Publications by authors named "Liang Chen"

4,219 Publications

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Danger control and fear control during public health emergencies: Considering the roles of fear and hope in the EPPM across different levels of trust.

Risk Anal 2022 Jun 24. Epub 2022 Jun 24.

Wee Kim Wee School of Communication and Information, Nanyang Technological University, Singapore.

Public health emergencies pose considerable threats to global health and safety. The control of these emergencies requires the efforts of healthcare professionals and calls for the public to take protective actions. The present study not only puts fear back in the extended parallel process model (EPPM) but also considers another similarly productive emotion: hope. We examined the mechanisms behind the effects of four cognitive perceptions on protective actions (i.e., danger control) and information avoidance (i.e., fear control). A national online survey was conducted with 1676 participants during the outbreak of COVID-19 in China from February 1 to 29, 2020. The results revealed that perceived severity and susceptibility could lead to fear, positively affecting protective actions. On the other hand, perceived response efficacy and self-efficacy induced hope, which was positively associated with protective actions but negatively associated with information avoidance. Furthermore, the mechanisms behind the relationships among cognitions, emotions, and behaviors varied across levels of trust in healthcare systems.
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http://dx.doi.org/10.1111/risa.13985DOI Listing
June 2022

SARS-CoV-2 Accessory Protein ORF8 Decreases Antibody-Dependent Cellular Cytotoxicity.

Viruses 2022 Jun 7;14(6). Epub 2022 Jun 7.

Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.

Viruses use many different strategies to evade host immune responses. In the case of SARS-CoV-2, its Spike mutates rapidly to escape from neutralizing antibodies. In addition to this strategy, ORF8, a small accessory protein encoded by SARS-CoV-2, helps immune evasion by reducing the susceptibility of SARS-CoV-2-infected cells to the cytotoxic CD8+ T cell response. Interestingly, among all accessory proteins, ORF8 is rapidly evolving and a deletion in this protein has been linked to milder disease. Here, we studied the effect of ORF8 on peripheral blood mononuclear cells (PBMC). Specifically, we found that ORF8 can bind monocytes as well as NK cells. Strikingly, ORF8 binds CD16a (FcγRIIIA) with nanomolar affinity and decreases the overall level of CD16 at the surface of monocytes and, to a lesser extent, NK cells. This decrease significantly reduces the capacity of PBMCs and particularly monocytes to mediate antibody-dependent cellular cytotoxicity (ADCC). Overall, our data identifies a new immune-evasion activity used by SARS-CoV-2 to escape humoral responses.
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http://dx.doi.org/10.3390/v14061237DOI Listing
June 2022

Self-Assembled pH-Responsive Metal-Organic Frameworks for Enhancing the Encapsulation and Anti-Oxidation and Melanogenesis Inhibition Activities of Glabridin.

Molecules 2022 Jun 18;27(12). Epub 2022 Jun 18.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

Metal organic frameworks (MOFs) are formed by self-assembly of metal ions and organic ligands. A special type of MOF called ZIF-8, which is formed by self-assembly of zinc ions and 2-methylimidazole, shows excellent stability in aqueous solutions and disintegrates under acidic conditions. These properties make ZIF-8 a suitable carrier material for pH-stimulated drug delivery systems. Glabridin is an isoflavane compound that is widely present in the roots of . Because of its outstanding skin whitening properties, glabridin is widely used as a whitener in the cosmetics industry. In this study, ZIF-8 was employed to encapsulate glabridin. Glabridin-loaded ZIF-8 was successfully prepared with a drug encapsulation efficiency of 98.67%. The prepared sample showed a fusiform or cruciate flower-like structure, and its size was about 3 μm. ZIF-8 enabled pH-controlled release of glabridin. Moreover, ZIF-8 encapsulation significantly enhanced the intracellular anti-oxidant activity and melanogenesis inhibitory activity of glabridin. This study provides a new approach that shows great potential to improve the biological application of glabridin.
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http://dx.doi.org/10.3390/molecules27123908DOI Listing
June 2022

Designing Magnesium Phosphate Cement for Stabilization/Solidification of Zn-Rich Electroplating Sludge.

Environ Sci Technol 2022 Jun 23. Epub 2022 Jun 23.

Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.

Electroplating sludge is a hazardous waste due to its high potential to leach toxic elements into the natural environment. To alleviate this issue, we tailored magnesium phosphate cement (MPC) as a low-carbon material for stabilization/solidification (S/S) of Zn-rich electroplating sludge. The interaction between MPC and ZnO was investigated to clarify the precipitate chemistry, microstructure transition, and chemical environment of Zn species in the MPC-treated Zn sludge system. Comprehensive characterization (by X-ray diffraction (XRD), P nuclear magnetic resonance (NMR), and extended X-ray absorption fine structure spectroscopy (EXAFS)) and thermodynamic modeling results revealed that the incorporated ZnO preferentially reacted with phosphate to form Zn(PO)·2HO/Zn(PO)·4HO, changing the orthophosphate environment in the MPC system. Stronger chemical bonding between Zn and phosphate in comparison to the bonding between Mg and phosphate also resulted in the formation of amorphous Zn(PO)·2HO/Zn(PO)·4HO. Zn(PO)·4HO precipitate appears to predominate at high {K}{H}{HPO} values, and the formation of Zn(PO)·2HO/Zn(PO)·4HO competed for the Mg sites in the MPC system, leading to the inhibition of formation of Mg-phosphate precipitates. Overall, this work uncovers the precipitate chemistry and microstructure transition of Zn species in the MPC system, providing new insights into the sustainable S/S of Zn-contaminated wastes by adopting MPC.
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http://dx.doi.org/10.1021/acs.est.2c01450DOI Listing
June 2022

Comment on: Treatment efficacy for rectal Neisseria gonorrhoeae: a systematic review and meta-analysis of randomized controlled trials.

J Antimicrob Chemother 2022 Jun 23. Epub 2022 Jun 23.

Emergency Department, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

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http://dx.doi.org/10.1093/jac/dkac194DOI Listing
June 2022

Infertility, recurrent pregnancy loss, and risk of stroke: pooled analysis of individual patient data of 618 851 women.

BMJ 2022 Jun 22;377:e070603. Epub 2022 Jun 22.

