Lung microbiota participated in fibrous microplastics (MPs) aggravating OVA-induced asthma disease in mice.

Environmental pollution is one of the risk factors for asthma. Currently, whether micro-plastics could aggravate asthma, is still unclear. In the air, fibrous MPs are the predominant shape. Since fibrous micro-plastics are reported to be detected in the lower respiratory tract and other body parts, the relationship of fibrous MP and asthma, as well as the potential mechanism is not well investigated. In this study, we produced fibrous MPs, whose lengths and widths were in accordance with the natural environment, and further, investigated the potential adverse effect of which on the asthma in a OVA (ovalbumin)-induced mice model, aiming at exploring the true life hazard of MP to the respiratory system. Following nasal exposure to fibrous MPs, the airway inflammation, mucus hypersecretion and fibrosis were aggravated in asthmatic mice. Fibrous MPs exposure also significantly increased the levels of total IgE, and, cardinal Th2 and Th1 pro-inflammatory cytokines participated in the etiopathogenesis of allergic airway inflammation. In addition, MP fibers exposure induced lung epithelial cells apoptosis, disruption of epithelial barrier integrity and activation of NLRP3 related signaling pathways. Moreover, fibrous MPs significantly altered the bacterial composition at the genus level. Compared to the control group, the relative abundance of Escherichia-Shigella and Uncultured were decreased to 4.47% and 0.15% in OVA group, while Blautia and Prevotella were elevated to 4.96% and 2.94%. For the OVA+MPs group, the relative abundance of Blautia and Uncultured were decreased to 2.27% and 0.006%, while Prevotella was increased to 3.05%. Our study highlights the detrimental effect of fibrous MPs on asthmatic population and facilitates an indication of the latent mechanisms of fibrous MPs induced airway pathology.

Salvianolate ameliorates inflammation and oxidative stress in high-glucose induced HK-2 cells by blocking TGF-ß/Smad signal pathway.

The objective of this research is to assess how salvianolate impacts inflammation and oxidative stress in a laboratory setting, as well as to investigate the underlying mechanisms. HK-2 cells were subjected to different treatments, including normal glucose, mannitol, high glucose and high glucose plus salvianolate. Cell proliferation, death, MDA levels, IL-1ß, IL-6, TNF-α, MCP-1 concentrations, ROS levels, MMP, MPTP and ATP levels were assessed using various kits. The protein expressions of NOX4, TGF-ß1, P-Smad2, P-Smad3, Smad4 and Smad7 were ascertained through western blot analysis. Our results indicated salvianolate could reduce the release of IL-1ß, IL-6, TNF-α, as well as MCP-1, alleviate the levels of oxidative stress markers NOX4 and MDA, and improve mitochondrial function by increasing MMP and ATP levels while reducing ROS and MPTP opening. Furthermore, salvianolate inhibited the TGF-ß1/Smad2, Smad3 signaling pathway, suppressed Smad4 expression and increased Smad7 expression. Salvianolate seems to mitigate inflammation and oxidative stress through a variety of mechanisms. These discoveries offer valuable understanding into the possible mechanisms by which salvianolate may be employed in the treatment of diabetic nephropathy.

MMP11 and MMP17 are potential biomarkers for uterine corpus endometrial carcinoma prognosis

Background Matrix metalloproteinases (MMP) are important proteases that degrade the extracellular matrix (ECM) and thus essentially mediate tumor vascularization, metastasis, and invasion. However, their potential roles in uterine corpus endometrial carcinoma (UCEC) are not fully understood. Patients and methods The expression, prognostic value, and correlation of UCEC patients with MMP were investigated using data from The Cancer Genome Atlas (TCGA) and other databases. Furthermore, differentially expressed genes (DEGs) were identified and their biological functions and correlations with infiltrating immune cells were analyzed. Results A total of 22 MMPs were found to be abnormally expressed in UCEC tumor tissues, and high expression of MMP11 and MMP17 were associated with a better UCEC prognosis. MMP11 and MMP17 were observed to be significantly enriched in tumor tissue ECM and were associated with pathways involving degradation, glycolytic metabolism, and PI3K-Akt signaling. Infiltration of natural killer (NK), mast, and NK CD56bright cells was enhanced in tumor tissues with high MMP11 and MMP17 expression. Conclusion MMP11 and MMP17 may affect UCEC prognosis by influencing immune cell infiltration and may be potential UCEC biomarkers (AU)

