DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding.

Hyaline cartilage fibrosis is typically considered an end-stage pathology of osteoarthritis (OA), which results in changes to the extracellular matrix. However, the mechanism behind this is largely unclear. Here, we found that the RNA helicase DDX5 was dramatically downregulated during the progression of OA. DDX5 deficiency increased fibrosis phenotype by upregulating COL1 expression and downregulating COL2 expression. In addition, loss of DDX5 aggravated cartilage degradation by inducing the production of cartilage-degrading enzymes. Chondrocyte-specific deletion of Ddx5 led to more severe cartilage lesions in the mouse OA model. Mechanistically, weakened DDX5 resulted in abundance of the Fn1-AS-WT and Plod2-AS-WT transcripts, which promoted expression of fibrosis-related genes (Col1, Acta2) and extracellular matrix degradation genes (Mmp13, Nos2 and so on), respectively. Additionally, loss of DDX5 prevented the unfolding Col2 promoter G-quadruplex, thereby reducing COL2 production. Together, our data suggest that strategies aimed at the upregulation of DDX5 hold significant potential for the treatment of cartilage fibrosis and degradation in OA.

The association between cadmium exposure and the risk of chronic obstructive pulmonary disease: A systematic review and meta-analysis.

According to the World Health Organization, chronic obstructive pulmonary disease (COPD) was one of the top ten causes of death worldwide in 2019. The ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) provides a useful indicator for the diagnosis of COPD. Existing data have demonstrated that cadmium (Cd) exposure is associated with COPD. However, data concerning the incidence and progression of cadmium-induced COPD is inconsistent. To explore the relationship between cadmium exposure and the risk of COPD in humans, through January 12, 2023, we conducted a thorough search of the PubMed, Cochrane, Web of Science, Embase and Scopus databases for relevant material. In this study, a meta-analysis was conducted to evaluate the association between cadmium and COPD. This meta-analysis indicated that exposure to cadmium (per 1 µg/L increase) was associated with reduced FEV1/FVC (% change = -47.54%, 95% CI: -54.99% to -40.09%). Subgroup analysis showed that the combined effect estimates were significantly higher in the COPD patient group (% change = -54.66%, 95% CI: -83.32% to -26.00%) than in the general population (% change = -52.11%, 95%CI: -60.53% to -43.70%). Therefore, we conclude that cadmium exposure is associated with reduced FEV1/FVC, which suggests a risk for COPD.

Optical vortex coronagraphy for high-contrast imaging of femtosecond laser filaments.

A high-contrast imaging technique for phase objects based on the optical vortex coronagraph (OVC) is proposed. This method offers the unique advantage of background-free imaging due to the introduction of azimuthal phase in the Fourier plane. We employed the OVC method to detect femtosecond laser-induced air plasma and compared it with the classic diffractometry and fluorescent imaging methods. We achieved a phase sensitivity of ∼0.035 waves that surpassed the capabilities of the other two methods. The combination of this highly sensitive imaging technique with the pump-probe method holds promise for applications in ultrafast imaging of laser-material interactions.

Association of urinary arsenic with the oxidative DNA damage marker 8-hydroxy-2 deoxyguanosine: A meta-analysis.

