Publications by authors named "Yan Wu"

2,283 Publications

  • Page 1 of 1

Safety, tolerability, pharmacokinetic characteristics, and immunogenicity of MW33: A Phase 1 clinical study of the SARS-CoV-2 RBD-targeting monoclonal antibody.

Emerg Microbes Infect 2021 Aug 4:1-11. Epub 2021 Aug 4.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

MW33 is a fully humanized IgG1κ monoclonal neutralizing antibody, and may be used for the prevention and treatment of coronavirus disease 2019 (COVID-19). We conducted a randomized, double-blind, placebo-controlled, single-dose, dose-escalation Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of MW33. Healthy adults aged 18-45 years were sequentially enrolled into the 4, 10, 20, 40, and 60 mg/kg dose groups and infused with MW33 over 60±15 min and followed for 85 days. All 42 enrolled participants completed the MW33 infusion, and 40 participants completed the 85-day follow-up period. 34 participants received a single infusion of 4 (n=2), 10 (n=8), 20 (n=8), 40 (n=8), and 60 mg/kg (n=8) of MW33. 27 subjects in the test groups experienced 78 adverse events (AEs) post-dose, with an incidence of 79.4% (27/34). The most common AEs included abnormal laboratory test results, vascular and lymphatic disorders, and infectious diseases. The severity of AEs was mainly Grade 1 (92 AEs), and three Grade 2 and one Grade 4. The main PK parameters, maximum concentration (C), and area under the concentration-time curve (AUC, and AUC) in 34 subjects showed a linear kinetic relationship in the range of 10 to 60 mg/kg. The plasma half-life was approximately 25 days. The positive rates of serum ADAs and antibody titers were low with no evidence of an impact on safety or PK. In conclusion, MW33 was well-tolerated, demonstrated linear PK, with a lower positive rate of serum ADAs and antibody titers in healthy subjects. ClinicalTrials.gov identifier: NCT04427501.. ClinicalTrials.gov identifier: NCT04533048.. ClinicalTrials.gov identifier: NCT04627584..
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http://dx.doi.org/10.1080/22221751.2021.1960900DOI Listing
August 2021

Metformin improves glycemic variability in adults with type 1 diabetes mellitus: an open-label randomized control trial.

Endocr Connect 2021 Aug 1. Epub 2021 Aug 1.

F Yuan, Shenzhen, China.

Introduction: Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM.

Objectives: In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored.

Patients And Methods: A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000- 2000 mg metformin daily add-on insulin (MET group, n=34) or insulin (Non-MET group, n=31). After, baseline measurements were repeated.

Results: The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with Non-MET group [-1.58 (-3.35,0.31) mmol/L versus 1.36 (-1.12,2.24) mmol/L, P=0.004]. In parallel, the largest amplitude of glycemic excursions [-2.83 (-5.47,-0.06) mmol/L versus 0.45 (-1.29,4.48) mmol/L, P=0.004], the standard deviation of blood glucose [-0.85 (-1.51,0.01) mmol/L versus -0.14 (-0.68,1.21) mmol/L, P=0.015], and the coefficient of variation [-6.66 (-15.00,1.50) % versus -1.60 (-6.28,11.71) %, P=0.012] all demonstrated improvement in the MET group, compared with the Non-MET group. Significant reduction in insulin dose, body mass index and body weight were observed in patients in MET, not those in Non-MET group.

Conclusion: Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.
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http://dx.doi.org/10.1530/EC-21-0146DOI Listing
August 2021

Patients with New-Onset Tumor of Severe Coronary Artery Disease May be at a Higher Risk of Arrhythmia.

Cardiol Res Pract 2021 22;2021:1948624. Epub 2021 Jul 22.

Department of Cardiovascular Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-set University, Guangzhou, China.

Background: Arrhythmia is one of the causes of death in severe coronary artery disease patients who also suffered from cancer. Our research aims to compare the incidence of arrhythmia between severe coronary artery disease patient with and without new-onset tumor. . We enrolled 79 patients (December 2019-December 2020) with severe coronary artery disease in this study, and 40 of them were complicated with new-onset tumor. The details of all subjects were thoroughly obtained; the laboratory tests were implemented including creatinine before coronary angiography. The appraisal of the severity of coronary artery disease was applied by Gensini score. The cardiac inspection includes UCG, 12-lead ECG, and Holter monitor.

Results: Among them, there were 40 patients in the experimental group and 39 patients in the control group. The difference at the baseline between the two sets of figures was not statistically significant ( > 0.05). The incidence of arrhythmia between the two groups was statistically significant ( < 0.05).

Conclusions: The incidence of arrhythmia in severe coronary artery disease patients who were complicated with new-onset tumor was higher than that in patients with severe coronary artery disease alone, and attention should be paid to arrhythmia before tumor treatment.
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http://dx.doi.org/10.1155/2021/1948624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324368PMC
July 2021

Identification and Characterization of the Succinate Dehydrogenase Complex Iron Sulfur Subunit B Gene in the Oriental River Prawn, .

Front Genet 2021 15;12:698318. Epub 2021 Jul 15.

Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, China.

Previous studies have revealed that has potential functions in the male sexual differentiation and development in . through providing ATP. In this study, the functions of were further analyzed in depth using quantitative polymerase chain reaction (qPCR), hybridization, western-blot, and RNA interference (RNAi), combined with the histological observations. The full-genome sequence of was 54,608 bp at Chromosome 34, including 7 introns and 6 exons. The full-length cDNA sequence of was 1,268 base pairs (bp) long with an open reading frame of 807 bp, encoding for 268 amino acids. The highest expression level of in different tissues was observed in the testis, and male prawns at post-larval developmental stage 25 during different developmental stages, indicating that was potentially involved in the male sexual development in . . hybridization and western-blot analysis indicated that plays essential roles in the testis development. The hybridization analysis also implies the potential roles of in ovarian development. The expressions of were decreased after dsRNA injection, indicating has the positive regulatory effects on in . . Thus, was involved in the mechanism of the male sexual development. The testis development was inhibited, and sperms were rarely observed after 10 days of dsRNA injection, indicating has positive effects on the male sexual development in . . This study highlights the functions of in . , which provide new insights for the future studies of the male sexual development in other crustacean species.
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http://dx.doi.org/10.3389/fgene.2021.698318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320353PMC
July 2021

Review on strategies of close-to-natural wetland restoration and a brief case plan for a typical wetland in northern China.

