Publications by authors named "Qin Liu"

1,371 Publications

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Effect of preconceptional, prenatal and postnatal exposure to home environmental factors on childhood pneumonia: A key role in early life exposure.

Environ Res 2022 Aug 15:114098. Epub 2022 Aug 15.

XiangYa School of Public Health, Central South University, Changsha, China.

Background: Increasing evidence have associated pneumonia with early exposure to ambient air pollution. However, the role of indoor environmental factors exposure in early life on childhood pneumonia remains unclear.

Objective: To examine the association between indoor environmental factors exposure during different timing windows and childhood pneumonia, and to identify the key indoor factor(s) in different critical window(s).

Methods: A retrospective cohort study of 8689 pre-schoolers was performed in Changsha, China during 2019-2020. Our questionnaire survey was designed to collect information on pre-schooler's outcome and residential environmental exposure containing indoor pollution and allergens during 1 year before pregnancy, pregnancy, first year, and past year. The associations were further estimated stratified by personal exposure level of outdoor NO, CO, temperature (T) and different covariates. Associations were assessed by multiple logistic regression model in terms of odds ratio (OR) of 95% confidence interval (CI).

Results: Pre-schooler's pneumonia was significantly related with exposure of new furniture, redecoration, mold/damp stains, and mold or damp clothing or bedding exposure during the four periods, with the strongest associations observed during 1 year before pregnancy based on multi-window model, with ORs (95% CI) of 1.27 (1.12-1.44), 1.26 (1.09-1.46), 1.34 (1.14-1.57), and 1.28 (1.05-1.56) respectively. Environmental tobacco smoke (ETS) including both parental and grandparental smoking were significantly related with increased risk of pre-schooler's pneumonia, and ETS played a more important role in early life, with ORs (95% CI) of 1.17 (1.01-1.36) and 1.19 (1.02-1.39) in pregnancy and first year. Indoor plants particularly nonflowering plants significantly elevated pneumonia risk but only in past year, with ORs (95% CI) of 1.17 (1.05-1.30) and 1.14 (1.03-1.26). Higher pneumonia risk was observed for renovation exposure in pre-birth compared to post-birth, while mold/dampness exerted an accumulative effect with the highest risk for exposure during both pre- and post-birth. Living near traffic road and exposure to high level of traffic-related air pollution and high temperature significantly increased pneumonia risk. Sensitivity analysis found that some sub-groups were more susceptible to pneumonia risk of home environment exposure.

Conclusion: Early life exposure to indoor environmental factors plays an important role in pneumonia development, supporting the hypothesis of "Preconceptional and Fetal Origin of Childhood Pneumonia" and "Developmental Origins of Health and Pneumonia".
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http://dx.doi.org/10.1016/j.envres.2022.114098DOI Listing
August 2022

Post-acute COVID-19 syndrome and gut dysbiosis linger beyond 1 year after SARS-CoV-2 clearance.

Gut 2022 Aug 8. Epub 2022 Aug 8.

Microbiota I-Center (MagIC), Hong Kong SAR, People's Republic of China

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http://dx.doi.org/10.1136/gutjnl-2022-328319DOI Listing
August 2022

A Demographic Analysis of Hearing Impairments among People of Uyghur and Han Ethnicity in Xinjiang, China.

Iran J Public Health 2022 Apr;51(4):770-778

The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, Xinjiang, P.R. China.

Background: We aimed to investigate the demographic situation relating to people with hearing loss in Xinjiang, the largest province in China. The situation may vary between regions and races.

Methods: We conducted a population-based demographic study. We analyzed data obtained from 3931 people with hearing impairments (i.e., from the Han or Uyghur ethnic groups) including children and adults. We accounted for the survey design and sampling size in order to ensure that estimates were regionally representative. Basic characteristics were determined, and an ethnic distribution analysis was conducted based on age group, level of educational, marital status, and level of disability.

Results: Of the 3931 participants, 2228 (56.68%) were male and 1703 (43.32%) were female. The mean age of the participants was 46.02 (±19.46) years. Most of the participants (26.20%) were in the 45-59 yr age group. Illiterate people constituted the largest group (34.19%) in the Uyghur population, while a substantial proportion of participants of Han nationality had obtained a junior education (28.98%). The number of unmarried people in both ethnic groups accounted for the highest proportion (more than 70%). Grade 3 was the highest grade observed in the Uyghur population (32.35%), while Grade 1 hearing impairments were the most prevalent in the Han population (28.28%).

Conclusion: The difference in basic characteristics between participants of Uyghur and Han ethnicity revealed that different provinces should set different prevention and control targets. Different policy measures should be taken to allocate medical resources and provide rehabilitation services to assist people with hearing impairments in Xinjiang, China.
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http://dx.doi.org/10.18502/ijph.v51i4.9237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288393PMC
April 2022

The V-shaped double-layer patch technique for complete atrioventricular septal defect: A novel surgical technique.

J Thorac Cardiovasc Surg 2022 May 17. Epub 2022 May 17.

Cardiac Center of Guangdong Women and Children Hospital, Guangzhou, Guangdong, P.R. China.

Objective: Several surgical techniques for repair of a complete atrioventricular septal defect have been developed. However, the postoperative complications with these methods may lead to reoperation during follow-up. The aim of this report is to share our experience with a modified surgical technique for complete atrioventricular septal defect that has anatomic advantages postoperatively and could reduce the reoperation rate.

Methods: Twenty-nine patients who underwent repair of complete atrioventricular septal defect using a V-shaped double-layer patch between April 2011 and September 2019 were retrospectively investigated.

Results: There were no deaths (0%) and only 1 reoperation (3.4%) in the series. The aortic crossclamp and cardiopulmonary bypass times were 62.7 ± 16.0 minutes and 113.9 ± 25.9 minutes, respectively. The median follow-up duration was 5.1 years. To date, no significant residual ventricular septal defects have been detected and no left ventricular outflow tract obstruction has been seen on echocardiography in any patient. During follow-up, the left atrioventricular valve status was assessed as no incompetence in 9 patients (31.0%), trivial in 18 patients (62.1%), and mild in 2 patients (6.9%).

