Publications by authors named "Jin Yang"

2,137 Publications

  • Page 1 of 1

Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression.

Pharm Biol 2022 Dec;60(1):1616-1624

Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China.

Context: Aidi injection (ADI), a traditional Chinese medicine antitumor injection, is usually combined with doxorubicin (DOX) for the treatment of malignant tumours. The cardiotoxicity of DOX is ameliorated by ADI in the clinic. However, the relevant mechanism is unknown.

Objective: To investigate the effects of ADI on DOX-induced cardiotoxicity and its mechanism.

Materials And Methods: ICR mice were randomly divided into six groups: control, ADI-L, ADI-H, DOX, DOX + ADI-L and DOX + ADI-H. DOX (, 0.03 mg/10 g) was administered in the presence or absence of ADI ( 0.1 or 0.2 mL/10 g) for two weeks. Heart pathology and levels of AST, LDH, CK, CK-MB and BNP were assessed. H9c2 cells were treated with DOX in the presence or absence of ADI (1, 4, 10%). Cell viability, caspase-3 activity, nuclear morphology, and CBR1 expression were then evaluated. DOX and doxorubicinol (DOXol) concentrations in heart, liver, kidneys, serum, and cells were analysed by UPLC-MS/MS.

Results: High-dose ADI significantly reduced DOX-induced pathological changes and the levels of AST, LDH, CK, CK-MB and BNP to normal. Combined treatment with ADI (1, 4, 10%) improved the cell viability, and IC50 increased from 68.51 μM (DOX alone) to 83.47, 176.9, and 310.8 μM, reduced caspase-3 activity by 39.17, 43.96, and 61.82%, respectively. High-dose ADI inhibited the expression of CBR1 protein by 32.3%, reduced DOXol levels in heart, serum and H9c2 cells by 59.8, 72.5 and 48.99%, respectively.

Discussion And Conclusions: ADI reduces DOX-induced cardiotoxicity by inhibiting CBR1 expression, which provides a scientific basis for the rational use of ADI.
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http://dx.doi.org/10.1080/13880209.2022.2110127DOI Listing
December 2022

Fabrication of multifunctional metal-organic frameworks nanoparticles via layer-by-layer self-assembly to efficiently discover PSD95-nNOS uncouplers for stroke treatment.

J Nanobiotechnology 2022 Aug 13;20(1):379. Epub 2022 Aug 13.

School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, 211166, People's Republic of China.

Background: Disruption of the postsynaptic density protein-95 (PSD95)-neuronal nitric oxide synthase (nNOS) coupling is an effective way to treat ischemic stroke, however, it still faces some challenges, especially lack of satisfactory PSD95-nNOS uncouplers and the efficient high throughput screening model to discover them.

Results: Herein, the multifunctional metal-organic framework (MMOF) nanoparticles as a new screening system were innovatively fabricated via layer-by-layer self-assembly in which His-tagged nNOS was selectively immobilized on the surface of magnetic MOF, and then PSD95 with green fluorescent protein (GFP-PSD95) was specifically bound on it. It was found that MMOF nanoparticles not only exhibited the superior performances including the high loading efficiency, reusability, and anti-interference ability, but also possessed the good fluorescent sensitivity to detect the coupled GFP-PSD95. After MMOF nanoparticles interacted with the uncouplers, they would be rapidly separated from uncoupled GFP-PSD95 by magnet, and the fluorescent intensities could be determined to assay the uncoupling efficiency at high throughput level.

Conclusions: In conclusion, MMOF nanoparticles were successfully fabricated and applied to screen the natural actives as potential PSD95-nNOS uncouplers. Taken together, our newly developed method provided a new material as a platform for efficiently discovering PSD95-nNOS uncouplers for stoke treatment.
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http://dx.doi.org/10.1186/s12951-022-01583-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375364PMC
August 2022

Association of Time in Range with Endothelial Injury in Patients with Type 2 Diabetes Treated with Exenatide.

Diabetes Ther 2022 Aug 13. Epub 2022 Aug 13.

Department of Endocrinology and Metabolism, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China.

Introduction: We aimed to investigate whether treatment with exenatide could increase time in range (TIR) and decrease glycemic variability, and to evaluate the association between TIR and endothelial injury in patients with type 2 diabetes mellitus (T2DM).

Methods: Two-hundred patients with T2DM treated with exenatide for 16 weeks were included in this study. Seven-point fingerstick blood glucose was used to evaluate derived TIR and glycemic variability. The serum levels of soluble endothelial cell protein C receptor (sEPCR) and von Willebrand factor (vWF) were measured. Ninety-three patients having the data of endothelial injury markers were categorized as derived TIR > 70% or ≤ 70% after the treatment and the association between TIR and endothelial injury were evaluated.

Results: Treatment with exenatide for 16 weeks resulted in a significant reduction in fasting blood glucose, postprandial 2 h blood glucose, and glycated hemoglobin A1c (HbA1c) levels in patients with T2DM. Compared with baseline, derived TIR value was significantly increased [85.7 (57.1, 100.0) % vs. 42.9 (14.9, 71.4) %, P < 0.001], and the parameters of glycemic variability were remarkably decreased after the treatment. After the treatment, serum sEPCR level was significantly decreased from baseline in patients with TIR > 70% [74.5 (32.8, 122.5) ng/mL vs. 96.9 (48.5, 150.9) ng/mL, P = 0.006] but not in those with TIR ≤ 70%; serum vWF level was remarkably decreased in patients with TIR > 70% [from 1166.2 (848.1, 1335.5) mIU/mL to 907.4 (674.3, 1335.1) mIU/mL, P = 0.001] while this effect was modest in those with TIR ≤ 70%.

Conclusions: Treatment with exenatide increases TIR and decreases glycemic variability in patients with T2DM. Moreover, the amelioration of endothelial injury is more pronounced in patients with TIR > 70% after the treatment.

Trial Registration: ChiCTR-IPR-15006558 (registered, 27 May 2015).
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http://dx.doi.org/10.1007/s13300-022-01310-3DOI Listing
August 2022

Recognizing opportunities when individual engaged in intrapreneurship: The role of creative self-efficacy and support for innovation.

Front Psychol 2022 26;13:937971. Epub 2022 Jul 26.

School of Economics and Management, Southwest University of Science and Technology, Mianyang, China.