Chemosphere 2021 Jul 13;285:131534. Epub 2021 Jul 13.

Beijing Engineering Research Center of Process Pollution Control, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China.

Wetlands play an important role in sustaining ecosystems on the earth, which regulate water resources, adjust local climate and produce food for human beings, etc. However, wetlands are facing huge challenges due to human activities and other natural evolution, such as area shrinkage, function weakening and biodiversity decrease, and so on, therefore, some wetlands need to be urgently restored. In this study, the main technology components of close-to-natural restoration of wetlands were summarized. The ecological water requirement and water resource allocation can be optimized for the water balance between social, economy and ecology, which is a key prerequisite for maintaining wetland ecosystem. The pollution of wetland sediments and soils can be assessed by various indicators to provide the scientific basis for natural restoration of wetland base, and suitable strategies should be taken according to the actual conditions of wetland bases. The hydrological connectivity in wetlands and with related water system can be numerically simulated to make the optimal plan for improvement of hydrological connectivity. The ecological restoration of wetlands with the synergetic function of plants, animals and microorganisms was summarized, to improve the quality of wetland water environment and maintain the ecosystem stability. Based on the wetland close-to-natural restoration strategies, a brief ecological restoration plan for a typical wetland, Zaozhadian Wetland, near Xiong'an New Area in the north China was proposed from water resource guarantee, base pollution management, hydrological connectivity improvement and biological restoration. The close-to-natural restoration shows more effective, sustainable and long-lasting and thus a practical prospect.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131534DOI Listing
July 2021

Beyond the mean: Quantile regression to differentiate the distributional effects of ambient PM constituents on sperm quality among men.

Chemosphere 2021 Jul 8;285:131496. Epub 2021 Jul 8.

Division of Epidemiology and Biostatistics, School of Public Health, The University of Hong Kong, Hong Kong.

Ambient PM (particulate matter ≤ 2.5 μm in aerodynamic diameter) constituents have been related to mean changes in semen quality, but focusing on the mean response may not well capture distributional and heterogeneous effects of PM constituents on semen quality. In this study, 2314 semen samples of 622 men between Jan 1, 2019 and Dec 31, 2019 from Guangdong Human Sperm Bank were subjected to semen quality analysis. Daily average concentrations of PM constituents including 4 water-soluble ions and 15 metals/metalloid were measured for 7 days per month at 3 fixed atmospheric pollutant monitoring stations. We used quantile regression for longitudinal data to examine whether the associations between PM constituents and quality indicators of semen varied across quantiles of outcome distribution. Heterogeneous associations were found between PM constituents and sperm quality across different quantiles. An interquartile range (14.0 μg/m) increase in PM mass was negatively associated with lower tails of sperm concentration and upper tails of sperm count distribution. PM vanadium exposure was significantly related to the 90th percentile of sperm count distribution, but not to the lower quantiles. In addition, those subjects with relatively high sperm motility were more susceptible to sulfate, chromium, and manganese constituents in PM. Our results indicate that PM and certain constituents were associated with sperm quality, especially sperm motility, and the associations are more pronounced in men with relatively high or low sperm motility.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131496DOI Listing
July 2021

A Preliminary Randomized Controlled Trial of Different Treatment Regimens for Melancholic Depression.

Neuropsychiatr Dis Treat 2021 23;17:2441-2449. Epub 2021 Jul 23.

Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Background: Fluoxetine, bupropion, cognitive behavioral therapy (CBT), and physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation) can be used to manage melancholic depression.

Objective: To compare the efficacy and safety of various treatments in patients with melancholic depression.

Methods: This was a preliminary multicenter randomized controlled trial that included patients with depression in their first or recurrent acute episode between September 2016 and June 2019, and randomized to fluoxetine, fluoxetine+CBT, fluoxetine+bupropion, and fluoxetine+bupropion+brain stimulation. The primary endpoint was the decrease in the 17-item Hamilton Depression Rating Scale (17-HDRS). The secondary endpoint included the scores from the Quick Inventory of Depressive Symptomatology (QIDS-SR), QOL-6, and safety. Adverse events (AEs) were monitored. The follow-ups were performed at the end of the 0th, 2nd, 4th, 6th, 8th, and 12th weeks of treatment.

Results: Finally, 113 patients were included in the analyses: fluoxetine (n=37), fluoxetine+CBT (n=27), fluoxetine+bupropion (n=34), and fluoxetine+bupropion+brain stimulation (n=15). The 17-HDRS and QIDS-SR scores decreased in all four groups (all P<0.05). There were no differences in the 17-HDRS scores among the four groups at the end of treatment (P=0.779), except for fluoxetine alone showing a better response regarding self-consciousness than fluoxetine+bupropion. The QOL-6 scores increased in all four groups. The occurrence of AEs among the four groups showed no significant difference (P=0.053).

Conclusion: This preliminary trial suggests that all four interventions (fluoxetine, fluoxetine+CBT, fluoxetine+bupropion, and fluoxetine+bupropion+brain stimulation) achieved similar response and remission rates in patients with melancholic depression, but that fluoxetine had a better effect on self-consciousness than fluoxetine+bupropion. The safety profile was manageable.
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http://dx.doi.org/10.2147/NDT.S303938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315770PMC
July 2021

Del-1 in psoriasis induced the expression of αvβ3 and α5β1 in endothelial cells.

Curr Mol Med 2021 Jul 28. Epub 2021 Jul 28.

Department of Dermatology, The First Hospital of China Medical University, Shenyang, China.

Objective: Psoriasis is a chronic inflammatory skin disease highly depending on angiogenesis. Our prior results showed that the mRNA and protein of Del-1 in dermal mesenchymal stem cells (dMSCs) was up-regulated from psoriasis. Our aim was further to investigate the role of Del-1 from dMSCs in the pathogenesis of psoriasis and confirm the effect of Del-1 on the pathogenesis of psoriasis.

Methods: We conducted an immunohistochemistry experiment to further investigate the expression of Del-1in psoriatic lesions. In addition, dMSCs with over-expressed Del-1 via the lentiviral vector of Del-1 were co-cultured with ECs, and the protein expression of integrins (αvβ3, αvβ5 ,and α5β1) of ECs were detected by western blotting.