Conclusions: The V-shaped double-layer patch technique is a valuable surgical option for patients with complete atrioventricular septal defects. The midterm results in our series document excellent performance of this technique, which augments the area of the anterior valve of the left atrioventricular valve to make it closer to a normal mitral valve and may also reduce the need for reoperation.
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http://dx.doi.org/10.1016/j.jtcvs.2022.04.028DOI Listing
May 2022

An auristatin-based peptide-drug conjugate targeting Kita-Kyushu lung cancer antigen 1 for precision chemoradiotherapy in gastric cancer.

Eur J Med Chem 2022 Jul 19;241:114617. Epub 2022 Jul 19.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. Electronic address:

Gastric cancer is a worldwide health problem. Chemotherapy and radiotherapy are of great importance in the management of advanced gastric cancer. However, their therapeutic efficacy is limited by off-target side effects. Peptide-drug conjugates (PDCs) are a novel strategy for tumor-targeted drug delivery to overcome the existing drug resistance mechanisms and improve antitumor effects. Kita-Kyushu lung cancer antigen 1 (KK-LC-1) is exclusively expressed in several types of cancer including gastric cancer, representing a promising target for drug delivery. Here, we suggested KK-LC-1 as a potential target for PDC design for the first time and reported the first KK-LC-1-targeting PDC product 1131-MMAE, which is composed of a KK-LC-1-targeting peptide and an antimitotic drug conjugated by an enzymatically cleavable linker. We observed that 1131-MMAE could be efficiently endocytosed by KK-LC-1 positive gastric cancer cells for subsequent drug release and arrest the cell cycle at the most radiosensitive G2/M phase. We demonstrated that 1131-MMAE could significantly delay tumor growth with reduced toxicity than free drugs as a monotherapy. We further confirmed that 1131-MMAE was also a potent radiosensitizer. 1131-MMAE could selectively enhance the radiation response of KK-LC-1 positive tumor cells and achieve improved tumor control when combined with low-dose radiation. Overall, our study proposed an optimized therapeutic regimen for precision chemoradiotherapy, which has translational potential in multiple types of cancer.
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http://dx.doi.org/10.1016/j.ejmech.2022.114617DOI Listing
July 2022

Antiviral activity and underlying mechanisms of Baicalin against avian infectious bronchitis virus in .

Avian Pathol 2022 Aug 2:1-36. Epub 2022 Aug 2.

Engineering & Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730050, China

Baicalin, a flavonoid compound extracted from the dry root of Georgi, has been shown to have anti-inflammation, anti-viral, anti-bacterial, and immunomodulatory activity. However, the effect of baicalin against avian infectious bronchitis virus (IBV) remains unknown. The purpose of this study was to investigate the anti-IBV activity and underlying mechanism of baicalin in . The results showed that baicalin has a direct virucidal effect but no prophylactic effect on IBV infection. The mRNA and protein of IBV N were decreased obviously when IBV-infected cells were treated with baicalin during the multiple stages of the virus replication cycle, including viral adsorption, invasion, internalization, and release. Stress granule (SG) formation resulted from the increase of G3BP1 and the phosphorylation of the PKR/eIF2α due to the treatment of IBV-infected cells with baicalin. The inhibitory activity of baicalin on IBV replication was increased when G3BP1 expression was inhibited, and the down-regulation of G3BP1 expression occurred when the expression of PKR and eIF2α was inhibited. These findings revealed that baicalin activates phosphorylation of PKR/eIF2α pathway and induces SG formation by targeting G3BP1, initiating the antiviral response to suppress IBV replication on Vero cell. The results suggest that baicalin is a promising candidate drug to treat or prevent IBV infection.
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http://dx.doi.org/10.1080/03079457.2022.2109453DOI Listing
August 2022

Identification of Ferroptosis-Related lncRNA Pairs for Predicting the Prognosis of Head and Neck Squamous Cell Carcinoma.

J Oncol 2022 20;2022:7602482. Epub 2022 Jul 20.

Department of Neurosurgery, Anyue County People's Hospital, Ziyang 641300, Sichuan, China.

Background: Ferrogenesis was strongly associated with tumorigenesis and development, and activating the ferrogenic process was a novel regimen in treating cancer, especially conventional treatment-resistant cancers. The purpose of the article was to construct a ferroptosis-related long noncoding RNAs (FRlncRNAs) signature, regardless of expression levels to effectively predict prognosis and immunotherapeutic response for head and neck squamous cell carcinoma (HNSCC).

Methods: The RNA-seq data for HNSCC and corresponding clinical information were obtained in the TCGA database, and ferroptosis-related genes (FRGs) were extracted in the ferroptosis database. On this basis, differentially expressed FRlncRNAs (DEFRlncRNAs) pairs were identified through coexpression analysis, differential expression analysis, and a fresh pairing algorithm. Then, a risk assessment model was established with univariate Cox, LASSO, and multivariate Cox regression analysis. Finally, we evaluated the model from various aspects, including survival status, clinicopathological characteristics, infiltration status of immune cells, immune functions, chemotherapeutic sensitivity, immune checkpoint inhibitors (ICIs)-related molecules, and N6-methyladenosine (mA) mRNA status.

Result: We established a signature of 11-DEFRlncRNA pairs related to the prognosis of HNSCC that had AUC values above 0.75 in the one-, three-, and five-year ROC curves, underscoring the high susceptibility and specifiability of predicting HNSCC prognosis. Survival rates were remarkably higher for the low-risk patients than for the high-risk patients, and the signature was significantly correlated with survival, clinical, T, and N stages. Finally, immune cell infiltration status, immune functions, chemotherapeutic sensitivity, and expression levels of ICIs-related and mA-related molecules were statistically different among different groups.

Conclusion: Our study established a novel lncRNA signature, which is independent of specific expression levels, could predict patient prognosis, and might have promising clinical applications in HNCSS.
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http://dx.doi.org/10.1155/2022/7602482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328971PMC
July 2022

Descending aorta translocation for bronchial stenosis caused by shorter interaortic distance.

J Card Surg 2022 Jul 28. Epub 2022 Jul 28.

