The effect of pterostilbene and its active ingredients on experimental pulmonary fibrosis in asthma: a meta-analysis.

Introduction: Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease caused by a variety of factors. Aim: To systematically evaluate the therapeutic effect of pterostilbene (PTE) on experimental PF in asthma and other oxidative damage pathway-related diseases, and to provide evidence for clinical treatment. Material and methods: Chinese and English databases such as CNKI, Wanfang, VIP, PubMed, Embase, Cochrane Library, and CBM were searched by computer. The Chinese literature on pterostilbene for the treatment of asthma by evaluating experimental pulmonary fibrosis, diabetes, and myocardial infarction was collected from the establishment of a randomized controlled trial until May 2021.Outcome indicators include related physical and chemical indicators such as MDA and SOD. Data were analysed using Review Manager 5.4 software after screening by 2 researchers. Results: Seven randomized controlled animal experiments were included, with a total sample size of 62 cases. Meta-analysis results showed the following: 1) compared with pulmonary fibrosis, diabetes and other model groups, the pterostilbene intervention group were able to up-regulate SOD, and the effect was better than that of the model group (MD = 20.87, 95% CI: 19.41-22.33; n = 7, I 2 = 96%); the pterostilbene intervention group could also up-regulate the expression of GSH, and its effect was better than that of the model group (MD = 9.37, 95% CI: 8.67-10.07; n = 2, I 2 = 98%). The MDA level of the intervention group was significantly down regulated, and the intervention group was also better than the model group. Pterostilbene can prevent experimental PF by lowering the level of MDA. Conclusions: Pterostilbene can effectively improve experimental pulmonary fibrosis, diabetes, myocardial infarction, and other oxidative damage pathway-related diseases have certain guiding significance for clinical trials on asthma.

Thioredoxin-interacting protein promotes activation and inflammation of monocytes with DNA demethylation in coronary artery disease.

Numerous studies have demonstrated that thioredoxin-interacting protein (TXNIP) expression of peripheral blood leucocytes is increased in coronary artery disease (CAD). However, the molecular mechanism of this phenomenon remained unclear. DNA methylation plays important roles in the regulation of gene expression. Therefore, we speculated there might be a close association between the expression of TXNIP and methylation. In this study, we found that compared with controls, DNA methylation at cg19693031 was decreased in CAD, while mRNA expressions of TXNIP and inflammatory factors, NLRP3, IL-1ß, IL-18, were increased. Methylation at cg19693031 was negatively associated with TXNIP expression in the cohort, THP-1 and macrophages/foam cells. Furthermore, Transwell assay and co-cultured adhesion assay were performed to investigate functions of TXNIP on the migration of THP-1 or the adhesion of THP-1 on the surface of endothelial cells, respectively. Notably, overexpressed TXNIP promoted the migration and adhesion of THP-1 cells and expressions of NLRP3, IL-18 and IL-1ß. Oppositely, knock-down TXNIP inhibited the migration and adhesion of THP-1 and expressions of NLRP3, IL-18. In conclusion, increased TXNIP expression, related to cg19693031 demethylation orientates monocytes towards an inflammatory status through the NLRP3 inflammasome pathway involved in the development of CAD.

Small-Molecule-Triggered and Light-Controlled Reversible Regulation of Enzymatic Activity.

The fine control of enzyme activity is essential for the regulation of many important cellular and organismal functions. The light-regulation of proteins serves as an important method for the spatiotemporal control over the production and degradation of an enzyme product. This area is of intense interest for researchers. To the best of our knowledge, the use of small molecules as light-triggered molecular switches to reversibly control enzyme activity at the protein level has not yet been studied. In the present study, we demonstrate the light-controlled reversible regulation of the enzyme using a small-molecule-triggered switch, which is based on molecular recognition between an azobenzene derivative and telomere DNA. This molecule interconverts between the trans and cis states under alternate 365 nm UV and visible light irradiation, which consequently triggers the compaction and extension of telomere DNA. We further provide direct evidence for this structural switch using a circular dichroism study. Furthermore, our strategy has been successfully used to effectively control blood clotting in human plasma.

Elevated mtDNA content in RBCs promotes oxidative stress may be responsible for faster senescence in men.