University of Queensland, School of Public Health, Queensland, Australia

Objective: To examine the associations of infertility, recurrent miscarriage, and stillbirth with the risk of first non-fatal and fatal stroke, further stratified by stroke subtypes.

Design: Individual participant pooled analysis of eight prospective cohort studies.

Setting: Cohort studies across seven countries (Australia, China, Japan, Netherlands, Sweden, the United Kingdom, and the United States) participating in the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium, which was established in June 2012.

Participants: 618 851 women aged 32.0-73.0 years at baseline with data on infertility, miscarriage, or stillbirth, at least one outcome event (non-fatal or fatal stroke), and information on covariates were included; 93 119 women were excluded. Of the participants, 275 863 had data on non-fatal and fatal stroke, 54 716 only had data on non-fatal stroke, and 288 272 only had data on fatal stroke.

Main Outcome And Measures: Non-fatal strokes were identified through self-reported questionnaires, linked hospital data, or national patient registers. Fatal strokes were identified through death registry data.

Results: The median follow-up for non-fatal stroke and fatal stroke was 13.0 years (interquartile range 12.0-14.0) and 9.4 years (7.6-13.0), respectively. A first non-fatal stroke was experienced by 9265 (2.8%) women and 4003 (0.7%) experienced a fatal stroke. Hazard ratios for non-fatal or fatal stroke were stratified by hypertension and adjusted for race or ethnicity, body mass index, smoking status, education level, and study. Infertility was associated with an increased risk of non-fatal stroke (hazard ratio 1.14, 95% confidence interval 1.08 to 1.20). Recurrent miscarriage (at least three) was associated with higher risk of non-fatal and fatal stroke (1.35, 1.27 to 1.44, and 1.82, 1.58 to 2.10, respectively). Women with stillbirth were at 31% higher risk of non-fatal stroke (1.31, 1.10 to 1.57) and women with recurrent stillbirth were at 26% higher risk of fatal stroke (1.26, 1.15 to 1.39). The increased risk of stroke (non-fatal or fatal) associated with infertility or recurrent stillbirths was mainly driven by a single stroke subtype (non-fatal ischaemic stroke and fatal haemorrhagic stroke), while the increased risk of stroke (non-fatal or fatal) associated with recurrent miscarriages was driven by both subtypes.

Conclusion: A history of recurrent miscarriages and death or loss of a baby before or during birth could be considered a female specific risk factor for stroke, with differences in risk according to stroke subtypes. These findings could contribute to improved monitoring and stroke prevention for women with such a history.
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http://dx.doi.org/10.1136/bmj-2022-070603DOI Listing
June 2022

Outbreak of IncX8 Plasmid-Mediated KPC-3-Producing Enterobacterales Infection, China.

Emerg Infect Dis 2022 Jul;28(7):1421-1430

Carbapenem-resistant Enterobacterales (CRE) infection is highly endemic in China; Klebsiella pneumoniae carbapenemase (KPC) 2-producing CRE is the most common, whereas KPC-3-producing CRE is rare. We report an outbreak of KPC-3-producing Enterobacterales infection in China. During August 2020-June 2021, 25 bla-positive Enterobacteriale isolates were detected from 24 patients in China. Whole-genome sequencing analysis revealed that the bla genes were harbored by IncX8 plasmids. The outbreak involved clonal expansion of KPC-3-producing Serratia marcescens and transmission of bla plasmids across different species. The bla plasmids demonstrated high conjugation frequencies (10 to 10). A Galleria mellonella infection model showed that 2 sequence type 65 K2 K. pneumoniae strains containing bla plasmids were highly virulent. A ceftazidime/avibactam in vitro selection assay indicated that the KPC-3-producing strains can readily develop resistance. The spread of bla-harboring IncX8 plasmids and these KPC-3 strains should be closely monitored in China and globally.
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http://dx.doi.org/10.3201/eid2807.212181DOI Listing
July 2022

An effective detection method for wheat mold based on ultra weak luminescence.

Sci Rep 2022 Jun 21;12(1):10425. Epub 2022 Jun 21.

School of Mechanical and Electrical Engineering, Henan University of Technology, Zhengzhou, China.

It is widely known that mold is one of important indices in assessing the quality of stored wheat. First, mold will decrease the quality of wheat kernels; the wheat kernels infected by mold can produce secondary metabolites, such as aflatoxins, ochratoxin A, zearalenone, fumonisins and so on. Second, the mycotoxins metabolized by mycetes are extremely harmful to humans; once the food or feed is made of by those wheat kernels infected by mold, it will cause serious health problems on human beings as well as animals. Therefore, the effective and accurate detection of wheat mold is vitally important to evaluate the storage and subsequent processing quality of wheat kernels. However, traditional methods for detecting wheat mold mainly rely on biochemical methods, which always involve complex and long pretreatment processes, and waste part of wheat samples for each detection. In view of this, this paper proposes a type of eco-friendly and nondestructive wheat mold detection method based on ultra weak luminescence. The specific implementation process is as follows: firstly, ultra weak luminescence signals of the healthy and the moldy wheat subsamples are measured by a photon analyzer; secondly, the approximate entropy and multiscale approximate entropy are introduced as the main classification features separately; finally, the detection model has been established based on the support vector machine in order to classify two types of wheat subsamples. The receiver operating characteristic curve of the newly established detection model shows that the highest classification accuracy rate can reach 93.1%, which illustrates that our proposed detection model is feasible and promising for detecting wheat mold.
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http://dx.doi.org/10.1038/s41598-022-14344-1DOI Listing
June 2022

Intestinal colonisation with hypervirulent or third-generation cephalosporin-resistant Klebsiella pneumoniae strains upon hospital admission in a general ward in Taiwan.

Int J Antimicrob Agents 2022 Jun 18:106624. Epub 2022 Jun 18.

Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ, USA; Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, USA.