Heart Center, Guangdong Maternal and Child Hospital, Guangdong, People's Republic of China.

Background And Aim Of The Study: Numerous anatomic relationships of arteries could cause extrinsic compression of the trachea or bronchus. We report a rare left bronchial stenosis just caused by shorter inter-aortic distance.

Methods: One patient wih recurrent coughing and wheezing was diagnosed as left emphysema.Cardiac computed tomography (CTA) shows a shorter distance between ascending aorta (AAo) and descending aorta (DAo) caused left bronchial stenosis with extrinsic compression of right pulmonary artery.

Results: A translocation of the descending aorta was performed in this patient, and postoperative CTA showed that the DAo was translocated to the AAo and the left main bronchial stenosis was relieved.

Conclusions: Translocation of the DAo was necessary for the rare left bronchial stenosis caused by shorter inter-aortic distance and could bring a good outcome.
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http://dx.doi.org/10.1111/jocs.16811DOI Listing
July 2022

Single-Cell Transcriptomic Analysis Reveals Neutrophil as Orchestrator during β-Glucan-Induced Trained Immunity in a Teleost Fish.

J Immunol 2022 Aug 27;209(4):783-795. Epub 2022 Jul 27.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China;

Trained immunity defines long-term memory of innate immunity based on transcriptional, epigenetic, and metabolic modifications of myeloid cells, which are characterized by elevated proinflammatory responses toward homologous or heterologous secondary stimuli in mammals. However, the evidence of trained immunity-associated immune cells and its molecular mechanism in teleost fish remains largely unknown. In this study, we established a trained immunity activation model in turbot () and found that administration with β-glucan induces protection against a bacterial infection. Through single-cell RNA sequencing to annotate 14 clusters of innate and adaptive immune cells, as well as two clusters of blood cells, from head kidney and spleen, respectively, we characterized that neutrophil displays cardinal features of trained immunity by analyzing the expression abundance of trained immunity database-related genes at the single-cell level. Subsequently, through establishing an in vivo training and in vitro neutrophil challenge model, we found that the trained neutrophils exhibit a significant elevation of the IL-1R signaling pathway after infection. Furthermore, inhibition of neutrophil's IL-1R signaling pathway through anakinra treatment impaired the heightened production of reactive oxygen, nitrogen species, lactate, as well as the neutrophil extracellular traps formation and bacterial killing ability. Taken together, these findings characterized neutrophil as the orchestrator to express features of trained immunity, and revealed that the IL-1R signaling pathway plays a critical role in induction of trained immunity for bacterial clearance in teleost fish.
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http://dx.doi.org/10.4049/jimmunol.2200225DOI Listing
August 2022

Construction of PPSU-MoS/PA-MIL-101(Cr) Membrane with Highly Enhanced Permeance and Stability for Organic Solvent Nanofiltration.

Membranes (Basel) 2022 Jun 21;12(7). Epub 2022 Jun 21.

Key Laboratory of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China.

Membranes with excellent separation performance and stability are needed for organic solvent nanofiltration in industrial separation and purification processes. Here we reported a newly PPSU-MoS/PA-MIL-101(Cr) composite membrane with high permeance, good selectivity and stability. The MIL-101(Cr) was introduced in the polyamide (PA) layer via the PIP/TMC interfacial polymerization process on a microporous PPSU-MoS substrate. At a small doping amount of 0.005 wt% MIL-101(Cr), the PPSU-MoS/PA-MIL-101(Cr) composite membrane exhibited a high methanol permeance of 12.03 L m h bar, twice higher than that of the pristine membrane without sacrificing selectivity. Furthermore, embedding MIL-101(Cr) notably enhanced the stability of the composite membrane, with permeance only decreasing by 8% after a long time operation of 80 h (pristine membrane decreased by 25%). This work demonstrated a composite membrane modified by MIL-101(Cr) with superior separation performance, which provides potential application of MOF materials for high-performance membranes in organic solvent nanofiltration and a theoretical foundation for future research in studying MOF's influence on membrane properties.
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http://dx.doi.org/10.3390/membranes12070639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322855PMC
June 2022

Bacterial infection induces pyroptotic signaling-mediated neutrophil extracellular traps (NETs) formation in turbot (Scophthalmus maximus).

Fish Shellfish Immunol 2022 Aug 20;127:982-990. Epub 2022 Jul 20.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. Electronic address:

Neutrophils can capture and kill pathogens by releasing neutrophils extracellular traps (NETs), which play critical roles in anti-microbial infection in mammals; however, the mechanisms involved in NETs formation and its role in anti-bacterial infection in teleost fish remains largely unknown. In this study, to explore the function of NETs in turbot, we established an in vitro bacterial infection model in head kidney derived neutrophils, and found that the haemolysin over-expressed Edwardsiella piscicida (ethA) could induce a robust phenotype of NETs, compared with that in wild type or ethA mutant (ethA -ΔethA) strains. Besides, the NETosis was mediated by ethA -induced pyroptosis, and arms the ability of bacterial killing in neutrophils of turbot. Moreover, we found that neutrophils elastase (NE) might involves in this pyroptotic signaling, rather than inflammatory Smcaspase. Taken together, this study reveals the important role of pyroptosis in NETs formation in turbot neutrophils, suggesting that NETs formation is a critical immune response during bacterial infection in teleost fish.
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http://dx.doi.org/10.1016/j.fsi.2022.07.026DOI Listing
August 2022

Polycyclic aromatic hydrocarbons are associated with later puberty in girls: A longitudinal study.

Sci Total Environ 2022 Jul 19:157497. Epub 2022 Jul 19.