BACKGROUND: Both we and others have found that RBC counts are significantly lower in older compared to younger. However, when gender is factored in, a significant age-related decrease of RBC counts is observed only in men but not in women. METHODS: qPCR and confocal microscopy were used to detect the presence of mtDNA in RBCs. Flow cytometry and specific inhibitors were used to determine how RBCs uptake cf-mtDNA. The peripheral blood was collected from 202 young adults and 207 older adults and RBC and plasma were isolated. The levels of TLR9+RBCs and apoptotic RBCs after uptake of cf-mtDNA by RBCs were measured by flow cytometry. The kit detects changes in SOD and MDA levels after cf-mtDNA uptake by RBCs. Young RBCs (YR) and old RBCs (OR) from single individuals were separated by Percoll centrifugation. RESULTS: We found a significant decrease in RBC counts and a significant increase in the RDW with aging only in men. We also found that significantly elevated mtDNA content in RBCs was observed only in men during aging and was not found in women. Further studies demonstrated that RBCs could take up cf-mtDNA via TLR9, and the uptake of mtDNA might lead to a decrease in the RBC number and an increase in RDW due to an increase of oxidative stress. CONCLUSIONS: The RBC mtDNA content might be a potential marker of RBC aging and the elevated RBC mtDNA content might be the cause of faster senescence in males than females.

Primary infection enhances neutrophil-mediated host defense by educating HSPCs.

Hematopoietic stem and progenitor cells (HSPCs) can give rise to all kinds of immune cells including neutrophils. Neutrophils are the first line of defense in the innate immune system with a short lifespan, due to which it is well-accepted that neutrophils have no immune memory. However, recent reports showed that the changes in HSPCs induced by primary stimulation could last a long time, which contributes to enhancing response to subsequent infection by generating more monocytes or macrophages equipped with stronger anti-bacterial function. Here, we used the reinfection mice model to reveal that primary infection could improve neutrophil-mediated host defense by training neutrophil progenitors in mammals, providing a new idea to enhance neutrophil number and improve neutrophil functions, which is pretty pivotal for patients with compromised or disordered immunity.

Epidemiological characteristics of seasonal influenza under implementation of zero-COVID-19 strategy in China.

OBJECTIVE: Respiratory viral diseases have posed a persistent threat to public health due to their high transmissibility. Influenza virus and SARS-Cov-2 are both respiratory viruses that have caused global pandemics. A zero-COVID-19 strategy is a public health policy imposed to stop community transmission of COVID-19 as soon as it is detected. In this study, we aim to examine the epidemiological characteristics of seasonal influenza in the past five years before and after the emergence of COVID-19 in China and observe the possible impact of the strategy on influenza. METHODS: Data from two data sources were retrospectively analyzed. A comparison on influenza incidence rate between Hubei and Zhejiang provinces was conducted based on data from the Chinese Center for Disease Control and Prevention (CDC). Then a descriptive and comparative analysis on seasonal influenza based on data from Zhongnan Hospital of Wuhan University and Hangzhou Ninth People`s Hospital before and after the outbreak of SARS-CoV-2 was conducted. RESULTS: From 2010-2017, both provinces experienced relatively low influenza activity until the 1st week of 2018, when they reached peak incidence rates of 78.16/100000PY, 34.05/100000PY respectively. Since then, influenza showed an obvious seasonality in Hubei and Zhejiang until the onset of COVID-19. During 2020 and 2021, there was a dramatic decline in influenza activity compared to 2018 and 2019. However, influenza activity seemed to rebound at the beginning of 2022 and surged in summer, with positive rates of 20.52% and 31.53% in Zhongnan Hospital of Wuhan University and Hangzhou Ninth People`s Hospital respectively as of the time writing this article. CONCLUSIONS: Our results reinforce the hypothesis that zero-COVID-19 strategy may impact the epidemiological pattern of influenza. Under the complex pandemic situation, implementation of NPIs could be a beneficial strategy containing not only COVID-19 but also influenza.

APOA1 Level is Negatively Correlated with the Severity of COVID-19.

