Publications by authors named "Xu Wang"

3,457 Publications

  • Page 1 of 1

The circadian regulation of extracellular ATP.

Purinergic Signal 2022 Aug 8. Epub 2022 Aug 8.

School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 37 Shi-er Qiao Road, Chengdu, 610075, China.

Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the nervous system and immune system by activating P2 purinergic receptors. Recent increasingly studies showed that extracellular ATP exhibits circadian oscillation with an approximately 24-h periodicity, which participates in regulatory pathways of central oscillator suprachiasmatic nucleus and peripheral oscillator bladder, respectively. Oscillators modulate the protein expression of ATP release channels and ectonucleotidase activity through clock genes; indeed, real-time alterations of ATP release and degradation determine outcomes of temporal character on extracellular ATP rhythm. The regulatory pathways on extracellular ATP rhythm are different in central and peripheral systems. In this review, we summarize the circadian rhythm of extracellular ATP and discuss several circadian regulatory pathways in different organs via ATP release and degradation, to provide a new understanding for purinergic signaling in the regulatory mechanism of circadian rhythm and a potential target to research the circadian regulation of extracellular ATP in other circadian oscillators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11302-022-09881-3DOI Listing
August 2022

USP25 deficiency exacerbates acute pancreatitis via upregulating TBK1-NF-κB signaling in macrophages.

Cell Mol Gastroenterol Hepatol 2022 Aug 4. Epub 2022 Aug 4.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Affiliated Xiangshan Hospital of Wenzhou Medial University (Xiangshan First People's Hospital Medical and Health Group), Xiangshan, Zhejiang, 315799, China. Electronic address:

Background & Aims: Severe acute pancreatitis can easily lead to systemic inflammatory response syndrome and death. Macrophages are known to be involved in the pathophysiology of acute pancreatitis (AP), and macrophage activation correlates with disease severity. In this study, we examined the role of ubiquitin-specific protease 25 (USP25), a deubiquitinating enzyme and known regulator of macrophages, in the pathogenesis of AP.

Methods: We utilized L-arginine, cerulein, and choline-deficient ethionine-supplemented diet (CDE)-induced models of AP in Usp25 mice and wild-type mice. We also generated bone marrow Usp25 chimeric mice and initiated L-arginine-mediated AP. Primary acinar cells and bone marrow-derived macrophages (BMDMs) were isolated from wild-type and Usp25 mice to dissect molecular mechanisms.

Results: Our results show that Usp25 deficiency exacerbates pancreatic and lung injury, neutrophil and macrophage infiltration, and systemic inflammatory responses in L-arginine, cerulein, and CDE-induced models of AP. Bone marrow Usp25 chimeric mice challenged with L-arginine shows that Usp25 deficiency in macrophages exaggerates AP by upregulating the TBK1-NF-κB signaling pathway. Similarly, in vitro data confirm that Usp25-deficiency enhances TBK1-NF-κB pathway, leading to increased expression of inflammatory cytokines in BMDMs.

Conclusions: Usp25 deficiency in macrophages enhances TBK1-NF-κB signaling and the induction of inflammatory chemokines and type I interferon-related genes exacerbates pancreatic and lung injury in AP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmgh.2022.07.013DOI Listing
August 2022

Evaluation of Herb-Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes.

Front Pharmacol 2022 19;13:950525. Epub 2022 Jul 19.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China.

The combination of (Danshen) and rivaroxaban is a promising treatment option in clinical practice in China, but the herb-drug interaction between Danshen and rivaroxaban remains unclear. Therefore, this study aims to reveal the interaction between Danshen and rivaroxaban. We not only investigated the inhibitory properties of Danshen tablet on rivaroxaban metabolism in rat and human liver microsomes but also evaluated the inhibitory effects of Danshen tablet and its eight active components (dihydrotanshinone I, tanshinone I, tanshinone IIA, cryptotanshinone, danshensu, salvianolic acid A, salvianolic acid B, and salvianolic acid C) on cytochrome P450 (CYP) enzymes. The results showed that Danshen tablet potently inhibited the metabolism of rivaroxaban in rat and human liver microsomes. In the CYP inhibition study, we found that dihydrotanshinone I, the active component of Danshen tablet, potently inhibited the activities of rat CYP3A and CYP2J, with IC values at 13.85 and 6.39 μM, respectively. In further inhibition kinetic study, we found that Danshen tablet is a mixed inhibitor in rivaroxaban metabolism in rat and human liver microsomes, with the value at 0.72 and 0.25 mg/ml, respectively. In conclusion, there is a potential interaction between Danshen tablet and rivaroxaban. Danshen tablet inhibits the metabolism of rivaroxaban, which may be because its lipid-soluble components such as dihydrotanshinone I strongly inhibit the activities of CYP enzymes, especially CYP3A and CYP2J. Therefore, when Danshen tablet and rivaroxaban are used simultaneously in the clinic, it is necessary to strengthen the drug monitoring of rivaroxaban and adjust the dosage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.950525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343791PMC
July 2022

Immunogenicity and protective potential of chimeric virus-like particles containing SARS-CoV-2 spike and H5N1 matrix 1 proteins.

Front Cell Infect Microbiol 2022 18;12:967493. Epub 2022 Jul 18.

Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has posed a constant threat to human beings and the world economy for more than two years. Vaccination is the first choice to control and prevent the pandemic. However, an effective SARS-CoV-2 vaccine against the virus infection is still needed. This study designed and prepared four kinds of virus-like particles (VLPs) using an insect expression system. Two constructs encoded wild-type SARS-CoV-2 spike (S) fused with or without H5N1 matrix 1 (M1) (S and SM). The other two constructs contained a codon-optimized spike gene and/or M1 gene (mS and mSM) based on protein expression, stability, and ADE avoidance. The results showed that the VLP-based vaccine could induce high SARS-CoV-2 specific antibodies in mice, including specific IgG, IgG1, and IgG2a. Moreover, the mSM group has the most robust ability to stimulate humoral immunity and cellular immunity than the other VLPs, suggesting the mSM is the best immunogen. Further studies showed that the mSM combined with Al/CpG adjuvant could stimulate animals to produce sustained high-level antibodies and establish an effective protective barrier to protect mice from challenges with mouse-adapted strain. The vaccine based on mSM and Al/CpG adjuvant is a promising candidate vaccine to prevent the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2022.967493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339902PMC
August 2022

Modified Perineal Reconstruction Combined with Anal Sphincter Repair for Obstetric Anal Sphincter Injuries.

