Epigenetic regulation by KDM5A mediates the effects of prenatal PM2.5 exposure on hippocampal development and synaptic integrity through the Shh signaling pathway.

Prenatal environmental exposure could be an essential health risk factor associated with neurodevelopmental disorders in offspring. However, the exact mechanisms underlying the impact of prenatal PM2.5 exposure on offspring cognition remain unclear. In our recent study using a PM2.5 exposed pregnant mouse model, we observed significant synaptic dysfunction in the hippocampi of the offspring. Concurrently, the epigenetic regulator of KDM5A and the Shh signaling pathway exhibited decreased activities. Significantly, changes in hippocampal KDM5A and Shh levels directly correlated with PM2.5 exposure intensity. Subsequent experiments revealed a marked reduction in the expression of Shh signaling and related synaptic proteins when KDM5A was silenced in cells. Notably, the effects of KDM5A deficiency were reversed significantly with the supplementation of a Shh activator. Furthermore, our findings indicate that Shh activation significantly attenuates PM2.5-induced synaptic impairments in hippocampal neurons. We further demonstrated that EGR1, a transcriptional inhibitor, plays a direct role in KDM5A's regulation of the Shh pathway under conditions of PM2.5 exposure. Our results suggest that the KDM5A's inhibitory regulation on the Shh pathway through the EGR1 gene is a crucial epigenetic mechanism underlying the synaptic dysfunction in hippocampal neurons caused by maternal PM2.5 exposure. This emphasizes the role of epigenetic regulations in neurodevelopmental disorders caused by environmental factors.

Association of obstructive sleep apnea symptoms with all-cause mortality and cause-specific mortality in adults with or without diabetes: A cohort study based on the NHANES.

BACKGROUND: The association between obstructive sleep apnea syndrome (OSAS) and mortality has not been extensively researched among individuals with varying diabetic status. This study aimed to compare the relationship of OSAS with all-cause and cause-specific mortality in US individuals with or without diabetes based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The study included participants from the NHANES 2005-2008 and 2015-2018 cycles with follow-up information. OSAS data (OSAS.MAP10) was estimated from the questionnaire. Hazard ratios (HRs) and the 95% confidence interval (CI) of OSAS for mortality were calculated by Cox regression analysis in populations with different diabetes status. The relationships between OSAS and mortality risk were examined using survival curves and restricted cubic spline curves. RESULTS: A total of 13 761 participants with 7.68 ± 0.042 follow-up years were included. In the nondiabetic group, OSAS.MAP10 was positively associated with all-cause, cardiovascular, and cancer mortality. In individuals with prediabetes, OSAS.MAP10 was positively related to all-cause mortality (HR 1.11 [95% CI: 1.03-1.20]) and cardiovascular mortality (HR 1.17 [95% CI: 1.03-1.33]). The relationship between OSAS.MAP10 and the risk of all-cause mortality and cancer mortality exhibited L-shaped curves in diabetes patients (both with nonlinear p values <.01). Further threshold effect analysis revealed that OSAS was positively related to death risk when OSAS.MAP10 exceeded the threshold scores. CONCLUSION: The relationship between OSAS and mortality differed among participants with or without diabetes. Individualized clinical treatment plans should be developed in clinical practice to reduce the risk of death for patients with different metabolic conditions.

Preparation and application of curcumin loaded with citric acid crosslinked chitosan-gelatin hydrogels.

While oral administration offers safety benefits, its therapeutic efficacy is hindered by various physiological factors within the body. In this study, a novel approach was explored using a matrix consisting of 2 % chitosan and 2 % gelatin, with citric acid (CA) serving as a green cross-linking agent (ranging from 0.4 % to 1.0 %), and curcumin (Cur) as the model drug to formulate hydrogel carriers. The results showed that a 0.4 % CA concentration, the hydrogel (CGA0.4) reached swelling equilibrium in deionized water within 40 min, exhibiting a maximum swelling index was 539 g/g. The addition of Cur to the CGA hydrogel (CGACur) notably enhanced release efficiency, particularly in simulated intestinal fluid, where Cur release rates exceeded 40 % within 100 min compared to below 8 % in other solutions. Among these hydrogels, CGA0.4Cur exhibited the fastest degradation rate in the combined solution, reaching >90 % degradation after 7 days. Additionally, Cur and CA demonstrated positive effects on the tensile strength, antioxidant activity and antibacterial activity of hydrogels. Compare to the bioaccessibility of CGC (27 %), those of CGACur had increased to over 34 %. These findings offer provide theoretical support for CA-crosslinked chitosan/gelatin gels in delivering hydrophobic bioactive molecules and their application in intestinal drug delivery system.