According to social cognitive theory, this study explored the relationship between intrapreneurship and opportunity recognition. We developed a moderated mediation model of creative self-efficacy as a mediator and support for innovation as a moderator linking intrapreneurship with opportunity recognition. Using a sample of 206 college students from Chinese universities, we found that intrapreneurship is positively related to opportunity recognition, and this relationship was mediated by creative self-efficacy. Our research further found that the effect of intrapreneurship on opportunity recognition was conditional on support for innovation. Finally, the theoretical and practical implications are discussed.
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http://dx.doi.org/10.3389/fpsyg.2022.937971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360980PMC
July 2022

Effect of Ultrafine Fly Ash and Water Glass Content on the Performance of Phosphorus Slag-Based Geopolymer.

Materials (Basel) 2022 Aug 5;15(15). Epub 2022 Aug 5.

China Construction Third Bureau First Engineering Co., Ltd., Wuhan 430040, China.

Phosphorus slag (PS), an industrial waste slag, has been used in geopolymers because it is rich in silicon and calcium. The poor performance of phosphorus slag-based geopolymer is due to its aluminum deficiency. In this work, low-calcium fly ash, treated by a wet-grinding process, named wet-grinding ultrafine fly ash (WUFA) was used as an Al supplement to replace some of the phosphorus slag, and the wet-grinding, ultrafine fly ash-phosphorus slag (WUFA-PS)-based geopolymer was prepared. The effects of the substitution amount of WUFA and the activator dosage on the hydration properties, mechanical properties, pore structure and SEM of the WUFA-PS geopolymer were discussed in detail. The results indicate that WUFA and more activators contribute to the Al and high alkalinity environment, which positively induces the production of more geopolymer gels, thus releasing more heat and optimizing the pore structure of the matrix. The compressive strength increased by up to 28.1%. The enhanced performance of the WUFA-PS-based geopolymer may also arise from the filling effect and activity improvement of WUFA. This study has proved the feasibility of preparing a geopolymer by blending wet-grinding ultrafine fly ash and phosphorus slag and has provided references for the ratio and performance evaluation of WUFA-PS-based geopolymer concrete.
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http://dx.doi.org/10.3390/ma15155395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369517PMC
August 2022

Diadenosine tetraphosphate regulates biosynthesis of GTP in Bacillus subtilis.

Nat Microbiol 2022 Aug 11. Epub 2022 Aug 11.

Department of Chemistry and Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany.

Diadenosine tetraphosphate (Ap4A) is a putative second messenger molecule that is conserved from bacteria to humans. Nevertheless, its physiological role and the underlying molecular mechanisms are poorly characterized. We investigated the molecular mechanism by which Ap4A regulates inosine-5'-monophosphate dehydrogenase (IMPDH, a key branching point enzyme for the biosynthesis of adenosine or guanosine nucleotides) in Bacillus subtilis. We solved the crystal structure of BsIMPDH bound to Ap4A at a resolution of 2.45 Å to show that Ap4A binds to the interface between two IMPDH subunits, acting as the glue that switches active IMPDH tetramers into less active octamers. Guided by these insights, we engineered mutant strains of B. subtilis that bypass Ap4A-dependent IMPDH regulation without perturbing intracellular Ap4A pools themselves. We used metabolomics, which suggests that these mutants have a dysregulated purine, and in particular GTP, metabolome and phenotypic analysis, which shows increased sensitivity of B. subtilis IMPDH mutant strains to heat compared with wild-type strains. Our study identifies a central role for IMPDH in remodelling metabolism and heat resistance, and provides evidence that Ap4A can function as an alarmone.
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http://dx.doi.org/10.1038/s41564-022-01193-xDOI Listing
August 2022

Moroidin, a Cyclopeptide from the Seeds of That Induces Apoptosis in A549 Human Lung Cancer Cells.

J Nat Prod 2022 Aug 11. Epub 2022 Aug 11.

School of Pharmacy, Nanjing Medical University, Nanjing, 211166, People's Republic of China.

Interference of microtubule dynamics with tubulin-targeted drugs is a validated approach for cancer chemotherapy. Moroidin () is an Urticaceae-type cyclopeptide having a potent inhibitory effect on purified tubulin polymerization. So far, moroidin has not been chemically synthesized, and its effect on cancer cells remains unknown. Herein, the cyclopeptide moroidin was isolated and identified from the seeds of , and a revised assignment of its NMR data was presented. For the first time, moroidin () was demonstrated as having cytotoxic effects for several cancer cells, especially A549 lung cancer cells. The cellular evidence obtained showed that moroidin disrupts microtubule polymerization and decreases β-tubulin protein levels, but is not as potent as colchicine. Molecular docking indicated that has a high binding potential to the vinca alkaloid site on tubulin. Moreover, moroidin arrested A549 cells in the G2/M phase and induced cell apoptosis. The intrinsic mitochondrial pathway and AKT were involved in the moroidin-induced cell apoptosis. In addition, moroidin () inhibited the migration and invasion of A549 cells at sublethal concentrations.
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http://dx.doi.org/10.1021/acs.jnatprod.1c01215DOI Listing
August 2022

Hair Zidovudine Concentrations Predict Virologic Outcomes Among People Living with HIV/AIDS in China.

Patient Prefer Adherence 2022 3;16:1885-1896. Epub 2022 Aug 3.

Unit of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, People's Republic of China.

Background: Hair antiretroviral concentrations are an objective and non-invasive measure of adherence to long-term antiretroviral therapy (ART) and can further predict virologic outcomes among people living with HIV/AIDS (PLWH). Zidovudine, one of the mainstream antiretrovirals in China, has been verified to have high reliability in adherence assessment, especially for its hair concentrations. However, data are limited in its predicting virologic outcomes. Therefore, this study aimed to characterize whether hair zidovudine concentrations can predict virologic suppression among Chinese PLWH compared with hair lamivudine concentrations and two self-reported measures, the overall frequency of adherence behaviors and percentage adherence.

Methods: This cross-sectional study randomly recruited 564 PLWH currently treated with zidovudine, lamivudine, and other ART agents (efavirenz, nevirapine, or lopinavir/ritonavir) in Guangxi, China. Hair antiretroviral concentrations were determined using the LC-ESI-MS/MS method. Receiver operating characteristic (ROC) curves were used to estimate the optimal classification thresholds of hair concentrations of zidovudine and lamivudine, and the two self-reported measures. Based on those optimal classification thresholds, logistic regression was used to examine whether those four adherence measures can predict virologic suppression (HIV-1 RNA <200 copies/mL).