Ther Clin Risk Manag 2022 28;18:739-744. Epub 2022 Jul 28.

Department of Colorectal Surgery, The First Hospital of Jilin University, Changchun, 130000, People's Republic of China.

Objective: The aim of this study was to investigate the clinical effectiveness of modified perineal reconstruction combined with anal sphincter repair in the treatment of obstetric anal sphincter injuries (OASIS).

Methods: Twenty consecutive patients with an OASI who underwent modified perineal reconstruction combined with anal sphincter repair in the Department of Colorectal and Anal Surgery of the First Hospital of Jilin University from October 2015 to September 2017 were retrospectively enrolled in this study. Anal function was evaluated using the Williams grade, the Wexner score, anorectal manometry, and transrectal ultrasound.

Results: Differences in both the Williams grade and the Wexner score prior to operation and following surgery indicated that anal function had improved, and these differences were statistically significant ( < 0.05). These indices also showed further improvement six months after surgery as compared with values at one month, and again, these differences were statistically significant ( < 0.05). In addition, anorectal manometry at six months following surgery showed statistically significant differences in the maximum anal resting pressure, maximum anal systolic pressure, and anal defecation pressure as compared with values prior to operation ( < 0.05). Postoperative endorectal ultrasound revealed that the anal sphincter presented with close imbricated overlapping.

Conclusion: Modified perineal reconstruction combined with anal sphincter repair in the treatment of female perineal defect is associated with a good clinical outcome, strengthening anal function, and reconstructing the perineum, and is a possible method for clinical treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/TCRM.S346899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342695PMC
July 2022

Systematic analysis of expression profiles of HMGB family members for prognostic application in non-small cell lung cancer.

Front Mol Biosci 2022 18;9:844618. Epub 2022 Jul 18.

Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

Lung cancer is a significant challenge to human health. Members of the high mobility group (HMG) superfamily (HMGB proteins) are implicated in a wide variety of physiological and pathophysiological processes, but the expression and prognostic value of HMGB family members in non-small cell lung cancer (NSCLC) have not been elucidated. In this study, ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, starBase, OncomiR databases, and GeneMANIA were utilized to evaluate the prognostic significance of HMGB family members in NSCLC. HMGB2/3 expression levels were higher in NSCLC patients. HMGB1 expression was higher in lung squamous cell carcinoma (LUSC) and was lower in lung adenocarcinoma (LUAD) tissue than in normal lung tissue. HMGB2 expression was related to cancer stage. Increased HMGB1 mRNA expression levels were associated with improved lung cancer prognosis, including overall survival (OS), first-progression survival (FP), and post-progression survival (PPS). There was no significant association between HMGB2 levels and prognostic indicators. HMGB3 expression was associated with poorer OS. GeneMANIA and GO/KEGG pathway analysis showed that HMGB family members mainly associated with chromosome condensation, regulation of chromatin organization, and nucleosome binding in NSCLC. HMGBs expression were closely correlated with infiltrating levels of specific types of immune cells in NSCLC, especially Th2 cells, Th17 cells, and mast cells. hsa-miR-25-3p, hsa-miR-374a-3p, and hsa-miR-93-5p were significantly positively correlated with HMGB1, HMGB2, and HMGB3, respectively. However, hsa-miR-30a-5p was predicted to significantly negatively regulate HMGB3 expression. Our study revealed that HMGB1 is positively related to the improved prognosis in NSCLC, and demonstrate that HMGB3 might be a risk factor for poorer survival of NSCLC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2022.844618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340210PMC
July 2022

CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder.

Cell Metab 2022 Aug;34(8):1088-1103.e6

Division of Immunotherapy, Institute of Human Virology and Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; OncoImmune, Inc., Rockville, MD 20850, USA; OncoC4, Inc., Rockville, MD 20850, USA. Electronic address:

The molecular interactions that regulate chronic inflammation underlying metabolic disease remain largely unknown. Since the CD24-Siglec interaction regulates inflammatory response to danger-associated molecular patterns (DAMPs), we have generated multiple mouse strains with single or combined mutations of Cd24 or Siglec genes to explore the role of the CD24-Siglec interaction in metaflammation and metabolic disorder. Here, we report that the CD24-Siglec-E axis, but not other Siglecs, is a key suppressor of obesity-related metabolic dysfunction. Inactivation of the CD24-Siglec-E pathway exacerbates, while CD24Fc treatment alleviates, diet-induced metabolic disorders, including obesity, dyslipidemia, insulin resistance, and nonalcoholic steatohepatitis (NASH). Mechanistically, sialylation-dependent recognition of CD24 by Siglec-E induces SHP-1 recruitment and represses metaflammation to protect against metabolic syndrome. A first-in-human study of CD24Fc (NCT02650895) supports the significance of this pathway in human lipid metabolism and inflammation. These findings identify the CD24-Siglec-E axis as an innate immune checkpoint against metaflammation and metabolic disorder and suggest a promising therapeutic target for metabolic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2022.07.005DOI Listing
August 2022

Letter to the editor.

J Oral Pathol Med 2022 Aug 3. Epub 2022 Aug 3.

Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.13344DOI Listing
August 2022

Inhibition of c-MYC-miRNA 19 Pathway Sensitized CML K562 Cells to Etoposide via NHE1 Upregulation.

Oxid Med Cell Longev 2022 23;2022:9306614. Epub 2022 Jul 23.

Department of Immunology, Department of Biotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.

As a previously discovered target of DNA damage, Na/H exchanger 1 (NHE1) plays a role in regulation of intracellular pH (pH) through the extrusion of intracellular proton (H) in exchange for extracellular sodium (Na). Its abnormal expression and dysfunction have been reported in solid tumor and hematopoietic malignancies. Here, we reported that suppression of NHE1 in BCR-ABL hematopoietic malignancies' K562 cells treated with Etoposide was manipulated by miR-19 and c-MYC. Inhibition of miR-19 or c-MYC enhanced the expression of NHE1 and sensitized K562 cells to Etoposide . The nude mouse transplantation model was also performed to confirm the enhanced sensitivity of K562 cells to Etoposide by inhibiting the miR-19 or c-MYC pathway. TCGA analysis conferred a negative correlation between miR-19 level and leukemia patients' survival. Thus, our results provided a potential management by which the c-MYC-miRNA 19 pathway might have a crucial impact on sensitizing K562 cells to Etoposide in the therapeutic approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/9306614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338868PMC
August 2022

Platelet Aggregation Before Aspirin Initiation in Pediatric Patients With Congenital Heart Disease at High Risk of Thrombosis.

