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BACKGROUND: Traumatic brain injury (TBI) is a common condition in veterinary medicine that is difficult to manage.Veterinary regenerative therapy based on adipose mesenchymal stem cells seem to be an effective strategy for the treatment of traumatic brain injury. In this study, we evaluated therapeutic efficacy of canine Adipose-derived mesenchymal stem cells (AD-MSCs)in a rat TBI model, in terms of improved nerve function and anti-neuroinflammation. RESULTS: Canine AD-MSCs promoted neural functional recovery, reduced neuronal apoptosis, and inhibited the activation of microglia and astrocytes in TBI rats. According to the results in vivo, we further investigated the regulatory mechanism of AD-MSCs on activated microglia by co-culture in vitro. Finally, we found that canine AD-MSCs promoted their polarization to the M2 phenotype, and inhibited their polarization to the M1 phenotype. What's more, AD-MSCs could reduce the migration, proliferation and Inflammatory cytokines of activated microglia, which is able to inhibit inflammation in the central system. CONCLUSIONS: Collectively, the present study demonstrates that transplantation of canine AD-MSCs can promote functional recovery in TBI rats via inhibition of neuronal apoptosis, glial cell activation and central system inflammation, thus providing a theoretical basis for canine AD-MSCs therapy for TBI in veterinary clinic.
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Lesões Encefálicas Traumáticas , Doenças do Cão , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doenças dos Roedores , Ratos , Animais , Cães , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/veterinária , Microglia , Macrófagos , Inflamação/veterinária , Transplante de Células-Tronco Mesenquimais/veterinária , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
BACKGROUND: Tuberculosis (TB), a highly contagious respiratory disease, presents a significant global health threat, with a notable increase in incidence reported by the WHO in 2022. Particularly, the interplay between TB and non-small cell lung cancer (NSCLC) gains attention, especially considering the rising use of immune checkpoint inhibitors (ICIs) in cancer treatment. This interplay may influence TB diagnostics and reactivation, warranting a closer examination. METHODS: A retrospective analysis was conducted on clinical data of NSCLC patients with positive T-SPOT results before undergoing anti-tumor treatment at Zhongshan Hospital (Xiamen), Fudan University, from January 1, 2021 to December 31, 2022. We assessed the incidence of tuberculosis reactivation and treatment outcomes among these patients. Moreover, we compared the differences in tuberculosis activity between the ICIs and non-ICIs treatment groups. Additionally, we observed the changes in T-SPOT spot count before and after immunotherapy, analyzing their association with tuberculosis activity and prognosis. RESULTS: A total of 40 NSCLC patients with positive T-SPOT results before treatment were included in the study, with 26 patients in the ICIs treatment group and 14 patients in the non-ICIs treatment group. The study found no significant differences between the two groups in terms of gender, age, stage, histological type, performance status, driver gene expression, and distant metastasis. With a median follow-up time of 10.0 (6.0-14.5) months, three cases (11.5%) in the ICIs treatment group developed tuberculosis activity, diagnosed at 2, 3, and 12 months after ICIs treatment initiation. Conversely, no tuberculosis activity was observed in the non-ICIs treatment group, and the difference between the two groups was not significant (P = 0.186). Among the 32 patients who received ICIs treatment, spot count dynamics were diverse: four cases (12.5%) showed an increase, 12 cases (37.5%) had no change, and 16 cases (50.0%) had a decrease. During the follow-up, the progression rate (PD) was 50.0%, 75.0%, and 62.5% in the three groups, respectively (P = 0.527). Similarly, the mortality rate was 0%, 25.0%, and 25.0%, respectively (P = 0.106). Interestingly, among the patients with decreased spot counts, three cases (18.75%) were diagnosed with active pulmonary tuberculosis. CONCLUSIONS: For NSCLC patients with a positive T-SPOT response undergoing ICIs treatment, our study observed indications of active tuberculosis. The varied T-SPOT spot count changes post-ICIs treatment suggest a complex interaction, potentially linking T-SPOT spot count reduction to tuberculosis reactivation risk. These preliminary findings underscore the importance of further research to more accurately assess T-SPOT's diagnostic utility in this context.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Tuberculose Pulmonar , Humanos , Testes de Liberação de Interferon-gama , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