Analysis of therapeutic effects on type II respiratory failure and impact on blood gas changes: high-flow nasal oxygen therapy vs. non-invasive positive pressure ventilation.

OBJECTIVE: To evaluate the efficacy of high-flow nasal oxygen therapy (HFNO) vs. non-invasive positive pressure ventilation (NIPPV) in type II respiratory failure, and analyze their impact on blood gas parameters. METHODS: A retrospective analysis of 110 cases of type II respiratory failure treated from April 2021 to March 2023 categorized patients into control (NIPPV, n=50) and observation (HFNO, n=60) groups. Both groups received comprehensive nursing interventions. Treatment outcomes, respiratory and hemodynamic parameters, blood gas parameters, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were compared before and 48 hours after treatment. Additionally, the complication rates and independent risk factors affecting prognosis were analyzed. RESULTS: The observation group exhibited superior treatment efficacy compared to the control group (P=0.001). Both groups showed significant improvements in APACHE II scores and respiratory, hemodynamic, and blood gas parameters after treatment (P<0.001), with the observation group experiencing more pronounced improvements (P<0.001). The observation group also had a lower incidence of complications than the control group (P=0.013). Logistic regression identified PaCO2 and treatment protocol as independent risk factors affecting adverse outcomes (P<0.05). CONCLUSION: HFNO demonstrates superior therapeutic efficacy in type II respiratory failure, significantly improving blood gas parameters with a high level of safety, supporting its clinical applicability.

The relationship between cancer associated fibroblasts biomarkers and prognosis of breast cancer: a systematic review and meta-analysis.

Background: To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment. Methodology: PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. Results: Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-ß (PDGFR-ß) (P = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < 0.0001), matrix metalloproteinase (MMP) 9 (P < 0.0001), MMP 11 (P < 0.0001) and MMP 13 (P = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P = 0.0002), podoplanin (PDPN) (P = 0.0008), and PDGFR-ß (P = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-ß expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2). Conclusions: The high expression of α-SMA, PDPN, PDGFR-ß in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.

Early-stage neutralizing antibody level associated with the re-positive risk of Omicron SARS-CoV-2 RNA in patients recovered from COVID-19.

Post-discharge re-positivity of Omicron SARS-CoV-2 is challenging for the sufficient control of this pandemic. However, there are few studies about the risk of re-positivity. We aimed to explore the association of neutralizing antibodies (nAbs, AU/mL) with the incidence of re-positivity among patients recovered from COVID-19. A retrospective cohort study selected 318 Omicron-infected patients was conducted in China between December 2021 and April 2022. The peak value of nAb levels (nAb-peak) within 14 days of disease onset was defined as the baseline and was mainly used for the subsequent analyses. In the unadjusted, minimally adjusted, fully adjusted, and additionally adjusted for IgG models, a per-standard deviation (SD) increase in the nAb-peak values was significantly associated with a 59 %, 59 %, 50 %, and 75 % decreased risk of Omicron SARS-CoV-2 re-positivity during post-discharge surveillance, respectively. Stratified analyses showed no significant changes in the relationship between nAbs and re-positivity. Our study suggested that the increase in baseline nAb levels independently associated with a low risk of re-positivity in patients recovered from COVID-19.

Ferroptotic alveolar epithelial type II cells drive TH2 and TH17 mixed asthma triggered by birch pollen allergen Bet v 1.