School of Public Health and Management, Research Center for Medicine and Social Development, Collaborative Innovation Center of Social Risks Governance in Health, Chongqing Medical University, Chongqing, China. Electronic address:

The objective of this study is to explore associations between PAH exposures and puberty timing in girls. Beginning in May 2014, 734 girls age 7.2-11.8 years in Chongqing, China, were enrolled in a prospective cohort study. They were followed up every 6 months from enrollment through June 2021, at which point participants were ages 13.6-18.3 years. Metabolite concentrations of four PAHs (1-hydroxypyrene [1-OHPyr], 2-hydroxynaphthalene [2-OHNap], 2-hydroxyfluorine [2-OHFlu], and 9-hydroxyphenanthrene [9-OHPhe]) were measured in urine samples at baseline. At each follow up visit, the Tanner's Sexual Maturity Rating scale was administered. Cox proportional hazards models were used to estimate associations between four urinary PAH metabolite concentrations and four markers of puberty: menarche, breast development, pubic hair development, and axillary hair development. Geometric mean concentrations of 1-OHPyr, 2-OHNap, 2-OHFlu and 9-OHPhe in urine were 0.47 μg/L, 3.31 μg/L, 1.49 μg/L, 3.75 μg/L, respectively. There were statistically significant associations between several urinary PAH metabolite concentrations and puberty outcomes. PAH metabolite concentrations were grouped as Low (<25th percentile, referent group), Moderate (25th-75th percentile) or High (>75th). Girls with moderate levels of 1-OHPyr were at higher risk of delayed pubic hair development (hazard ratio [HR]: 0.82, 95 % confidence interval [CI]: 0.68-0.99). Delayed breast development (HR: 0.77, 95 % CI: 0.60-0.99) and pubic hair development (HR: 0.76, 95 % CI: 0.60-0.95) were associated with high 2-OHNap. High c 2-OHFlu was associated with delayed pubic hair development (HR: 0.77, 95 % CI: 0.61-0.96). Delayed breast (HR: 0.79, 95 % CI: 0.64-0.97), pubic hair (HR: 0.79, 95 % CI: 0.65-0.96) and axillary hair development (HR: 0.80, 95 % CI: 0.65-0.99) was associated with moderate 9-OHPhe. In conclusion, PAH exposure may delay puberty onset in girls.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157497DOI Listing
July 2022

Association Between Gestational Diabetes Mellitus and the Risks of Type-Specific Cardiovascular Diseases.

Front Public Health 2022 5;10:940335. Epub 2022 Jul 5.

Department of Obstetrics and Gynecology, The First People's Hospital of Kunshan Affiliated With Jiangsu University, Suzhou, China.

Objective: Gestational diabetes mellitus (GDM) has been linked to subsequent overall cardiovascular diseases. However, evidence on the associations of GDM with type-specific cardiovascular diseases is lacking, and findings on the potential impact of type 2 diabetes on the associations are not consistent. This study aimed to explore the associations between GDM and the risks of type-specific cardiovascular diseases.

Methods: Data were from 12,025 women (≥20 years) who had delivered at least one live birth in the National Health and Nutrition Examination Survey, 2007-2018. GDM history and type-specific cardiovascular diseases including coronary heart disease (CHD), heart failure and stroke were defined by self-report. We also combined our results with those from previously related publications on the associations between GDM and risks of type-specific cardiovascular diseases with a random-effect model.

Results: Compared with women without GDM, the multivariable-adjusted odds ratios (95% confidence intervals) were 1.82 (1.21-2.72) for CHD, 1.43 (0.80-2.53) for heart failure, and 1.19 (0.76-1.86) for stroke among women with a history of GDM. Type 2 diabetes was associated with 43.90, 67.44, and 63.16% of the excess odds of CHD, heart failure and stroke associated with GDM, respectively. Combining results from this study with those from previously related studies yielded odds ratios (95% confidence intervals) of 1.81 (1.60-2.05) for CHD (12 studies, 7,615,322 participants, = 72.6%), 1.66 (1.25-2.21) for heart failure (5 studies, 4,491,665 participants, = 88.6%), and 1.25 (1.07-1.46) for cerebrovascular disease (9 studies, 6,090,848 participants, = 77.8%).

Conclusions: GDM showed stronger associations with coronary heart diseases and heart failure than cerebrovascular disease, and the excess risks are attributable, in part, to type 2 diabetes.
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http://dx.doi.org/10.3389/fpubh.2022.940335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294140PMC
July 2022

Miswiring of Merkel cell and pruriceptive C fiber drives the itch-scratch cycle.

Sci Transl Med 2022 Jul 13;14(653):eabn4819. Epub 2022 Jul 13.

Department of Anesthesiology, The Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, Saint Louis, MO 63110, USA.

Itch sensation provokes the scratch reflex to protect us from harmful stimuli in the skin. Although scratching transiently relieves acute itch through activation of mechanoreceptors, it propagates the vicious itch-scratch cycle in chronic itch by further aggravating itch over time. Although well recognized clinically, the peripheral mechanisms underlying the itch-scratch cycle remain poorly understood. Here, we show that mechanical stimulation of the skin results in activation of the Piezo2 channels on Merkel cells that pathologically promotes spontaneous itch in experimental dry skin. Three-dimensional reconstruction and immunoelectron microscopy revealed structural alteration of MRGPRA3 pruriceptor nerve endings directed toward Merkel cells in the setting of dry skin. Our results uncover a functional miswiring mechanism under pathologic conditions, resulting in touch receptors triggering the firing of pruriceptors in the skin to drive the itch-scratch cycle.
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http://dx.doi.org/10.1126/scitranslmed.abn4819DOI Listing
July 2022

Compliance with Health Recommendations and Vaccine Hesitancy During the COVID Pandemic in Nine Countries.

Prev Sci 2022 Jul 20. Epub 2022 Jul 20.

Universidad de San Buenaventura, Medellín, Colombia.

Longitudinal data from the Parenting Across Cultures study of children, mothers, and fathers in 12 cultural groups in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the USA; N = 1331 families) were used to understand predictors of compliance with COVID-19 mitigation strategies and vaccine hesitancy. Confidence in government responses to the COVID pandemic was also examined as a potential moderator of links between pre-COVID risk factors and compliance with COVID mitigation strategies and vaccine hesitancy. Greater confidence in government responses to the COVID pandemic was associated with greater compliance with COVID mitigation strategies and less vaccine hesitancy across cultures and reporters. Pre-COVID financial strain and family stress were less consistent predictors of compliance with COVID mitigation strategies and vaccine hesitancy than confidence in government responses to the pandemic. Findings suggest the importance of bolstering confidence in government responses to future human ecosystem disruptions, perhaps through consistent, clear, non-partisan messaging and transparency in acknowledging limitations and admitting mistakes to inspire compliance with government and public health recommendations.
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http://dx.doi.org/10.1007/s11121-022-01399-9DOI Listing
July 2022

Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma.