Results: ROC curves demonstrated good classification performance for association with virologic suppression of zidovudine with the optimal threshold at 58 pg/mg and lamivudine at 255 pg/mg but no self-reported measures. PLWH with hair zidovudine concentrations >58 pg/mg had an adjusted odds ratio (aOR) of 43.191 (95% confidence interval (CI) = 10.171‒183.418, < 0.001) for virologic suppression. Hair lamivudine concentrations were also associated with virologic suppression (aOR = 10.656, 95% CI = 3.670‒30.943, < 0.001). However, two self-reported measures did not predict virologic suppression (aORs = 1.157 and 2.488, s >0.149).

Conclusion: Hair zidovudine concentrations can be served as an alternative tool for clinically predicting virologic suppression among PLWH in China.
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http://dx.doi.org/10.2147/PPA.S371623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357394PMC
August 2022

A study of simulation training in laparoscopic bilioenteric anastomosis on a 3D-printed dry lab model.

Surg Endosc 2022 Aug 9. Epub 2022 Aug 9.

Department of General Surgery, Sir Run-Run Shaw Hospital, School of Medical College, Zhejiang University, No. 3 East Qing Chun Road, Hangzhou, 310016, China.

Background: There are few studies on simulation training in laparoscopic bilioenteric anastomosis. There is also a lack of mature and reliable training models for bilioenteric anastomosis. In this study, we aimed to assess a feasible training model for bilioenteric anastomosis. Surgeons can improve their surgical ability by performing laparoscopic bilioenteric anastomosis on this model through repeated training.

Method: The original articles related to simulation training in surgical anastomosis were identified from January 2000 to November 2021 in the Clarivate Analytics Web of Science Core Collection database. We conducted a bibliometric analysis based on the country of these publications and the type of anastomosis. A 3D-printed bilioenteric anastomosis model was applied in this study. Baseline data of 15 surgeons (5 surgeons of Attendings, 5 surgeons of Fellows, and 5 surgeons of Residents) were collected. The bilioenteric anastomosis data, including the operation time and operation score, were recorded and analyzed. A study of the learning curve was also performed for further assessment.

Result: Surgeons at different levels of experience exhibited different levels of performance in conducting laparoscopic bilioenteric anastomosis on this model. Experienced surgeons completed their first training session in a shorter time and obtained a higher surgical score. In turn, repeated training significantly shortened the time of laparoscopic bilioenteric anastomosis for each trainer and improved the surgical score. Surgeons with different levels of experience needed different numbers of cases to reach the stable period of the learning curve. Experienced surgeons were able to reach a proficient level through fewer training cases.

Conclusion: A suitable biliary-enteric anastomosis model can help surgeons conduct simulation training and provide experience and skill accumulation for future real operations. Our training model performed well in this study and can effectively accomplish this goal.
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http://dx.doi.org/10.1007/s00464-022-09465-7DOI Listing
August 2022

Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis.

Open Med (Wars) 2022 22;17(1):1330-1337. Epub 2022 Jul 22.

Department of Joint Orthopaedic, Baoji Hospital of Traditional Chinese Medicine, Baoji, Shaanxi, 721000, China.

The purpose of this study was to investigate the correlation between fibular head height and the incidence and severity of osteoarthritis associated with varus knee deformity. The fibular head height, joint line convergence angle (JLCA) and medial proximal tibial angle (MPTA) were measured in a three-dimensional model. Ordinal multivariate logistic regression was used to analyze the correlation between fibular head height and Kellgren-Lawrence (K-L) grade. Pearson correlation was used to analyze the correlation between fibular head height and K-L grade. A total of 232 patients (232 knees) were finally included in the study. There were significant differences in JLCA and hip-knee-ankle angle ( < 0.05), and both JLCA and hip-knee-ankle angle increased with severe aggravation of K-L grade. Both fibular head height and MPTA decreased as the K-L grade was severely aggravated. There was a significant negative correlation between K-L grade and fibular head height ( = -0.812, < 0.001). Furthermore, there was a significant negative correlation between fibular head height and hip-knee-ankle angle ( = -0.7905, < 0.001). In addition to body mass index, fibular head height is a risk factor for the pathogenesis of osteoarthritis associated with varus knee deformity; the smaller the fibular head height, the more severe the degree of varus deformity.
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http://dx.doi.org/10.1515/med-2022-0523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307141PMC
July 2022

Effectiveness and safety of tafluprost in primary open-angle glaucoma and ocular hypertension: a post-marketing phase IV study in China.

BMC Ophthalmol 2022 Aug 5;22(1):332. Epub 2022 Aug 5.

Department of Cataract and Glaucoma, Wuhan Eyegood Ophthalmic Hospital, Wuhan, 430064, Hubei Province, China.

Background: Prostaglandin analogs (PGAs) are the first-line treatment for primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study aimed to confirm the effectiveness and safety of Tapros® (0.0015% tafluprost eye drops) in Chinese patients with POAG and OH.

Methods: This phase IV, multicenter, non-comparative, prospective study enrolled patients with POAG and OH in China between 12/27/2017 and 04/15/2020. Patients who were treatment-naïve or untreated within one month (group A) or with unreached intraocular pressure (IOP) target after previous monotherapy of other PGAs (group B) or non-PGA IOP-lowering drugs (group C) were treated with 0.0015% tafluprost for three months. The IOP reduction, response rate, and safety were observed.

Results: There were 165, 89, and 31 patients in groups A, B, and C, with baseline IOPs of 22.4 ± 4.7, 21.0 ± 3.5, and 22.5 ± 3.2 mmHg, respectively. The least-square means and percentages of IOP reduction at 3 months for groups A, B, and C were 4.7 (19.8%), 1.6 (6.1%), and 4.6 mmHg (20.3%), respectively. A significant reduction in IOP was observed at each visit compared with baseline (all P < 0.05). At the final visit, 57.0% of the participants in group A achieved an IOP reduction of ≥ 20%, while 40.4% and 77.4% in groups B and C achieved an IOP reduction of ≥ 10%. Fifty-eight treatment-related adverse events occurred in 46 participants (15.7%), of which the most common one was conjunctival hyperemia (34/293, 11.6%).