Results: This research showed that Del-1 was significantly increased in lesions of patients with psoriasis (p< .05, 9.96 vs. 2.18), and Del-1 from dMSCs successfully induced up-regulation of integrins α5β1 and αvβ3 (all p < .05).

Conclusion: This study demonstrated that Del-1 from dMSCs was involved in the pathogenesis of psoriasis through induced angiogenesis. And Del-1, αvβ3 and α5β1 may be potential new targets for inhibiting angiogenesis in psoriasis.
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http://dx.doi.org/10.2174/1566524021666210729112700DOI Listing
July 2021

The relation between incisal guidance angle and the growth and development of temporomandibular joint: a multi-cross-sectional retrospective study.

BMC Oral Health 2021 07 28;21(1):380. Epub 2021 Jul 28.

Stomatological Hospital of Chongqing Medical University, No. 426 Songshi North Road, Chongqing, China.

Background: The incisal guidance angle (IGA) is related to temporomandibular joint (TMJ), and changes to the IGA are often involved in the prosthetic and orthodontic treatment of anterior teeth. However, the influence of incisal guidance on the growth, development and remodelling of the TMJ is not yet clear. The aim of this study was to investigate age-related morphological differences in the TMJ in subjects with different IGAs.

Methods: Cone-beam computed tomography (CBCT) images of 274 patients were included (group 1, IGA < 45°; group 2, 45° ≤ IGA ≤ 60°; group 3, IGA > 60°). Each group was then divided into 4 age groups (group a, 6-12 years; group b, 13-16 years; group c, 17-25 years; group d, 26-33 years). TMJ morphology was assessed by linear measurements, angular measurements, and subjective evaluations. The IGA and occlusal plane angle were also measured.

Results: Anterior inclination of condyle (AIC) increased with age in the three IGA groups but decreased from 17 years onward in group 2 (P < 0.05). In the age groups analysis, the AIC in group 1 was smaller than that in group 3 but larger than that in group 2 (P > 0.05). Articular eminence inclination (AEI) decreased with age in group 1 (P = 0.027) but increased with age in group 3 (P = 0.053). The AEI in group 2 was larger than that in group 1 at 17-25 years (P = 0.046), and it was larger in group 3 than in group 1 at 26-33 years (P = 0.047). The IGA had a weak correlation with AEI (P < 0.05).

Conclusion: The articular fossa of patients with shallower incisal guidance changed to a flatter shape with age, whereas the condylar anterior slope and articular eminence of patients with steeper incisal guidance changed towards a steeper alignment. There was a correlation between IGA and TMJ shape.
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http://dx.doi.org/10.1186/s12903-021-01716-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317419PMC
July 2021

Long-term changes in the anterior alveolar bone after orthodontic treatment with premolar extraction: A retrospective study.

Orthod Craniofac Res 2021 Jul 28. Epub 2021 Jul 28.

Stomatological Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.

Objectives: To evaluate the morphometric changes in maxillary and mandibular anterior alveolar bone after orthodontic treatment and retention for 18-24 months by cone-beam computed tomography (CBCT).

Setting And Sample Population: Thirty-four adolescent patients (12 males and 22 females; mean age: 14.29 ± 1.24 years) diagnosed with bimaxillary dentoalveolar protrusion and with extractions of the 4 first premolars were included.

Materials And Methods: The labial and lingual (palatal) alveolar bone thickness, height and root length of the maxillary and mandibular anterior teeth were assessed using CBCT imaging at the pre-treatment (T1), post-treatment (T2) and retention phases (T3). Voxel-based superimpositions of the T2 and T3 images were performed, and the distances of incisal and apical movement between T2 and T3 were measured to determine whether relapses occurred.

Results: After orthodontic treatment, the labial and lingual (palatal) bone height decreased significantly (P < .05) and the labial thickness at the crestal (L1), midroot (L2), and apical levels (L3) had no significant change, while the lingual (palatal) bone thickness at all three levels decreased significantly (P < .05). After 18-24 months of retention, the lingual (palatal) height and the lingual (palatal) thickness at the crestal (L1) level increased significantly (P < .05). There were no obvious incisal and apical movements of the anterior teeth between T2 and T3 (P > .05), indicating that no relapses occurred.

Conclusions: Even though lingual (palatal) alveolar loss occurred due to the orthodontic treatment, the cervical alveolar bone seemed to recover over time. Therefore, appropriate camouflage treatment can be used in patients with bimaxillary dentoalveolar protrusion, and this treatment will not irreversibly deteriorate periodontal health and affect the orthodontic treatment stability.
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http://dx.doi.org/10.1111/ocr.12523DOI Listing
July 2021

Overexpression of circRNA circFAT1 in Endometrial Cancer Cells Increases Their Stemness by Upregulating miR-21 Through Methylation.

Cancer Biother Radiopharm 2021 Jul 27. Epub 2021 Jul 27.

Department of Obstetrics and Gynecology, Regional Specialized Disease Center of Northern Zhejiang, Jiaxing Maternal and Child Health Hospital Affiliated to Jiaxing University, Jiaxing, P.R. China.

Circular (Circ)RNA circFAT1 play tumor-suppressive or oncogenic roles in different cancers. Microarray analysis observed altered expression of circFAT1 in endometrial cancer (EC) and its inverse correlation with miR-21. Expression of circFAT1 and miR-21 in EC and paired nontumor tissues collected from 62 EC patients was analyzed by quantitative reverse transcription PCR (RT-qPCR). An experiment was conducted to evaluate the expression and interaction between circFAT1 and miR-21, followed by RT-qPCR and methylation-specific PCR. The role of circFAT1 and miR-21 in regulating the stemness was assessed by cell stemness assay. Heml 1.0 software was used to show differential gene expression. ANOVA Tukey's test and Pearson's correlation coefficient was used. CircFAT1 was upregulated in EC and positively correlated with miR-21 across EC tissues. In RL95-2 and HEC-1-A cells, overexpression of circFAT1 increased the expression levels of miR-21 and decreased the methylation of miR-21 gene, whereas overexpression of miR-21 did not alter the expression of circFAT1. Cell stemness analysis showed that overexpression of circFAT1 and miR-21 increased cell stemness, and miR-21 inhibition decreased cell stemness. Moreover, inhibitor of miR-21 suppressed the role of circFAT1. In conclusion, circFAT1 is upregulated in EC and it may increase cancer cell stemness by upregulating miR-21.
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http://dx.doi.org/10.1089/cbr.2020.4506DOI Listing
July 2021

Iodine Immobilized Metal-Organic Framework for NIR-Triggered Antibacterial Therapy on Orthopedic Implants.