Front Cell Dev Biol 2022 1;10:879278. Epub 2022 Jul 1.

Immune Cells and Antibody Engineering Research Center of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang, China.

Messenger RNA vaccines are considered to be a promising strategy in cancer immunotherapy, while their application on mesothelioma is still largely uncharacterized. This study aimed to identify potential antigens in mesothelioma for anti-mesothelioma mRNA vaccine development, and further determine the immune subtypes of mesothelioma for selection of suitable candidates from an extremely heterogeneous population. Gene expression data and corresponding clinicopathological information were obtained from the TCGA and gene expression omnibus, respectively. Then, the genetic alterations were compared and visualized using cBioPortal, and differentially expressed genes and their prognostic signatures were identified by GEPIA. The relationship between tumor-infiltrating immune cells and the expression of tumor antigens was systematically evaluated by TIMER online. Finally, the immune subtypes and immune landscape of mesothelioma were separately analyzed using consensus cluster and graph learning-based dimensional reduction. A total of five potential tumor antigens correlated with prognosis and infiltration of antigen-presenting cells, including AUNIP, FANCI, LASP1, PSMD8, and XPO5 were identified. Based on the expression of immune-related genes, patients with mesothelioma were divided into two immune subtypes (IS1 and IS2). Each subtype exhibited differential molecular, cellular and clinical properties. Patients with the IS1 subtype were characterized by an immune "cold" phenotype, displaying superior survival outcomes, whereas those with the IS2 subtype were characterized by an immune "hot" and immunosuppressive phenotype. Furthermore, immune checkpoints and immunogenic cell death modulators were differentially expressed between the IS1 and IS2 immune subtype tumors. The immunogenomic landscape of mesothelioma revealed a complex tumor immune microenvironment between individual patients. AUNIP, FANCI, LASP1, PSMD8, and XPO5 are putative antigens for the development of anti-mesothelioma mRNA vaccine and patients with the IS1 subtype may be considered for vaccination.
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http://dx.doi.org/10.3389/fcell.2022.879278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284534PMC
July 2022

A compound ginseng stem leaf saponins and aluminium adjuvant enhances the potency of inactivated Aeromonas salmonicida vaccine in turbot.

Fish Shellfish Immunol 2022 Jul 14;128:60-66. Epub 2022 Jul 14.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, 200237, China. Electronic address:

Furunculosis caused by Aeromonas salmonicida in turbot farming is increasingly leading to huge economic losses. In this study, an inactivated vaccine containing a compound adjuvant of ginseng stem leaf saponins and aluminum hydroxide gel (GSLS/Alum) was developed against A. salmonicida and evaluated on turbot. As a result, serum antibody titer in vaccinated group was significantly higher than that in control group and the relative percentage survival (RPS) was up to 75.7%. Comparatively, the RPS of groups that vaccinated with only inactivated vaccine and vaccine containing Alum adjuvant or an oil emulsion Montanide™ ISA 763A were 32.4%, 48.6% and 64.9%, respectively. Although the vaccine containing oil adjuvant elicited comparable IgM level as that containing the compound GSLS/Alum adjuvant, the latter had no obvious side effects. Moreover, the inactivated vaccine containing the compound adjuvant was more likely to induce a higher cellular immune response according to the expressions of some immune related genes. Most importantly, an excellent protection of the vaccine containing GSLS/Alum adjuvant was obtained when turbots were naturally infected under clinical condition. In summary, our study demonstrated that the formulation of GSLS and Alum is a potential compound adjuvant in turbot vaccine development.
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http://dx.doi.org/10.1016/j.fsi.2022.07.027DOI Listing
July 2022

Therapeutic efficacies of two newly isolated Edwardsiella phages against Edwardsiella piscicida infection.

Microbiol Res 2022 Oct 30;263:127043. Epub 2022 Apr 30.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai 200237, China. Electronic address:

The spread of multi-drug resistant (MDR) bacteria has posed a threat to the development of aquaculture. Due to its effective bactericidal ability, phage therapy has been considered as an alternative to antibiotics to reduce infection caused by MDR bacteria. In this study, two Edwardsiella piscicida phages were newly-isolated and characterized to prevent or treat infection in aquaculture. The phages were designated as vB_EpM_ZHS and vB_EpP_ZHX belonging to Myoviridae and Podoviridae families, respectively, in terms of genome sequence and morphology analyses. The combination of vB_EpM_ZHS and vB_EpP_ZHX improved the therapeutic efficacy both in vitro and in vivo. The phage cocktail significantly inhibited bacterial growth in vitro and decreased approximately 40% of mortality rate and an order of magnitude of bacterial burden in zebrafish and turbot infected by E. piscicida. Moreover, the phage cocktail increased transcription levels of tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and alleviated inflammatory levels in the hindgut and spleen of turbots. The results indicate that the phage has a promising potential for therapeutic use against E. piscicida as the antimicrobial alternative to antibiotics in aquaculture.
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http://dx.doi.org/10.1016/j.micres.2022.127043DOI Listing
October 2022

High-Efficiency Electrosynthesis of Ammonia with Selective Reduction of Nitrate in Neutral Media Enabled by Self-Supported MnCoO Nanoarray.

ACS Appl Mater Interfaces 2022 Jul 14. Epub 2022 Jul 14.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.

Ambient ammonia synthesis by electroreduction of nitrate (NO) provides us a sustainable and environmentally friendly alternative to the traditional Haber-Bosch process. In this work, MnCoO nanoarray grown on carbon cloth (MnCoO/CC) serves as a superior electrocatalyst for efficient NH synthesis by selective reduction of NO. When operated in 0.1 M PBS with 0.1 M NaNO, MnCoO/CC reaches a high Faraday efficiency of 98.6% and a large NH yield up to 11.19 mg/h/cm. Moreover, it exhibits excellent electrocatalytic stability. Theory calculations show that the MnCoO surface has strong interaction with NO, which can effectively inhibit the occurrence of hydrogen evolution, beneficial for NO-to-NH conversion.
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http://dx.doi.org/10.1021/acsami.2c07818DOI Listing
July 2022

The Mediating Role of Coping Style in the Relationship Between Sleep Quality and Burnout: A Cross-Sectional Study Among Psychiatric Nurses.