MMP11 and MMP17 are potential biomarkers for uterine corpus endometrial carcinoma prognosis.

BACKGROUND: Matrix metalloproteinases (MMP) are important proteases that degrade the extracellular matrix (ECM) and thus essentially mediate tumor vascularization, metastasis, and invasion. However, their potential roles in uterine corpus endometrial carcinoma (UCEC) are not fully understood. PATIENTS AND METHODS: The expression, prognostic value, and correlation of UCEC patients with MMP were investigated using data from The Cancer Genome Atlas (TCGA) and other databases. Furthermore, differentially expressed genes (DEGs) were identified and their biological functions and correlations with infiltrating immune cells were analyzed. RESULTS: A total of 22 MMPs were found to be abnormally expressed in UCEC tumor tissues, and high expression of MMP11 and MMP17 were associated with a better UCEC prognosis. MMP11 and MMP17 were observed to be significantly enriched in tumor tissue ECM and were associated with pathways involving degradation, glycolytic metabolism, and PI3K-Akt signaling. Infiltration of natural killer (NK), mast, and NK CD56bright cells was enhanced in tumor tissues with high MMP11 and MMP17 expression. CONCLUSION: MMP11 and MMP17 may affect UCEC prognosis by influencing immune cell infiltration and may be potential UCEC biomarkers.

Insights into current bio-processes and future perspectives of carbon-neutral treatment of industrial organic wastewater: A critical review.

With the rise of the concept of carbon neutrality, the current wastewater treatment process of industrial organic wastewater is moving towards the goal of energy conservation and carbon emission reduction. The advantages of anaerobic digestion (AD) processes in industrial organic wastewater treatment for bio-energy recovery, which is in line with the concept of carbon neutrality. This study summarized the significance and advantages of the state-of-the-art AD processes were reviewed in detail. The application of expanded granular sludge bed (EGSB) reactors and anaerobic membrane bioreactor (AnMBR) were particularly introduced for the effective treatment of industrial organic wastewater treatment due to its remarkable prospect of engineering application for the high-strength wastewater. This study also looks forward to the optimization of the AD processes through the enhancement strategies of micro-aeration pretreatment, acidic-alkaline pretreatment, co-digestion, and biochar addition to improve the stability of the AD system and energy recovery from of industrial organic wastewater. The integration of anaerobic ammonia oxidation (Anammox) with the AD processes for the post-treatment of nitrogenous pollutants for the industrial organic wastewater is also introduced as a feasible carbon-neutral process. The combination of AnMBR and Anammox is highly recommended as a promising carbon-neutral process for the removal of both organic and inorganic pollutants from the industrial organic wastewater for future perspective. It is also suggested that the AD processes combined with biological hydrogen production, microalgae culture, bioelectrochemical technology and other bio-processes are suitable for the low-carbon treatment of industrial organic wastewater with the concept of carbon neutrality in future.

Effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF.

