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Objective: To evaluate the effect of midkine on lipopolysaccharide (LPS)-induced airway smooth muscle cells (ASMCs). Methods: LPS-stimulated acute lung injury model was used to analyze the effect of midkine on ASMCs in vitro. Recombinant midkine and midkine siRNA were used to investigate the role of Notch2 signaling pathway. Cell proliferation was assessed using Cell Counting Kit-8 assay. Additionally, apoptosis was measured by flow cytometry and protein and mRNA expression of midkine and Notch2 was assessed by Western blotting and qPCR, respectively. Immunofluorescence analysis was also conducted. Results: LPS increased the mRNA and protein expression of midkine and Notch2. Midkine silencing reduced LPS-induced midkine and Notch2 expression. In addition, midkine silencing further reduced the viability and increased apoptosis of ASMCs induced by LPS, which was attenuated by recombinant midkine. Conclusions: The midkine/Notch2 signaling pathway plays a regulatory role in ASMC proliferation and apoptosis in airway inflammation.

Objective: To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019 (COVID-19) vaccination. Methods: We systematically searched PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang Data, and VIP Database from the inception of each database to August 31, 2021. Randomized controlled clinical trials (RCTs) on the safety of different types of COVID-19 vaccines were retrieved and analyzed. A random or fixed-effects model was used with an odds ratio as the effect size. The quality of each reference was evaluated. The incidence of the adverse reactions of the placebo group and the vaccination group was compared. Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses. Results: A total of 13 articles were included, with 81 287 subjects. Compared with the placebo group, the vaccination group showed a higher combined risk ratio (RR) of total adverse reactions (RR=1.67, 95% CI: 1.46-1.91, P

Objective: To explore the protective effects of anthrahydroquinone- 2,6-disulfonate (AH2QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH2QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH2QDS group was given AH2QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL- 6, TNF-α, apelin-APJ (the apelin-angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH2QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH2QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH2QDS group (P

Abstract Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2’s expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.

AimTo study the microecological characteristics of the airway and similarities and differences between healthy people and patients with the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Inner Mongolia, and analyze the correlation between the characteristics of the airway microecological structure and clinical indicators of AECOPD patients.MethodsSputum samples from 36 healthy volunteers and 34 patients with AECOPD were detected by 16S rDNA high-throughput sequencing, and the airway microecological characteristics of healthy people and AECOPD patients were revealed by an alpha diversity analysis, beta diversity analysis, and LefSe difference analysis.ResultsThere were differences in the airway microecological structure between healthy people and AECOPD patients in Inner Mongolia. The airway microbiota composition of AECOPD patients showed an increase in the abundance of common pathogens and a decrease in the abundance of commensal bacteria, and the airway microbial diversity in AECOPD patients was lower than that in healthy people. Long-term use of inhaled glucocorticoid + long-acting β2 agonist mixture (ICS + LABA), procalcitonin (PCT), blood monocyte count (MONO), hemoglobin (HGB), D-dimer (D-D), and body temperature were negatively correlated with the alpha diversity of the airway micro-ecosystem.ConclusionThe airway microecological composition of the AECOPD population in Inner Mongolia was different from that of the healthy population, and the airway microecological diversity was lower than that of the healthy population. The long-term use of ICS + LABA preparation by patients with AECOPD leads to lower alpha diversity. Alpha diversity was negatively correlated with inflammatory markers (PCT, MONO, D-dimer, body temperature) and HGB in AECOPD patients.

Background and Objectives: Although the pathogenesis and treatment of coronavirus disease 2019 (COVID-19) have been gradually revealed, the risk for re-emergence of coronavirus nucleic acids in recovered patients remains poorly understood. Hence, this study evaluated the risk predictors associated with re-positivity for virus nucleic acid.Methods: Between February 1 and March 20, 2020, we retrospectively reviewed the clinical epidemiological data of 129 COVID-19 patients who were treated at Zhongxiang People's Hospital of Hubei Province in China. Subsequently, a risk prediction model for the re-positivity of virus nucleic acid was developed, and a receiver operating characteristic (ROC) curve was drawn for further validation.Results: In this study, the rate of re-positivity for virus nucleic acid was 17.8% (23/129) where all re-positivity cases were asymptomatic. The median time interval from discharge to nucleic acid re-positivity to discharge after being cured again was 11.5 days (range: 7–23 days). Multivariate logistic regression analysis showed that leukocytopenia [odds ratio (OR) 7.316, 95% confidence interval (CI) 2.319–23.080, p = 0.001], prealbumin < 150 mg/L (OR 4.199, 95% CI 1.461–12.071, p = 0.008), and hyperpyrexia (body temperature >39°C, OR 4.643, 95% CI 1.426–15.117, p = 0.011) were independent risk factors associated with re-positivity. The area under the ROC curve was 0.815 (95% CI, 0.729–0.902).Conclusion: COVID-19 patients with leukocytopenia, low prealbumin level, and hyperpyrexia are more likely to test positive for virus nucleic acid after discharge. Timely and effective treatment and appropriate extension of hospital stays and quarantine periods may be feasible strategies for managing such patients.

Aluminum (Al) is present in approximately 50% of the arable land worldwide and is regarded as the main limiting factor of crop yield on acidic soil. Al-induced root malate efflux plays an important role in the Al tolerance of plants. Here, the aluminum induced malate transporter BoALMT1 (KF322104) was cloned from cabbage (Brassica oleracea). BoALMT1 showed higher expression in roots than in shoots. The expression of BoALMT1 was specifically induced by Al treatment, but not the trivalent cations lanthanum (La), cadmium (Cd), zinc (Zn), or copper (Cu). Subcellular localization studies were performed in onion epidermal cells and revealed that BoALMT1 was localized at the plasma membrane. Scanning Ion-selective Electrode Technique was used to analyze H+ flux. Xenopus oocytes and Arabidopsis thaliana expressing BoALMT1 excreted more H+ under Al treatment. Overexpressing BoALMT1 in transgenic Arabidopsis resulted in enhanced Al tolerance and increased malate secretion. The results suggested that BoALMT1 functions as an Al-resistant gene and encodes a malate transporter. Expressing BoALMT1 in Xenopus oocytes or A. thaliana indicated that BoALMT1 could increase malate secretion and H+ efflux to resist Al tolerance.

Paraquat (PQ) is a bipyridine dichloride non-selective herbicide, which was widely used in the world in the last century. It is banned in most countries because of the extremely high death rate and the lack of specific detoxification drugs, but the death cases of poisoning still occur frequently, so it is of great clinical significance to study the molecular mechanism of poisoning and detoxification drugs. Its poisoning causes dysfunction of lung, liver, kidney, myocardium, brain and other organs with complex molecular mechanism. There are excessive inflammatory reaction theory, REDOX reaction imbalance, oxidative stress free radical damage, calcium overload, NO molecular damage, apoptosis, etc. For the treatment of poisoning, PQ antibody, pathway target blocker and related factor antibody have been newly developed in recent years. Although certain effects have been achieved, the treatment efficiency has not been significantly improved. This paper summarized the mechanism of signal transduction pathways involved in lung injury caused by PQ poisoning in order to provide a theoretical basis for further research. [ABSTRACT FROM AUTHOR]