Conclusions: Tafluprost showed a sustained and significant effect with tolerable adverse events in Chinese patients with POAG and OH who were treatment-naïve or untreated within one month or received prior treatments with unsatisfying outcomes.
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http://dx.doi.org/10.1186/s12886-022-02553-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356508PMC
August 2022

A new co-processing mode of organic anaerobic fermentation liquid and municipal solid waste incineration fly ash.

Waste Manag 2022 Aug 2;151:70-80. Epub 2022 Aug 2.

National Engineering Laboratory for Reducing Emissions from Coal Combustion, Engineering Research Center of Environmental Thermal Technology of Ministry of Education, Shandong Key Laboratory of Energy Carbon Reduction and Resource Utilization, School of Energy and Power Engineering, Shandong University, Jinan, Shandong 250061, China.

A new co-processing mode of waste liquid from anaerobic fermentation of organic wastes and municipal solid waste incineration fly ash (MSWI-FA) dechlorination is reported in this paper. Taking acetic acid, the most common organic acid in anaerobic fermentation systems, as the representative of anaerobic fermentation organic acids, the improvement of the dechlorination effect and the mechanism of washing MSWI-FA with low concentrations of organic acid lotion were explored. The chlorine content of MSWI-FA was reduced to 0.82% after the optimal process washing pretreatment. Three anaerobic fermentation waste liquids (AFWLs) were used to verify that the chlorine content of MSWI-FA could be reduced to less than 1%, and the dechlorination effect of brewery wastewater, which reduced the chlorine content of MSWI-FA to 0.91%, was the best at this. The influence of the washing process on MSWI-FA pyrolysis was reflected in the whole process. The release of chloride decreased and the weight loss was mainly due to the release of CO. The melting point of MSWI-FA, washed by the optimal process, was reduced by nearly 30 ℃, and only 0.06% chlorine remained after calcination at 1100 ℃, which was extremely beneficial in reducing the release of trace elements in MSWI-FA during heat treatment, and for the preparation of cement raw meal.
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http://dx.doi.org/10.1016/j.wasman.2022.07.016DOI Listing
August 2022

Barley GRIK1-SnRK1 kinases subvert a viral virulence protein to upregulate antiviral RNAi and inhibit infection.

EMBO J 2022 Aug 5:e110521. Epub 2022 Aug 5.

State Key Laboratory of Wheat and Maize Crop Science, College of Agronomy, National Wheat Innovation Center, and Center for Crop Genome Engineering, Longzi Lake Campus, Henan Agricultural University, Zhengzhou, China.

Viruses often usurp host machineries for their amplification, but it remains unclear if hosts may subvert virus proteins to regulate viral proliferation. Here, we show that the 17K protein, an important virulence factor conserved in barley yellow dwarf viruses (BYDVs) and related poleroviruses, is phosphorylated by host GRIK1-SnRK1 kinases, with the phosphorylated 17K (P17K) capable of enhancing the abundance of virus-derived small interfering RNAs (vsiRNAs) and thus antiviral RNAi. Furthermore, P17K interacts with barley small RNA-degrading nuclease 1 (HvSDN1) and impedes HvSDN1-catalyzed vsiRNA degradation. Additionally, P17K weakens the HvSDN1-HvAGO1 interaction, thus hindering HvSDN1 from accessing and degrading HvAGO1-carried vsiRNAs. Importantly, transgenic expression of 17K phosphomimetics (17K ), or genome editing of SDN1, generates stable resistance to BYDV through elevating vsiRNA abundance. These data validate a novel mechanism that enhances antiviral RNAi through host subversion of a viral virulence protein to inhibit SDN1-catalyzed vsiRNA degradation and suggest new ways for engineering BYDV-resistant crops.
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http://dx.doi.org/10.15252/embj.2021110521DOI Listing
August 2022

Stem Cells from Human Exfoliated Deciduous Teeth Attenuate Atopic Dermatitis Symptoms in Mice through Modulating Immune Balance and Skin Barrier Function.

Mediators Inflamm 2022 21;2022:6206883. Epub 2022 Jul 21.

Department of Dermatology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Atopic dermatitis (AD) is a chronic skin inflammatory disease associated with immune abnormalities and disrupted skin barrier function. Mesenchymal stem cells (MSCs) have been suggested as an alternative therapeutic option in AD. Stem cells from human exfoliated deciduous teeth (SHEDs) are a unique postnatal stem cell population with high immunomodulatory properties. The aim of this study was to explore the effects of SHEDs on AD in the BALB/c mouse model induced by 2,4-dinitrochlorobenzene (DNCB). SHEDs were administrated intravenously or subcutaneously, and clinical severity, histopathological findings, skin barrier function, and organ indexes were evaluated. Skin tissue cytokine mRNA levels and serum cytokine protein levels were further analysed. SHED administration significantly alleviated AD clinical severity, including dermatitis scores, ear thickness, scratching behaviour, and infiltration of mast cells. In addition, disrupted skin barrier function and enlarged spleens were restored by SHED administration. Further, SHED treatment reduced the levels of IgE, IgG1, and thymic stromal lymphopoietin (TSLP) in the serum and the modulated expression of Th1-, Th2-, and Th17-associated cytokines in skin lesions. In conclusion, SHEDs attenuated AD-like skin lesions in mice by modulating the immune balance and skin barrier function. SHEDs could be a potential new treatment agent for AD.
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http://dx.doi.org/10.1155/2022/6206883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334056PMC
August 2022

Molecular Regulation of Biosynthesis of Long Chain Polyunsaturated Fatty Acids in Atlantic Salmon.

Mar Biotechnol (NY) 2022 Aug 30;24(4):661-670. Epub 2022 Jul 30.

Center for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, Ås, Norway.