Front Cardiovasc Med 2022 13;9:813190. Epub 2022 Jul 13.

Department of Cardiac Surgery, Pediatric Cardiac Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Background: Aspirin following unfractionated heparin is the most common anticoagulation strategy for pediatric patients who experienced cardiac surgery at high risk of thrombosis. The platelet aggregation test is the golden method to evaluate the aspirin effect on platelet function. However, the platelet aggregation basal status before postoperative aspirin initiation and the related clinical influencing factors hasn't been investigated systemically in this population.

Methods: In a prospective cohort of 247 children, arachidonic acid-induced platelet aggregation (PAG-AA) was measured by means of light transmission aggregometry (LTA) before the first dose of aspirin after cardiac surgical procedure and the perioperative variables were also collected. Distribution of this population's PAG-AA basal status was described. Univariate and multivariate logistic regression analysis were performed to identify the main influencing factors of PAG-AA.

Results: The median time of aspirin administration was 2 (1-27) days after surgery and the corresponding median value of basal PAG-AA was 20.70% (1.28-86.49%), with 67.6% population under 55% and 47.8% population under 20%. Patients undergoing cardiopulmonary bypass (CPB) had a significantly lower basal PAG-AA than those without (30.63 ± 27.35 vs. 57.91 ± 27.58, = 0.013). While patients whose test done within 3 days after CPB had a significantly lower PAG-AA than those out of 3 days (25.61 ± 25.59 vs. 48.59 ± 26.45, = 0.001). Univariate analysis implied that the influencing factors of the basal PAG-AA including CPB use, test time point, cyanosis, and platelet count. Multivariate regression analysis indicated that only CPB use, test time point, and platelet count were the main independent influencing factors for the basal PAG-AA.

Conclusion: The majority of children have impaired basal platelet aggregometry responses before postoperative aspirin initiation. The main influencing factors are CPB use, test time point, and platelet count. To establish the platelet aggregometry baseline prior to commencement of aspirin therapy, testing should be performed 3 days later following the procedure when effect of CPB is basically over.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2022.813190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328390PMC
July 2022

Effects of a virtual reality serious game training program on the cognitive function of people diagnosed with schizophrenia: A randomized controlled trial.

Front Psychiatry 2022 15;13:952828. Epub 2022 Jul 15.

West China Hospital, Sichuan University, Chengdu, China.

Background: Cognitive impairment persists through the course of schizophrenia and affects patients' activities of daily living.

Aim: This study aims to investigate the effects of a virtual reality (VR) serious game training program on the cognitive function of people diagnosed with schizophrenia.

Materials And Methods: Sixty-four eligible people diagnosed with schizophrenia were recruited and randomly assigned to the intervention group ( = 31) and the control group ( = 33). The control group received standard psychiatric care. The intervention group was trained with an additional VR game twice a day for at least 10 days during hospitalization. Cognitive function was measured at enrollment and before discharge using the Brief Cognitive Assessment Tool for Schizophrenia.

Results: Compared with those of the control group, the results of the working memory ( = 3.463, Cohen's d = 0.87, = 0.001) and executive function (TMTA: Z = -2.272, Cohen's d = 0.59, = 0.023; TMTB:Z = -2.365, Cohen's d = 0.62, = 0.018) of the intervention group after intervention were significantly better. However, there was no significant difference in the results of social cognition ( = -1.394, Cohen's d = 0.35, = 0.163) between the two groups.

Conclusion: Intensive active virtual reality serious game training in addition to standard psychiatric care can significantly improve working memory and executive function in people diagnosed with schizophrenia.

Implications For Practice: When helping improve the cognitive function of people diagnosed with schizophrenia, mental health professionals should identify cognitive domains to be enhanced and develop corresponding serious game training strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2022.952828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334918PMC
July 2022

Atypical Mucin Expression Predicts Worse Overall Survival in Resectable Pancreatic Ductal Adenocarcinoma.

J Immunol Res 2022 21;2022:7353572. Epub 2022 Jul 21.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) displays a typical mucin expression pattern which is characterized by MUC1 positive, MUC2 negative, and MUC5AC positive. More and more evidences show that mucins are involved in the development of pancreatic diseases. However, the relationship between mucin expression and prognosis of PDAC patients has been controversial in the past decades; therefore, we aim to figure out the association of mucin expression with survival in PDAC patients who underwent radical resection.

Methods: We performed immunohistochemistry (IHC) to detect the expression of MUC1, MUC2, and MUC5AC in resected PDAC specimens from Shanghai Cancer Center, Fudan University (FUSCC, = 427) and obtained the corresponding clinical statistical data for retrospective study. Kaplan-Meier methods and Mantel-Cox tests were used to compare the survival curves, and the Cox regression model was employed for multivariate analyses to determine the independent risk factors. Survival analysis was also performed in the Queensland Centre for Medical Genomics (QCMG, = 70) PDAC cohort to verify the conclusion.

Results: Both the FUSCC cohort and the QCMG cohort demonstrated that MUC1 absence was significantly correlated with worse overall survival (OS). The presence of MUC2 showed marginal significance in predicting shorter OS of PDAC patients, while MUC5AC had no prognostic value. In the FUSCC cohort, MUC1 absence was associated with increased proportion of stage III PDAC ( = 0.011), and MUC1 absence and MUC2 presence were associated with tumour perineural aggression ( = 0.011 and = 0.030, respectively). Multivariable adjusted hazard ratios (HRs) for mortality of MUC1 and MUC2 were 0.492 (95% CI: 0.274-0.883, = 0.017) and 1.596 (95% CI: 1.061-2.401, = 0.025), respectively.

Conclusions: MUC1 absence or MUC2 presence is independently associated with poor OS among patients with resectable PDAC. MUC5AC absence tended to be associated with short-term death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/7353572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334048PMC
August 2022

Targeting the splicing factor NONO inhibits GBM progression through GPX1 intron retention.