BACKGROUND: The International Agency for Research on Cancer has classified arsenic as a class I carcinogen. Oxidative DNA damage is a typical early precursor to recognized malignancies. The most sensitive early independent marker of oxidative DNA damage is believed to be 8-hydroxy-2 deoxyguanosine (8-OHdG). To date, research on the link between urinary arsenic and 8-OHdG has not been consistent. OBJECTIVE: This study was aimed at exploring the effects of urinary arsenic on 8-OHdG in human urine. METHODS: A literature search until January 2023 was performed on the PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases through a combination of computer and manual retrieval. Stata 12.0 was used to examine the degree of heterogeneity among included studies. The percentage change and 95 % confidence interval (95 % CI) of 8-OHdG were calculated between populations exposed to different doses. We used a random effect model because the degree of heterogeneity exceeded 50 %. Sensitivity analysis and testing for publication bias were performed. RESULTS: This meta-analysis included nine studies, most of which were performed in China. After exposure to arsenic, urinary arsenic (per 10 µg/g creatinine increase) was associated with the increased 8-OHdG (% change = 41.49 %, 95 % CI: 19.73 %, 63.25 %). Subgroup analysis indicated that the percentage change in 8-OHdG in urine was more pronounced in people exposed to arsenic <50 µg/L (% change = 24.60 %, 95 % CI: 17.35 %, 37.85 %). In studies using total urinary arsenic content as an indicator, the percentage change in 8-OHdG in urine was more significant (% change = 60.38 %, 95 % CI: 15.08 %, 105.68 %). CONCLUSION: The 8-OHdG levels in human urine significantly increased after exposure to environmental arsenic, thus suggesting that arsenic exposure is correlated with oxidative DNA damage.

Hypoglycemic effects of dendrobium officinale leaves.

Introduction: Numerous studies have demonstrated that the stems of D. officinale have the effect of lowering blood glucose, but the leaves of D. officinale have seldom been investigated. In this study, we mainly studied the hypoglycemic effect and mechanism of D. officinale leaves. Methods: Initially in vivo, male C57BL/6 mice were administered either standard feed (10 kcal% fat) or high-fat feed (60 kcal% fat) along with either normal drinking water or drinking water containing 5 g/L water extract of D. officinale leaves (EDL) for 16 weeks, and changes in body weight, food intake, blood glucose, etc., were monitored weekly. Next in vitro, C2C12 myofiber precursor cells which were induced to differentiate into myofibroblasts and cultured with EDL to detect the expression of insulin signaling pathway related proteins. HEPA cells were also cultured with EDL to detect the expression of hepatic gluconeogenesis or hepatic glycogen synthesis related proteins. Eventually after separating the components from EDL by ethanol and 3 kDa ultrafiltration centrifuge tube, we conducted animal experiments using the ethanol-soluble fraction of EDL (ESFE), ethanol-insoluble fraction of EDL (EIFE), ESFE with a molecular weight of >3 kDa (>3 kDa ESFE), and ESFE with a molecular weight of <3 kDa (<3 kDa ESFE) for intensive study. Results: The results in vivo revealed that the mice fed the high-fat diet exhibited significantly decreased blood glucose levels and significantly increased glucose tolerance after the EDL treatment, whereas the mice fed the low-fat diet did not. The results in vitro showed that EDL activated the expression of protein kinase B (AKT), the phosphorylation of AKT, and the expression of downstream GSK3ß in the insulin signaling pathway. EDL treatment of HEPA cells confirmed that EDL did not affect hepatic gluconeogenesis or hepatic glycogen synthesis. In the experiment of studying the composition of EDL, we found that the >3 kDa ESFE displayed the effect of lowering blood glucose. In summary, the effect of EDL in lowering blood glucose may bethanole achieved by activating the insulin signaling pathway to increase insulin sensitivity, and the main functional substance was contained within the >3 kDa ESFE. Discussion: The findings of this study represent a reference point for further exploration of the hypoglycemic effects of D. officinale leaves and may assist in both the identification of new molecular mechanisms to improve insulin sensitivity and the isolation of monomeric substances that lower blood glucose. Furthermore, the obtained results may provide a theoretical basis for the development of hypoglycemic drugs with D. officinale leaves as the main component.

Taxonomic and functional biogeographies of soil bacterial communities across the Tibet plateau are better explained by abiotic conditions than distance and plant community composition.