Asthma is a common allergic disease characterized by airway hypersensitivity and airway remodeling. Ferroptosis is a regulated death marked by iron accumulation and lipid peroxidation. Several environmental pollutants and allergens have been shown to cause ferroptosis in epithelial cells, but the relationship between birch pollinosis and ferroptosis in asthma is poorly defined. Here, for the first time, we have identified ferroptosis of type II alveolar epithelial cells in mice with Bet v 1-induced asthma. Further analysis revealed that treatment with ferrostatin-1 reduced TH2/TH17-related inflammation and alleviated epithelial damage in mice with Bet v 1-induced asthma. In addition, ACSL4-knocked-down A549 cells are more resistant to Bet v 1-induced ferroptosis. Analysis of clinical samples verified higher serum MDA and 4-HNE concentrations compared to healthy individuals. We demonstrate that birch pollen allergen Bet v 1 induces ferroptosis underlaid TH2 and TH17 hybrid asthma. Lipid peroxidation levels can be considered as a biomarker of asthma severity, and treatment with a specific ferroptosis inhibitor could be a novel therapeutic strategy.

Correction: The Role of the Mammalian DNA End-processing Enzyme Polynucleotide Kinase 3'-Phosphatase in Spinocerebellar Ataxia Type 3 Pathogenesis.

[This corrects the article DOI: 10.1371/journal.pgen.1004749.].

Efficacy and safety of intratonsillar immunotherapy for allergic rhinitis: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary. OBJECTIVE: To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed. RESULTS: The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed. CONCLUSION: The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach. TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.

CIRC_0033530 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY MODEL OF HUMAN LUNG FIBROBLASTS BY MIR-1184/TLR4 AXIS.

ABSTRACT: Background: Circular RNAs have been reported to be involved in regulating the progression of sepsis and sepsis-associated damage. Herein, this work investigated whether circ_0033530 had roles in the process of septic acute lung injury (sepsis-ALI) and its associated mechanism. Methods: Lipopolysaccharide (LPS)-stimulated human lung fibroblasts MRC-5 were used to mimic the cell model of sepsis-ALI in vitro . Levels of genes and proteins were detected by quantitative real-time polymerase chain reaction and Western blotting. Functional experiments were conducted using 5-ethynyl-2'-deoxyuridine assay, Cell Counting Kit-8 assay, flow cytometry, and enzyme-linked immunosorbent assay. The interaction between miR-1184 and circ_0033530 or toll-like receptor 4 (TLR4) was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0033530 expression was lower in sepsis patients and LPS-induced fibroblasts than those in healthy control and untreated cells. Functionally, knockdown of circ_0033530 protected fibroblasts against LPS-induced proliferation arrest, apoptosis, and inflammatory response. Mechanistically, circ_0033530 acted as a sponge for miR-1184, and TLR4 RNA was targeted by miR-1184, indicating the circ_0033530/miR-1184/TLR4 axis. Further rescue experiments showed that circ_0033530 silencing-mediated growth inhibition and inflammation on fibroblasts were attenuated by miR-1184 downregulation or TLR4 upregulation. Conclusion: Circ_0033530 knockdown alleviated LPS-induced proliferation arrest, apoptosis, and inflammation in lung fibroblasts by miR-1184/TLR4 axis, and provided molecular theoretical basis for circ_0033530 on the pathogenesis of sepsis-ALI.

Carbon emissions and low-carbon development in Olefin industry.

Olefin industry as a vital part in economic development is facing a problem of high CO2 emission. In this work, for the global and China's olefin industry under different development scenario, the carbon emission is predicted after the revealing of carbon footprint in different olefin routes. The results show that the carbon footprint of the natural gas liquids (NGLs)-derived route is highly lower than that of the oil- and coal-derived routes. The carbon emission from the global olefin industry in 2015 is 553 million ton CO2 (MtCO2). In 2030, it will be ranged between 739 and 924 MtCO2 under different scenarios. Under sustainable development scenario, 15% reduction space is existed, whereas 6% growth is observed under the hybrid-development scenario compared to the business-as-usual situation. In the case of China, its carbon emission is 120 MtCO2 in 2015. Its potential carbon emission in 2030 will increase to 264-925 MtCO2, depending on the rest new capacity from low-carbon or high-carbon routes. The large gap implies the significant influence of the development route choice. However, if most new capacity is from the existed planned olefin projects, the carbon emission will be ranged between 390 and 594 MtCO2. Finally, the low-carbon roadmaps as well as polices are proposed for sustainable development of olefin industry.