We aimed to investigate the clinical characteristics of patients with hypervirulent and/or third-generation cephalosporin-resistant (3GCR) Klebsiella pneumoniae intestinal colonisation upon admission to a general ward at the Taipei Veterans General Hospital in Taiwan in 2017. Stool surveillance culture was obtained from the patients, and clinical characteristics of these patients were studied retrospectively. The K. pneumoniae strains were characterised for antimicrobial susceptibility, mechanisms of the 3GCR phenotype, and the presence of rmpA/A2 genes, which are markers of hypervirulent strains. Whole genome sequencing (WGS) was used to identify the relationship between the colonising and subsequent infection strains. Of the 408 patients admitted to the general ward, 87 patients with intestinal K. pneumoniae colonisation were identified. Twenty-eight (32.2 %) and nine (10.3 %) patients carried 3GCR and hypervirulent K. pneumoniae strains, respectively. Long-term care facility residents and diabetes mellitus were more common in patients colonised with 3GCR strains than those with hypervirulent strains. The 28-d mortality rate was similar between the two groups. The major resistance mechanisms among the 3GCR strains involved the production of extended-spectrum beta-lactamases genes (67.9 %) and bla (64.3 %). One patient colonised with K. pneumoniae developed subsequent bacteraemia caused by the same strain. In conclusion, 3GCR strains were more common than hypervirulent strains in the patients, but the clinical outcomes were similar. Future studies to elucidate the risk factors for intestinal carriage of hypervirulent and 3GCR K. pneumoniae strains are needed for early identification and better management of these patients.
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http://dx.doi.org/10.1016/j.ijantimicag.2022.106624DOI Listing
June 2022

Preconception reproductive tract infections status and adverse pregnancy outcomes: a population-based retrospective cohort study.

BMC Pregnancy Childbirth 2022 Jun 20;22(1):501. Epub 2022 Jun 20.

NHC Key Lab. of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, 400020, Shanghai, China.

Background: Reproductive tract infections can cause serious adverse outcomes for pregnant women such as spontaneous abortion and preterm birth. However, it is unclear whether maternal reproductive tract infection before pregnancy would also be related to any adverse pregnancy outcomes. This study aims to investigate the association of maternal preconception reproductive tract infections with subsequent adverse pregnancy outcomes.

Methods: A retrospective cohort study was conducted in the Chongqing Municipality of China between April 2010 and December 2016. A total of 57,586 women (57,708 pregnancies) from all 39 counties of Chongqing who participated in the National Free Preconception Health Examination Project were included. They all took preconception examinations for gonorrhea, chlamydia, trichomoniasis, syphilis, bacterial vaginosis and candidiasis before pregnancy within one year. Primary outcomes included spontaneous abortion (< 28 weeks gestation), preterm birth (< 37 weeks gestation), macrosomia and low birthweight.

Results: Of the 57,708 pregnancies, 2438 (4.22%) had at least one type of reproductive tract infections. Compared with women who were not infected with any reproductive tract infection before pregnancy, women with reproductive tract infections had a higher rate of spontaneous abortion (7.88% vs. 5.62%, p < 0.001). After analyzing by each infection, there were few significant associations between pre-pregnancy infections and adverse outcomes. Preconception syphilis infection was significantly associated with increased odds of spontaneous abortion (aOR = 2.07, 95%CI 1.50-2.85), induced abortion/labour due to medical reasons (aOR = 1.60, 95%CI 1.01-2.54) and preterm birth (aOR = 1.60, 95%CI 1.12-2.30) after adjusting for potential confounders. Preconception trichomoniasis was intended to relate to a higher risk of spontaneous abortion (aOR = 1.65, 95%CI 1.01-2.71), but its impact seemed to be attributed to its co-infection with other RTIs. Women who were chlamydia or bacterial vaginosis positive before pregnancy showed higher odds of macrosomia (aOR = 2.00, 95% CI 1.07-3.74 for chlamydia; aOR = 1.58, 95% CI 1.06-2.34 for bacterial vaginosis). Preconception bacterial vaginosis might also be associated with higher risks of very preterm birth (aOR = 2.16, 95%CI 1.23-3.78) and large for gestational age (aOR = 1.36, 95%CI 1.02-1.81).

Conclusions: Women with infections of the genital tract before pregnancy might also have increased risks of subsequent adverse outcomes including spontaneous abortion, preterm birth and macrosomia.
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http://dx.doi.org/10.1186/s12884-022-04836-3DOI Listing
June 2022

Long-term effects of total partial pancreatectomy among patients with pancreatic cancer: a population-based study.

Ann Transl Med 2022 May;10(10):539

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Total pancreatectomy (TP) for pancreatic cancer (PC) has been limited historically for fear of elevated perioperative morbidity and mortality. With advances in perioperative care, TP may be an alternative option to partial pancreatectomy (PP). Limited evidence clarified the indication for these two procedures in PC patients, especially in patients with different tumor staging and location. Thus, this study aims to compare the outcomes after TP and PP for PCs of different T stages and locations.

Methods: The study identified 14,456 PC patients with potentially curable primary tumor (T1-3) who received TP or PP from the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2016. Detailed clinical and tumor covariates were all collected. Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints of interest in this study. OS and CSS were compared between patients after TP and PP using log-rank analysis.

Results: For all patients, except for tumor location, TP group was comparable to the PP group. OS and CSS of the TP group were worse than of the PP group (median OS: 19 20 months, P=0.0058; median CSS: 24 26 months, P=0.00098, respectively). In stratifying analyses, TP was significantly related to worse OS and CSS than PP in pancreatic head and neck cancer patients with T2-stage tumors (median OS: 18 19 months, P=0.0016; median CSS: 22 24 months, P=0.00055, respectively), whereas for patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer, OS and CSS of the two groups were similar (all P>0.05).

Conclusions: Compared with PP, TP offered worse prognosis in pancreatic head and neck cancer patients with T2-stage tumors, furthermore, TP and PP achieved comparable prognosis in patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer.
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http://dx.doi.org/10.21037/atm-22-2217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201187PMC
May 2022

The emerging roles of machine learning in cardiovascular diseases: a narrative review.

Ann Transl Med 2022 May;10(10):611

Department of Cardiology, Wuxi Second People's Hospital of Nanjing Medical University, Wuxi, China.

Background And Objective: With the wide application of electronic medical record systems in hospitals, massive medical data are available. This type of medical data has the characteristics of heterogeneity and multi-dimensionality. Traditional statistical methods cannot fully extract and use such data, but with their non-linear and cross-learning modes, machine-learning (ML) algorithms based on artificial intelligence can address these shortcomings. To explore the application of ML algorithms in the cardiovascular field, we retrieved and reviewed relevant articles published in the last 6 years and found that ML is practical and accurate in the auxiliary diagnosis of cardiovascular diseases. Thus, this article reviewed the research progress of ML in cardiovascular disease.