The processes governing soil bacteria biogeography are still not fully understood. It remains unknown how the importance of environmental filtering and dispersal differs between bacterial taxonomic and functional biogeography, and whether their importance is scale-dependent. We sampled soils across the Tibet plateau, with distances among plots ranging from 20 m to 1550 km. Taxonomic composition of bacterial community was characterized by 16S amplicon sequencing and functional community composition by qPCR targeting 9 functional groups involved in N dynamics. Factors representing climate, soil and plant community were measured to assess different facets of environmental dissimilarity. Both bacterial taxonomic and functional dissimilarities were more related to abiotic dissimilarity than biotic (vegetation) dissimilarity or distance. Taxonomic dissimilarity was mostly explained by differences in soil pH and mean annual temperature (MAT), while functional dissimilarity was linked to differences in soil N and P availabilities and N:P ratio. Soil pH and MAT remained the main determinants of taxonomic dissimilarity across spatial scales. In contrast, the explanatory variables of N-related functional dissimilarity varied across the scales, with soil moisture and organic matter having the highest role across short distances (<~330 km), and available P, N:P ratio and distance being important over long distances (>~660 km). Our results demonstrate how biodiversity dimension (taxonomic versus functional aspects) and spatial scale influence the factors driving soil bacterial biogeography.

Ferritinophagy was involved in long-term SiNPs exposure induced ferroptosis and liver fibrosis.

SiNPs could induce liver fibrosisinvivo, but the mechanism was not completely clear. This study focused on exploring whether long-term SiNPs exposure at human-related exposure dosage could lead to ferritinophagy-mediated ferroptosis and liver fibrosis. In vivo, long-term SiNPs exposure induced liver fibrosis inrats accompanied by ferritinophagy and ferroptosis in hepatocytes. Interestingly, the progression of liver fibrosis was alleviated after exposure cessation and recovery, meanwhile ferritinophagy and ferroptosis were not further activated. In vitro, after long-term SiNPs exposure, the mitochondrial membrane ruptured, lipid peroxidation intensified, the level of redox active iron increased and the repair protein of lipid peroxidation were consumed in L-02 cells, demonstrating ferroptosis occurrence. Notably, NCOA4 knockdown inhibited ferritin degradation, alleviated the increase of intracellular ferrous iron level, reduced lipid peroxidation and the depletion of glutathione peroxidase 4 (GPX4). In conclusion, ferritinophagy mediated by NCOA4 was responsible for long-term SiNPs exposure induced hepatocytes ferroptosis and liver fibrosis, which provided a scientific basis for toxicological assessment of SiNPs and would be benefited for the safety design of SiNPs-based products.

Spectral splitting of the lasing emission of nitrogen ions pumped by 800-nm femtosecond laser pulses.

We report on a spectral splitting effect of the cavity-less lasing emission of nitrogen ions at 391.4 nm pumped by 800-nm femtosecond laser pulses. It was found that with the increase of the nitrogen gas pressure and pump pulse energy, both R and P branches experience spectral splitting. With an external injected seeding pulse, a similar split spectral line is observed for the amplified emission. In contrast, for the fluorescence radiation, no such spectral splitting phenomenon is observed with much more abundant R branch structures. Our theoretical model considers gas ionization by the pump pulse, the competition of excitation of all relevant electronic and vibrational states, and an amplification of the seeding pulse in the plasma with a population inversion. Our simulation reproduces this spectral splitting effect, which is attributed to the gain saturation resulting in the oscillation of the amplitude of the amplified signal.

Gut commensal Parabacteroides distasonis alleviates inflammatory arthritis.

OBJECTIVE: Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA. DESIGN: Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal Parabacteroides distasonis in RA. The effects of P. distasonis-derived microbial metabolites on the differentiation of CD4+ T cells and macrophage polarisation were also investigated. RESULTS: The relative abundance of P. distasonis in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live P. distasonis (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of P. distasonis. CONCLUSIONS: P. distasonis and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.

Adverse effects and underlying mechanism of amorphous silica nanoparticles in liver.