OBJECTIVE: We used public data to analyze the proteomics, metabolomics and transcriptomics characteristics of COVID-19 patients to identify potential therapeutic targets. More importantly, we also collected clinical data for verification to make the analysis results more reliable. METHODS: Download the serum proteomics and metabolomics data of COVID-19 patients and describe their changes in serum proteins and metabolites, and use bioinformatics analysis methods to identify potential biomarkers and therapeutic targets. Finally, clinical data and experimental data of cell infection were combined for verification. RESULTS: It was found that the serum apolipoprotein A1 (APOA1) protein level in COVID-19 patients was down-regulated (log2FC = -0.39, false discovery rate (FDR) < 0.001), and the degree of reduction in the severe group was more significant (kruskal-test p = 2.5e-05). What is more, APOA1 was not only expressed lower in male patients (Wilcox-test p = 0.012), but also negatively correlated with C-reactive protein (CRP, r = -0.37, p = 0.019). The experiment data from SARS-CoV-2 infected cells further showed that the protein and transcript level of APOA1 gradually decreased as the infection time increased, and the transcription level (log2FC = -8.3, FDR = 0.0015) was more down-regulated than protein level (log2FC = -0.95, FDR = 0.0014). More importantly, the collected clinical data also confirmed that APOA1 was down-regulated in COVID-19 patients (kruskal-test p = 0.001), and APOA1 levels are negatively correlated with IL6 (r = -0.396, p = 2.22e-07), D-dimers (DD, r = -0.262, p = 8.19e-04), prothrombin time (PT, r = -0.464, p = 6.68e-10) and thrombin time (TT, r = -0.279, p = 3.46e-04). CONCLUSION: The degree of down-regulation of APOA1 is positively correlated with the severity of COVID-19, and the expression level of APOA1 is negatively correlated with CRP, IL6, DD, PT, TT, and positively correlated with HD and LDL. This indicates that APOA1 may be a key molecule in tandem acute inflammatory response, coagulation abnormalities and cholesterol metabolism disorder in COVID-19, and could be a potential therapeutic target.

Tumor-Educated Platelet miR-18a-3p as a Novel Liquid-Biopsy Biomarker for Early Diagnosis and Chemotherapy Efficacy Monitoring in Nasopharyngeal Carcinoma.

AIMS: To evaluate the value of tumor-educated platelet (TEP) miR-18a-3p in the early diagnosis and chemotherapy efficacy monitoring of nasopharyngeal carcinoma (NPC). METHODS: Expression levels of miR-18a-3p in platelets and plasma were detected by relative quantitative real-time PCR in NPC patients (n=54) and normal subjects (n=36). Diagnostic values of TEP miR-18a-3p for NPC was assessed by receiver operating characteristic (ROC) curve analysis. Follow up study was carried out to observe the dynamic changes of TEP miR-18a-3p with chemotherapy on 3 NPC patients. RESULTS: The expression levels of TEP miR-18a-3p in NPC patients were significantly higher than that in healthy controls (p < 0.0001). ROC curve analysis showed that the area under the curve (AUC) value was 0.841, the sensitivity and specificity for the diagnosis of NPC were 87% and 72.7%. No correlation was found between expression levels of TEP miR-18a-3p and patients' clinical parameters and their NPC tumor-node-metastasis (TNM) stage. The positive rate of TEP miR-18a-3p and EBV DNA for NPC diagnosis were 85.4% and 66.7%. TEP miR-18a-3p expression were down-regulated after 77.8% (7 of 9) of chemotherapy, and in 66.7% (2 of 3) patients, TEP miR-18a-3p levels decreased after 3 cycles of chemotherapy. CONCLUSION: The expression levels of TEP miR-18a-3p are upregulated in NPC and have a high probability to downregulated after chemotherapy, indicating a significant clinical value. TEP miR-18a-3p might serve as a novel type of liquid-biopsy biomarker for early diagnosis and chemotherapy efficacy monitoring in NPC.

The incidence of influenza in children was decreased in the first flu season after COVID-19 pandemic in Wuhan.

Wuhan, China was the first city to discover COVID-19. With the government's macro-control and the active cooperation of the public, the spread of COVID-19 has been effectively controlled. In order to understand the additional impact of these measures on the prevalence of common influenza, we have collected flu test data from the Pediatric Clinic of Zhongnan Hospital of Wuhan University from September to December 2020, and compared them with the same period in 2018 and 2019. It is found that compared with the same period in 2018 and 2019, the rate of children's influenza activity in 2020 has significantly decreased, which indicates that the protective measures against COVID-19 have effectively reduced the level of influenza activity.

Letter to the Editor: Low-density lipoprotein is a potential predictor of poor prognosis in patients with coronavirus disease 2019.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has become a global threat to public health. The lipid pathophysiology in COVID-19 is unknown. METHODS: In this retrospective longitudinal study, we monitored the serum lipids in 17 surviving and 4 non-surviving COVID-19 cases prior to their viral infections and duration the entire disease courses. RESULTS: In surviving cases, the low-density lipoprotein (LDL) levels decreased significantly on admission as compared with the levels before infection; the LDL levels remained constantly low during the disease progression and resumed to the original levels when patients recovered (pre-infection: 3.5 (3.0-4.4); on admission: 2.8 (2.3-3.1), p < 0.01; progression: 2.5 (2.3-3.0); discharge: 3.6 (2.7-4.1); median (IQR), in mmol/L). In non-surviving patients, LDL levels showed an irreversible and continuous decrease until death (1.1 (0.9-1.2), p = 0.02 versus the levels on admission). The ratio changes of LDL levels inversely correlated with ratio changes of high-sensitivity C-reactive protein levels. Logistic regression analysis showed increasing odds of lowered LDL levels associated with disease progression (odds ratio: 4.48, 95% IC: 1.55-12.92, p = 0.006) and in-hospital death (odds ratio: 21.72, 95% IC: 1.40-337.54, p = 0.028). CONCLUSIONS: LDL levels inversely correlated to disease severities, which could be a predictor for disease progress and poor prognosis.