Small 2021 Jul 26:e2102315. Epub 2021 Jul 26.

Orthopedics Research Institute of Zhejiang University, Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, P. R. China.

Iodine has been known as an effective disinfectant with broad-spectrum antimicrobial potency yet without drug resistance risk when used in clinic. However, the exploration of iodine for antibacterial therapy in orthopedics remains sparse due to its volatile nature and poor solubility. Herein, leveraging the superior absorption capability of metal-organic frameworks (MOFs) and their inherent photocatalytic properties, iodine-loaded MOF surface is presented to realize responsive iodine release along with intracellular reactive oxygen species(ROS) oxidation under near-infrared (NIR) exposure to achieve synergistic antibacterial effect. Iodine is successfully loaded using vapor deposition process onto zeolitic imidazolate framework-8(ZIF-8), which is immobilized onto micro arc oxidized titanium via a hydrothermal approach. The combination of NIR-triggered iodine release and ZIF-8 mediated ROS oxidative stress substantially augments the antibacterial efficacy of this approach both in vitro and in vivo. Furthermore, this composite coating also supported osteogenic differentiation of bone marrow stromal cells, as well as improved osseointegration of coated implants using an intramedullary rat model, suggesting improvement of antibacterial efficacy does not impair osteogenic potential of the implants. Altogether, immobilization of iodine via MOF on orthopedic implants with synergistic antibacterial effect can be a promising strategy to combat bacterial infections.
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http://dx.doi.org/10.1002/smll.202102315DOI Listing
July 2021

Clinical significance of combined detection of anti-Mullerian hormone and follicular output rate in women of late reproductive age.

Am J Transl Res 2021 15;13(6):6270-6278. Epub 2021 Jun 15.

Department of Reproductive Medicine, Hengshui People's Hospital Hengshui 053000, Hebei Province, China.

Objective: This study was designed to explore the clinical significance of anti-Mullerian hormone (AMH) combined with follicular output rate (FORT) in women of late reproductive age.

Methods: A total of 258 women (age range: 35-45 years old) who underwent pre-pregnancy examination in our hospital were collected as the research group (RG), among whom 184 were treated with fertilization-embryo transfer (IVF-ET). Concurrently, 126 women aged 24-30 years who came to our hospital for pre-pregnancy examination were enrolled as the control group (CG). AMH and FORT were detected and compared between the two groups to analyze the clinical significance of the two in women of late reproductive age.

Results: Compared with the CG, AMH was decreased statistically in the RG (P<0.05). AMH was statistically higher in the regular menstrual group than in the menstrual disorder group (P<0.05), and FORT was statistically higher in the pregnancy group in comparison with the non-pregnancy group (P<0.05). AMH decreased with age (P<0.05), while FORT did not correlate with any notable difference among the three subgroups (P>0.05). High, medium and low AMH groups showed no significant difference in the number of retrieved oocytes and transplantable embryos, as well as FORT (P<0.05). A lower AMH level, was correlated with fewer number of retrieved oocytes and transplantable embryos, and higher the FORT level. Significant differences were present among the high, middle and low FORT groups regarding the number of retrieved oocytes and transplantable embryos, the clinical pregnancy rate and AMH level (P<0.05). The lower the level of FORT was, the less the number of retrieved oocytes and transplantable embryos was, the lower clinical pregnancy rate was, and the higher the AMH level was.

Conclusions: AMH decreases gradually in women with an increase of age, and FORT can effectively predict pregnancy outcome. AMH detection combined FORT is of great significance in predicting the ovarian reserve function in women of late reproductive age.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290787PMC
June 2021

The Psychological Impact of COVID-19 Pandemic on Health Care Workers: A Systematic Review and Meta-Analysis.

Front Psychol 2021 8;12:626547. Epub 2021 Jul 8.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.

The COVID-19 epidemic has generated great stress throughout healthcare workers (HCWs). The situation of HCWs should be fully and timely understood. The aim of this meta-analysis is to determine the psychological impact of COVID-19 pandemic on health care workers. We searched the original literatures published from 1 Nov 2019 to 20 Sep 2020 in electronic databases of PUBMED, EMBASE and WEB OF SCIENCE. Forty-seven studies were included in the meta-analysis with a combined total of 81,277 participants. The pooled prevalence of anxiety is 37% (95% CI 0.31-0.42, I = 99.9%) from 44 studies. Depression is estimated in 39 studies, and the pooled prevalence of depression is 36% (95% CI 0.31-0.41, I = 99.6%). There are 10 studies reported the prevalence of insomnia, and the overall prevalence of insomnia is 32% (95% CI 0.23-0.42, I = 99.5%). The subgroup analysis showed a higher incidence of anxiety and depression among women and the frontline HCWs compared to men and non-frontline HCWs respectively. The COVID-19 pandemic has caused heavy psychological impact among healthcare professionals especially women and frontline workers. Timely psychological counseling and intervention ought to be implemented for HCWs in order to alleviate their anxiety and improve their general mental health.
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http://dx.doi.org/10.3389/fpsyg.2021.626547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297953PMC
July 2021

A key antisense sRNA modulates the oxidative stress response and virulence in Xanthomonas oryzae pv. oryzicola.

PLoS Pathog 2021 Jul 23;17(7):e1009762. Epub 2021 Jul 23.