Amorphous silica nanoparticles (SiNPs) have been widely used and mass-producted due to its unique properties. With the life cycle of SiNPs-based products, SiNPs are further released into the air, soil, surface water and sediment, resulting in an increasing risk to humans. SiNPs could enter into the human body through vein, respiratory tract, digestive tract or skin. Moreover, recent evidences have showed that, regardless of exposure pathways, SiNPs could even be traced in liver, which is gradually considered as one of the main organs that SiNPs accumulate. Increasing evidences supported the link between SiNPs exposure and adverse liver effects. However, the research models are diverse and the molecular mechanisms have not been well integrated. In this review, the liver-related studies of SiNPs in vivo and in vitro were screened from the PubMed database by systematic retrieval method. We explored the interaction between SiNPs and the liver, and especially proposed a framework of SiNPs-caused liver toxicity, considering AOP Wiki and existing studies. We identified increased reactive oxygen species (ROS) as a molecular initiating event (MIE), oxidative stress, endoplasmic reticulum stress, lysosome disruption and mitochondrial dysfunction as subsequent key events (KEs), which gradually led to adverse outcomes (AOs) containing liver dysfunction and liver fibrosis through a series of key events about cell inflammation and death such as hepatocyte apoptosis/pyroptosis, hepatocyte autophagy dysfuncton and hepatic macrophages pyroptosis. To our best knowledge, this is the first AOP proposed on SiNPs-related liver toxicity. In the future, more epidemiological studies need to be performed and more biomarkers need to be explored to improve the AOP framework for SiNPs-associated liver toxicity.

Vascularized dental pulp regeneration using cell-laden microfiber aggregates.

Regeneration of dental pulp via the transplantation of dental pulp stem cells (DPSCs) has emerged as a novel therapy for dental pulp necrosis after inflammation and injury. However, providing sufficient oxygen and nutrients to support stem cell survival, self-renewal, and differentiation in the narrow root canal remains a great challenge. In this study, we explored a novel strategy based on cell-laden microfibers for dental pulp regeneration. Firstly, we fabricated suitable GelMA hydrogels that facilitate the survival and proliferation of DPSCs and human umbilical vein endothelial cells (HUVECs) and possess satisfactory biomechanical properties to generate microfibers. Two kinds of GelMA microfibers were fabricated with DPSCs and HUVECs via a silicone-tube-based coagulant bath-free method. Live/dead and Ki-67 immunofluorescence staining assays identified that these two cell lines maintained high survival rate and proliferation ability in GelMA microfibers. Immunofluorescence staining confirmed that DPSCs fully spread in the microfibers and highly expressed CD90 and laminin. HUVECs positively express CD31 and VE-cad in microfibers and could migrate well in the GelMA hydrogel. In vitro permeation experiments confirmed the superiority of microfiber aggregates (MAs) in liquid permeation compared to GelMA hydrogel blocks. We further adopted an ectopic pulp regeneration assay in nude mice to validate the regeneration of the aggregates of mixed DPSC-microfibers and HUVEC-microfibers in vivo. Compared to a conventional mixture of DPSCs and HUVECs in GelMA hydrogel blocks, the aggregates of cell-laden microfibers generated more pulp-like tissue, blood vessels, and odontoblast-like cells that positively express DMP-1 and DSPP. To our knowledge, this is the first attempt to apply cell-laden MAs for pulp regeneration. Our study proposes a new solution to the challenge of pulp regeneration, which might promote the clinical translation and application of stem cell-based therapy.

Quantum and quasi-classical effects in the strong field ionization and subsequent excitation of nitrogen molecules.

The processes leading to the N2 + lasing are rather complex and even the population distribution after the pump laser excitation is unknown. In this paper, we study the population distribution at electronic and vibrational levels in N2 + driven by ultra-short laser pulse at the wavelengths of 800 nm and 400 nm by using the quantum-mechanical time-domain incoherent superposition model based on the time-dependent Schrödinger equation and the quasi-classical model assuming instantaneous ionization injection described by density matrix. It is shown that while both models provide qualitatively similar results, the quasi-classical instantaneous ionization injection model underestimates the population inversions corresponding to the optical transitions at 391 nm, 423 nm and 428 nm due to the assumption of quantum mixed states at the ionization time. A fast and accurate correction to this error is proposed. This work solidifies the theoretical models for population at vibrational states in N2 + and paves the way to uncover the mechanism of the N2 + lasing.