Salmon is a rich source of health-promoting omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). The LC-PUFA biosynthetic pathway in Atlantic salmon is one of the most studied compared to other teleosts. This has largely been due to the massive replacement of LC-PUFA-rich ingredients in aquafeeds with terrestrial plant oils devoid of these essential fatty acids (EFA) which ultimately pushed dietary content towards the minimal requirement of EFA. The practice would also reduce tissue content of n-3 LC-PUFA compromising the nutritional value of salmon to the human consumer. These necessitated detailed studies of endogenous biosynthetic capability as a contributor to these EFA. This review seeks to provide a comprehensive and concise overview of the current knowledge about the molecular genetics of PUFA biosynthesis in Atlantic salmon, highlighting the enzymology and nutritional regulation as well as transcriptional control networks. Furthermore, we discuss the impact of genome duplication on the complexity of salmon LC-PUFA pathway and highlight probable implications on endogenous biosynthetic capabilities. Finally, we have also compiled and made available a large RNAseq dataset from 316 salmon liver samples together with an R-script visualization resource to aid in explorative and hypothesis-driven research into salmon lipid metabolism.
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http://dx.doi.org/10.1007/s10126-022-10144-wDOI Listing
August 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

Preoperative Inflammatory Markers and the Risk of Postoperative Delirium in Patients Undergoing Lumbar Spinal Fusion Surgery.

J Clin Med 2022 Jul 14;11(14). Epub 2022 Jul 14.

Institute of New Frontier Research Team, Hallym University College of Medicine, Chuncheon-si 24252, Korea.

We investigated the possible associations between postoperative delirium (POD) and routinely available preoperative inflammatory markers in patients undergoing lumbar spinal fusion surgery (LSFS) to explore the role of neuroinflammation and oxidative stress as risk factors for POD. We analyzed 11 years' worth of data from the Smart Clinical Data Warehouse. We evaluated whether preoperative inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the CRP-to-albumin ratio (CAR), affected the development of POD in patients undergoing LSFS. Of the 3081 subjects included, 187 (7.4%) developed POD. A significant increase in NLR, MLR, and CAR levels was observed in POD patients ( < 0.001). A multivariate analysis showed that the second, third, and highest quartiles of the NLR were significantly associated with the development of POD (adjusted OR (95% CI): 2.28 (1.25-4.16], 2.48 (1.3-4.73], and 2.88 (1.39-5.96], respectively). A receiver operating characteristic curve analysis showed that the discriminative ability of the NLR, MLR, and CAR for predicting POD was low, but almost acceptable (AUC (95% CI): 0.60 (0.56-0.64], 0.61 (0.57-0.65], and 0.63 (0.59-0.67], respectively, < 0.001). Increases in preoperative inflammatory markers, particularly the NLR, were associated with the development of POD, suggesting that a proinflammatory state is a potential pathophysiological mechanism of POD.
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http://dx.doi.org/10.3390/jcm11144085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324332PMC
July 2022

Identification of Ubiquitin-Related Gene-Pair Signatures for Predicting Tumor Microenvironment Infiltration and Drug Sensitivity of Lung Adenocarcinoma.

Cancers (Basel) 2022 Jul 18;14(14). Epub 2022 Jul 18.

NHC Key Laboratory of Pulmonary Diseases, Hubei Province Engineering Research Center for Tumor-Targeted Biochemotherapy, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer worldwide, and new biomarkers are urgently required to guide more effective individualized therapy for patients. Ubiquitin-related genes (UbRGs) partially participate in the initiation and progression of lung cancer. In this study, we used ubiquitin-related gene pairs (UbRGPs) in tumor tissues to access the function of UbRGs in overall survival, immunocyte infiltration, and tumor mutation burden (TMB) of patients with LUAD from The Cancer Genome Atlas (TCGA) database. In addition, we constructed a prognostic signature based on six UbRGPs and evaluated its performance in an internal (TCGA testing set) and an external validation set (GSE13213). The prognostic signature revealed that risk scores were negatively correlated with the overall survival, immunocyte infiltration, and expression of immune checkpoint inhibitor-related genes and positively correlated with the TMB. Patients in the high-risk group showed higher sensitivity to partially targeted and chemotherapeutic drugs than those in the low-risk group. This study contributes to the understanding of the characteristics of UbRGPs in LUAD and provides guidance for effective immuno-, chemo-, and targeted therapy.
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http://dx.doi.org/10.3390/cancers14143478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317993PMC
July 2022

Genetic variation of Golgi membrane protein 1 is associated with COVID-19 disease.

J Infect 2022 Jul 22. Epub 2022 Jul 22.

Department of Translational Medicine Center, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, Zhejiang, PR China; Institute of Hepatology and Metabolic Diseases, Hangzhou Normal University, Hangzhou 310015, Zhejiang, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2022.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335158PMC
July 2022

Self-Powered High-Voltage Recharging System for Removing Noxious Tobacco Smoke by Biomimetic Hairy-Contact Triboelectric Nanogenerator.

Small 2022 Aug 24;18(33):e2202835. Epub 2022 Jul 24.

Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, P. R. China.

The most common size range of particulate matter (PM) in tobacco smoke is 1.0 to 5.0 microns; however, a high number of the most harmful PM is as small as 0.5 micron that is a serious threat to human health, and it is difficult to remove. There is an urgent need to develop a new purification technology for high-efficiency removing tobacco smoke with easily construction and low cost. Here, a method of self-powered high-voltage recharging system is demonstrated by designing biomimetic hairy-contact triboelectric nanogenerator (BHC-TENG) for long-lasting adsorption with a wide range from PM 0.5 to PM 10. The open-circuit voltage of BHC-TENGs reaches 8.42 KV, which can continuously charge injection to the melt-blown fabric, whose surface potential is able to maintain nearly 260 V level and create a uniform electrostatic adsorption field on the surface. This high-voltage recharging system reduces the concentration of PMs to World Health Organization (WHO) standards, maintaining the purification efficiency of PM 0.5- PM 10 persistently over 90%.
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http://dx.doi.org/10.1002/smll.202202835DOI Listing
August 2022

Role and mechanism of IL - 17 and its gene polymorphisms in dyslipidemia caused by obstructive sleep apnea syndrome in children.

Authors:
Jin Yang

Cell Mol Biol (Noisy-le-grand) 2022 Feb 28;68(2):208-212. Epub 2022 Feb 28.

Hubei Province Wuhan DongXihu District Maternal and Child Health Hospital, Wuhan, Hubei430040, China..