Shanghai Yangtze River Delta Eco-Environmental Change and Management Observation and Research Station, Ministry of Science and Technology, Ministry of Education, Shanghai Urban Forest Ecosystem Research Station, National Forestry and Grassland Administration, Shanghai Cooperative Innovation Center for Modern Seed Industry, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

Pathogens integrate multiple environmental signals to navigate the host and control the expression of virulence genes. In this process, small regulatory noncoding RNAs (sRNAs) may function in gene expression as post-transcriptional regulators. In this study, the sRNA Xonc3711 functioned in the response of the rice pathogen, Xanthomonas oryzae pv. oryzicola (Xoc), to oxidative stress. Xonc3711 repressed production of the DNA-binding protein Xoc_3982 by binding to the xoc_3982 mRNA within the coding region. Mutational analysis showed that regulation required an antisense interaction between Xonc3711 and xoc_3982 mRNA, and RNase E was needed for degradation of the xoc_3982 transcript. Deletion of Xonc3711 resulted in a lower tolerance to oxidative stress due to the repression of flagella-associated genes and reduced biofilm formation. Furthermore, ChIP-seq and electrophoretic mobility shift assays showed that Xoc_3982 repressed the transcription of effector xopC2, which contributes to virulence in Xoc BLS256. This study describes how sRNA Xonc3711 modulates multiple traits in Xoc via signals perceived from the external environment.
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http://dx.doi.org/10.1371/journal.ppat.1009762DOI Listing
July 2021

Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates.

Acta Pharmacol Sin 2021 Jul 22. Epub 2021 Jul 22.

CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (K) of 22.14 μM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.
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http://dx.doi.org/10.1038/s41401-021-00732-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295639PMC
July 2021

Salidroside activates the AMP-activated protein kinase pathway to suppress non-alcoholic steatohepatitis.

Hepatology 2021 Jul 22. Epub 2021 Jul 22.

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is becoming a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Salidroside (p-hydroxyphenethyl-β-d-glucoside) has various biological and pharmacological activities, including anti-inflammatory, antioxidant and anticancer activities. However, the therapeutic effect and underlying molecular mechanism of salidroside in NASH remain to be further clarified.

Methods & Results: In this study, we found that salidroside alleviated lipid accumulation and inflammatory response in primary hepatocytes after palmitic acid/oleic acid (PO) stimulation. In addition, salidroside effectively prevented high-fat/high-cholesterol (HFHC) diet induced NASH progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation and fibrosis. Mechanistically, integrated RNA sequencing and bioinformatic analysis showed that salidroside promoted AMPK signaling pathway activation in vitro and in vivo, and this finding was further verified by determining the phosphorylation levels of AMPK. Furthermore, the protective effects of salidroside on lipid accumulation and inflammation in hepatocytes and livers induced by PO- or HFHC- stimulation were blocked by AMPK interruption.

Conclusion: Our studies demonstrate that salidroside protects against metabolic stress-induced NASH progression through activation of AMPK signaling, indicating that salidroside could be a potential new drug component for NASH therapy.
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http://dx.doi.org/10.1002/hep.32066DOI Listing
July 2021

Knockdown of astrocytic Grin2a aggravates β-amyloid-induced memory and cognitive deficits through regulating nerve growth factor.

Aging Cell 2021 Jul 22:e13437. Epub 2021 Jul 22.

Beijing Key Laboratory of Neural Regeneration and Repair, Department of Anatomy, School of Basic Medical Sciences, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.

Synapse degeneration correlates strongly with cognitive impairments in Alzheimer's disease (AD) patients. Soluble Amyloid-beta (Aβ) oligomers are thought as the major trigger of synaptic malfunctions. Our earlier studies have demonstrated that Aβ oligomers interfere with synaptic function through N-methyl-D-aspartate receptors (NMDARs). Our recent in vitro study found the neuroprotective role of astrocytic GluN2A in the promotion of synapse survival and identified nerve growth factor (NGF) derived from astrocytes, as a likely mediator of astrocytic GluN2A buffering against Aβ synaptotoxicity. Our present in vivo study focused on exploring the precise mechanism of astrocytic GluN2A influencing Aβ synaptotoxicity through regulating NGF. We generated an adeno-associated virus (AAV) expressing an astrocytic promoter (GfaABC1D) shRNA targeted to Grin2a (the gene encoding GluN2A) to perform astrocyte-specific Grin2a knockdown in the hippocampal dentate gyrus, after 3 weeks of virus vector expression, Aβ were bilaterally injected into the intracerebral ventricle. Our results showed that astrocyte-specific knockdown of Grin2a and Aβ application both significantly impaired spatial memory and cognition, which associated with the reduced synaptic proteins PSD95, synaptophysin and compensatory increased NGF. The reduced astrocytic GluN2A can counteract Aβ-induced compensatory protective increase of NGF through regulating pNF-κB, Furin and VAMP3, which modulating the synthesis, mature and secretion of NGF respectively. Our present data reveal, for the first time, a novel mechanism of astrocytic GluN2A in exerting protective effects on synapses at the early stage of Aβ exposure, which may contribute to establish new targets for AD prevention and early therapy.
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http://dx.doi.org/10.1111/acel.13437DOI Listing
July 2021

Grape Seed Proanthocyanidin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway.

J Inflamm Res 2021 12;14:3129-3143. Epub 2021 Jul 12.

Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, People's Republic of China.

Background: Retinal pigment epithelium (RPE) cellular senescence is an important process in degenerative retinal disorders. Grape seed proanthocyanidin extract (GSPE) alleviates senescence-related degenerative disorders; however, the potential effects of GSPE intake on RPE cellular senescence through regulating NAMPT/SIRT1/NLRP3 pathway remain unclear.

Methods: The effects of GSPE on NAMPT expression and NAD+ contents were detected with Western blot and assay kit in both in-vivo and in-vitro AMD models. Senescence-related biomarkers, including p16, p21 expressions and β-gal staining, were conducted in different groups. The protective effects of GSPE treatment on the mitochondrial homeostasis and barrier function of RPE cells were detected using mtDNA lesions analyses, JC-1 staining, ZO1 staining and trans-epithelial cell resistance (TEER) detection. The expression of senescence-associated secretory phenotype (SASP) in different groups would be conducted with qPCR. To demonstrate the potential effects of NAMPT/SIRT1/NLRP3 pathway after GSPE treatment, the protein levels of relevant key regulators after applications of NAMPT inhibitor, Fk866, and SIRT1 inhibitor, EX-527.