BACKGROUND: Studies on aspirin's effects on metabolic-associated fatty liver disease (MAFLD) are limited. The aim of this study was to assess the association between aspirin and all-cause and cardiovascular disease (CVD) mortality in individuals with MAFLD. METHODS: Data were acquired from the National Health And Nutrition Examination Survey (NHANES) III. MAFLD diagnosis was consistent with that of international expert consensus. The independent association between aspirin and all-cause and CVD mortality in participants with MAFLD was evaluated by multiple Cox regression. Stratified analyses and interaction tests were performed to investigate whether covariates modified the association between aspirin and MAFLD mortality. RESULTS: Of 4594 eligible participants, 3,162 (68.83%) never took aspirin (0 times/month), 962 (20.94%) took it occasionally (1-14 times/month) and 470 (10.23%) took it regularly (≥15 times/month). Multiple cox regression showed that aspirin was not associated with overall mortality for MAFLD individuals. Stratified analysis revealed that in middle-aged (45-59 years) participants with MAFLD, occasional aspirin use was associated with low all-cause mortality risk (HR = 0.61, 95% CI = 0.43-0.86), while there was no significant association between aspirin and all-cause mortality among the young or the elderly. CONCLUSIONS: We found that the association between aspirin and all-cause MAFLD mortality varies by both age and frequency of administration. More prospective studies are needed to explore aspirin's influence on MALFD mortality.
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Doenças Cardiovasculares , Hepatopatia Gordurosa não Alcoólica , Idoso , Pessoa de Meia-Idade , Humanos , Inquéritos Nutricionais , Aspirina/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
UDP-glycosyltransferases (UGTs) are widely involved in plant growth and stress responses. However, UGT family are not well understood in cassava. Here, we identified 121 MeUGT genes and classified them into 14 subfamilies by phylogenetic analysis. All MeUGT proteins have typical feature of the UGTs family. Tandem duplications are the crucial driving force for the expansion of MeUGT family. Cis-Acting elements analysis uncovered those 14 kinds of cis-elements associated with biotic and abiotic stress responses. Transcriptomic and qRT-PCR analyses indicated that MeUGT genes participate in postharvest physiological deterioration of storage root and the responses of biotic and abiotic stresses. Of which, MeUGT-14/41 were significantly induced after Xam treatment. Silencing of MeUGT-14 or MeUGT-41 reduced cassava resistance to Xam, verifying the accuracy of transcriptomic data for function prediction. Together, this study characterized the MeUGTs family and revealed their potential functions, which build a solid foundation for MeUGTs associated genetic improvement of cassava.
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Manihot , Regulação da Expressão Gênica de Plantas , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Manihot/genética , Manihot/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Difosfato de UridinaRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. RESULTS: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. AD-MSCs presented normal karyotype, and did not form in vivo tumors. No adverse events were noted in the case treated with intravenously AD-MSCs. CONCLUSIONS: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.
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Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais/veterinária , Células-Tronco Mesenquimais/citologia , Bancos de Tecidos , Animais , Testes de Carcinogenicidade , Técnicas de Cultura de Células/veterinária , Separação Celular/veterinária , Criopreservação/veterinária , Cães , Feminino , Leucopenia/veterinária , Masculino , Camundongos SCID , Infecções por Parvoviridae/terapia , Infecções por Parvoviridae/veterinária , Parvovirus , Controle de QualidadeRESUMO
BACKGROUND: Exosomes, internal proteins, lipids, and nucleic acids coated by phospholipid bilayer membranes, are one type of small extracellular vesicles, which can mediate cell-cell communication. In recent years, exosomes have gained considerable scientific interest due to their widely applied prospect in the diagnosis and therapeutics of human and animal diseases. In this study, we describe for the first time a feasible method designed to isolate and characterize exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells. RESULTS: Exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells were successfully isolated by differential centrifugation. Quantification and sizing of exosomes were assessed by transmission electron microscopy, flow nano analysis and western blotting. Detected particles showed the normal size (30-100 nm) and morphology described for exosomes, as well as presence of the transmembrane protein (TSG101, CD9, CD63, and CD81) known as exosomal marker. CONCLUSIONS: The results suggest that differential centrifugation is a feasible method for isolation of exosomes from different types of feline samples. Moreover, these exosomes can be used to further diagnosis and therapeutics in veterinary pre-clinical and clinical studies.