Relationship between systemic immune inflammation index and mortality among US adults with different diabetic status: Evidence from NHANES 1999-2018.

OBJECTIVE: To investigate the association between systemic immune inflammation index (SII) and all-cause or cardiovascular diseases (CVDs) mortality in US adults with different diabetic status based on the National Health and Nutrition Examination Survey (NHANES) database. STUDY DESIGN AND SETTING: Adults with follow-up data in the NHANES 1999-2018 cycles were included in this study. The SII was calculated based on blood cells counts (including neutrophils, lymphocytes, and platelets) measured in the laboratory data. According to the quartiles of SII, population were divided into four groups (Q1-Q4). Mortality data was determined by linking NHANES survey participants to the National Death Index records, which collect mortality data and determine their vital status. Cox regression models were also performed to explore the hazard ratio (HR) and the corresponding 95 % confidence interval (95 % CI) of SII related with all-cause and CVDs mortality. In addition, restricted cubic spline was used to explore the nonlinear relationship between SII and mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of our results. RESULTS: In this study, there were 45,454 participants were enrolled (50.43 % females), with a mean age of 47.35 ± 0.19 years. Among of which, 7971 were diabetes patients and 3281 were pre-diabetes. With the mean 9.89 ± 0.08 follow-up years, there were 6935 (15.26 %) deaths occurred. Of which, 1795 deaths were caused by CVDs. The age-adjusted death rates were higher in participants with high SII levels compared to those with low SII levels. Cox regression analysis, after adjusting for covariates, revealed that SII levels were associated with an increased risk of all-cause mortality (HR, 1.02; 95 % CI, 1.02-1.03, P < 0.0001) and CVDs mortality (HR, 1.05; 95 % CI, 1.02-1.08, P = 0.002) in the fully adjusted Model. Moreover, there was a slight increase in HR values with the progression of diabetes status. Restricted cubic spline analysis demonstrated a "U-shaped" relationship between SII and all-cause mortality in diabetic, pre-diabetic and non-diabetic populations (all the P for nonlinear < 0.001). In addition, the relationship between SII and CVDs mortality was also nonlinear in both the pre-diabetic and non-diabetic populations (both P < 0.001). However, there was a linear relationship between SII and cardiovascular mortality in individuals with diabetes (P = 0.528). CONCLUSION: The SII is closely associated with the risk of all-cause and cardiovascular mortality. These associations vary among individuals with different diabetic states. Therefore, monitoring systemic inflammation and SII values is crucial in mitigating the risk of mortality.

Gallic acid promotes ferroptosis in hepatocellular carcinoma via inactivating Wnt/ß-catenin signaling pathway.

Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking ß-catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/ß-catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.

Changing trends of the diseases burden attributable to high BMI in Asia from 1990 to 2019: results from the global burden of disease study 2019.

OBJECTIVE: To analyse the trends of diseases burden attributed to high body mass index (BMI), including overweight and obesity, in Asia from 1990 to 2019. DESIGN: Observational study. SETTING: The data of 45 countries and regions in Asia were obtained from the Global Burden of Disease Study 2019 database. MAIN OUTCOME MEASURES: Numbers, age-standardised rate (ASR) of deaths and disability-adjusted life years (DALYs), and the corresponding estimated annual percentage changes (EAPCs), attributable to high BMI in Asia from 1990 to 2019, were analysed by regions, genders and age. We also analysed changes in the causes of deaths and DALYs that are attributable to high BMI over this period. RESULTS: In 2019, all causes deaths attributable to high BMI in Asia were 2 329 503, with increases by 265% compared with 1990. Over three decades, DALYs related to high BMI have increased by 268%. The ASRs of deaths and DALYs in Asia both showed continuous upward trends during this period (EAPC 1.39; 95% certainty interval [95% CI] 1.35 to 1.43 for deaths; EAPC 1.8; 95% CI 1.76 to 1.84 for DALYs), while both were declined in high-income areas (EAPC -2.03 and -1.26). By geographical regions, disease burden in Central Asia and West Asia have been fluctuating at high levels, but high-income Asia Pacific showed decreasing trends of ASR of deaths (EAPC -2.03) and DALYs (EAPC -1.26). Over this period, disease burden in Asia was changing from women to men, and tends to ageing. In addition, diabetes were the diseases most affected by high BMI, and cancer burden was high in middle-aged and elderly people. CONCLUSIONS: The disease burden attributed to high BMI in Asia has experienced great changes. It is necessary to promote the prevention of obesity and chronic diseases in a comprehensive manner, especially in low-income areas, men and elderly.