Results: GSPE significantly improves the NAMPT expression and NAD+ content in aging mice, and thus alleviates the RPE cellular senescence. In advanced in-vitro studies, GSPE significantly up-regulated NAMPT content and thus relieved HO induced NAD+ depression through analyzing the NAD+ contents in different groups. In advanced analyses, it was reported that GSPE could alleviate mitochondrial permeability, mtDNA damage, ZO1 expression and SASP levels in aging RPE cells. Thus, GSPE treatment significantly decreased senescence-related protein p16 and p21, as well as SASP levels in in-vitro aging model, and it was demonstrated that GSPE could illustrate a significant anti-aging effect. The Western blot data in GSPE treatment of aging RPE cells demonstrated that GSPE could significantly improve NAMPT and SIRT1 levels, and thus depressed NLRP3 expression.

Conclusion: This study indicated that GSPE alleviated RPE cellular senescence through NAMPT/SIRT1/NLRP3 pathway. This study highlighted the potential effects of GSPE on degenerative retinopathy through the crosstalk of NAD+ metabolism, SIRT1 function and NLRP3 activation.
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http://dx.doi.org/10.2147/JIR.S306456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286255PMC
July 2021

The association between circulating neutrophil extracellular trap related biomarkers and retinal vein occlusion incidence: A case-control pilot study.

Exp Eye Res 2021 Jul 13;210:108702. Epub 2021 Jul 13.

Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China; Mois Biotech Company, Shanghai, China. Electronic address:

Retinal vein occlusion (RVO) is the second most common retinal vascular disorders and causes visual damage in a large population. Neutrophil extracellular traps (NETs) formation (NETosis) is an important cause of vascular diseases, however, the association between NETs related biomarkers and RVO development remained unclear. In this pilot study, a total of 77 RVO cases and 48 controls were included between Jan 2020 and July 2020. Besides, the circulating levels of three NETs related markers, cell-free DNA (cfDNA), myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit), were detected in all the participants and thus the association between NETosis and RVO incidence was analyzed. Advanced assays were conducted to investigate the inflammation and thrombosis related biomarkers in RVO cases with higher or lower NETs biomarkers. When the results were considered, it was found that NETs biomarkers, including cfDNA, MPO-DNA and H3Cit, were increased in the RVO cases comparing with the controls (P < 0.05). Through the receiver operating characteristic (ROC) analyses, we found that circulating NETs related biomarkers demonstrated potential diagnostic effects for RVO and the AUCs of plasma cfDNA, MPO-DNA and H3Cit were 0.859, 0.871 and 0.928, respectively (P < 0.001). Through analyzing the correlations between circulating NETs markers and RVO stages and durations, inflammatory markers as well as thrombotic indexes, it was found that NETs were related with the RVO subtypes, inflammatory status and thrombus formation. In conclusion, the plasma NETs remnants are significantly increased in RVO cases. Besides, advanced studies demonstrate that inflammation as well as thrombus formation might be involved in this association.
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http://dx.doi.org/10.1016/j.exer.2021.108702DOI Listing
July 2021

[Efficacy and safety of lactase additive in preterm infants with lactose intolerance: a prospective randomized controlled trial].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Jul;23(7):671-676

Department of Neonatology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.

Objective: To study the efficacy and safety of lactase additive in improving lactose intolerance in preterm infants.

Methods: A total of 60 preterm infants with lactose intolerance who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2019 were randomly divided into a lactase treatment group and a control group, with 30 infants in each group. The infants in the lactase treatment group were given 4 drops of lactase additive (180 mg) added into preterm formula or breast milk, and those in the control group were given placebo, oral administration of probiotics (live combined , and powder) at half an hour after feeding (1 g each time, twice a day), and clockwise abdominal massage around the belly button at 1 hour after feeding for 15 minutes each time, 3 times a day. Fecal pH, fecal reducing sugar, growth indicators, symptoms of lactose intolerance, and laboratory markers were measured at the end of the first and second weeks after intervention.

Results: Finally 29 infants in the lactase treatment group and 26 infants in the control group completed the trial. At the end of the first week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and gastric retention amount ( < 0.05) and a significantly higher proportion of infants with fecal pH > 5.0 ( < 0.05). At the end of the second week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and 24-hour abdominal circumference difference ( < 0.05) and a significantly higher proportion of infants with the absence of gastric retention, fecal pH > 5.0, or negative reducing sugar in feces ( < 0.05). No adverse reactions associated with the lactase additive or probiotics were observed during the trial.

Conclusions: Lactase additive can safely and effectively improve the clinical symptoms caused by lactose intolerance in preterm infants.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292650PMC
July 2021

Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status and identification of frequent HRAS and BRAF mutations.

Endocr Connect 2021 Jul 1. Epub 2021 Jul 1.

X Chang, Peking Union Medical College Hospital Department of Pathology, Beijing, China.

Introduction: Composite pheochromocytoma/paraganglioma (CP) is a rare neoplasm with most cases presented as single reports. Little is known about its pathogenesis and relationship with ordinary pheochromocytoma (PCC) or paraganglioma (PGL). Our study is aimed at analyzing the status of SDH and ATRX and identifying novel genetic changes in CP.

Methods: 18 CP cases were collected. SDH and ATRX status was screened by immunohistochemistry. Targeted region sequencing (TRS) was successfully performed on formalin-fixed paraffin-embedded tissues in 2 cases within 3 years. Based on the TRS result, Sanger sequencing of BRAF and HRAS was performed in 15 cases (including the 2 cases with TRS performed), with 3 cases excluded due to the limited amount of tissue.

Results: Histopathologically, all the cases were composite PCC/PGL-ganglioneuroma (GN). The GN components were either closely admixed or juxtaposed with the PCC/PGL component, with highly variable percentage (10-80%). All cases stained positive for SDHB and ATRX. HRAS and BRAF mutations were identified during TRS. In the subsequent Sanger sequencing, 20.0% (3/15) harbored BRAF mutations (K601E and K601N) and 46.7% (7/15) harbored HRAS mutations (Q61R, Q61L, G13R). The mutation rates were both significantly higher than reported in ordinary PCC/PGL.

Conclusions: We demonstrated that composite PCC/PGL-GN might be a unique entity with frequent HRAS and BRAF mutations rather than genetic changes of SDH and ATRX. Our findings revealed the possible pathogenesis of composite PCC/PGL-GN and provided clues for potential treatment targets.
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http://dx.doi.org/10.1530/EC-21-0300DOI Listing
July 2021

Cross-ethnic comparison of the association between central sleep apnea and atrial fibrillation/flutter: The Kuakini Honolulu-Asia Aging Study and the Osteoporotic Fractures in Men (Mr.OS) study.