Front Psychiatry 2022 23;13:926040. Epub 2022 Jun 23.

Suzhou Guangji Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, China.

Background: Although sleep quality is clearly associated with job burnout as shown in the existing research, the mechanism underpinning such relationship remains undefined. This work, thus, aimed to assess the current situation of sleep quality and burnout in Chinese psychiatric nurses, and to analyze the relationships between sleep quality, burnout and coping style, in order to provide possible targets to enhance mental health and wellbeing among psychiatric nurses.

Method: This cross-sectional study was carried out in seven rehabilitation centers located in four different regions of China. The Pittsburgh Sleep Quality Index, the Epworth Sleeping Scale, the Maslach Burnout Inventory General Survey, and the Coping Style Questionnaire were distributed to 853 nurses in various mental hospitals, with a total of 664 participants being recruited in the final research.

Results: The results of this current study showed a high prevalence of sleep disorders and burnout in Chinese psychiatric nurses. Moreover, emotional exhaustion ( = 0.456), cynicism ( = 0.323) and negative coping style ( = 0.191) in nurses were all positively correlated with total Pittsburgh Sleep Quality Index (PSQI) score, while professional efficacy ( = -0.079) and positive coping style ( = -0.140) were negatively correlated with total PSQI score. More interestingly, of all negative coping strategies, we found that self-blame had the most significant effect (β = 0.156).

Conclusions: The above results showed that coping style mediates the association of poor sleep quality with job burnout in Chinese psychiatric nurses. This study claimed that there is an urgent need to development the coping skills to sustain a healthy work life for nurses.
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http://dx.doi.org/10.3389/fpsyt.2022.926040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260227PMC
June 2022

The complete chloroplast genome sequence of (D. Don) Benn. 1844 (Simaroubaceae).

Mitochondrial DNA B Resour 2022 23;7(6):1114-1116. Epub 2022 Jun 23.

Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, Yulin Normal University, Yulin, PR China.

is a member of the Simaroubaceae family and is widely used as a medicinal plant. In this study, we sequenced and assembled the complete chloroplast genome of . The chloroplast genome is 160,015 bp in length, with a large single-copy region of 87,136 bp, a small single-copy region of 18,069 bp, and a pair of inverted repeat regions of 27,405 bp. It contains a total of 110 unique genes, including 77 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. Phylogenetic analysis showed that clustered well with Simaroubaceae plants, , , and .
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http://dx.doi.org/10.1080/23802359.2022.2087545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245974PMC
June 2022

Versatile Protein Coronation Approach with Multiple Depleted Serum for Creating Biocompatible, Precision Nanomedicine.

Small 2022 Jul 1;18(30):e2202002. Epub 2022 Jul 1.

Department of Medicinal Chemistry, Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, P. R. China.

The protein corona effect has long been treated as the evil source behind delivery efficacy issues. In this study, this concept is challenged by showcasing that the protein corona can serve as a versatile functionalization approach to improve the delivery efficacy or mitigate nanocytotoxicity. To this end, the depleted serum is introduced to create nanomaterials carrying functionally distinct protein corona, referred to as PCylated nanomaterials. It is confirmed that the passivation with depleted serum helps reduce the toxicity and pro-inflammatory response. Furthermore, the same method can be leveraged to enhance the capacity of nanomaterials to undergo endocytosis as well as their potential as an agonist for the NF-κB pathways. The comparable stability of protein corona created by late and early-stage serum reveals that the chanceless interaction with nanomaterials, rather than an inadequate binding strength, may be behind the failure of enriching certain components. The PCylation strategy is extended to cancer patient-derived fluid, creating a set of T1 and T3-stage cancer-specific nanotherapeutics to retard the metastasis of cancer cells, while leaving normal endothelial negligibly affected. It is hoped the novel PCylation approach validated here can shed light on the future development of precision nanomedicine with improved delivery efficacy.
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http://dx.doi.org/10.1002/smll.202202002DOI Listing
July 2022

Efficacy and Safety of Sintilimab in Combination with Concurrent Chemoradiotherapy for Locally Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (SHARED): Study Protocol of a Prospective, Multi-Center, Single-Arm Phase 2 Trial.

Cancer Manag Res 2022 17;14:2007-2015. Epub 2022 Jun 17.

The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, People's Republic of China.

Purpose: Concurrent chemoradiotherapy (cCRT) is the mainstay therapy of locally advanced gastric (G) and gastroesophageal junction (GEJ) cancers with a poor prognosis. Programmed cell death receptor-1 (PD-1) inhibitor has been approved and recommended to treat ≥3 line G/GEJ patients. A significant clinical benefit of PD-1 inhibitors in addition to cCRT has been observed in locally advanced lung cancer. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with an overall response rate of 85% in combination with chemotherapy in gastric cancer in a phase Ib study (NCT02937116).

Patients And Methods: SHARED is a prospective, multicentre, single-arm Phase II trial in China, exploring the efficacy of sintilimab in combination with cCRT in locally advanced G/GEJ adenocarcinoma. According to a Simon optimal two-stage clinical design, 34 patients will be enrolled. All the eligible patients will receive one cycle of induction chemotherapy (S-1 plus nab-PTX) combined with sintilimab, followed by cCRT (radiotherapy plus nab-PTX) combined with sintilimab. Prior to the surgery, patients will receive another cycle of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. In the adjuvant setting, all participants will be treated with 3 cycles of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. The primary endpoint is the rate of pathological complete response (pCR). The secondary endpoints include disease-free survival (DFS), major pathological response (MPR), R0 resection rate, surgical AEs, overall survival (OS), event-free survival (EFS), and safety profile. Moreover, the prognostic value of tumor biomarkers and immune biomarkers will be explored.