Dynamic changes of throat swabs RNA and serum antibodies for SARS-CoV-2 and their diagnostic performances in patients with COVID-19.

Dynamic changes of RNA and antibodies in SARS-CoV-2 infected patients remain largely unknown, and influence factors for antibody production have not been fully clarified. In this study, consecutive throat swabs specimens (n = 1875) from 187 patients were collected to analyse the dynamic changes of RNA. Moreover, 162 serial serum samples from 31 patients were tested for seroconversion of IgM and IgG. Meanwhile, IgM and IgG were also detected in 409 COVID-19 patients and 389 controls. Additionally, the logistic regression analysis was executed to identify the possible influence factors for antibody production. The median positive conversion time for RNA was day 7 (IQR, 3-11), and the positive rate was highest in day 1-5 (74.59 %) and then gradually decreased. The median time of seroconversion for IgM and IgG were both day 12 (IQR, 10-15). The sensitivity and specificity for IgM (or IgG) was 87.04% and 96.92%, respectively. Multivariate logistic regression indicated that reduced lymphocytes and short positive conversion time for SARS-CoV-2 RNA were independent factors for negative results of IgM and IgG. In conclusion, RNA and antibodies should be combined for COVID-19 diagnosis, and delayed seroconversion was influenced by the decreased lymphocytes and short positive conversion time for RNA.

Stage I lung adenocarcinoma: the value of quantitative CT in differentiating pathological subtypes and predicting growth of subsolid nodules.

The aim of this study was to investigate feasibility of quantitative computed tomography (CT) measurements in predicting invasiveness and growth of nodular ground glass opacities (nGGOs).A set of 203 patients (group A) with nGGOs that were confirmed stage-I adenocarcinomas and 79 patients (group B) with nGGOs that were completely followed up were included. Lesions diameters, volume (VOL), maximum (MAX), mean (MEN), and standard deviation (STD) of CT attenuation were measured. P53 labeling index (LI) was evaluated through immunohistochemistry in group-A patients. Multivariate linear stepwise regressions were performed based on group-A lesions to calculate P53-LI prediction from CT measurements. The receiver operating characteristic (ROC) curve analyses were performed to assess the performance of P53-LI prediction in predicting invasiveness and growth of nGGOs. The Cox regression analysis was conducted to identify correlation between P53-LI Prediction and volume doubling time (VDT) of lesions in group B.Diameter, VOL, MEN, STD, and the P53 LI showed significant differences between lesions of different pathological invasiveness (P < .01). By multivariate linear regressions, MEN and STD were identified as independent variables indicating P53 LI (P < .001); thus, an equation was established to calculate P53-LI Prediction as: P53LI Prediction = 0.013 ×  MEN + 0.024 × STD + 9.741 (R square = 0.411, P < .001). The P53-LI Prediction showed good performance, similar as the actual one, in differentiating pathological invasiveness of nGGOs. In addition, the P53-LI Prediction demonstrated excellent performance in predicting growth of nGGOs (AUC = 0.833, P < .001) and independently forecasted VDT of nGGOs (ß = 1.773, P < .001).The P53-LI Prediction that was calculated from preoperative quantitative CT measurements of nGGOs indicates lesions' invasiveness and allows for predicting growth of nGGOs.

Clinicopathological significance of forkhead box protein A1 in breast cancer: A meta-analysis.

The aim of the present study was to investigate the associations between the expression of forkhead box protein A1 (FOXA1) and differential clinicopathological characteristics in breast cancer using a meta-analysis method. Eligible studies that investigated the correlation between FOXA1 expression and the clinical characteristics of breast cancer were collected through searching numerous databases, including PubMed, EMBASE, the Chinese National Knowledge Infrastructure and the VIP database. In total, eight studies were included in the meta-analysis. Following a systematic analysis, the expression of FOXA1 was found to be significantly associated with the estrogen receptor α status, the progesterone receptor status, lymph node metastasis and the histological grade in breast cancer. However, no statistically significant association was observed between FOXA1 expression and the human epidermal growth factor receptor-2 status in breast cancer patients.