Int J Cardiol Heart Vasc 2021 Aug 1;35:100834. Epub 2021 Jul 1.

University of Hawai'i at Mānoa, Department of Geriatric Medicine, John A. Burns School of Medicine, 347 N Kuakini St, Honolulu, HI, USA.

Introduction: Few studies indicated the impact of ethnicity on an association between central sleep apnea (CSA) and atrial fibrillation/flutter (AF) in older populations. We assessed possible ethnic differences in the association among elderly Japanese-American and White-American men.

Methods: We performed a cross-sectional analysis using two population studies of Japanese-American and White-American men. The Kuakini Honolulu-Asia Aging Study is a longitudinal cohort study of Japanese-American men living in Hawaii. Sleep data were collected between 1999 and 2000. The Osteoporotic Fractures in Men (Mr.OS) Sleep Study was conducted between 2003 and 2005 on the continental U.S. The majority of Mr.OS participants were White-American. We selected 79-90 year old males, who had overnight polysomnography from both studies. Total participants were 690 Japanese-American and 871 White-American men. The central apnea index (CAI) was the measure of the number of central apneas. CSA was defined by CAI>=5. Cheyne-Stokes breathing (CSB) was defined as a minimum consecutive 5-10 min period of a crescendo-decrescendo respiratory pattern associated with CSA.

Results: The prevalence of AF was 5.7% in Japanese-American men and 9.0% in White-American men. The prevalence of CSA and CSB in White-Americans were higher than in Japanese-Americans (11.5% vs 6.5% and 5.7% vs 3.3%, respectively). In multivariable-adjusted logistic regression models, CSA was associated with higher odds of AF, and the association was stronger in Japanese-Americans [Odds Ratio (OR) = 4.77, 95% confidence interval (CI): 1.95-11.67] than in White-Americans (OR = 2.09, 95 %CI: 1.09-4.01). CSB showed similar trends as CSA.

Conclusions: After adjustment, CSA and CSB were significantly associated with AF in both Japanese-American and White-American men.
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http://dx.doi.org/10.1016/j.ijcha.2021.100834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256179PMC
August 2021

LncRNA MALAT1 Regulating Lung Carcinoma Progression via the miR-491-5p/UBE2C Axis.

Pathol Oncol Res 2021 29;27:610159. Epub 2021 Mar 29.

Cancer Research Institute, Binzhou Medical University Hospital, Binzhou, China.

Long noncoding RNAs (lncRNAs) play a critical role in the development of lung carcinoma. The mechanism of MALAT1 in lung carcinoma development is not understood very well. This study aimed to investigate the role of MALAT1 in lung carcinoma progression and the mechanism underlying the role of miR-491-5p in the MALAT1 mediated regulation of UBE2C expression. The results indicated that the expression of MALAT1 was often augmented in lung carcinoma cells. Suppression of MALAT1 blocked the proliferation, invasion and migration ability of cancer cells and inhibited the expression of UBE2C. UBE2C restoration attenuated the MALAT1 knockdown-induced anti-cancer effects. Moreover, UBE2C and MALAT1 were indicated as targets of miR-491-5p and inhibition of miR-491-5p restored the MALAT1 knockdown-induced inhibition of the progression of lung carcinoma. Furthermore, MALAT1 sponged miR-491-5p to upregulate UBE2C expression, causing it to act as a competing endogenous RNA. Collectively, MALAT1 downregulation suppressed lung carcinoma progression by regulating the miR-491-5p/UBE2C axis. These results indicate that MALAT1 could be a molecular target for lung carcinoma treatment and prognosis.
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http://dx.doi.org/10.3389/pore.2021.610159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262150PMC
March 2021

Long Noncoding RNA LIT3527 Knockdown induces Apoptosis and Autophagy through inhibiting mTOR pathway in Gastric Cancer Cells.

J Cancer 2021 11;12(16):4901-4911. Epub 2021 Jun 11.

Department of pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China.

Gastric cancer is one of the most common cancers and the leading causes of cancer mortality. However, the molecular mechanisms of gastric cancer malignancy remain unclear. Long noncoding RNAs (lncRNAs) have been well documented in controlling cancer progression. Identification of critical lncRNAs in gastric cancer will provide new sights into the regulation mechanism of gastric cancer. Here, we screened differentially expressed lncRNAs in gastric cancer tissues and matched adjacent tissues and found that lncRNA LIT3527, a 486-nucleotide (nt) sense transcript, was frequently upregulated in gastric cancer tissues. Knockdown of LIT3527 dramatically suppressed proliferation and migration of gastric cancer cells through inducing severe cell death but not affecting cell cycle. Mechanistically, we uncovered that depletion of LIT35227 induced significant cell apoptosis and autophagy through inhibiting AKT/ERK/mTOR signaling pathway. Targeting LIT3527 showed a robust inhibition of lung metastasis of gastric cancer cells. Taken together, these results suggest that LIT3527 is essential for gastric cancer cell survival through maintaining mTOR activity, suggesting that it may be clinically valuable as a therapeutic target for gastric cancer.
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http://dx.doi.org/10.7150/jca.58185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247385PMC
June 2021

Bacterial cytoplasmic membranes synergistically enhance the antitumor activity of autologous cancer vaccines.

Sci Transl Med 2021 07;13(601)

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China.

Cancer vaccines based on resected tumors from patients have gained great interest as an individualized cancer treatment strategy. However, eliciting a robust therapeutic effect with personalized vaccines remains a challenge because of the weak immunogenicity of autologous tumor antigens. Utilizing exogenous prokaryotic constituents that act as adjuvants to enhance immunogenicity is a promising strategy to overcome this limitation. However, nonspecific stimulation of the immune system may elicit an undesirable immunopathological state. To specifically trigger sufficient antitumor reactivity without notable adverse effects, we developed an antigen and adjuvant codelivery nanoparticle vaccine based on cytoplasmic membranes (EMs) and tumor cell membranes (TMs) from resected autologous tumor tissue. Introduction of the EM into the hybrid membrane nanoparticle vaccines (HM-NPs) induced dendritic cell maturation, thus activating splenic T cells. HM-NPs showed efficacy in immunogenic CT26 colon and 4T1 breast tumor mouse models and also efficiently induced tumor regression in B16-F10 melanoma and EMT6 breast tumor mouse models. Furthermore, HM-NPs provoked a strong tumor-specific immune response, which not only extended postoperative animal survival but also conferred long-term protection (up to 3 months) against tumor rechallenge in a CT26 colon tumor mouse model. Specific depletion of different immune cell populations revealed that CD8 T and NK cells were crucial to the vaccine-elicited tumor regression. Individualized autologous tumor antigen vaccines based on effective activation of the innate immune system by bacterial cytoplasmic membranes hold great potential for personalized treatment of postoperative patients with cancer.
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http://dx.doi.org/10.1126/scitranslmed.abc2816DOI Listing
July 2021

Spatio-temporal model of Meox1 expression control involvement of Sca-1-positive stem cells in neointima formation through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4.