Methods: This study searched relevant literature published in National Center for Biotechnology Information (NCBI) PubMed from 2016 to 2022. The relevant literature was extracted from NCBI PubMed with the following keywords and their combinations: "machine learning", "artificial intelligence", "cardiology", "cardiovascular disease", "echocardiography", "electrocardiogram" and "prediction model". All articles included in the review are English.

Key Content And Findings: The review found that ML is practical and accurate in the diagnosis of cardiovascular diseases. Besides, ML can build clinical risk prediction models and help doctors evaluate the prognosis of patients.

Conclusions: The study summarized the progress of ML in cardiovascular diseases and confirmed its advantages in clinical application. In the future, models and software based on ML will be common auxiliary tools in clinical practice.
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http://dx.doi.org/10.21037/atm-22-1853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201135PMC
May 2022

Transcutaneous Electrical Acupoint Stimulation Improved Preoperative Blood Pressure in Gynecological Malignant Tumor Patients With Hypertension: A Randomized, Controlled Trial.

Front Oncol 2022 1;12:906528. Epub 2022 Jun 1.

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.

Objective: Gynecological malignant tumor patients with hypertension, even if blood pressure is well controlled, are prone to hypertension before surgery. We plan to verify the effect of transcutaneous electrical acupoint stimulation (TEAS) on stabilizing blood pressure before operation.

Methods: We enrolled 91 patients and randomly divided them into TEAS group (n=46) and control group (n=45). Patients in TEAS group received TEAS at acupoints Hegu and Neiguan. Patients in control group received transcutaneous electrical stimulation at the nonacupoint position of the upper limbs. After entering the operating room, the blood pressure before and after induction was measured. The main results were the occurrence of preinduction hypertension and postinduction hypotension.

Results: There was no difference in the general information of the two groups. There were four cases (9%) of preinduction hypertension in TEAS group and 13 cases (29%) in control group. The incidence in TEAS group was significantly lower (P=0.013). There were five cases (11%) of postinduction hypotension in TEAS group and eight cases (18%) in control group. There was no significant difference between the two groups (P=0.346). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of the highest blood pressure before induction in TEAS group were lower than those in control group (P=0.002, 0.002, and 0.001). There was no difference in SBP, DBP, or MBP between the two groups on the day before the operation. There was no difference in the lowest blood pressure before operation between the two groups after induction.

Conclusion: TEAS can prevent preinduction hypertension in patients with gynecological malignant tumors.

Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=143276, identifier ChiCTR2100054336.
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http://dx.doi.org/10.3389/fonc.2022.906528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198572PMC
June 2022

Time Management Disposition Mediates the Influence of Childhood Psychological Maltreatment on Undergraduates' Procrastination.

Authors:
Helin Ma Liang Chen

Psychol Res Behav Manag 2022 13;15:1489-1494. Epub 2022 Jun 13.

School of Marxism, University of Science and Technology Liaoning, Anshan, 114051, People's Republic of China.

Objective: The present study explores the relationship between childhood psychological maltreatment and procrastination among college students and the mediating effect of time management disposition.

Materials And Methods: The present study surveyed 682 college students from two universities with the Children's Psychological Maltreatment Scale, Aitken Procrastination Questionnaire, and Adolescence Time Management Disposition Scale.

Results: There are significant positive correlations between childhood psychological maltreatment and undergraduates' procrastination ( = 0.197, < 0.01), namely, individuals with more severe childhood psychological maltreatment are more likely to procrastinate. Time management disposition negatively correlates with childhood psychological maltreatment ( = -0.136, < 0.01) and procrastination ( = -0.573, < 0.01). The mediating roles of the time management disposition in the association between childhood psychological maltreatment and undergraduates' procrastination are significant.

Conclusion: Time management disposition plays a mediating role in the relationship between childhood psychological maltreatment and college students' procrastination behavior.
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http://dx.doi.org/10.2147/PRBM.S367446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205439PMC
June 2022

Statistical Optimization of Novel Medium to Maximize the Yield of Exopolysaccharide From ZFM216 and Its Immunomodulatory Activity.

Front Nutr 2022 2;9:924495. Epub 2022 Jun 2.

Key Laboratory for Food Microbial Technology of Zhejiang Province, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China.

The traditional media used for the fermentation of always contain carbohydrate polymers, which interfere with the analysis of the exopolysaccharide (EPS) produced by the bacteria. In this investigation, a novel medium formulation that could avoid such interference was successfully developed. The beef extract, yeast extract, and peptone used in this formulation were subjected to the removal of polysaccharides before use. The factors affecting the EPS production were optimized by a single factor test, Plackett-Burman design, and Box-Behnken design. The optimum formula was ascertained as: 7.5 g L yeast extract, 12.5 g L beef extract, 10 g L peptone, 21.23 g L maltose, 5.51 g L yeast nitrogen base, 2 g L KHPO, 5 g L anhydrous sodium acetate, 2 g L ammonium citrate, 0.58 g L MgSO⋅7HO, 0.25 g L MnSO⋅HO, and 1 mL L Tween 80. The initial pH of the medium was 6.5. The optimized conditions for fermentation of the strain to produce EPS were as follows: seed size 1%, culture temperature 37°C, and culture time 20 h. Optimum results showed that EPS yield was 496.64 ± 3.15 mg L, being 76.70% higher than that of unoptimized conditions (281.07 ± 5.90 mg L). The EPS was mainly comprised of glucose and guluronic acid, with a weight average molecular weight of 19.9 kDa; it was also characterized by Fourier transform infrared spectroscopy and UV analysis. EPS was found to significantly enhance the phagocytic capacity, promote the NO, TNF-α, IL-1β, and IL-6 secretion, and improve mRNA expression of cytokines in RAW 264.7 macrophages, indicating its considerable immunomodulatory activity. Western bolt and immunofluorescence results demonstrated that the EPS was able to increase p65 nuclear translocation in the macrophages, indicating that EPS enhanced immunity via the NF-κB signaling pathway. EPS investigated in this work has potential as an attractive functional food supplement candidate for the hypoimmunity population.
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http://dx.doi.org/10.3389/fnut.2022.924495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201479PMC
June 2022

Celecoxib attenuates hepatosteatosis by impairing de novo lipogenesis via Akt-dependent lipogenic pathway.

J Cell Mol Med 2022 Jun 17. Epub 2022 Jun 17.