Theranostics 2022 11;12(12):5451-5469. Epub 2022 Jul 11.

Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China.

Splicing factors are essential for nascent pre-mRNA processing and critical in cancer progression, suggesting that proteins with splicing functions represent potential molecular targets for cancer therapy. Here, we investigate the role of splicing factors in glioblastoma multiforme (GBM) progression and the possibility of targeting them for the treatment of the disease. The TCGA and CGGA public databases were used to screen for differentially expressed mRNA splicing factors. Immunohistochemistry and qRT-PCR were used to analyze the expression of non-POU domain-containing octamer-binding protein (NONO), a Drosophila behavior human splicing (DBHS) protein. Knockdown/overexpression of NONO with siRNA and lentiviral expression constructs was used to examine cell growth, apoptosis, and invasion in GBM cells. RNA sequencing was used to identify potential downstream molecular targets of NONO. RIP-PCR and RNA pulldown were used to determine the interaction between NONO and pre-mRNA. JC-1 staining and the seahorse assay were performed to assess redox homeostasis. Expression of NONO was increased in GBM samples and associated with poor survival in patients ( = 0.04). Knockdown of NONO suppressed GBM growth, and overexpression of NONO promoted GBM tumorigenesis and . RNA sequencing-based transcriptomic profiling confirmed that knockdown of NONO in U251 and P3 cells resulted in global intron retention of pre-mRNA and led to abnormal splicing of specific pre-mRNAs for and . NONO bound to a consensus motif in the intron of pre-mRNA in association with another DBHS protein family member, PSPC1. Knockdown of NONO impaired tumor growth, invasion, and redox homeostasis through aberrant splicing of . Finally, Auranofin, a small molecule inhibitor of NONO, suppressed GBM tumor growth in an orthotopic xenograft model in mice. We demonstrated that intron retention was a critical alternative RNA splicing event to occur in GBM progression, and that NONO was a key regulator of mRNA splicing in GBM. Targeting NONO represents a novel, potential therapeutic strategy for GBM treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.72248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330516PMC
August 2022

Cost of Cigarette Smoking‒Attributable Productivity Losses, U.S., 2018.

Am J Prev Med 2022 Jul 27. Epub 2022 Jul 27.

Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.

Introduction: Information on morbidity-related productivity losses attributable to cigarette smoking, an important component of the economic burden of cigarette smoking, is limited. This study fills this gap by estimating these costs in the U.S. and by state.

Methods: A human capital approach was used to estimate the cost of the morbidity-related productivity losses (absenteeism, presenteeism, household productivity, and inability to work) attributable to cigarette smoking among adults aged ≥18 years in the U.S. and by state. A combination of data, including the 2014-2018 National Health Interview Survey, 2018 Current Population Survey Annual Social and Economic Supplement, 2018 Behavioral Risk Factor Surveillance System, 2018 value of daily housework, and literature-based estimate of lost productivity while at work (presenteeism), was used. Costs were estimated for 2018, and all analyses were conducted in 2021.

Results: Estimated total cost of morbidity-related productivity losses attributable to cigarette smoking in the U.S. in 2018 was $184.9 billion. Absenteeism, presenteeism, home productivity, and the inability to work accounted for $9.4 billion, $46.8 billion, $12.8 billion, and $116.0 billion, respectively. State-level total costs ranged from $291 million to $16.9 billion with a median cost of $2.7 billion.

Conclusions: The cost of morbidity-related productivity losses attributable to cigarette smoking in the U.S. and in each state was substantial in 2018 and varied across the states. These estimates can guide public health policymakers and practitioners planning and evaluating interventions designed to alleviate the burden of cigarette smoking at the state and national levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amepre.2022.04.032DOI Listing
July 2022

Chlorpyrifos induces apoptosis and necroptosis via the activation of CYP450s pathway mediated by nuclear receptors in LMH cells.

Environ Sci Pollut Res Int 2022 Jul 31. Epub 2022 Jul 31.

College of Jilin Agricultural Science and Technology University, Jilin, 132101, People's Republic of China.

Chlorpyrifos (CPF), an organophosphorus pesticide, is detected commonly in environments, where it is thought to be highly toxic to non-target organisms. However, the mechanism of CYP450s pathway mediated by nuclear receptors on CPF-induced apoptosis and necroptosis at the cellular level and the effect of CPF on the cytotoxicity of the chicken hepatocarcinoma cell line (LMH) has also not been reported in detail. Therefore, this experiment aims to explore whether CPF can improve apoptosis and necroptosis in LMH cells by activating the nuclear receptors/CYP450s axis. LMH cells, the subject of this study, were exposed to 5 μg/mL, 10 μg/mL, and 15 μg/mL doses of CPF. With the increase of CPF concentration, the increase of nuclear receptor level led to the up-regulation of CYP450s activity. With the massive production of ROS, the expression of apoptotic pathway genes (Bax, Caspase9, and Caspase3) enhanced, while Bcl-2 expression dropped sharply. The expression of programmed necroptosis genes (RIPK1, RIPK3, and MLKL) heightened, and Caspase8 reduced considerably. In short, our data suggests that excessive activation of nuclear receptors and CYP450s induced by CPF promotes ROS production, which directs apoptosis and programmed necroptosis in LMH cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-022-22285-5DOI Listing
July 2022

Spatiotemporal patterns of firearm acquisition in the United States in different presidential terms.

Chaos 2022 Jul;32(7):073115

Center for Urban Science and Progress, Tandon School of Engineering, New York University, Brooklyn, New York 11201, USA.

This study develops mathematical tools and approaches to investigate spatiotemporal patterns of firearm acquisition in the U.S. complemented by hypothesis testing and statistical analysis. First, state-level and nation-level instant background check (BC) data are employed as proxy of firearm acquisition corresponding to 1999-2021. The relative-phase time-series of BC in each U.S. state is recovered and utilized to calculate the time-series of the U.S. states' synchronization degree. We reveal that U.S. states present a high-level degree of synchronization except in 2010-2011 and after 2018. Comparing these results with respect to a sitting U.S. president provides additional information: specifically, any two presidential terms are characterized by statistically different synchronization degrees except G. W. Bush's first term and B. H. Obama's second term. Next, to detail variations of BC, short-time Fourier transform, dimensionality reduction techniques, and diffusion maps are implemented within a time-frequency representation. Firearm acquisition in the high frequency band is described by a low-dimensional embedding, in the form of a plane with two embedding coordinates. Data points on the embedding plane identify separate clusters that signify state transitions in the original BC data with respect to different time windows. Through this analysis, we reveal that the frequency content of the BC data has a time-dependent characteristic. By comparing the diffusion map at hand with respect to a presidential term, we find that at least one of the embedding coordinates presents statistically significant variations between any two presidential terms except B. H. Obama's first term and D. J. Trump's pre-COVID term. The results point at a possible interplay between firearm acquisition in the U.S. and a presidential term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0096773DOI Listing
July 2022

Severity of Hospitalized Children with Anti-NMDAR Autoimmune Encephalitis.