Combined exposure to PM2.5 and high-fat diet facilitates the hepatic lipid metabolism disorders via ROS/miR-155/PPARγ pathway.

Environmental fine particulate matter (PM2.5), which has attracted worldwide attention, is associated with the progression of metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether dietary habit exacerbate liver damage caused by PM2.5. The current study aimed to investigate the combined negative effects of PM2.5 and high-fat diet (HFD) on liver lipid metabolism in C57BL/6J mice. Histopathological and Oil-Red O staining analysis illustrated that PM2.5 exposure resulted in increased liver fat content in HFD-fed C57BL/6J mice, but not in standard chow diet (STD)-fed mice. And there was a synergistic effect between PM2.5 and HFD on hepatic lipotoxicity. The increased ROS levels and augmented oxidative damage were evaluated in liver tissue of mice treated with PM2.5 and HFD together. In addition, excessive ROS production could activate the miR-155/peroxisome proliferator-activated receptor gamma (PPARγ) pathway, including up-regulation of lipid accumulation-related protein expressions of recombinant liver X receptor alpha (LXRα), sterol regulatory element binding protein-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1).The use of miR-155 inhibitors demonstrated the indispensable role of miR-155 in the activation of lipid-regulated proteins by PM2.5 and palmitic acid (PA). Collectively, altering high-fat dietary habits could protect against MAFLD motivated by air pollution, and miR-155 might be an effective preventive and therapeutic target for this process.

Melatonin alleviates PM2.5 -induced glucose metabolism disorder and lipidome alteration by regulating endoplasmic reticulum stress.

Exposure to fine particulate matter (PM2.5 ) was associated with an increased incidence of liver metabolic disease. Melatonin has been shown to prevent liver glucolipid metabolism disorders. However, whether melatonin could rescue PM2.5 -induced liver metabolic abnormalities remains uncertain. This study was to evaluate the mitigating effect of melatonin on PM2.5 -accelerated hepatic glucose metabolism imbalance in vivo and in vitro. Schiff periodic acid shiff staining and other results showed that PM2.5 led to a decrease in hepatic glycogen reserve and an increase in glucose content, which was effectively alleviated by melatonin. Targeted lipidomics is used to identify lipid biomarkers associated with this process, including glycerolipids, glycerophospholipids, and sphingolipids. In addition, gene microarray and quantitative polymerase chain reaction analysis of ApoE-/- mice liver suggested that PM2.5 activated the miR-200a-3p and inhibited DNAJB9, and the targeting relationship was verified by luciferase reports for the first time. Further investigation demonstrated that DNAJB9 might motivate endoplasmic reticulum (ER) stress by regulating Ca2+ homeostasis, thus altering the protein expression of GSK3B, FOXO1, and PCK2. Meanwhile, melatonin effectively inhibited miR-200a-3p and glucose metabolism disorder. Knockout of miR-200a-3p in L02 cells revealed that miR-200a-3p is indispensable in the damage of PM2.5 and the therapeutic effect of melatonin. In summary, melatonin alleviated PM2.5 -induced liver metabolic dysregulation by regulating ER stress via miR-200a-3p/DNAJB9 signaling pathway. Our data provide a prospective targeted therapy for air pollution-related liver metabolism disorders.

Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis: therapeutic potential for endogenous pulp regeneration.

Pulp loss is accompanied by the functional impairment of defense, sensory, and nutrition supply. The approach based on endogenous stem cells is a potential strategy for pulp regeneration. However, endogenous stem cell sources, exogenous regenerative signals, and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells. Therefore, the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration. In in vitro study, we investigated the effects of Wnt3a, transforming growth factor-beta 1, and bone morphogenetic protein 7 (BMP7) on human dental pulp stem cells (h-DPSCs) and human umbilical vein endothelial cells. 2D and 3D culture systems based on collagen gel, matrigel, and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs. In in vivo study, an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7. We concluded that BMP7 promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation. Collagen gel maintained the cell adhesion, cell spreading, and cell viability of h-DPSCs in 2D or 3D culture. The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo. The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.