Plasma levels of 12 different cytokines correlate to PD-1 inhibitor combined chemotherapy responses in advanced non-small-cell lung cancer patient.

BACKGROUND: Targeted anti-programmed death receptor 1 (PD-1) monoclonal antibodies, when combined with chemotherapy, have shown improved outcomes in non-small cell lung cancer (NSCLC). However, it is important to note that not all patients benefit from this treatment, and there is a pressing need for more reliable efficacy measures and potential predictors of outcome. Cytokines, which are important molecules in the immune system, have been considered as potential biomarkers in clinical settings, but their precise clinical use remains unclear. In this study, our objective was to assess whether the levels of cytokines in the patient's blood sample are associated with tumor response to anti-PD-1 monoclonal antibodies combined with chemotherapy as well as the survival of patients with advanced non-small cell lung cancer. MATERIALS AND METHODS: A total of 12 plasma cytokines were measured in advanced NSCLC patients (n = 35) and healthy individuals (n = 26) using multi-microsphere flow immunofluorescence. The relationship between cytokine levels and clinical response was analyzed using nonparametric Wilcoxon matched-pair ranked tests. Progression-free survival (PFS) time was recorded for all patients through radiographic outcome assessment and telephone follow-up. Survival curves were generated using the Kaplan-Meier and log-rank tests, and the thresholds for cytokines were determined using receiver operating characteristic analysis (ROC). RESULTS: The expression levels of interleukin IL-6, IL-1 ß, IFN-γ, IL-12p70, and TNF-α were significantly lower in the control group than those in the NSCLC group (p = 0.001, p = 0.0028, p = 0.019, p = 0.0001, p = 0.0021). High IL-10 levels at baseline and after 4 cycles of treatment conferred a worse prognosis; in addition, high TNF-α levels in patients after two cycles of immunochemotherapy suggested drug resistance. High levels of IL-6 and IFN-γ in patients undergoing four cycles of immunochemotherapy were associated with worse PFS. CONCLUSIONS: Our study suggests that cytokines can serve as detection indicators for predicting efficacy in non-small cell lung cancer patients undergoing anti-PD-1 combined with chemotherapy treatment. Elevated levels of IL-10, TNF-α, IL-6, and IFN-γ in the plasma may indicate a higher likelihood of experiencing a worse clinical outcome.

An Integrated Extraction-Purification Process for Raspberry Leaf Polyphenols and Their In Vitro Activities.

To improve the utilization value of raspberry leaves, the extraction and purification conditions of phenolic compounds from raspberry leaves were optimized, and the contents of phenolic compounds and the biological activities of extracts were studied. After steam explosion pretreatment at 115 °C for 15 min, raspberry leaf extract with a total phenolic content (TPC) of 136.30~140.51 mg GAE/g was obtained via homogenization and ultrasound-assisted extraction. In addition, the adsorption relationship between raspberry leaf polyphenols and middle polar XDA-6 macroporous resin was best described by the Langmuir model, and tended to be monolayer adsorption. Its adsorption kinetics best resembled the pseudo second-order kinetic model, and it was speculated that this was influenced by multiple factors. According to the optimal integrated extraction-purification process, the TPC of the extracts increased to 738.98 mg GAE/g after one application of purification and 905.27 mg GAE/g after two applications of purification. Moreover, the latter case showed the highest antioxidant activity and α-glucosidase inhibition activity, and the content of the most typical compound, quercetin-3-glucuronide, reached 199.69 mg/g. SE has a double-edged effect, and is more conducive to the release of active substances as a pre-treatment method. This study provides a theoretical basis for the efficient use of raspberry leaves, further improving their medicinal and economic value.