College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.

Mounting evidence indicates that hepatic de novo lipogenesis is a common abnormality in non-alcoholic fatty liver disease (NAFLD) patients. We investigated whether a selective COX-2 inhibitor, celecoxib, alleviates hepatic steatosis by targeting an Akt-driven lipogenic pathway. We estimated the efficacy of celecoxib in a novel Akt-driven NAFLD mouse model established via hydrodynamic transfection of activated forms of AKT and in fructose-fed NAFLD mice that exhibited increased insulin-independent hepatic lipogenesis. AKT-transfected and insulin-stimulated human hepatoma cells were used for the in vitro experiments. Haematoxylin and eosin staining, immunohistochemistry and immunoblotting were performed for mechanistic studies. The results revealed that celecoxib ameliorated hepatic steatosis in the AKT-triggered NAFLD mice. Mechanistically, celecoxib effectively suppressed AKT/mTORC1 signalling and its downstream lipogenic cascade in the Akt-driven NAFLD mice and in vitro. Furthermore, celecoxib had limited efficacy in alleviating hepatic lipid accumulation and showed no influence on lipogenic proteins associated with hepatic lipogenesis in fructose-administered mice. This study suggests that celecoxib may be favourable for the treatment of NAFLD, especially in the subset with Akt-triggered hepatic lipogenesis.
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http://dx.doi.org/10.1111/jcmm.17435DOI Listing
June 2022

The therapeutic effect of balloon dilatation with different duration for biliary duct calculi: A network meta-analysis.

J Minim Access Surg 2022 Jul-Sep;18(3):327-337

Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

Objective: To systematically evaluate the application effect of endoscopic papillary balloon dilatation (EPBD) with different balloon dilatation duration for biliary duct calculi, and find the most appropriate dilatation duration for EPBD using a network meta-analysis.

Materials And Methods: PubMed, Embase and Cochrane Library databases were searched for relevant randomised controlled trials (RCTs) published up to August 2020. Node split, consistency and inconsistency models analysis were all conducted in network meta-analysis.

Results: Eighteen RCTs with 2256 participants were finally analysed. EPBD was divided into four categories based on balloon dilatation duration, including EPBD (P0.5), EPBD (>0.5, ≤1), EPBD (1, ≤2) and EPBD (>2, ≤5). Compared with EPBD (>0.5, ≤1), EPBD (>2, ≤5) had a lower risk of early complications (odds ratio [OR] = 0.23, 95% credible interval [CI] = 0.05-0.96) and post-endoscopic procedure pancreatitis (PEP) (OR = 0.17, 95% CI = 0.03-0.72). Endoscopic sphincterotomy (EST) tended to have less need for mechanical lithotripsy (OR = 0.37, 95% CI = 0.16-0.88) and PEP (OR = 0.26, 95% CI = 0.08-0.71) than EPBD (>0.5, ≤1). EPBD (>2, ≤5) was the safest endoscopic procedure with respect to early complications (surface area under cumulative ranking curves [SUCRA] = 79.0) and PEP (SUCRA = 85.3). In addition, EPBD (>2, ≤5) and EST had the highest probability of being the best (SUCRA = 82.6) and the worst (SUCRA = 10.8), respectively, regarding late complications.

Conclusion: EPBD and EST are two methods used to treat uncomplicated choledocholithiasis (stone diameter <10 mm and stone number <3). The extension of balloon dilatation duration has no significant influence on successful stone removal in the first endoscopic session or preventing the need for mechanical lithotripsy. However, it can reduce the risk of early complications, especially PEP. What's more, EPBD seems to have less late complications compared with EST, and the effect of prolonged balloon dilatation duration on late complications still needs to be further explored. Therefore, 2-5 min is the recommended dilatation duration range for EPBD using balloon with ≤10 mm diameter. Further research based on a specific population and with a longer follow-up time are needed.
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http://dx.doi.org/10.4103/jmas.JMAS_304_20DOI Listing
June 2022

Side-by-side versus stent-in-stent bilateral stenting for malignant hilar biliary obstruction: a meta-analysis.

Wideochir Inne Tech Maloinwazyjne 2022 Jun 9;17(2):279-288. Epub 2022 Jan 9.

Department of Interventional Therapy, Affiliated Hospital of Gansu Medical College, Pingliang, China.

Introduction: Both side-by-side (SBS) and stent-in-stent (SIS) bilateral stenting have been used for patients with malignant hilar biliary obstruction (MHBO). However, it is unclear which technique is better.

Aim: This meta-analysis is conducted to investigate the clinical efficacy and safety of SBS and SIS bilateral stenting for patients with MHBO.

Material And Methods: Relevant studies were searched in PubMed, Embase, Cochrane Library, Wanfang, VIP, and CINK databases. The timeline for the searches was from the establishment of the database to September 2021. The relative outcomes are pooled.

Results: A total of 7 studies fulfilled the inclusion criteria and entered into this meta-analysis. The pooled technical success rate was significant higher in the SIS group than that in the SBS group (p = 0.04). The pooled early complication rate was significantly lower in the SIS group than in the SBS group (p = 0.04). The pooled stent re-obstruction rate was significantly lower in the SBS group than in the SIS group (p = 0.04). The pooled stent patency duration was significantly longer in the SBS group than in the SIS group (p = 0.01). The pooled functional success rates (p = 0.79), total complication rates (p = 0.34), and overall survival duration (p = 0.27) were comparable between 2 groups. Egger test did not show any publication bias.

Conclusions: When comparing the SBS and SIS bilateral stenting for patients with MHBO, although SIS technique may have the superiorities of technical success and early complication rates, the longer stent patency was achieved by the SBS technique.
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http://dx.doi.org/10.5114/wiitm.2021.112477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186079PMC
June 2022

Analysis of Pharmacological Activities and Mechanisms of Essential Oil in Leaves of C. grandis 'Tomentosa' by GC-MS/MS and Network Pharmacology.

Comb Chem High Throughput Screen 2022 Jun 10. Epub 2022 Jun 10.

School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.

Background: Citrus grandis 'Tomentosa', as the fruit epicarp of C. grandis 'Tomentosa' or C. grandis (L.) Osbeck, is widely used in health food and medicine. Actually, based on our survey results, there are also rich essential oils with bioativities in leaves, but the chemical compounds in this part and relevant pharmacological activities have never been studied systematically yet. Therefore, this study was to preliminarily decipher the pharmacological activities and mechanisms of the essential oil in leaves of C. grandis 'Tomentosa' by an integrated network pharmacology approach.