The current study evaluated the effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF. 60 patients were randomized (1:1) to receive dapagliflozin 10 mg once daily, or placebo double blind for 1 year. Patients underwent transthoracic echocardiography and doppler evaluation prior to dapagliflozin initiation and at 1 year. At 1year, adjusted mean difference versus placebo in change from baseline in LVEF was 2.5% (95% CI: 1.00-4.06, P = 0.002). Adjusted mean difference versus placebo in change from baseline in LVED volume was - 6.0ml (95% CI: -8.07 --3.87, P<0.001). Adjusted mean difference versus placebo in change from baseline in LVES volume was - 8.1ml (95% CI: -11.07 --5.14, P<0.001). Similarly, adjusted mean difference versus placebo in change from baseline in LVED diameter was - 1.6 mm (95% CI: -2.67 --0.62, P = 0.002). Adjusted mean difference versus placebo in change from baseline in VTI was 0.20 cm (95% CI: 0.01-0.38, P = 0.036). Dapagliflozin was well tolerated. Dapagliflozin was associated with significant and clinically meaningful improvement in echocardiographic parameters versus placebo in patients with type 2 diabetes and HFrEF.Registration number and date: ChiCTR2300072707, 21/06/2023.

Role of body mass index in pregnancy outcomes after emergency cerclage for cervical insufficiency in singleton pregnant patients.

BACKGROUND: The study aims were to analyze pregnancy outcomes after the use of emergency cerclage in patients with different BMIs. METHODS: A total of 76 singleton pregnant patients who underwent emergency cerclage at a tertiary comprehensive hospital in China between Jan 2017 and Dec 2021 were retrospectively divided into an obesity group of 37 patients with BMIs ≥ 28 kg/m2 and a non-obesity group of 39 patients with BMIs < 28 kg/m2. The medical records of patients were reviewed and all relevant clinical data were further collected into an itemized data spreadsheet for various analyses. RESULTS: Emergent cerclage, along with amnioreduction if needed, could be safely performed on both obese and non-obese pregnant women with a dilated external cervix (> 1 cm), which effectively prolonged the gestational week up to ≥ 25 weeks. Obese gravidae had shorter suture-to-delivery intervals and mean pregnancy lengths but more spontaneous preterm births before 37 weeks, and a lower live birth rate (P < 0.05). Logistic regression analysis revealed that BMI, how many times cerclages have been performed during pregnancy (frequency of cerclage) and bacterial vaginosis, aerobic vaginitis and vulvovaginal candidiasis (vaginal microecology) were significantly correlated with fetal loss (P < 0.05), while rank correlation analysis established a negative correlation between BMI values and the suture-to-delivery interval (P = 0.031). CONCLUSIONS: Pregnant cervical insufficiency patients with BMIs > 28 kg/m2 may ill-serve the gestational outcomes and suture-to-delivery interval after their emergent cerclage. Additionally, BMI, frequency of cerclage and vaginal microecology accounted for higher fetal loss in patients who underwent emergency cerclage.

Estrogenic and non-estrogenic effects of bisphenol A and its action mechanism in the zebrafish model: An overview of the past two decades of work.

Bisphenol A (BPA) is the most simple and predominant component of the Bisphenol family. BPA is widely present in the environment and the human body as a result of its extensive usage in the plastic and epoxy resins of consumer goods like water bottles, food containers, and tableware. Since the 1930s, when BPA's estrogenic activity was first observed, and it was labeled as a "mimic hormone of E2", studies on the endocrine-disrupting effects of BPA then have been widely conducted. As a top vertebrate model for genetic and developmental studies, the zebrafish has caught tremendous attention in the past two decades. By using the zebrafish, the negative effects of BPA either through estrogenic signaling pathways or non-estrogenic signaling pathways were largely found. In this review, we tried to draw a full picture of the current state of knowledge on the estrogenic and non-estrogenic effects of BPA with their mechanisms of action through the zebrafish model of the past two decades, which may help to fully understand the endocrine-disrupting effects of BPA and its action mechanism, and give a direction for the future studies.

Luteolin restored Treg/Th17 balance to ameliorate allergic rhinitis in a mouse model.