J Child Neurol 2022 Jul 29:8830738221075886. Epub 2022 Jul 29.

Department of endocrinology, 159388Children's Hospital of Nanjing Medical University, Nanjing , China.

Information on the clinical characteristics and severity of autoimmune encephalitis with antibodies against the -methyl-d-aspartate receptor (NMDAR) in children is attracting more and more attention in the field of pediatric research. In this retrospective cohort study, all cases (n = 67) were enrolled from a tertiary children's hospital, from 2017 to 2020. We compared severe cases that received intensive care unit (ICU) care with nonsevere cases that did not receive ICU care and used machine learning algorithm to predict the severity of children, as well as using immunologic and viral nucleic acid tests to identify possible pathogenic triggers. Mean age of children was 8.29 (standard deviation 4.09) years, and 41 (61.19%) were girls. Eleven (16.42%) were admitted to the ICU, and 56 (83.58%) were admitted to neurology ward. Ten individual parameters were statistically significant differences between severe cases and nonsevere cases ( < .05), including headache, abnormal mental behavior or cognitive impairment, seizures, concomitant tumors, sputum/blood pathogens, blood globulin, blood urea nitrogen, blood immunoglobulin G, blood immunoglobulin M, and number of polynucleated cells in cerebrospinal fluid. Random forest regression model presented that the overall prediction power of severity reached 0.806, among which the number of polynucleated cells in cerebrospinal fluid contributed the most. Potential pathogenic causes exhibited that the proportion of mycoplasma was the highest, followed by Epstein-Barr virus. Our findings provided evidence for early identification of autoimmune encephalitis in children, especially in severe cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/08830738221075886DOI Listing
July 2022

Edaravone Modulates Neuronal GPX4/ACSL4/5-LOX to Promote Recovery After Spinal Cord Injury.

Front Cell Dev Biol 2022 18;10:849854. Epub 2022 May 18.

Tianjin Key Laboratory of Spine and Spinal Cord, International Science and Technology Cooperation Base of Spinal Cord Injury, Department of Orthopedics, International Chinese Musculoskeletal Research Society Collaborating Center for Spinal Cord Injury, Tianjin Medical University General Hospital, Tianjin, China.

The FDA-approved drug edaravone has a neuroprotective effect on spinal cord injury (SCI) and many other central nervous system diseases. However, its molecular mechanism remains unclear. Since edaravone is a lipid peroxidation scavenger, we hypothesize that edaravone exerts its neuroprotective effect by inhibiting ferroptosis in SCI. Edaravone treatment after SCI upregulates glutathione peroxidase 4 (GPX4) and system Xc-light chain (xCT), which are anti-ferroptosis proteins. It downregulates pro-ferroptosis proteins Acyl-CoA synthetase long-chain family member 4 (ACSL4) and 5-lipoxygenase (5-LOX). The most significant changes in edaravone treatment occur in the acute phase, two days post injury. Edaravone modulates neuronal GPX4/ACSL4/5-LOX in the spinal segment below the lesion, which is critical for maintaining locomotion. Moreover, the GPX4/ACSL4/5-LOX in motor neuron is also modulated by edaravone in the spinal cord. Therefore, secondary injury below the lesion site is reversed by edaravone ferroptosis inhibition. The cytokine array revealed that edaravone upregulated some anti-inflammatory cytokines such as IL-10, IL-13, and adiponectin. Edaravone reduced microgliosis and astrogliosis, indicating reduced neuroinflammation. Edaravone has a long-term effect on neuronal survival, spinal cord tissue sparing, and motor function recovery. In summary, we revealed a novel mechanism of edaravone in inhibiting neuronal ferroptosis in SCI. This mechanism may be generalizable to other neurological diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2022.849854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318422PMC
May 2022

Identification Principle and Thought of "Medical Malpractice" Based on Theoretical Analysis.

Fa Yi Xue Za Zhi 2022 Apr;38(2):166-172

Key Laboratory of Evidence Science, Ministry of Education, China University of Political Science and Law, Beijing 100088, China.

At present, medical disputes are still widely-concerned social problems and occasionally evolve into severe social events. In the dispute settlement mechanism, forensic identification opinion is the important technical support. Due to the high professionalism and complexity of medicine, the identification of medical malpractice has become major and difficult problem in the identification. This paper systematically analyze the concept of medical malpractice and five legal theories of malpractice determination, pointing out that China's forensic identification of medical damage should be led by the theory of "medical standards", supplemented by "prudent patient" standard and strengthen "peer review" in form. At the same time, seven main identification principles should be followed in practice: (1) take "obligation of diagnosis and treatment" as the basic principle of medical malpractice identification; (2) take whether to fulfill the obligation of diagnosis and treatment corresponding to current medical level as the specific principle; (3) take diagnosis and treatment routine, norms and guidelines as the main basis; (4) the principle of "peer review"; (5) the principle of "the generality of medical emergency action"; (6) the principle of "notification-informed-consent"; (7) the principle of "review of complications". This paper also puts forward the corresponding identification ideas in view of the above principles, hoping this helps standardize medical damage forensic identification activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12116/j.issn.1004-5619.2022.220203DOI Listing
April 2022

Gaze Estimation Approach Using Deep Differential Residual Network.

Sensors (Basel) 2022 Jul 21;22(14). Epub 2022 Jul 21.

School of Artificial Intelligence, Guilin University of Electronic Technology, Jinji Road, Guilin 541004, China.