The current research was carried out to explore the role and mechanism of IL - 17 and its gene polymorphisms in dyslipidemia caused by obstructive sleep apnea syndrome in children. For this aim, a total of 86 children with obstructive sleep apnea syndrome admitted to our hospital from January 2018 to January 2020 were selected as the study subjects, and the lipid-related indexes of the children were detected by a fully automatic biochemical analyzer, and they were divided into OSAHS group (54 cases), combined dyslipidemia group (32 cases), and another 40 healthy children who underwent physical examination in our hospital during the same period were selected as the healthy group. Levels of IL-7 and AHI, FEV1 / FVC were analyzed in each group, and levels of TC, TG, and LDL-C were compared to observe different sites of IL-17, namely IL-17A (rs3748067; The loci of IL-17F (rs763780, rs2397084) were genotyped in different groups to analyze the association between IL-17 and dyslipidemia in children with OSAHS. Results showed that higher IL-7 and AHI levels and lower FEV1 / FVC levels were found in the combined dyslipidemia and OSAHS groups compared with the healthy group, and higher IL-7 and AHI levels and lower FEV1 / FVC levels were found in the combined dyslipidemia group compared with the OSAHS group (P < 0.05); TC, TG and LDL-C level expression were higher in the combined dyslipidemia and OSAHS groups compared with the healthy group, and TC, TG and LDL-C level expression were higher in the combined dyslipidemia group compared with the OSAHS group (P < 0.05). IL-17 was positively correlated with TC, TG and LDL-C. It was concluded that in the development of OSAHS, IL-7 levels are significantly expressed, at the same time OSAHS children progress dyslipidemia, which has some correlation with IL-17, and IL-17 gene polymorphism, IL-17A (rs3748067); All were significantly expressed in the IL-17F (rs763780, rs2397084) locus.
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http://dx.doi.org/10.14715/cmb/2022.68.2.30DOI Listing
February 2022

Predictive Risk Factors at Admission and a "Burning Point" During Hospitalization Serve as Sequential Alerts for Critical Illness in Patients With COVID-19.

Front Med (Lausanne) 2022 4;9:816314. Epub 2022 Jul 4.

Key Laboratory of Pulmonary Diseases of National Health Commission, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: We intended to establish a novel critical illness prediction system combining baseline risk factors with dynamic laboratory tests for patients with coronavirus disease 2019 (COVID-19).

Methods: We evaluated patients with COVID-19 admitted to Wuhan West Union Hospital between 12 January and 25 February 2020. The data of patients were collected, and the illness severity was assessed.

Results: Among 1,150 enrolled patients, 296 (25.7%) patients developed into critical illness. A baseline nomogram model consists of seven variables including age [odds ratio (OR), 1.028; 95% confidence interval (CI), 1.004-1.052], sequential organ failure assessment (SOFA) score (OR, 4.367; 95% CI, 3.230-5.903), neutrophil-to-lymphocyte ratio (NLR; OR, 1.094; 95% CI, 1.024-1.168), D-dimer (OR, 1.476; 95% CI, 1.107-1.968), lactate dehydrogenase (LDH; OR, 1.004; 95% CI, 1.001-1.006), international normalised ratio (INR; OR, 1.027; 95% CI, 0.999-1.055), and pneumonia area interpreted from computed tomography (CT) images (medium vs. small [OR, 4.358; 95% CI, 2.188-8.678], and large vs. small [OR, 9.567; 95% CI, 3.982-22.986]) were established to predict the risk for critical illness at admission. The differentiating power of this nomogram scoring system was perfect with an area under the curve (AUC) of 0.960 (95% CI, 0.941-0.972) in the training set and an AUC of 0.958 (95% CI, 0.936-0.980) in the testing set. In addition, a linear mixed model (LMM) based on dynamic change of seven variables consisting of SOFA score (value, 2; increase per day [I/d], +0.49), NLR (value, 10.61; I/d, +2.07), C-reactive protein (CRP; value, 46.9 mg/L; I/d, +4.95), glucose (value, 7.83 mmol/L; I/d, +0.2), D-dimer (value, 6.08 μg/L; I/d, +0.28), LDH (value, 461 U/L; I/d, +13.95), and blood urea nitrogen (BUN value, 6.51 mmol/L; I/d, +0.55) were established to assist in predicting occurrence time of critical illness onset during hospitalization.

Conclusion: The two-checkpoint system could assist in accurately and dynamically predicting critical illness and timely adjusting the treatment regimen for patients with COVID-19.
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http://dx.doi.org/10.3389/fmed.2022.816314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291637PMC
July 2022

Development of STEAP1 targeting chimeric antigen receptor for adoptive cell therapy against cancer.

Mol Ther Oncolytics 2022 Sep 22;26:189-206. Epub 2022 Jun 22.

Department of Cancer Immunology, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, Mail Box 4950 Nydalen, 0424 Oslo, Norway.

Chimeric antigen receptors (CARs) that retarget T cells against CD19 show clinical efficacy against B cell malignancies. Here, we describe the development of a CAR against the six-transmembrane epithelial antigen of prostate-1 (STEAP1), which is expressed in ∼90% of prostate cancers, and subgroups of other malignancies. STEAP1 is an attractive target, as it is associated with tumor invasiveness and progression and only expressed at low levels in normal tissues, apart from the non-vital prostate gland. We identified the antibody coding sequences from a hybridoma and designed a CAR that is efficiently expressed in primary T cells. The T cells acquired the desired anti-STEAP1 specificity, with a polyfunctional response including production of multiple cytokines, proliferation, and the killing of cancer cells. The response was observed for both CD4 and CD8 T cells, and against all STEAP1 target cell lines tested. We evaluated the CAR T activity in both subcutaneous and metastatic xenograft mouse models of prostate cancer. Here, the CAR T cells infiltrated tumors and significantly inhibited tumor growth and extended survival in a STEAP1-dependent manner. We conclude that the STEAP1 CAR exhibits potent and functionality and can be further developed toward potential clinical use.
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http://dx.doi.org/10.1016/j.omto.2022.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278049PMC
September 2022

Phenotypic screening with deep learning identifies HDAC6 inhibitors as cardioprotective in a BAG3 mouse model of dilated cardiomyopathy.

Sci Transl Med 2022 Jul 6;14(652):eabl5654. Epub 2022 Jul 6.

Tenaya Therapeutics, South San Francisco, CA 94080, USA.