Silica nanoparticles induce pulmonary autophagy dysfunction and epithelial-to-mesenchymal transition via p62/NF-κB signaling pathway.

It has been reported that silica nanoparticles (SiNPs) could cause epithelial-to-mesenchymal transition (EMT), but the specific mechanism is still unclear. Thus, the purpose of this study was to investigate the underlying mechanisms of pulmonary EMT after subacute exposure to SiNPs. The results showed intratracheal instillation of SiNPs increased the pulmonary MDA content, while decreased the activity of SOD and GSH-Px in rats. Western blot analysis demonstrated that SiNPs induced autophagy dysfunction via the upregulation of p62. Meanwhile, the inflammation cytokines (TNF-α, IL-18, IL-1ß) were released in rat lung. Immunohistochemistry and western blot assays both showed that SiNPs could regulate the related protein biomarkers of EMT through decreasing E-cadherin and increasing vimentin in a dose-dependent manner. Besides, SiNPs activated the proteins expression involved in p62/NF-κB signaling pathway, whereas the pulmonary EMT induced by SiNPs was significantly dampened after the knock down of p62. In this study, we illustrated that subacute exposure to SiNPs could trigger the autophagy dysfunction and pulmonary inflammation, further lead to EMT via activating the p62/NF-κB signaling pathway. Our findings provide new molecular evidence for SiNPs-induced pulmonary toxicity.

Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 pathway.

Growing literatures suggest that silica nanoparticles (SiNPs) exposure is correlated with adverse cardiovascular effects. Cardiac hypertrophy is one of the most common risk factors for heart failure. However, whether SiNPs involved in cardiac hypertrophy and the underlying mechanisms was remained unexploited. Our study aimed to investigate the molecular mechanisms of SiNPs on pyroptosis and cardiac hypertrophy. The in vivo results found that SiNPs induced ultrastructural change and histopathological damage, accompanied by oxidative damage occurred and increased levels of inflammatory factors (IL-18 and IL-1ß) in heart tissue. In addition, SiNPs could upregulate the expressions of cardiac hypertrophy-related special marker including ANP, BNP, ß-MHC, it also elevated the pyroptosis-related protein, such as NLRP3, Cleaved-Caspase-1, GSDMD, IL-18 and Cleaved-IL-1ß in vivo. For in vitro study, SiNPs increased the intracellular ROS generation and activated the NLRP3/Caspase-1/GSDMD signaling pathway in cardiomyocytes. Whereas, the NADPH oxidase (NOX) inhibitor VAS2870 had effectively inhibited the ROS level and suppressed the expression of NLRP3, ASC, Pro-Caspase-1, Cleaved-Caspase-1, N-GSDMD, IL-18, Cleaved-IL-1ß, ANP, BNP and ß-MHC. Moreover, transfected with si-NLRP3 or adopted with Caspase-1 inhibitor VX-765 in cardiomyocytes showed an inhibitory effect on SiNPs-induced pyroptosis and cardiac hypertrophy. In summary, our results demonstrated that SiNPs could trigger pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 signaling pathway.

Global association between atmospheric particulate matter and obesity: A systematic review and meta-analysis.

BACKGROUND: Among various air pollutants, particulate matter (PM) is the most harmful and representative pollutant. Although several studies have shown a link between particulate pollution and obesity, the conclusions are still inconsistent. METHODS: We conducted a systematic review and meta-analysis to pool the effect of PM exposure on obesity. Five databases (including PubMed, Web of Science, Scopus, Embase, and Cochrane) were searched for relevant studies up to Jan 2022. Adjusted risk ratio (RR) with corresponding 95% confidence interval (CI) were retrieved from individual studies and pooled with random effect models by STATA software. Besides, we tested the stability of results by Egger's test, Begg's test, funnel plot, and using the trim-and-fill method to modify the possible asymmetric funnel graph. The NTP-OHAT guidelines were followed to assess the risk of bias. Then the GRADE was used to evaluate the certainty of evidence. RESULTS: 26 studies were included in this meta-analysis. 19 studies have shown that PM2.5 can increase the risk of obesity per 10 µg/m3 increment (RR: 1.159, 95% CI: 1.111-1.209), while 15 studies have indicated that PM10 increase the risk of obesity per 10 µg/m3 increment (RR: 1.092, 95% CI: 1.070-1.116). Besides, 5 other articles with maternal exposure showed that PM2.5 increases the risk of obesity in children (RR: 1.06, 95% CI: 1.02-1.11). And we explored the source of heterogeneity by subgroup analysis, which suggested associations between PM and obesity tended to vary by region, age group, participants number, etc. The analysis results showed publication bias and other biases are well controlled, but most certainties of the evidence were low, and more research is required to reduce these uncertainties. CONCLUSION: Exposure to PM2.5 and PM10 with per 10 µg/m3 increment could increase the risk of obesity in the global population.