Gaze estimation, which is a method to determine where a person is looking at given the person's full face, is a valuable clue for understanding human intention. Similarly to other domains of computer vision, deep learning (DL) methods have gained recognition in the gaze estimation domain. However, there are still gaze calibration problems in the gaze estimation domain, thus preventing existing methods from further improving the performances. An effective solution is to directly predict the difference information of two human eyes, such as the differential network (Diff-Nn). However, this solution results in a loss of accuracy when using only one inference image. We propose a differential residual model (DRNet) combined with a new loss function to make use of the difference information of two eye images. We treat the difference information as auxiliary information. We assess the proposed model (DRNet) mainly using two public datasets (1) MpiiGaze and (2) Eyediap. Considering only the eye features, DRNet outperforms the state-of-the-art gaze estimation methods with of 4.57 and 6.14 using MpiiGaze and Eyediap datasets, respectively. Furthermore, the experimental results also demonstrate that DRNet is extremely robust to noise images.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s22145462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322334PMC
July 2022

Deep Learning-Based Non-Intrusive Commercial Load Monitoring.

Sensors (Basel) 2022 Jul 13;22(14). Epub 2022 Jul 13.

School of Electrical and Information Engineering, Anhui University of Science and Technology, Huainan 232001, China.

Commercial load is an essential demand-side resource. Monitoring commercial loads helps not only commercial customers understand their energy usage to improve energy efficiency but also helps electric utilities develop demand-side management strategies to ensure stable operation of the power system. However, existing non-intrusive methods cannot monitor multiple commercial loads simultaneously and do not consider the high correlation and severe imbalance among commercial loads. Therefore, this paper proposes a deep learning-based non-intrusive commercial load monitoring method to solve these problems. The method takes the total power signal of the commercial building as input and directly determines the state and power consumption of several specific appliances. The key elements of the method are a new neural network structure called TTRNet and a new loss function called MLFL. TTRNet is a multi-label classification model that can autonomously learn correlation information through its unique network structure. MLFL is a loss function specifically designed for multi-label classification tasks, which solves the imbalance problem and improves the monitoring accuracy for challenging loads. To validate the proposed method, experiments are performed separately in seen and unseen scenarios using a public dataset. In the seen scenario, the method achieves an average F1 score of 0.957, which is 7.77% better than existing multi-label classification methods. In the unseen scenario, the average F1 score is 0.904, which is 1.92% better than existing methods. The experimental results show that the method proposed in this paper is both effective and practical.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s22145250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320136PMC
July 2022

Preparation of Micro-Pit-Textured PCD Tools and Micro-Turning Experiment on SiCp/Al Composites.

Micromachines (Basel) 2022 Jul 19;13(7). Epub 2022 Jul 19.

School of Mechanical and Aerospace Engineering, Jilin University, Changchun 130015, China.

Serious tool wear occurs very often during machining due to the reinforcing phases in the workpiece. In this study, micro-pit-textures were prepared on the surfaces of PCD tools with a nanosecond laser to improve their cutting performance on SiCp/Al composites. The micro-pits were designed with rounded corners to improve the chip flow. The location and size of the texture were determined by analyzing the tool-chip contact area of the non-textured tool. The cutting performance of these textured PCD tools was investigated through orthogonal cutting experiments. It was found that the optimal cutting performance of the textured tools was achieved with the proper distance of the texture from the main cutting edge (35 μm) and the pit spacing (60 μm), aa a result of which the main cutting force reduced by about 14%, and the tool wear and surface adhesion significantly reduced. This texture was then applied in the micro-turning experiments of the PCD tool on the SiCp/Al composites. The cutting force in this experiment reduced by 22%, and the textured tool provided better chip transfer and tool anti-tipping. In this study, the role of SiC particles as a third body between the tool and the chip surface is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/mi13071141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317894PMC
July 2022

Selenium Combined with Methyl Jasmonate to Control Tomato Gray Mold by Optimizing Microbial Community Structure in Plants.

J Fungi (Basel) 2022 Jul 14;8(7). Epub 2022 Jul 14.

Fujian Key Laboratory for Monitoring and Integrated Management of Crop Pests, Fuzhou 350013, China.

Tomato cultivation is seriously affected by infection from . The safe and effective control of tomato gray mold remains elusive. Plant-related microbial communities regulate not only plant metabolism but also plant immune systems. In this study, we observed that Selenium application in soil combined with foliar spraying of methyl jasmonate could reduce infection in tomato fruits and leaves and improve tomato fruit quality. The infection rate of leaves decreased from 42.19% to 25.00%, and the vitamin C content increased by 22.14%. The bacterial community structure of the tomato was studied by using amplicon sequencing technology. The leaf bacterial alpha diversity of tomatoes treated with Se plus methyl jasmonate was significantly higher than that of the control. Then we isolated five strains antagonistic to in vitro from tomato leaves in the treatment of Se plus methyl jasmonate. The antagonistic strains were identified as and . Spraying mixed antagonistic strain suspension significantly inhibited the diameter of with an inhibition rate of 40.99%. This study revealed the key role of plant-beneficial bacteria recruited by Se combined with methyl jasmonate in improving tomato plant disease resistance. These findings may benefit our understanding of the new regulation of microorganisms on .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jof8070731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319442PMC
July 2022

Transcriptome Analysis Reveals Key Gene Expression Changes in Blue Catfish Sperm in Response to Cryopreservation.

Int J Mol Sci 2022 Jul 10;23(14). Epub 2022 Jul 10.

Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.

The hybrids of female channel catfish () and male blue catfish () account for >50% of US catfish production due to superior growth, feed conversion, and disease resistance compared to both parental species. However, these hybrids can rarely be naturally spawned. Sperm collection is a lethal procedure, and sperm samples are now cryopreserved for fertilization needs. Previous studies showed that variation in sperm quality causes variable embryo hatch rates, which is the limiting factor in hybrid catfish breeding. Biomarkers as indicators for sperm quality and reproductive success are currently lacking. To address this, we investigated expression changes caused by cryopreservation using transcriptome profiles of fresh and cryopreserved sperm. Sperm quality measurements revealed that cryopreservation significantly increased oxidative stress levels and DNA fragmentation, and reduced sperm kinematic parameters. The present RNA-seq study identified 849 upregulated genes after cryopreservation, including members of all five complexes in the mitochondrial electron transport chain, suggesting a boost in oxidative phosphorylation activities, which often lead to excessive production of reactive oxygen species (ROS) associated with cell death. Interestingly, functional enrichment analyses revealed compensatory changes in gene expression after cryopreservation to offset detrimental effects of ultra-cold storage: MnSOD was induced to control ROS production; chaperones and ubiquitin ligases were upregulated to correct misfolded proteins or direct them to degradation; negative regulators of apoptosis, amide biosynthesis, and cilium-related functions were also enriched. Our study provides insight into underlying molecular mechanisms of sperm cryoinjury and lays a foundation to further explore molecular biomarkers on cryo-survival and gamete quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23147618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316979PMC
July 2022

Interaction with TopBP1 Is Required for Human Papillomavirus 16 E2 Plasmid Segregation/Retention Function during Mitosis.