Dilated cardiomyopathy (DCM) is characterized by reduced cardiac output, as well as thinning and enlargement of left ventricular chambers. These characteristics eventually lead to heart failure. Current standards of care do not target the underlying molecular mechanisms associated with genetic forms of heart failure, driving a need to develop novel therapeutics for DCM. To identify candidate therapeutics, we developed an in vitro DCM model using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) deficient in B-cell lymphoma 2 (BCL2)-associated athanogene 3 (BAG3). With these BAG3-deficient iPSC-CMs, we identified cardioprotective drugs using a phenotypic screen and deep learning. From a library of 5500 bioactive compounds and siRNA validation, we found that inhibiting histone deacetylase 6 (HDAC6) was cardioprotective at the sarcomere level. We translated this finding to a BAG3 cardiomyocyte-knockout (BAG3) mouse model of DCM, showing that inhibiting HDAC6 with two isoform-selective inhibitors (tubastatin A and a novel inhibitor TYA-018) protected heart function. In BAG3 and BAG3 mice, HDAC6 inhibitors improved left ventricular ejection fraction and reduced left ventricular diameter at diastole and systole. In BAG3 mice, TYA-018 protected against sarcomere damage and reduced expression. Based on integrated transcriptomics and proteomics and mitochondrial function analysis, TYA-018 also enhanced energetics in these mice by increasing expression of targets associated with fatty acid metabolism, protein metabolism, and oxidative phosphorylation. Our results demonstrate the power of combining iPSC-CMs with phenotypic screening and deep learning to accelerate drug discovery, and they support developing novel therapies that address underlying mechanisms associated with heart disease.
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http://dx.doi.org/10.1126/scitranslmed.abl5654DOI Listing
July 2022

Loss of EMP1 promotes the metastasis of human bladder cancer cells by promoting migration and conferring resistance to ferroptosis through activation of PPAR gamma signaling.

Free Radic Biol Med 2022 Aug 16;189:42-57. Epub 2022 Jul 16.

Department of Cell Biology, Third Military Medical University, Chongqing, China. Electronic address:

Metastasis, in which cancer cells detach from the original site and colonise other organs, is the primary cause of death induced by bladder cancer (BCa). Epithelial Membrane Protein 1 (EMP1) is dysregulated in many human cancers, and its clinical significance and biological function in diseases, including BCa, are largely unclear. Here, we demonstrated that EMP1 was downregulated in BCa cells. The deficiency of EMP1 promotes migration and confers resistance to ferroptosis/oxidative stress in BCa cells, favouring tumour cell metastasis. Mechanistically, we demonstrated that EMP1 deficiency enhanced tumour metastasis by increasing PPARG expression and promoting its activation, leading to upregulation of pFAK(Y397) and SLC7A11, which promoted cell migration and anti-ferroptotic cell death respectively. Moreover, we found EMP1-deficient sensitized cells to PPARG's ligand, which effect are metastatic phenotype promoted and could be mitigated by FABP4 knockdown. In conclusion, our study, for the first time, reveals that EMP1 deficiency promotes BCa cell migration and confers resistance to ferroptosis/oxidative stress, thus promoting metastasis of BCa via PPARG. These results revealed a novel role of EMP1-mediated PPARG in bladder cancer metastasis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.06.247DOI Listing
August 2022

Construction of Protective Films on Zn Metal Anodes Natural Protein Additives Enabling High-Performance Zinc Ion Batteries.

ACS Nano 2022 Jul 18. Epub 2022 Jul 18.

Centre for Clean Energy Technology, School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Ultimo New South Wales 2007, Australia.

The strong activity of water molecules causes a series of parasitic side reactions on Zn anodes in the aqueous electrolytes. Herein, we introduce silk fibroin (SF) as a multifunctional electrolyte additive for aqueous zinc-ion (Zn-ion) batteries. The secondary structure transformation of SF molecules from α-helices to random coils in the aqueous electrolytes allows them to break the hydrogen bond network among free water molecules and participate in Zn ion solvation structure. The SF molecules released from the [Zn(HO)(SF)] solvation sheath appear to be gradually adsorbed on the surface of Zn anodes and form a hydrostable and self-healable protective film. This SF-based protective film not only shows strong Zn ion affinity to promote homogeneous Zn deposition but also has good insulating behavior to suppress parasitic reactions. Benefiting from these multifunctional advantages, the cycle life of the Zn||Zn symmetric cells reaches over 1600 h in SF-containing ZnSO electrolytes. In addition, by adopting a potassium vanadate cathode, the full cell shows excellent cycling stability for 1000 cycles at 3 A g. The construction of a protective film on the Zn anode from natural protein molecules provides an effective strategy to achieve high-performance Zn metal anodes for Zn-ion batteries.
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http://dx.doi.org/10.1021/acsnano.2c05285DOI Listing
July 2022

RAC3 Inhibition Induces Autophagy to Impair Metastasis in Bladder Cancer Cells the PI3K/AKT/mTOR Pathway.

Front Oncol 2022 30;12:915240. Epub 2022 Jun 30.

Urology Institute of People's Liberation Army, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Background: Bladder cancer (BCa) is one of the most frequent malignant tumors globally, with a significant morbidity and mortality rate. Gene expression dysregulation has been proven to play a critical role in tumorigenesis. Ras-related C3 botulinum toxin substrate3 (RAC3), which is overexpressed in several malignancies and promotes tumor progression, has been identified as an oncogene. However, RAC3 has important but not fully understood biological functions in cancer. Our research aims to reveal the new functions and potential mechanisms of RAC3 involved in BCa progression.

Methods: We explored the expression level of RAC3 and its relationship with prognosis by publicly accessible BCa datasets, while the correlation of RAC3 expression with clinicopathological variables of patients was analyzed. and proliferation, migration, autophagy, and other phenotypic changes were examined by constructing knockdown(KD)/overexpression(OE) RAC3 cells and their association with PI3K/AKT/mTOR pathway was explored by adding autophagy-related compounds.

Results: Compared with non-tumor samples, RAC3 was highly expressed in BCa and negatively correlated with prognosis. KD/OE RAC3 inhibited/promoted the proliferation and migration of BCa cells. Knockdown RAC3 caused cell cycle arrest and decreased adhesion without affecting apoptosis. Inhibition of RAC3 activates PI3K/AKT/mTOR mediated autophagy and inhibits proliferation and migration of BCa cells and . Autophagy inhibitor 3MA can partially rescue the metastasis and proliferation inhibition effect caused by RAC3 inhibition. Inhibit/activate mTOR enhanced/impaired autophagy, resulting in shRAC3-mediated migration defect exacerbated/rescued.