OBJECTIVE: Luteolin (LO) has been reported to be a potential drug for allergic rhinitis (AR). This paper explored the mechanism of LO in AR. MATERIALS AND METHODS: Mice were treated with ovalbumin (OVA) to construct an AR model in vivo before LO or 3-methyladenine (3-MA) treatment. The frequency of nasal sneezing was counted. The nasal mucosa thickness was assessed by hematoxylin-eosin staining assay. The levels of anti-OVA-immunoglobulin E (IgE)/IgG2a, autophagy-related factors (Beclin1, LC3II/LC3I), and T helper cell 17 (Th17)/regulatory T cell (Treg) markers (interleukin (IL)-17A, retinoic acid receptor-related orphan nuclear receptor γt (RORγt)/IL-10, forkhead box P3 (Foxp3)) were detected through enzyme-linked immunosorbent assay, western blot, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Flow cytometry assay was performed to test the percentage of Th17 and Treg cells. RESULTS: The nasal sneezing frequency, nasal mucosa thickness, and levels of anti-OVA-IgE, Beclin1, LC3II/LC3I, IL-17A as well as RORγt were enhanced whereas anti-OVA-IgG2a, IL-10, and Foxp3 levels were inhibited in a mouse model of OVA-induced AR, which were reversed by LO or 3-MA treatment. CONCLUSIONS: LO restored Treg/Th17 balance to ameliorate AR in a mouse model.

Loss of growth differentiation factor 9 causes an arrest of early folliculogenesis in zebrafish-A novel insight into its action mechanism.

Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9-null follicles, the expression of activin ßAa (inhbaa), but not ßAb (inhbab) and ßB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported.

Comparative Study of the Gut Microbiota Community between the Farmed and Wild Mastacembelus armatus (Zig-Zag Eel).

Cultivated and wild fish of the same species may exhibit different characteristics, such as in their flavor, growth and development. In some wild fish species, reproductive functions may even be retarded when wild individuals are moved into cultivated conditions. The gut microbiota may be one of the reasons for these phenomena as they have been reported to play an important role in host growth and development, as well as in normal reproductive functioning. Here, we used Mastacembelus armatus (zig-zag eel), a freshwater fish which shows anormal reproductive function in cultivated conditions, as a model to comparatively study the diversity, structure and function of gut microbiota in cultivated and wild groups by analyzing the 16S rRNA sequence of each group's microbiota. The results showed that Proteobacteria and Firmicutes were the dominant phyla in the gut microbiota of wild (accounting for 45.8% and 20.3% of the total number of Proteobacteria and Firmicutes, respectively) and farmed (accounting for 21.4% and 75.6% of the total number of Proteobacteria and Firmicutes, respectively) zig-zag eel. Wild zig-zag eels (Shannon = 3.56; Chao = 583.08; Ace = 579.18) had significantly higher alpha diversity than those in cultivated populations (Shannon = 2.09; Chao = 85.45; Ace = 86.14). A significant difference in the community structure of the gut microbiota was found between wild and cultivated populations. The wild zig-zag eel showed a high abundance of functional pathways in metabolism, genetic information processing and organismal system function. These results suggested that the diversity and function of gut microbiota in zig-zag eel were correlated with their diet and habitat conditions, which indicated that the management of cultivated populations should mimic the wild diet and habitat to improve the productivity and quality of farmed zig-zag eel.

Chemical oxygen demand and nitrogen removal from real membrane-manufacturing wastewater by a pilot-scale internal circulation reactor integrated with partial nitritation-anammox.

A pilot-scale system integrating internal circulation and partial nitritation-anammox successfully treated real high-strength membrane-manufacturing wastewater in this study. With this pilot-scale system, a high chemical oxygen demand (COD) removal efficiency of 85 % and a nitrogen removal of 90 % are achieved at an organic loading rate of 6.0 kg COD/m3/d. The nitrogenous organic matters in the internal circulation zone are degraded into ammonia nitrogen. In the partial nitrification zone, nitrite accumulation is achieved, providing a suitable NH4+-N/NO2--N ratio for anammox reaction. Partial nitritation is achieved by maintaining an operational temperature at 30-35 °C, free ammonia concentration at 5-7 mg/L and dissolved oxygen at 0.4-0.7 mg/L with a reflux ratio of 150 %. The COD to nitrogen ratio in the internal circulation effluent is maintained below 3.0 to inhibit nitrite oxidizing bacteria. This study demonstrates that a pilot-scale system can efficiently remove organic matters and nitrogen from wastewater of membrane-manufacturing industry.