Association of the pri-miR-124-1 rs531564 polymorphism with cancer risk: A meta-analysis.

Recently, several studies regarding the association between the pri-miR-124-1 rs531564 polymorphism and cancer susceptibility were explored. Owing to inconsistent results of these studies, a meta-analysis was conducted to determine the association of this polymorphism with cancer risk. Relevant studies were identified by a systematic search of PubMed, EMBASE, Web of Science and CNKI on-line databases. Odds ratios (ORs) and 95% confidence intervals (CIs) from eligible studies were pooled, and heterogeneity and publication bias were also evaluated. A total of five studies with 2,253 cases and 2,510 controls were included in the meta-analysis. Overall, the results showed that the pri-miR-124-1 rs531564 polymorphism was significantly associated with a reduced cancer risk (G vs. C: OR, 0.86; 95% CI, 0.77-0.96; GG vs. CC: OR, 0.52; 95% CI, 0.34-0.79; GG vs. CG/CC: OR, 0.54; 95% CI, 0.36-0.81). Furthermore, in the subgroup analysis by cancer sites, a statistical association was identified between the rs531564 polymorphism and a decreased esophageal squamous cell carcinoma (ESCC) risk (G vs. C: OR, 0.87; 95% CI, 0.77-0.98; GG vs. CC: OR, 0.54; 95% CI, 0.34-0.84). These findings suggested that the genetic variant of rs531564 may have a potential value in decreasing cancer risk, particularly in ESCC patients.

Androgen receptor, EGFR, and BRCA1 as biomarkers in triple-negative breast cancer: a meta-analysis.

OBJECTIVE: More and more evidences demonstrate that androgen receptor (AR), epidermal growth factor receptor (EGFR), and breast cancer susceptibility gene 1 (BRCA1) have unique clinical implications for targeted therapy or prognosis in triple-negative breast cancer (TNBC). Therefore, we conducted a meta-analysis to summarize the possible associations. METHODS: We retrieved published articles about AR, EGFR, and BRCA1 in TNBC from PubMed and EMBASE. The analysis was performed with Rev-Man 5.2 software. RESULTS: A total of 38 articles were eligible for the meta-analysis. Our study showed that the expression level of EGFR (OR = 6.88, P < 0.00001) and the prevalence of BRCA1 mutation (RR = 5.26, P < 0.00001) were higher in TNBC than non-TNBC. In contrast, the expression level of AR was lower in TNBC than non-TNBC (OR = 0.07, P < 0.00001). In the subgroup related to EGFR expression, the level of EGFR expression was significantly increased in Asians (OR = 9.60) compared with Caucasians (OR = 5.53) for TNBC patients. Additionally, the prevalence of BRCA1 mutation in Asians (RR = 5.43, P < 0.00001) was higher than that in Caucasians (RR = 5.16, P < 0.00001). CONCLUSIONS: The distinct expression of AR and EGFR and the prevalence of BRCA1 mutation indicated that AR, EGFR, and BRCA1 might be unique biomarkers for targeted therapy and prognosis in TNBC.

Influence of interleukin-1 beta genetic polymorphism, smoking and alcohol drinking on the risk of non-small cell lung cancer.

BACKGROUND: Non-small cell cancer (NSCLC) accounts for approximately 80% of all lung cancers. Reports suggested an association between the interleukin-1beta (IL-1beta) -31 and -511 gene loci and NSCLC, but few studies took into account the effect of smoking and/or alcohol drinking on the association. METHODS: Two-hundred thirteen cases of NSCLC (aged 58.2 + or - 10.1) and 213 controls (aged 59.4 + or - 10.3y) were included in this research. Information about the smoking and drinking behaviors, dietary customs, and anamnesis were obtained from all subjects by questionnaires, and genomic DNA was extracted. IL-1beta -31 and -511 gene polymorphisms were detected using PCR-RFLP. The interactions between the genotypes and alcohol drinking/smoking were analyzed using multivariate logistic regression models. RESULTS: (The T/T genotype and the T allele of the IL-1beta -31 gene were associated with higher incidence of NSCLC (P<0.05). For the IL-1beta -511 locus, no difference was found in different genotypes between the NSCLC and control groups. After the adjustment of confounding variables, such as age and gender, the binary logistic analysis showed a significant gene-environment interaction (P<0.05). CONCLUSIONS: The IL-1beta -31T allele was positively associated with a risk of NSCLC, and the carriers of IL-1beta -31T/T or -511C/C would have a higher risk of suffering from NSCLC if they drank alcohol or smoke heavily.