Conclusion: SHARED is designed to primally evaluate the efficacy and safety of sintilimab in combination with cCRT in locally advanced G/GEJ cancers and to prospectively validate the prognostic value of tumor biomarkers and immune biomarkers.
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http://dx.doi.org/10.2147/CMAR.S355687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9211075PMC
June 2022

Effects of Different Doses of Clopidogrel plus Early Rehabilitation Therapy on Motor Function and Inflammatory Factors in Patients with Ischemic Stroke.

Evid Based Complement Alternat Med 2022 14;2022:9692382. Epub 2022 Jun 14.

Department of Neurosurgery, The Second People's Hospital of Yibin, Yibin, China.

This prospective randomized controlled study was intended to assess the effects of different doses of clopidogrel plus early rehabilitation therapy on motor function and inflammatory factors in patients with ischemic stroke. Between August 2018 and October 2020, 90 cases of ischemic stroke treated in the Second People's Hospital of Yibin were randomized at a ratio of 1 : 1 to receive either oral 50 mg/d clopidogrel plus early rehabilitation therapy (low-dose group) or oral 75 mg/d clopidogrel plus early rehabilitation therapy (high-dose group), with 45 cases in each group. The outcome measures including the Barthel Index (BI), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer simplified scale, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor- (TNF-), and occurrence of adverse events were collected. After treatment, the high-dose group had higher BI results than the low-dose group. All eligible patients showed significantly declined NIHSS scores, and the high-dose group had markedly lower results ( < 0.05). After treatment, the Fugl-Meyer scores of both upper and lower extremities of the high-dose group were significantly higher than those in the low-dose group. The high-dose group achieved a greater decrease in inflammatory factor levels after treatment versus the low-dose group. The two groups showed a similar incidence of adverse events. High-dose clopidogrel plus early rehabilitation outperforms the low-dose treatment for patients with ischemic stroke by effectively mitigating the inflammatory response in the body, promoting the restoration of neurological function, improving the level of motor function, and enhancing the patient's quality of life, with manageable safety.
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http://dx.doi.org/10.1155/2022/9692382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213124PMC
June 2022

Machine Learning of Dose-Volume Histogram Parameters Predicting Overall Survival in Patients with Cervical Cancer Treated with Definitive Radiotherapy.

J Oncol 2022 14;2022:2643376. Epub 2022 Jun 14.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.

Purpose: To analyze the effects of dosimetric parameters and clinical characteristics on overall survival (OS) by machine learning algorithms.

Methods And Materials: 128 patients with cervical cancer were treated with definitive pelvic radiotherapy with or without chemotherapy followed by image-guided brachytherapy. The elastic-net models with integrating DVH parameters and baseline clinical factors, only DVH parameters and only baseline clinical factors were constructed in 5-folds cross-validations for 100 iteration bootstrapping, and then were compared using concordance index (C-index) criteria. Finally, the selected important factors were used to build multivariable Cox-pH models for OS and also shown in nomograms for clinical usage.

Results: The median OS occurred was 25.78 months with 25 (19.53%) deaths. The elastic-net models integrating clinical and DVH factors had the best prediction performances (C-index 0.76 in the train set and C-index 0.74 in the test set). Three important factors were selected, including baseline hemoglobin level as the protective factor, primary tumor volume (GTV_P) volume, and body V5 as the risk factors. The final multivariable Cox-pH models were constructed using these important factors and had prediction performance (C-index: 0.78, 95%CI: 0.73-0.81).

Conclusions: This is the first attempt to establish elastic-net models to study the contributions of DVH parameters for predicting OS in patients with cervical cancer. These results can facilitate individualized tailoring of radiation treatment in cervical cancer patients.
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http://dx.doi.org/10.1155/2022/2643376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213181PMC
June 2022

Percutaneous Ablation of Hepatic Tumors at the Hepatocaval Confluence Using Irreversible Electroporation: A Preliminary Study.

Curr Oncol 2022 05 31;29(6):3950-3961. Epub 2022 May 31.

Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Background: Tumors at the hepatocaval confluence are difficult to treat, either surgically or ablatively.

Methods: A retrospective longitudinal study on patients ineligible for thermal ablation who underwent computed tomography-guided IRE for hepatic tumors at the hepatocaval confluence was conducted. Factors analyzed included patient and tumor characteristics, IRE procedure details, treatment-related complications, and prognosis.

Results: Between 2017 and 2021, 21 patients at our institute received percutaneous IRE. Of the 38 lesions, 21 were at the hepatocaval confluence. Complete ablation was achieved in all cases. Local and distant recurrence was observed in 4.8% (1/21) and 42.6% (9/21) of the ablated tumors, respectively. All postcava remained perfused at follow-up, except for 1 (4.8%) hepatic vein near the lesion found to be temporarily occluded and restored within 1 month. The ratio of the maximum diameter of ablation area at 1, 3, and 6 months post procedure compared to that immediately after IRE was 0.68 (0.50-0.84), 0.49 (0.27-0.61), and 0.38 (0.25-0.59), respectively. Progression-free survival of the patients with recurrence was 121 (range, 25-566) days. Four (19.0%) patients died at the end of follow-up with median overall survival of 451.5 (range, 25-716) days.

Conclusions: IRE could be a safe and effective treatment for hepatic tumors at the hepatocaval confluence. This article provides valuable prognostic data; further clinical research is needed for better prognosis.
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http://dx.doi.org/10.3390/curroncol29060316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221598PMC
May 2022

In situ gelatinase-responsive and thermosensitive nanocomplex for local therapy of gastric cancer with peritoneal metastasis.

Mater Today Bio 2022 Jun 31;15:100305. Epub 2022 May 31.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, China.