Conclusion: RAC3 is highly expressed in BCa. It is associated with advanced clinicopathological variables and poor prognosis. Knockdown RAC3 exerts an antitumor effect by enhancing PI3K/AKT/mTOR mediated autophagy. Targeting RAC3 and autophagy simultaneously is a potential therapeutic strategy for inhibiting BCa progression and prolonging survival.
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http://dx.doi.org/10.3389/fonc.2022.915240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279623PMC
June 2022

Sphingosine-1-phosphate, a novel TREM2 ligand, promotes microglial phagocytosis to protect against ischemic brain injury.

Acta Pharm Sin B 2022 Apr 22;12(4):1885-1898. Epub 2021 Oct 22.

Department of Pharmacology, Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing 211166, China.

The mechanism of sphingosine-1-phosphate (S1P)-mediated phagocytosis remains unknown. Here, we found that S1P or FTY720 (an analog of S1P) promoted microglial phagocytosis in stroke independent of S1PRs. First, we used computer simulation of molecular docking to predict that S1P might be a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). Next, microscale thermophoresis (MST), surface plasmon resonance (SPR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to reveal that S1P was a novel TREM2 ligand. Then, we confirmed the pro-phagocytosis of S1P targeting in transfected CHO cells and TREM2 knockdown microglia. Point mutation analysis showed that D104 was the critical binding residue. mice were used to demonstrate the role of S1P-induced phagocytosis targeting on TREM2 in protecting against ischemic brain injury. Finally, further studies revealed that apolipoprotein E (APOE) loaded with S1P was released by microglia and bound to apoptotic neurons LDL receptor related protein 1B (LRP1B) and thereby induced microglia to phagocytose apoptotic neurons. Overall, the present work reveals for the first time that S1P acts as a novel endogenous ligand of TREM2 to effectively promote microglial phagocytosis. Our findings provide a new lead compound for developing immunomodulator targeting on TREM2.
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http://dx.doi.org/10.1016/j.apsb.2021.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279640PMC
April 2022

A Cross-Sectional Study on the Application of IS in Perioperative Pulmonary Function Training in Spine and Orthopedics.

Comput Intell Neurosci 2022 6;2022:4546549. Epub 2022 Jul 6.

Infection Control Administration Department, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

Background: The incentive spirometer (IS) is a mechanical device that promotes lung expansion and can be used to prevent and treat postoperative pulmonary complications. In this study, the preventive effect of pulmonary function training with IS on the improvement of pulmonary function and pulmonary complications was observed.

Methods: From May 2019 to April 2021, 69 scoliosis patients with impaired moderate and severe lung function were divided into the traditional pulmonary training group ( = 32) and IS-enhanced pulmonary training group ( = 35). The patient underwent lung function testing after admission and one week after the start of training and chest CT on the third day after surgery.

Results: The average age was 13.47 and 15.66, respectively ( = 0.223). The Cobb angles were 83.84 and 83.97 ( = 0.756), respectively, and no statistical difference between the parameters of lung function was detected. After 1 week of respiratory function training, significant improvement in lung function testing parameters including VC%, FVC%, FEV1%, FEV1/FVC, FEV1/VC, and MVV% was found in both groups. Analysis of covariance showed more significant improvement in IS-enhanced group compared to the conventional training group ( < 0.05). The incidence of postoperative pulmonary atelectasis was lower in IS-enhanced group than in traditional groups (2.9% vs. 21.9%,  = 0.043) with no difference in the overall incidence of pulmonary complications ( = 0.164) and shorter preoperative and total hospitalization in the IS-enhanced group.

Conclusion: Compared to traditional pulmonary function training, IS-enhanced training can significantly accelerate the improvement of pulmonary function testing parameters, shorten the preoperative pulmonary function training time, reduce the incidence of postoperative pulmonary tension complications, and accelerate postoperative rehabilitation.
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http://dx.doi.org/10.1155/2022/4546549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279051PMC
July 2022

Seroprevalence and dynamics of anti-SARS-CoV-2 antibodies: a longitudinal study based on patients with underlying diseases in Wuhan.

Respir Res 2022 Jul 15;23(1):188. Epub 2022 Jul 15.

School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Assessing the humoral immunity of patients with underlying diseases after being infected with SARS-CoV-2 is essential for adopting effective prevention and control strategies. The purpose of this study is to analyze the seroprevalence of people with underlying diseases and the dynamic change features of anti-SARS-CoV-2 antibodies.

Methods: We selected 100 communities in Wuhan using the probability-proportional-to-size sampling method. From these 100 communities, we randomly selected households according to a list provided by the local government. Individuals who have lived in Wuhan for at least 14 days since December 2019 and were ≥ 40 years old were included. From April 9-13, 2020, community staff invited all selected individuals to the community healthcare center in batches by going door-to-door or telephone. All participants completed a standardized electronic questionnaire simultaneously. Finally, 5 ml of venous blood was collected from all participants. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. During the period June 11-13, 2020 and October 9-December 5, 2020, all family members of a positive family and matched negative families were followed up twice.

Results: The seroprevalence of anti-SARS-CoV-2 antibodies in people with underlying diseases was 6.30% (95% CI [5.09-7.52]), and that of people without underlying diseases was 6.12% (95% CI [5.33-6.91]). A total of 313 people were positive for total antibodies at baseline, of which 97 had underlying disease. At the first follow-up, a total of 212 people were positive for total antibodies, of which 66 had underlying disease. At the second follow-up, a total of 238 people were positive for total antibodies, of which 68 had underlying disease. A total of 219 participants had three consecutive serum samples with positive total antibodies at baseline. The IgG titers decreased significantly with or without underlying diseases (P < 0.05) within the 9 months at least, while the neutralizing antibody titer remained stable. The titer of asymptomatic patients was lower than that of symptomatic patients (baseline, P = 0.032, second follow-up, P = 0.018) in the underlying diseases group.

Conclusion: Our research focused on the serological changes of people with and without underlying diseases in a state of single natural infection. Regardless of the underlying diseases, the IgG titer decreased significantly over time, while there was no significant difference in the decline rate of IgG between with and without underlying diseases. Moreover, the neutralizing antibody titer remained relatively stable within the 9 months at least.
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http://dx.doi.org/10.1186/s12931-022-02096-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284953PMC
July 2022
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