Neurodevelopmental toxicity induced by PM2.5 Exposure and its possible role in Neurodegenerative and mental disorders.

Recent extensive evidence suggests that ambient fine particulate matter (PM2.5, with an aerodynamic diameter ≤2.5 µm) may be neurotoxic to the brain and cause central nervous system damage, contributing to neurodevelopmental disorders, such as autism spectrum disorders, neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and mental disorders, such as schizophrenia, depression, and bipolar disorder. PM2.5 can enter the brain via various pathways, including the blood-brain barrier, olfactory system, and gut-brain axis, leading to adverse effects on the CNS. Studies in humans and animals have revealed that PM2.5-mediated mechanisms, including neuroinflammation, oxidative stress, systemic inflammation, and gut flora dysbiosis, play a crucial role in CNS damage. Additionally, PM2.5 exposure can induce epigenetic alterations, such as hypomethylation of DNA, which may contribute to the pathogenesis of some CNS damage. Through literature analysis, we suggest that promising therapeutic targets for alleviating PM2.5-induced neurological damage include inhibiting microglia overactivation, regulating gut microbiota with antibiotics, and targeting signaling pathways, such as PKA/CREB/BDNF and WNT/ß-catenin. Additionally, several studies have observed an association between PM2.5 exposure and epigenetic changes in neuropsychiatric disorders. This review summarizes and discusses the association between PM2.5 exposure and CNS damage, including the possible mechanisms by which PM2.5 causes neurotoxicity.

A novel long noncoding RNA-lncRNA-AABR07066529.3 alleviates inflammation, apoptosis, and pyroptosis by inhibiting MyD88 in lipopolysaccharide-induced myocardial depression.

Sepsis-induced myocardial depression (SIMD) is common in pediatric intensive care units and seriously threatens children's health. Recently, long noncoding RNAs (lncRNAs) have been showed to play important roles in various diseases; however, its role in SIMD is unclear. In this study, we used lipopolysaccharide (LPS)-treated rats and H9c2 cardiomyocytes to mimic SIMD in vivo and in vitro. We found that the expression of a novel lncRNA, we named lncRNA-AABR07066529.3, was elevated in LPS-induced rat heart tissue and H9c2 cardiomyocytes. In addition, LPS-induced inflammation, apoptosis, and pyroptosis were significantly exacerbated after lncRNA-AABR07066529.3 knockdown. Moreover, we found that myeloid differentiation factor 88 (MyD88) was upregulated in LPS-treated groups and was inhibited by lncRNA-AABR07066529.3. Besides, MyD88 knockdown abolished lncRNA-AABR07066529.3 silencing effects on inflammation, apoptosis, and pyroptosis induced by LPS in H9c2 cardiomyocytes. In our study, we found lncRNA-AABR07066529.3 exerted protective effects on LPS-induced cardiomyocytes by regulating MyD88 and might serve as a potential treatment target for SIMD.

Optimizing glycation control in diabetes: An integrated approach for inhibiting nonenzymatic glycation reactions of biological macromolecules.

Diabetes is a multifactorial disorder that increases mortality and disability due to its complications. A key driver of these complications is nonenzymatic glycation, which generates advanced glycation end-products (AGEs) that impair tissue function. Therefore, effective nonenzymatic glycation prevention and control strategies are urgently needed. This review comprehensively describes the molecular mechanisms and pathological consequences of nonenzymatic glycation in diabetes and outlines various anti-glycation strategies, such as lowering plasma glucose, interfering with the glycation reaction, and degrading early and late glycation products. Diet, exercise, and hypoglycemic medications can reduce the onset of high glucose at the source. Glucose or amino acid analogs such as flavonoids, lysine and aminoguanidine competitively bind to proteins or glucose to block the initial nonenzymatic glycation reaction. In addition, deglycation enzymes such as amadoriase, fructosamine-3-kinase, parkinson's disease protein, glutamine amidotransferase-like class 1 domain-containing 3A and terminal FraB deglycase can eliminate existing nonenzymatic glycation products. These strategies involve nutritional, pharmacological, and enzymatic interventions that target different stages of nonenzymatic glycation. This review also emphasizes the therapeutic potential of anti-glycation drugs for preventing and treating diabetes complications.