Human placenta-based genome-wide mRNA sequencing to identify TEK/IGF1/CSF1/ANGPT2 as crucial segments in the pathogenesis of pre-eclampsia.

Pre-eclampsia is a pregnancy-specific disease commonly occurring in late pregnancy and has always been threatening maternal and fetal lives, yet the etiology and pathogenesis of pre-eclampsia are still uncertain. To depict the overall changes of genes at the genome-wide level and identify potential biomarkers for early diagnosis of pre-eclampsia, we conducted this study by collecting placenta samples donated by six pregnancy women, among whom three healthy women were included as controls and three women were diagnosed with pre-eclampsia. The placental sample tissues were then subjected to high-throughput sequencing. Furthermore, we proceeded with bioinformatics analysis and formulated the hypothesis of pre-eclampsia development and verified the potential targets of pre-eclampsia by immunohistochemistry. Demographically, we found that the baseline characteristics of study subjects were highly homogeneous except for gestational weeks and blood pressure, where the blood pressure was higher and gestational weeks were shorter in the pre-eclampsia group (systolic blood pressure 123.33 ± 4.62 vs. 148.67 ± 3.79 mmHg, p = 0.046; diastolic blood pressure 79.00 ± 5.20 vs. 88.33 ± 2.89 mmHg, p = 0.068; gestational weeks 39.33 ± 1.03 vs. 35.76 ± 2.41, p = 0.050). Specific pathological changes were identified, shown as syncytial knots, fibrinoid necrosis, perivillous fibrin deposition, and vasculitis. For high-throughput sequencing, a total of 1,891 dysregulated genes were determined, of which 960 genes were downregulated and 931 genes were upregulated. The bioinformatics analysis indicated that these genes, with different molecular functions in different parts of cells, were primarily responsible for endothelium development and vascular process in the circulatory system, and more than 10 signaling pathways were involved. By focusing on the PI3K-Akt signaling pathway, Rap1 signaling pathway, and disease enrichment analysis item pre-eclampsia, TEK, CSF1, IGF1, and ANGPT2 were identified to promote the development of pre-eclampsia. After confirming the placental expression of these genes at the protein level, we proposed the pathogenesis of pre-eclampsia as follows: the downregulation of TEK, CSF1, IGF1, and ANGPT2 may inhibit trophoblast proliferation and affect the remodeling of spiral arteries, causing maternal and fetal malperfusion and impeding nutrient exchange, thereby leading to clinical manifestations of pre-eclampsia.

Host Responses to Live-Attenuated ASFV (HLJ/18-7GD).

African swine fever (ASF) is a highly contagious and fatal disease caused by the African swine fever virus. Recently, the multigene family and CD2v gene-deleted ASF vaccine candidate HLJ/18-7GD was found to be safe and effective in laboratory and clinical trials. However, the immune-protective mechanisms underlying the effects of HLJ/18-7GD remain unclear. We assessed samples from pigs immunized with a single dose of 106 TCID50 HLJ/18-7GD. We found that pigs immunized with HLJ/18-7GD showed high levels of specific antibodies. T lymphocyte subsets (helper T cells (Th); cytotoxic T lymphocytes (CTL); double-positive T cells (DP-T cells)) were temporarily increased in peripheral blood mononuclear cells (PBMCs) after HLJ/18-7GD immunization. Once the HLJ/18-7GD-immunized pigs had been challenged with virulent HLJ/18, the percentage of Th, CTL, and DP-T cells increased significantly. PBMCs extracted from the pigs induced higher levels of CD8+ T cells after infection with the HLJ/18 strain in vitro. The levels of GM-CSF, IFN-γ, and TNF-α were upregulated at 7 days post-inoculation; this finding was contrary to the results obtained after HLJ/18 or HLJ/18ΔCD2v infection. The immune protection from HLJ/18-7GD resulted from many synergies, which could provide a theoretical basis for HLJ/18-7GD as a safe and effective ASF vaccine.