The relationship between exposure to PM2.5 and atrial fibrillation in older adults: A systematic review and meta-analysis.

Fine particle matter (PM2.5) is recognized as atrial fibrillation (AF) risk factor, especially for older adults. However, studies on the relationship between PM2.5 and AF were inconsistent. Herein, we present a systematic review to further assess the correlation between PM2.5 and AF in older adults (average age > 50 years old). A comprehensive search was conducted with the keywords in PubMed (675 records), Web of Science (1130 records), Embase (82 records), and the Cochrane Library (42 records). Using Stata12.0 software to test the heterogeneity between studies, and select the corresponding model to calculate the comprehensive effect value, odds ratio (OR, odds ratio), the pooled %-change (percentage change) and its 95% confidence interval (CL, confidence interval). A total of 16 observational studies were included, involving 10,580,394 participants, the results showed that PM2.5 had an adverse effects on AF in older adults. An association was found between exposure to PM2.5 (per 10 µg/m3 increase) and AF in older adults, with the corresponding pooled OR (1.11, 95% CI: 1.03-1.19) and pooled %-change (1.01%, 95% CI: 0.14%-1.88%). Our study indicated that PM2.5 exposure was significantly related to increased incidence of AF in older adults. Both the pooled OR and %-change value were higher in areas with higher levels of PM2.5(≥25 µg/m3).

Proliferation of MDA-MB-231 can be suppressed by dimeric-epigallocatechin gallate through competitive inhibition of amphiregulin-epidermal growth factor receptor signaling.

Triple-negative breast cancer (TNBC) is highly aggressive, with high rates of early relapse and very poor overall prognosis. Amphiregulin (AREG) is the most abundant epidermal growth factor receptor (EGFR) agonist in MDA-MB-231 TNBC cells, whose proliferation can be inhibited by (-)-epigallocatechin gallate (EGCG), a constituent of green tea that is prone to oxidative polymerization. The effect of dimeric-EGCG, a dimer of oxidized and polymerized EGCG, on MDA-MB-231 cell the proliferation warrants further exploration. In the present study, MTT, flow cytometry, migration scratch, transwell, western blotting, and surface plasmon resonance assays were used to evaluate the effect of dimeric-EGCG on MDA-MB-231 cells and explore the underlying mechanism. MDA-MB-231 cell proliferation and migration were significantly inhibited by dimeric-EGCG at concentrations as low as 10 µM. Levels of EGFR and p44/42 MAPK phosphorylation in MDA-MB-231 cells were significantly reduced by treatment with 10 µM dimeric-EGCG (P < 0.01). In addition, the levels of phosphorylation induced by exogenous AREG were also inhibited by dimeric-EGCG (P < 0.01); however, no significant effects of dimeric-EGCG were observed on epidermal growth factor or transforming growth factor-alpha signaling. Surface plasmon resonance analysis demonstrated that 10 µM dimeric-EGCG bound directly to the extracellular domain of EGFR, competitively inhibiting the binding of AREG to EGFR. These results suggest a novel mechanism underlying the inhibitory effect of dimeric-EGCG on MDA-MB-231 cells, with potential application in the development of drugs for the treatment of TNBC.