Methods: Essential oil compositions from leaves of C. grandis 'Tomentosa' were identified using GC-MS/MS. And then the targets of these oil compositions were predicted and screened from TCMSP, SwissTargetPrediction, STITCH and SEA databases. STRING database was used to construct the protein-protein interaction networks, and the eligible protein targets were input into WebGestalt 2019 to carry out GO enrichment and KEGG pathway enrichment analysis. Based on the potential targets, disease enrichment information was obtained by TTD databases. Cytoscape software was used to construct the component-target-disease network diagrams.

Results: Finally, 61 essential oil chemical components were identified by GC-MS/MS, which correspond to 679 potential targets. Biological function analysis showed that there were 12, 19, and 12 GO entries related to biological processes, cell components and molecular functions, respectively. 43 KEGG pathways were identified, of which the most significant categories were terpenoid backbone biosynthesis, TNF signaling pathway and leishmaniasis. The component-target-disease network diagram revealed that the essential oil compositions in leaves of C. grandis 'Tomentosa' could treat tumors, immune diseases, neurodegenerative diseases and respiratory diseases, which were highly related to CHRM1, PTGS2, CASP3, MAP2K1 and CDC25B.

Conclusion: This study may provide a new insight into C. grandis 'Tomentosa' or C. grandis (L.) Osbeck and may provide useful information for future utilization and development.
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http://dx.doi.org/10.2174/1386207325666220610182644DOI Listing
June 2022

GaN/MgI van der Waals heterostructure: a two-factor tunable photocatalyst for hydrogen evolution.

Phys Chem Chem Phys 2022 Jun 22;24(24):15075-15082. Epub 2022 Jun 22.

Institute of Optoelectronics Technology, China Jiliang University, Hangzhou, 310018, China.

With the increasing environmental pollution and energy crisis, it is significant to develop environmentally friendly and adjustable photocatalysts for water splitting. Here we explored the optoelectronic properties of several H-GaN/MgI vdW heterostructures by regulating different polarization surfaces and numbers of GaN layers. Our results demonstrate that all structures, except 2L-Ga-GaN/MgI, exhibit excellent physical stability. Moreover, the band structures and band edge positions demonstrate that only the heterostructure of 3L-Ga-GaN/MgI with both suitable band alignment (type-II) and an acceptable band gap (∼1.92 eV) is most satisfactory for water splitting. Additionally, the absorption coefficient of the 3L-Ga-GaN/MgI heterostructure can reach over ∼10 cm, which has further confirmed its excellent advantage in photocatalysis. Finally, in the case of 6% external strain for the 3L-Ga-GaN/MgI heterostructure, a rollover in band alignment (from type-II to type-I) is exhibited. These promising features of the GaN/MgI vdW heterostructure give a new paradigm for developing novel efficient and adjustable photocatalytic water-splitting materials.
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http://dx.doi.org/10.1039/d2cp01456dDOI Listing
June 2022

Engineered Stable Bioactive Per Se Amphiphilic Phosphorus Dendron Nanomicelles as a Highly Efficient Drug Delivery System To Take Down Breast Cancer In Vivo.

Biomacromolecules 2022 Jun 13. Epub 2022 Jun 13.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.

Conventional small molecular chemical drugs always have challenging limitations in cancer therapy due to their high systemic toxicity and low therapeutic efficacy. Nanotechnology has been applied in drug delivery, bringing new promising potential to realize effective cancer treatment. In this context, we develop here a new nanomicellar drug delivery platform generated by amphiphilic phosphorus dendrons (1-C17G3.HCl), which could form micelles for effective encapsulation of a hydrophobic anticancer drug doxorubicin (DOX) with a high drug loading content (42.4%) and encapsulation efficiency (96.7%). Owing to the unique dendritic rigid structure and surface hydrophilic groups, large steady void space of micelles can be created for drug encapsulation. The created DOX-loaded micelles with a mean diameter of 26.3 nm have good colloidal stability. Strikingly, we show that the drug-free micelles possess good intrinsic anticancer activity and act collectively with DOX to take down breast cancer cells in vitro and the xenografted tumor model in vivo through upregulation of Bax, PTEN, and p53 proteins for enhanced cell apoptosis. Meanwhile, the resulting [email protected] micelles significantly abolish the toxicity relevant to the free drug. The findings of this study demonstrate a unique nanomicelle-based drug delivery system created with the self-assembling amphiphilic phosphorus dendrons that may be adapted for chemotherapy of different cancer types.
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http://dx.doi.org/10.1021/acs.biomac.2c00197DOI Listing
June 2022

Sodium alkoxide-mediated g-CN immobilized on a composite nanofibrous membrane for preferable photocatalytic activity.

RSC Adv 2022 May 20;12(24):15378-15384. Epub 2022 May 20.

School of Chemistry and Materials Science, Institute of Advanced Materials and Flexible Electronics, Nanjing University of Information Science and Technology (NUIST) Nanjing 210044 P. R. China

g-CN is a classic photocatalyst not only owing to the metal-free semiconducting electronic structure but also tunable multifunctional properties. However, strategies for chemical exfoliation of g-CN based on organic bases have been rarely reported. A family of sodium alkoxide-mediated g-CN has been prepared a simple synthesis. The degradation rate of bulk g-CN is 39.8% when irradiation lasts 140 minutes. However, the degradation rate of g-CN-MeONa, g-CN-EtONa, and g-CN- BuONa is 55.1%, 68.6%, and 79.1%, respectively, under the same conditions. Furthermore, g-CN- BuONa has been immobilized on flexible electrospun PAN nanofibers to prepare floating photocatalysts. SEM analysis shows that the paper-based photocatalyst PAN/g-CN- BuONa becomes a nanofiber membrane (A4 size, 210 mm × 297 mm). The nanofiber is approximately 350 nm in diameter. Interestingly, once synthesized, the g-CN- BuONa particles move into the spinning solution, where the nanofiber wraps around them to form a monodisperse structure that resembles beads, or knots of 1-2 μm, on a string. The degradation efficiency of 10 mg L MB solution can reach 100% for 2 hours until the solution becomes colorless. In addition, the photocatalytic mechanism studies have been validated. Different from HSO or HNO, this work has proposed a facile strategy for designing preferable floating photocatalysts using sodium alkoxide.
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http://dx.doi.org/10.1039/d2ra02441aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121215PMC
May 2022

Ancient Mitogenomes Reveal the Origins and Genetic Structure of the Neolithic Shimao Population in Northern China.