Stem Cell Res Ther 2021 07 7;12(1):387. Epub 2021 Jul 7.

Department of Physiology, Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China.

Aims: Neointimal hyperplasia remains a major obstacle in vascular regeneration. Sca-1-positive progenitor cells residing within the vascular adventitia play a crucial role in the assemblage of vascular smooth muscle cell (VSMC) and the formation of the intimal lesion. However, the underlying mechanisms during vascular injury are still unknown.

Methods And Results: Aneointimal formation rat model was prepared by carotid artery injury using 2F-Forgaty. After vascular injury, Meox1 expressions time-dependently increased during the neointima formation, with its levels concurrently increasing in the adventitia, media, and neointima. Meox1 was highly expressed in the adventitia on the first day after vascular injury compared to the expression levels in the media. Conversely, by the 14th day post-injury, Meox1 was extensively expressed more in the media and neointima than the adventitia. Analogous to the change of Meox1 in injured artery, Sca-1+ progenitor cells increased in the adventitia wall in a time-dependent manner and reached peak levels on the 7th day after injury. More importantly, this effect was abolished by Meox1 knockdown with shRNA. The enhanced expression of SDF-1α after vascular injury was associated with the markedly enhanced expression levels of Sca1+ progenitor cell, and these levels were relatively synchronously increased within neointima by the 7th day after vascular injury. These special effects were abolished by the knockdown of Meox1 with shRNA and inhibition of CXCR4 by its inhibitor, AMD3100. Finally, Meox1 concurrently regulated SDF-1α expressions in VSMC via activating CDC42, and CDC42 inhibition abolished these effects by its inhibitor, ZCL278. Also, Meox1 was involved in activation of the CXCR4 expression of Sca-1+ progenitor cells by CDC42.

Conclusions: Spatio-temporal model of Meox1 expression regulates theSca-1+progenitor cell migration during the formation of the neointima through the synergistic effect of Rho/CDC42 and SDF-1α/CXCR4.
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http://dx.doi.org/10.1186/s13287-021-02466-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262022PMC
July 2021

Transcriptome analysis of five ovarian stages reveals gonad maturation in female Macrobrachium nipponense.

BMC Genomics 2021 Jul 6;22(1):510. Epub 2021 Jul 6.

Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Freshwater Fisheries Research Center, Ministry of Agriculture, Chinese Academy of Fishery Sciences, 214081, Wuxi, China.

Background: Macrobrachium nipponense is an economically important species of freshwater shrimp in China. Unlike other marine shrimps, the ovaries in adult female M. nipponense can mature rapidly and periodically during the reproductive period, but the resulting high stocking densities and environmental deterioration can negatively impact the harvest yield and economic benefits. To better understand ovary development in female M. nipponense, we performed systematic transcriptome sequencing of five different stages of ovarian maturation.

Results: We obtained 255,966 Gb of high quality transcriptome data from 15 samples. Of the 105,082 unigenes that were selected, 30,878 were successfully annotated. From these unigenes, we identified 17 differentially expressed genes and identified three distinct gene expression patterns related to different biological processes. We found that cathepins, legumains, and cystatin were enriched in the lysosome pathway, and they are related to vitellogenin hydrolysis. Additionally, we found that myosin heavy chain 67 participated in oocyte excretion.

Conclusions: We provide the first detailed transcriptome data relating to the ovarian maturation cycle in M. nipponense. Our results provide important reference information about the genomics, molecular biology, physiology, and population genetics of M. nipponense and other crustaceans. It is conducive to further solve the problem of M. nipponense rapid ovarian maturation from the aspects of energy supply and cell division.
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http://dx.doi.org/10.1186/s12864-021-07737-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262026PMC
July 2021

Resveratrol prevents inflammation and oxidative stress response in LPS-induced human gingival fibroblasts by targeting the PI3K/AKT and Wnt/β-catenin signaling pathways.

Genet Mol Biol 2021 2;44(3):e20200349. Epub 2021 Jul 2.

Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P.R. China.

This study aimed to elucidate the anti-inflammatory and antioxidant properties of resveratrol (RSV) in human gingival fibroblasts (HGFs) following stimulation by P. gingivalis lipopolysaccharide (LPS). The levels of the inflammatory cytokines IL-1β, IL-6, IL-8 and TNFα, the activity of the antioxidant enzymes SOD and GSH-Px, and the levels of MDA, were evaluated by ELISA. It was observed that the expression of IL-1β, IL-6, IL-8 and TNFα in LPS-induced HGFs was significantly downregulated by RSV in a dose-dependent manner. RSV also partly increased oxidative stress (OS)-related factors, including SOD and GSH-Px, which was accompanied by a decrease in MDA production, although the results were not statistically significant. Additionally, RSV-induced deactivation of the PI3K/AKT and Wnt/β-catenin pathways in LPS-induced HGFs was observed by western blot analysis. Subsequently, it was demonstrated treatment with PI3K/AKT pathway inhibitor (LY294002) or Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1) could further enhance the anti-inflammatory and antioxidant effects of RSV by downregulating the expression of IL-1β, IL-6, IL-8 and TNFα, and the production of MDA, and increasing the activity of SOD and GSH-Px in LPS-induced HGFs. These results suggested RSV attenuated the inflammation and OS injury of P. gingivalis LPS-treated HGFs by deactivating the PI3K/AKT and Wnt/β-catenin signaling pathways.
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http://dx.doi.org/10.1590/1678-4685-GMB-2020-0349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258621PMC
July 2021
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