested that the complexes could quench the fluorescence of BSA through static quenching with the binding constants K ( A )/(L·mol(-1)) of 1.44 × 10(6) (1), 1.14 × 10(7) (2) and 2.98 × 10(4) (3). And the main contribution was tryptophan residues of BSA. The antiproliferative activity test revealed that complexes showed more intense inhibition ratios against human hepatoma cells lines and human gastric cancer cells lines in vitro. Copper(II) complex (3) possesses the strongest inhibition ratio against human hepatoma cells.

Identification of a predictive gene signature related to pyroptosis for the prognosis of cutaneous melanoma.

Pyroptosis is a form of inflammatory programmed cell death. However, because of no specific molecular biomarker, pyroptosis has not been considered as a novel therapeutic method to treat cutaneous melanoma (CM). Here, we identified pyroptosis genes that associate with the prognosis of CM patients and constructed an effective model for the prognostic prediction of CM patients. To identify genes related to pyroptosis that are differentially expressed in CM, we obtained gene expression data of CM patients and normal skin tissues from the Cancer Genome Atlas and the Genotype-Tissue Expression databases, and used another cohort obtained from Gene Expression Omnibus database for validation. Three genes (BST2, GBP5, and AIM2) that were associated with prognosis were found and incorporated into our prognostic model. Furthermore, we divided the patients into 2 groups: a high-risk group and a low-risk group. Functional analyses indicated that our model was correlated with patient survival and cancer growth. Multivariate and univariate Cox regressions revealed that the constructed model could serve as an independent prognostic factor for CM patients. Meanwhile, compared with other clinical characteristics, our model significantly improved the diagnostic accuracy. Gene function analysis revealed that pyroptosis genes BST2, GBP5, and AIM2 were differentially expressed in CM patients and positively associated with patient prognosis. Finally, a risk score was used to generate nomograms that displayed favorable discriminatory abilities for CM. In summary, our model could significantly predict the prognosis of CM patients and be used for the development of CM therapy.

Binding of circulating anti-MUC1 antibody and serum MUC1 antigen in stage IV breast cancer.

The present study aimed to investigate the binding of circulating mucin 1 (MUC1) antibody with serum MUC1 antigen in stage IV breast cancer. Serum samples of 61 patients with stage IV breast cancer and 64 patients with early-stage breast cancer were collected. The anti­MUC1 antibody (IgG) and MUC1 antigen (cancer antigen 15­3; Ca15­3) were detected using an indirect enzyme-linked immunosorbent assay (I­ELISA) and ELISA, respectively. The MUC1 IgG affinity was detected using a urea degradation combining ELISA. Western blot analysis and an inhibition test were performed for verification of the binding of anti­MUC1 IgG with MUC1 antigen, and their correlation was analyzed. The results showed that there was a negative correlation between anti­MUC1 IgG and CA15­3 antigen in stage IV breast cancer when positive CA15­3 antigen and/or anti­MUC1 IgG were selected (r=­0.417; P=0.0044). The positive anti­MUC1 IgG with positive Ca15­3 antigen was more common in stage IV breast cancer, compared with early­stage breast cancer (χ2=4.629; P=0.031), however, Ca15­3 antigen positivity was higher in stage IV breast cancer, compared with early­stage breast cancer (χ2=10.58; P=0.001). Anti­MUC1 IgG was able to bind to the MUC1 antigen in stage IV breast cancer. No differences in the 8R-MUCPT inhibition ratio were found between the two groups (P=0.778), and there were no differences in the affinity of anti­MUC1 IgG (P=0.873). In stage IV breast cancer, circulating anti­MUC1 antibody was found to bind serum MUC1 antigen, although their compatibility was low. No significant difference was found in the affinity of the anti­MUC1 antibody between stage IV breast cancer and early­stage breast cancer.