Intraperitoneal chemotherapy (IPC) has been considered as an effective therapy for advanced gastric cancer (GC) especially those with peritoneal metastasis, while limited effectiveness, complications caused by chemotherapeutics and repeated infusion procedures restrict the application of IPC. In this study, to enhance the efficacy and safety of IPC, we intended to establish a biocompatible and biodegradable nanocomplex composed of intelligent gelatinase-responsive nanoparticles (NPs) and thermosensitive gel, which were prepared from different compositions of poly (ethyleneglycol)-poly (3-caprolactone) (PEG-PCL). Cancer stem cells (CSCs) inhibitor Salinomycin (SAL) and non-CSC inhibitor Docetaxel (DOC) were co-loaded in the NPs and delivered by liquid PEG-PCL-PEG gel (PECE) at room temperature, which was able to target tumor and formed a gel in situ at body temperature. Compared with free SAL-DOC solution administered at the same dose, PECE NP group inhibited intraperitoneal disseminated gastric cancer growth more remarkably, some of which even achieved complete response (CR) and continued for more than 2 weeks. Cytometric analysis of cellular suspension from abdominal tumor tissues showed that the proportion of CSCs (CD44+CD133+) and the expression of PD-L1 on the tumor cells in the PECE NP group were the lowest. In the allograft mouse models of GC, PECE NP significantly improved the infiltration of M1 macrophages into the tumor bed in vivo. This design may provide biodegradable smart drug-delivery system for potential application in IPC.
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http://dx.doi.org/10.1016/j.mtbio.2022.100305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207302PMC
June 2022

The secretome of microglia induced by IL-4 of IFN-γ differently regulate proliferation, differentiation and survival of adult neural stem/progenitor cell by targeting the PI3K-Akt pathway.

Cytotechnology 2022 Jun 24;74(3):407-420. Epub 2022 Apr 24.

Laboratory of neuropharmacology, Resource Institute for Chinese & Ethnic Materia Medica, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025 China.

Microglia has been reported to be able to regulate the proliferation, differentiation and survival of adult neural stem/progenitor cells (NSPCs) by modulating the microenvironment, which results in different consequences of adult neurogenesis. However, whether the microglial activation is beneficial or harmful to NSPCs is still controversial because of the complexity and variability of microglial activation phenotypes. In this study, we systematically explored the activation phenotypes of IFN-γ- or IL-4-induced microglia at different time after stimulation, and investigated the effects of the secretome of different phenotype of microglia on the process of proliferation, differentiation and survival of NSPCs. Moreover, the possible molecular pathways of secretory influence on NSPCS were further explored using western blotting. The result showed that IFN-γ and IL-4 differently regulate microglial phenotypes, IL-4 induced a M2-like phenotype, while IFN-γ induced a M1-like phenotype. These phenotypes of microglia can only be maintained for 24 h after removal of IFN-γ or IL-4 intervention. The secretome from IFN-γ- or IL-4-induced microglia also had opposite effects on NSPCs proliferation, differentiation and survival. The secretome from the IL-4-treated microglia promoted NSPCs proliferation, survival and differentiation into neurons and oligodendrocytes, while factors secreted by the INF-γ-treated microglia stimulated the NSPCs differentiation into astrocyte, inhibited the neurogenesis and oligodendrogliogenesis, and induced NSPCs apoptosis. Furthermore, the PI3K-Akt pathway mediates the effects of the secretome from IFN-γ- or IL-4-induced microglia on NSPC proliferation, differentiation, and survival. In conclusion, our results suggested that the secretome of microglia induced by IL-4 of IFN-γ differently regulate proliferation, differentiation and survival of adult neural stem/progenitor cell by targeting the PI3K-Akt pathway. These findings will help further study the biological mechanism of microglia regulating neurogenesis, and provide a therapeutic strategy for neurological diseases by regulating microglial phenotypes to affect neurogenesis.
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http://dx.doi.org/10.1007/s10616-022-00534-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206954PMC
June 2022

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.

JCI Insight 2022 Aug 8;7(15). Epub 2022 Aug 8.

The Wistar Institute, Philadelphia, Pennsylvania, USA.

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as β-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.
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http://dx.doi.org/10.1172/jci.insight.160989DOI Listing
August 2022

Exosomes Derived From Mesenchymal Stem Cells Pretreated With Ischemic Rat Heart Extracts Promote Angiogenesis via the Delivery of DMBT1.

Cell Transplant 2022 Jan-Dec;31:9636897221102898

Division of Cardiovascular, Xiangya Hospital, Central South University, Changsha, China.

Mesenchymal stem cell-derived exosomes (MSC-Exos) have been shown to promote angiogenesis. Treating MSCs with ischemic rat brain extracts was sufficient to augment their benefits in stroke. However, no similar analyses of ischemic heart extracts have been performed to date. We aim to determine whether MSC-Exos derived from MSCs pretreated with ischemic rat heart extract were able to promote angiogenesis and to clarify underlying mechanisms. ELISA (enzyme-linked immunosorbent assay) of heart extracts revealed a significant increase of vascular endothelial growth factor (VEGF) at 24 h post-MI (myocardial infarction) modeling, and time-dependent decreases in hypoxia inducible factor-1α (HIF-1α). MTT and wound healing assays revealed human umbilical vein endothelial cells (HUVECs) migration and proliferation increased following MSC-Exo treatment (exosomes derived from MSC pretreated with ischemic heart extracts of 24 h post-MI) relative to MSC-Exo treatment (exosomes derived from MSC pretreated with normal heart extracts). Proteomic analyses of MSC-Exo and MSC-Exo were conducted to screen for cargo proteins promoting angiogenesis. Result revealed several angiogenesis-related proteins were upregulated in MSC-Exo, including DMBT1 (deleted in malignant brain tumors 1). When DMBT1 was silenced in MSCs, HUVECs with MSC-Exo treatment exhibited impaired proliferative and migratory activity and reductions of DMBT1, p-Akt, β-catenin, and VEGF. To explore how ischemic heart extracts took effects, ELISA was conducted showing a significant increase of IL-22 at 24 h post-MI modeling. P-STAT3, IL22RA1, DMBT1, and VEGF proteins were increased in MSC relative to MSC, and VEGF and DMBT1 were increased in MSC-Exos. Together, these suggest that IL-22 upregulation in ischemic heart extracts can increase DMBT1 in MSCs. Exosomes derived from those MSCs deliver DMBT1 to HUVECs, thereby enhancing their migratory and proliferative activity.
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http://dx.doi.org/10.1177/09636897221102898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218457PMC
June 2022
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