J Virol 2022 Jul 26:e0083022. Epub 2022 Jul 26.

Virginia Commonwealth Universitygrid.224260.0 (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA.

Human papillomavirus 16 (HPV16) E2 is a DNA-binding protein that regulates transcription, replication and potentially, segregation of the HPV16 genome during the viral life cycle. In the segregation model, E2 simultaneously binds to viral and host chromatin, acting as a bridge to ensure that viral genomes reside in daughter nuclei following cell division. The host chromatin receptor for E2 mediating this function is unknown. Recently, we demonstrated that CK2 phosphorylation of E2 on serine 23 (S23) is required for interaction with TopBP1, and that this interaction promotes E2 and TopBP1 recruitment to mitotic chromatin. Here, we demonstrate that in U2OS cells expressing wild-type E2 and a non-TopBP1-binding mutant (S23A, serine 23 mutated to alanine), interaction with TopBP1 is essential for E2 recruitment of plasmids to mitotic chromatin. Using novel quantitative segregation assays, we demonstrate that interaction with TopBP1 is required for E2 plasmid segregation function in U2OS and N/Tert-1 cells. Small interfering RNA (siRNA) knockdown of TopBP1 or CK2 enzyme components disrupts E2 segregation/retention function. The interaction of E2 with TopBP1 promotes increased levels of E2 protein during mitosis in U2OS and N/Tert-1 cells, as well as in human foreskin keratinocytes (HFK) immortalized by the HPV16 genome. Overall, our results demonstrate that E2 has plasmid segregation activity, and that the E2-TopBP1 interaction is essential for this E2 function. HPV16 causes 3% to 4% of all human cancers. It is proposed that during the viral life cycle, the viral genome is actively segregated into daughter nuclei, ensuring viral replication in the subsequent S phase. The E2 protein potentially bridges the viral and host genomes during mitosis to mediate segregation of the circular viral plasmid. Here, we demonstrate that E2 has the ability to mediate plasmid segregation, and that this function is dependent upon interaction with the host protein TopBP1. Additionally, we demonstrate that the E2-TopBP1 interaction promotes enhanced E2 expression during mitosis, which likely promotes the plasmid segregation function of E2. Overall, our results present a mechanism of how HPV16 can segregate its viral genome during an active infection, a critical aspect of the viral life cycle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/jvi.00830-22DOI Listing
July 2022

CXCR2 Is Essential for Radiation-Induced Intestinal Injury by Initiating Neutrophil Infiltration.

J Immunol Res 2022 16;2022:7966089. Epub 2022 Jul 16.

Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.

Neutrophils, known as an important part of the immune system, are the most abundant leukocyte population in peripheral blood, but excessive recruitment will lead to tissue/organ injury. RNA sequencing showed that ionizing radiation significantly increased the expression of characteristic genes of neutrophils in intestinal tissues compared with liver and lung tissues. By clearing neutrophils with an anti-Ly6G antibody, we found that neutrophil infiltration is critical for irradiation-induced intestinal injury. CXCR2 is a G-protein-coupled receptor that mediates the migration of neutrophils by combining with its ligands. Compared with observations in liver and lung tissues, we found that CXCR2 and its ligands, including CXCL1, CXCL2, CXCL3, and CXCL5, were all significantly upregulated in irradiated intestinal tissues. Further studies showed that SB225002, an inhibitor of CXCR2, could effectively inhibit the chemotaxis of neutrophils and tissue damage mediated by the CXCL-CXCR2 signalling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/7966089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308512PMC
July 2022

Single-tube Multiplex Nested PCR System for Efficient Detection of Pathogenic Microorganisms in SPF Rodents.

J Am Assoc Lab Anim Sci 2022 Jul 25. Epub 2022 Jul 25.

Laboratory Animal Center, Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, China.

PCR testing is increasingly important for microbial control in SPF facilities. However, most current PCR methods are time-consuming and require compromise between high sensitivity and high multiplexing. We developed a one-tube multiplex nested PCR strategy (MN-PCR) for simultaneous direct (that is, without culturing) detection of multiple pathogens. We first aligned sequences for the 16S rDNA genes of selected target bacteria and a panel of closely related organisms. From these data, we designed a pair of universal primers and multiple sets of species-specific PCR primers to amplify the target sequences; the universal primers were modified to include various degenerate bases and locked nucleic acids. In a single tube, 16S rDNA sequences were amplified by using the nested PCR primers under high temperature (that is, above 65 °C) during the first stage of the MN-PCR procedure, when the target-species-specific PCR primers do not support amplification due to their short length. In addition, the concentration of the nested PCR primers during the first stage was adjusted to ensure that they were consumed and did not yield visible bands themselves. During the second stage, the enriched 16S rDNA sequences then served as templates for amplification of the species-specific fragments by using the multiple PCR primers at low annealing temperatures (that is, below 60 °C). The results showed that our MN-PCR method detected as little as 1 fg of target bacterial DNA in a 20-μL reaction volume, whereas conventional multiplex PCR detected a minimum of 1 pg only. Compared with traditional multiplex PCR assays, our MN-PCR system is an effective and efficient culture-free process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.30802/AALAS-JAALAS-21-000117DOI Listing
July 2022

Identification of Metabolic Syndrome-Related miRNA-mRNA Regulatory Networks and Key Genes Based on Bioinformatics Analysis.

Biochem Genet 2022 Jul 25. Epub 2022 Jul 25.

The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210029, China.