Less is More: Trace Amount of a Cyclic Sulfate Electrolyte Additive Enable Ultra-Stable Graphite Anode for High-Performance Potassium-Ion Batteries.

Graphite can be successfully used as an anode for potassium-ion batteries (PIBs), while its conversion to KC8 leads to huge volume expansion, destruction of solid electrolyte interphase (SEI), and thus poor cycling stability. Incorporating additives into electrolytes is an economical and effective way to construct robust SEI for high-performance PIBs. Herein, we developed a series of sulfur-containing additives for PIB graphite anodes, and the impacts of their molecular structure and contents on the SEI are also systematically investigated. Compared with butylene sulfites and 1,3-propane sultone, the 1,3,2-dioxathiolane 2,2-dioxide (DTD) additive endows the graphite electrode (GE) with a higher reversible capacity, and better cycling stability in both the dilute potassium bis(fluorosulfonyl)imide (KFSI)- and potassium hexafluorophosphate (KPF6)-based carbonate electrolyte, as a result of a thinner and sulfate-enriched SEI. Moreover, the addition of a trace amount (0.2 wt %) DTD to the electrolyte can effectively protect the GE running over 800 cycles at 1 C. Excessive additives in the electrolyte will induce continuous SEI growth and render a rapid capacity fading of the GE. This strategy using the electrolyte additive paves the way for the design of novel PIB electrolytes and thus provides a great opportunity for commercial PIBs.

D-dimer as a predictor of cardiovascular outcomes in patients with diabetes mellitus.

OBJECTIVE: This study aimed to investigate the association between D-dimer and cardiovascular diseases outcomes in patients with type 2 diabetes. METHODS: This is a single-center retrospective cohort study which was performed in a population who had health examinations between 2010 and 2015 in Jiangxi Provincial People's Hospital. All adult patients who were diagnosed with type 2 diabetes were screened. The cardiovascular diseases events were defined as all-cause mortality, new cardiovascular diseases incidence (acute myocardial infarction, unstable angina, stroke), or cardiovascular mortality. RESULTS: The median age was 59.6 years; 50.1% of participants were women; D-dimer was significantly associated with endpoint events. After multivariable adjustment for form of treatments and traditional risk factors, the odds ratio was 3.62 (95% CI 2.07-6.03) for the highest quartile of D-dimer with the lowest quartile as reference. Meanwhile, higher D-dimer levels were associated with a significant and independent higher risk of cause-specific cardiovascular disease events. CONCLUSION: High plasma concentrations of D-dimer were associated with increased risk of cardiovascular diseases events in patients with type 2 diabetes, even after adjusting for cardiovascular risk factors and form of treatments. Measurement of D-dimer may lead to a practical improvement in the current risk stratification criteria for patients with type 2 diabetes.

Effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and its possible mechanisms.

The current study evaluated the effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and investigated its possible mechanisms. 124 patients were randomized to receive 25 mg empagliflozin QD, or placebo double blind for 12 weeks. Patients underwent 24-h ABPM. Endothelial function and arterial stiffness were also measured prior to randomization and at week 12. At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h SBP was - 8.14 mmHg (95% CI - 10.32, - 3.96, P = 0.005). At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h DBP was - 5.27 mmHg (95% CI - 8.19, - 1.35, P < 0.001). Changes in office BP were consistent with ABPM. Empagliflozin was well tolerated. Empagliflozin was associated with significant and clinically meaningful reductions in BP versus placebo in Chinese elderly patients with type 2 diabetes and hypertension. The underlying mechanisms possiblely at least in part were the improvements of endothelial function and arterial stiffness associated with empagliflozin.Registration number: ChiCTR2100054678, Registration date: December 23, 2021.

Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome.

The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People's Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.

Hypomethylation and downregulation of miR-23b-3p are associated with upregulated PLAU: a diagnostic and prognostic biomarker in head and neck squamous cell carcinoma.

BACKGROUND: DNA methylation and miRNA-target genes play an important part in the early development of various tumors and have been studied as tumor biomarkers. Although previous studies have reported a cluster of molecular events (such as aberrant alterations of genomics and epigenetics), little is known of the potential biomarkers for early diagnosis and prognostic evaluation in head and neck squamous cell carcinoma (HNSCC). METHODS: Multiple bioinformatics tools based on The Cancer Genome Atlas (TCGA) database and clinical samples were applied to evaluate the beneficial biomarkers in HNSCC. We focused on the role of plasminogen activator urokinase (PLAU), including diagnostic and prognostic significance, gene expression analysis, aberrant DNA methylation characteristics, interaction of miRNAs and associated signaling pathways. RESULTS: We found that PLAU was aberrantly upregulated in HNSCC, regardless of the mRNA or protein level. The results of receiver operating characteristic (ROC) curve and Cox regression analysis revealed that PLAU was a diagnostic and independent prognostic factor for patients with HNSCC. Hypomethylation of PLAU was closely related to poor survival in HNSCC. Additionally, miR-23b-3p was predicted to target PLAU and was significantly downregulated in HNSCC tissues. Therefore, our findings suggested that PLAU functioned as a promoter in the pathological process of HNSCC. DNA hypomethylation and downregulation of miR-23b-3p were associated with PLAU overexpression. Finally, our findings provided evidence of a significant interaction between PLAU-target and miRNAs-target pathways, indicating that miR-23b-3p suppresses malignant properties of HNSCC by targeting PLAU via Ras/MAPK and Akt/mTOR signaling pathways. CONCLUSIONS: PLAU is overexpressed and may serve as an independent diagnostic and prognostic biomarker in HNSCC. Hypomethylation and downregulation of miR-23b-3p might account for the oncogenic role of PLAU in HNSCC.

MicroRNA-29a promotes the proliferation of human nasal epithelial cells and inhibits their apoptosis and promotes the development of allergic rhinitis by down-regulating FOS expression.

OBJECTIVE: To explore the regulation of microRNA-29a (miR-29a) on FOS in human nasal epithelial cells and its molecular mechanism, as well as the effects of miR-29a on the cell proliferation and apoptosis. METHODS: By cell transfection, gene silencing, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry and TUNEL assay (for cell apoptosis), CCK-8 assay (for cell proliferation), dual-luciferase reporter gene assay and Western Blot, it was validated that miR-29a promoted the proliferation of human nasal epithelial cells and inhibited their apoptosis by down-regulating FOS expression in RPMI2650 and HNEpC cell lines. RESULTS: ①Compared with healthy controls, miR-29a expression was up-regulated and FOS mRNA expression was down-regulated in the nasal tissues from the patients with allergic rhinitis (AR). ②MiR-29a over-expression promoted the proliferation of RPMI2650 cells and HNEpC cells but inhibited their apoptosis. ③MiR-29a targeted at FOS. ④MiR-29a over-expression and FOS silencing both significantly promoted cell proliferation and inhibited cell apoptosis. After transfection with both miR-29a and FOS, there was a decrease in the proliferation but an increase in the apoptosis of cells.⑤MiR-29a promoted the proliferation of human nasal epithelial cells and inhibited their apoptosis by down-regulating FOS expression. CONCLUSION: MiR-29a-/FOS axis can be regarded as a potential marker and a new therapy for AR.