Front Genet 2022 27;13:909267. Epub 2022 May 27.

Key Laboratory of Vertebrate Evolution and Human Origins, Institute of Vertebrate Paleontology and Paleoanthropology, Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Beijing, China.

Shimao City is considered an important political and religious center during the Late Neolithic Longshan period of the Middle Yellow River basin. The genetic history and population dynamics among the Shimao and other ancient populations, especially the Taosi-related populations, remain unknown. Here, we sequenced 172 complete mitochondrial genomes, ranging from the Yangshao to Longshan period, from individuals related to the Shimao culture in northern Shaanxi Province and Taosi culture in southern Shanxi Province, Middle Yellow River basin. Our results show that the populations inhabiting Shimao City had close genetic connections with an earlier population in the Middle Neolithic Yangshao period of northern Shaanxi Province, revealing a mostly local origin for the Shimao Society. In addition, among the populations in other regions of the Yellow River basin, the Shimao-related populations had the closest maternal affinity with the contemporaneous Taosi populations from the Longshan period. The Shimao-related populations also shared more affinity with present-day northern Han populations than with the minorities and southern Han in China. Our study provides a new perspective on the genetic origins and structure of the Shimao people and the population dynamics in the Middle Yellow River basin during the Neolithic period.
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http://dx.doi.org/10.3389/fgene.2022.909267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185412PMC
May 2022

Effects of fenugreek seed extracts on growth performance and intestinal health of broilers.

Poult Sci 2022 Jul 30;101(7):101939. Epub 2022 Apr 30.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, Hunan, China. Electronic address:

The purpose of this experiment was to study the effects of fenugreek seed extract (FSE) on the growth performance, intestinal morphology, intestinal immunity and cecal micro-organisms in yellow-feathered broilers. A total of 240 one-day-old male yellow-feathered broilers were selected and randomly assigned to four treatments with 6 replicates per group and ten broilers per replicate. Started from the third day, birds were fed with basal diet (CON group) or basal diet supplemented with 30 mg/kg Zinc bacitracin (ZB group), or basal diet supplemented with 50 (D-FSE group) or 100 (H-FSE group) mg/kg FSE, respectively. The experiment lasted for 56 d. The results showed that dietary FSE supplementation improved average daily weight gain (ADG) and ratio of feed to weight gain (F: G) (P < 0.01), increased intestinal villus height (VH), villus height to crypt depth ratio (V/C) (P < 0.05), serum concentrations of IL-10, and the contents of secretory immunoglobulin A (sIgA) (P < 0.05), as well as decreased the activity of iNOS (P < 0.05). The high-throughput sequencing results showed that dietary FSE supplementation increased the alpha diversity of cecal microbes, and Firmicutes, Bacteroidetes, Verrucomicrobia and Proteobacteria taken up 95% of all phyla detected, FSE significantly reduced Campylobacter, Synergistes, and Lachnoclostridium abundance (P ≤ 0.05). There were significant difference in more than 30 KEGG pathways between FSE added group and control group or ZB group. FSE supplementation, in other words, maintained gut microbiota homeostasis while improving broiler growth performance. As a result, FSE has the potential to replace prophylactic antibiotic use in poultry production system.
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http://dx.doi.org/10.1016/j.psj.2022.101939DOI Listing
July 2022

Comprehensive identification of RNA transcripts and construction of RNA network in chronic obstructive pulmonary disease.

Respir Res 2022 Jun 11;23(1):154. Epub 2022 Jun 11.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, 230601, Anhui Province, China.

Background: Chronic obstructive pulmonary disease (COPD) is one of the world's leading causes of death and a major chronic disease, highly prevalent in the aging population exposed to tobacco smoke and airborne pollutants, which calls for early and useful biomolecular predictors. Roles of noncoding RNAs in COPD have been proposed, however, not many studies have systematically investigated the crosstalk among various transcripts in this context. The construction of RNA functional networks such as lncRNA-mRNA, and circRNA-miRNA-mRNA interaction networks could therefore facilitate our understanding of RNA interactions in COPD. Here, we identified the expression of RNA transcripts in RNA sequencing from COPD patients, and the potential RNA networks were further constructed.

Methods: All fresh peripheral blood samples of three patients with COPD and three non-COPD patients were collected and examined for mRNA, miRNA, lncRNA, and circRNA expression followed by qRT-PCR validation. We also examined mRNA expression to enrich relevant biological pathways. lncRNA-mRNA coexpression network and circRNA-miRNA-mRNA network in COPD were constructed.

Results: In this study, we have comprehensively identified and analyzed the differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs in peripheral blood of COPD patients with high-throughput RNA sequencing. 282 mRNAs, 146 lncRNAs, 85 miRNAs, and 81 circRNAs were differentially expressed. GSEA analysis showed that these differentially expressed RNAs correlate with several critical biological processes such as "ncRNA metabolic process", "ncRNA processing", "ribosome biogenesis", "rRNAs metabolic process", "tRNA metabolic process" and "tRNA processing", which might be participating in the progression of COPD. RT-qPCR with more clinical COPD samples was used for the validation of some differentially expressed RNAs, and the results were in high accordance with the RNA sequencing. Given the putative regulatory function of lncRNAs and circRNAs, we have constructed the co-expression network between lncRNA and mRNA. To demonstrate the potential interactions between circRNAs and miRNAs, we have also constructed a competing endogenous RNA (ceRNA) network of differential expression circRNA-miRNA-mRNA in COPD.

Conclusions: In this study, we have identified and analyzed the differentially expressed mRNAs, lncRNAs, miRNAs, and circRNAs, providing a systematic view of the differentially expressed RNA in the context of COPD. We have also constructed the lncRNA-mRNA co-expression network, and for the first time constructed the circRNA-miRNA-mRNA in COPD. This study reveals the RNA involvement and potential regulatory roles in COPD, and further uncovers the interactions among those RNAs, which will assist the pathological investigations of COPD and shed light on therapeutic targets exploration for COPD.
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http://dx.doi.org/10.1186/s12931-022-02069-8DOI Listing
June 2022

Histone methyltransferase Dot1L recruits O-GlcNAc transferase to target chromatin sites to regulate histone O-GlcNAcylation.