Metabolic syndrome, which affects approximately one-quarter of the world's population, is a combination of multiple traits and is associated with high all-cause mortality, increased cancer risk, and other hazards. It has been shown that the epigenetic functions of miRNAs are closely related to metabolic syndrome, but epigenetic studies have not yet fully elucidated the regulatory network and key genes associated with metabolic syndrome. To perform data analysis and screening of potential differentially expressed target miRNAs, mRNAs and genes based on a bioinformatics approach using a metabolic syndrome mRNA and miRNA gene microarray, leading to further analysis and identification of metabolic syndrome-related miRNA-mRNA regulatory networks and key genes. The miRNA gene set (GSE98896) and mRNA gene set (GSE98895) of peripheral blood samples from patients with metabolic syndrome from the GEO database were screened, and set|logFC|> 1 and adjusted P < 0.05 were used to identify the differentially expressed miRNAs and mRNAs. Differentially expressed miRNA transcription factors were predicted using FunRich software and subjected to GO and KEGG enrichment analysis. Next, biological process enrichment analysis of differentially expressed mRNAs was performed with Metascape. Differentially expressed miRNAs and mRNAs were identified and visualized as miRNA-mRNA regulatory networks based on the complementary pairing principle. Data analysis of genome-wide metabolic syndrome-related mRNAs was performed using the gene set enrichment analysis (GSEA) database. Finally, further WGCNA of the set of genes most closely associated with metabolic syndrome was performed to validate the findings. A total of 217 differentially expressed mRNAs and 158 differentially expressed miRNAs were identified by screening the metabolic syndrome miRNA and mRNA gene sets, and these molecules mainly included transcription factors, such as SP1, SP4, and EGR1, that function in the IL-17 signalling pathway; cytokine-cytokine receptor interaction; proteoglycan syndecan-mediated signalling events; and the glypican pathway, which is involved in the inflammatory response and glucose and lipid metabolism. miR-34C-5P, which was identified by constructing a miRNA-mRNA regulatory network, could regulate DPYSL4 expression to influence insulin β-cells, the inflammatory response and glucose oxidative catabolism. Based on GSEA, metabolic syndrome is known to be closely related to oxidative phosphorylation, DNA repair, neuronal damage, and glycolysis. Finally, RStudio and DAVID were used to perform WGCNA of the gene sets most closely associated with metabolic syndrome, and the results further validated the conclusions. Metabolic syndrome is a common metabolic disease worldwide, and its mechanism of action is closely related to the inflammatory response, glycolipid metabolism, and impaired mitochondrial function. miR-34C-5P can regulate DPYSL4 expression and can be a potential research target. In addition, UQCRQ and NDUFA8 are core genes of oxidative phosphorylation and have also been identified as potential targets for the future treatment of metabolic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10528-022-10257-wDOI Listing
July 2022

Ang2-Targeted Combination Therapy for Cancer Treatment.

Front Immunol 2022 8;13:949553. Epub 2022 Jul 8.

Institute of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.

Angiopoietin-2 (Ang2), a member of the angiopoietin family, is widely involved in the process of vascular physiology, bone physiology, adipose tissue physiology and the occurrence and development of inflammation, cardiac hypertrophy, rheumatoid, tumor and other diseases under pathological conditions. Proliferation and metastasis of cancer largely depend on angiogenesis. Therefore, anti-angiogenesis has become the target of tumor therapy. Due to the Ang2 plays a key role in promoting angiogenesis and stability in vascular physiology, the imbalance of its expression is an important condition for the occurrence and development of cancer. It has been proved that blocking Ang2 can inhibit the growth, invasion and metastasis of cancer cells. In recent years, research has been constantly supplemented. We focus on the mechanisms that regulate the expression of Ang2 mRNA and protein levels in different cancers, contributing to a better understanding of how Ang2 exerts different effects in different cancers and stages, as well as facilitating more specific targeting of relevant molecules in cancer therapy. At the same time, the importance of Ang2 in cancer growth, metastasis, prognosis and combination therapy is pointed out. And finally, we will discuss the current investigations and future challenges of combining Ang2 inhibition with chemotherapy, immunotherapy, and radiotherapy to increase its efficacy in cancer patients. This review provides a theoretical reference for the development of new targets and effective combination therapy strategies for cancer treatment in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.949553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305611PMC
July 2022

Low IL7R Expression at Diagnosis Predicted Relapse in Adult Acute Myeloid Leukemia Patients With t(8;21).

Front Immunol 2022 7;13:909104. Epub 2022 Jul 7.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China.

Background: Acute myeloid leukemia (AML) with t(8;21) needs to be further stratified. In addition to leukemia cells, immune cells in tumor microenvironment participate in tumor initiation, growth and progression. Interleukins (ILs)/interleukin receptors (ILRs) interaction plays important roles in the antitumor immune response. IL7R is reported to be relevant to prognosis in solid tumor and acute lymphoblastic leukemia. However, the prognostic significance of IL7R in t(8;21) AML remains to be clarified.

Methods: Bone marrows collected from 156 newly diagnosed t(8;21) AML patients were used for testing IL7R transcript level by TaqMan-based real-time quantitative PCR (RQ-PCR), and RNAseq were performed in 15 of them. Moreover, IL7R expression at diagnosis were measured by RQ-PCR and flow cytometry (FCM) simultaneously in other 13 t(8;21) AML patients.

Results: t(8;21) AML patients had varied IL7R transcript levels and were categorized into low-expression (IL7R-L) and high-expression (IL7R-H) groups; IL7R-L was significantly associated with a lower relapse-free survival (RFS) rate (=0.0027) and KIT mutation (=0.0010). Furthermore, IL7R-L was associated with a lower RFS rate in KIT group (=0.013) and IL7R-H/KIT patients had similar RFS to KIT patients (=0.35). GO analysis enrichment showed that down-regulated genes were predominantly involved in the regulation of T cell and leukocyte activation, proliferation and differentiation in IL7R-L group. IL7R-L had significantly lower levels of Granzymes A/B, CCR7, CD28 and CD27 than IL7R-H group (all <0.05). FCM analysis showed IL7R protein was primarily expressed in CD4 T and CD8 T cell subset. A significant association was found between the transcript level of IL7R and the percentage of CD8 T cells in nucleated cells (=0.015) but not CD4 T cells (=0.47).

Conclusion: Low IL7R transcript level of bone marrow at diagnosis predicted relapse in t(8;21) AML, which might be caused by the difference in the amount, status and function of T cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.909104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302488PMC
July 2022
-->