J Biol Chem 2022 Jun 8:102115. Epub 2022 Jun 8.

College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei Province, China; Hubei Province key Laboratory of Allergy and Immunology, Wuhan University, Wuhan, 430072, Hubei Province, China. Electronic address:

O-GlcNAc transferase (OGT) is the distinctive enzyme responsible for catalyzing O-GlcNAc addition to the serine or threonine residues of thousands of cytoplasmic and nuclear proteins involved in such basic cellular processes as DNA damage repair, RNA splicing, and transcription preinitiation and initiation complex assembly. However, the molecular mechanism by which OGT regulates gene transcription remains elusive. Using proximity labeling-based mass spectrometry, here we searched for functional partners of OGT and identified interacting protein Dot1L, a conserved and unique histone methyltransferase known to mediate histone H3 Lys79 methylation, which is required for gene transcription, DNA damage repair, cell proliferation, and embryo development. Although this specific interaction with OGT does not regulate the enzymatic activity of Dot1L, we show that it does facilitate OGT-dependent histone O-GlcNAcylation. Moreover, we demonstrate that OGT associates with Dot1L at transcription start sites, and that depleting Dot1L decreases OGT associated with chromatin globally. Notably, we also show that downregulation of Dot1L reduces the levels of histone H2B S112 O-GlcNAcylation and histone H2B K120 ubiquitination in vivo, which are associated with gene transcription regulation. Taken together, these results reveal that O-GlcNAcylation of chromatin is dependent on Dot1L.
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http://dx.doi.org/10.1016/j.jbc.2022.102115DOI Listing
June 2022

Multilevel determinants of racial/ethnic disparities in severe maternal morbidity and mortality in the context of the COVID-19 pandemic in the USA: protocol for a concurrent triangulation, mixed-methods study.

BMJ Open 2022 Jun 10;12(6):e062294. Epub 2022 Jun 10.

Department of Health Promotion, Education, & Behavior, University of South Carolina Arnold School of Public Health, Columbia, South Carolina, USA.

Introduction: The COVID-19 pandemic has affected communities of colour the hardest. Non-Hispanic black and Hispanic pregnant women appear to have disproportionate SARS-CoV-2 infection and death rates.

Methods And Analysis: We will use the socioecological framework and employ a concurrent triangulation, mixed-methods study design to achieve three specific aims: (1) examine the impacts of the COVID-19 pandemic on racial/ethnic disparities in severe maternal morbidity and mortality (SMMM); (2) explore how social contexts (eg, racial/ethnic residential segregation) have contributed to the widening of racial/ethnic disparities in SMMM during the pandemic and identify distinct mediating pathways through maternity care and mental health; and (3) determine the role of social contextual factors on racial/ethnic disparities in pregnancy-related morbidities using machine learning algorithms. We will leverage an existing South Carolina COVID-19 Cohort by creating a pregnancy cohort that links COVID-19 testing data, electronic health records (EHRs), vital records data, healthcare utilisation data and billing data for all births in South Carolina (SC) between 2018 and 2021 (>200 000 births). We will also conduct similar analyses using EHR data from the National COVID-19 Cohort Collaborative including >270 000 women who had a childbirth between 2018 and 2021 in the USA. We will use a convergent parallel design which includes a quantitative analysis of data from the 2018-2021 SC Pregnancy Risk Assessment and Monitoring System (unweighted n>2000) and in-depth interviews of 40 postpartum women and 10 maternal care providers to identify distinct mediating pathways.

Ethics And Dissemination: The study was approved by institutional review boards at the University of SC (Pro00115169) and the SC Department of Health and Environmental Control (DHEC IRB.21-030). Informed consent will be provided by the participants in the in-depth interviews. Study findings will be disseminated with key stakeholders including patients, presented at academic conferences and published in peer-reviewed journals.
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http://dx.doi.org/10.1136/bmjopen-2022-062294DOI Listing
June 2022

Rosmarinic Acid Inhibits Platelet Aggregation and Neointimal Hyperplasia In Vivo and Vascular Smooth Muscle Cell Dedifferentiation, Proliferation, and Migration In Vitro via Activation of the Keap1-Nrf2-ARE Antioxidant System.

J Agric Food Chem 2022 Jun 10;70(24):7420-7440. Epub 2022 Jun 10.

Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun 13002, Jilin, China.

The activation of platelets and proliferation of vascular smooth muscle cells (VSMCs) in the vascular intima play an essential role in the pathological mechanism of vascular restenosis (RS). Rosmarinic acid (RA) is a natural phenolic acid compound. However, its mechanism of action on platelets and VSMCs is still unclear. This study investigated the effects of RA on platelet function, VSMCs phenotypic conversion, proliferation, and migration in vascular remodeling with a specific focus on the Keap1-Nrf2-ARE signaling pathway. RA inhibited platelet aggregation and Ca release and significantly reduced the release of platelet microvesicles. In addition, RA inhibited the phenotypic transition of VSMCs in vitro and in vivo. In vitro experiments showed that RA could effectively inhibit the proliferation and migration of VSMCs induced by the platelet-derived growth factor (PDGF)-BB. PDGF-BB triggered ROS generation and a decrease in mitochondrial membrane potential, which were inhibited by RA. Mechanistically, after artery injury or treatment with PDGF-BB, VSMCs presented with inhibition of the Nrf2/antioxidant response element (ARE) signaling pathway. RA treatment reversed this profile by activating the Nrf2/ARE signaling pathway; stabilizing Keap1 protein; upregulating HO-1, NQO1, GCLM, and GST protein levels; promoting typical Nrf2 nuclear translocation; and preventing VSMCs from oxidative stress damage. On the other hand, RA also inhibited the NF-κB pathway to reduce inflammation. In summary, these results indicate that RA inhibits platelet function and attenuates the proliferation, migration, and phenotypic transition of VSMCs induced by PDGF-BB in vitro and vascular remodeling in vivo. Therefore, RA treatment may be a potential therapy for preventing or treating RS.
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http://dx.doi.org/10.1021/acs.jafc.2c01176DOI Listing
June 2022
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