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Gatos/sangue , Gatos/urina , Exossomos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Animais , Feminino , Masculino , PlasmaRESUMO
Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy. Comparing the biological and transcriptome gene characteristics of MSCs from different sources provides an important basis for the screening of clinically used cells. The main purpose of this experiment was to establish methods for the isolation and culture of MSCs from five different canine sources, including adipose tissue, bone marrow, umbilical cord, amniotic membrane, and placenta, and compare biological and transcriptome characteristics of MSCs, in order to provide a basis for the clinical application of canine MSCs. MSCs were isolated from Chinese pastoral dogs, and the following experiments were performed: (1) the third, sixth, and ninth generations of cells were counted, respectively, and a growth curve was plotted to calculate the MSC population doubling time; (2) the expression of CD34 and CD44 surface markers was studied by immunofluorescence; (3) the third generation of cells were used for osteogenetic and adipogenic differentiation experiments; and (4) MSC transcriptome profiles were performed using RNA sequencing. All of the five types of MSCs showed fibroblast-like adherent growth. The cell surface expressed CD44 instead of CD34; the third-generation MSCs had the highest proliferative activity. The average population doubling time of adipose mesenchymal stem cells (AD-MSCs), placenta mesenchymal stem cells (P-MSCs), bone marrow mesenchymal stem cells (BM-MSCs), umbilical cord mesenchymal stem cells (UC-MSCs), and amniotic mesenchymal stem cells (AM-MSCs) were 15.8 h, 21.2 h, 26.2 h, 35 h, and 41.9 h, respectively. All five types of MSCs could be induced to differentiate into adipocytes and osteoblasts in vitro, with lipid droplets appearing after 8 days and bone formation occurring 5 days after AD-MSC induction. However, the multilineage differentiation for the remaining of MSCs was longer compared to that of the AD-MSCs. The MSC transcriptome profiles showed that AD-MSC and BM-MSCs had the highest homology, while P-MSCs were significantly different compared to the other four types of MSCs. All the isolated MSCs had the main biological characteristics of MSCs. AD-MSCs had the shortest time for proliferation, adipogenesis, and osteogenic differentiation.
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Cães/genética , Células-Tronco Mesenquimais/metabolismo , Especificidade de Órgãos/genética , Transcriptoma/genética , Animais , Biomarcadores/metabolismo , Adesão Celular , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Análise por Conglomerados , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/citologia , Reprodutibilidade dos TestesRESUMO
BACKGROUND: A better understanding of the molecular mechanisms in liver regeneration holds promise for exploring the new potential therapy for liver failure. The present study was to investigate the role of zinc finger and BTB domain-containing protein 20 (ZBTB20), a potential factor associated with liver regeneration, in a model of 70% hepatectomy in mice. METHODS: Parameters for liver proliferation such as liver/body ratio and BrdU positivity were obtained via direct measurement and immunohistochemistry. The levels of zinc fingers and homeoboxes 2 (ZHX2), ZBTB20, alpha-fetoprotein (AFP) and glypican 3 (GPC3) transcripts in the regenerating liver tissue of a 70% hepatectomy rodent model were monitored by real-time PCR analysis at different time points. Knockdown of ZBTB20 was performed to characterize its regulatory function. RESULTS: A negatively regulating relationship between ZHX2, ZBTB20 and AFP, GPC3 was revealed from 24 to 72 hours after 70% hepatectomy. ZBTB20 appears to negatively regulate AFP and GPC3 transcription since the knockdown of ZBTB20 promoted the proliferation of hepatocytes and the expression of AFP and GPC3. CONCLUSION: In addition to AFP, GPC3 and ZHX2, ZBTB20 is a new regulator in liver regeneration and the decrease of ZBTB20 expression following 70% hepatectomy promotes AFP and GPC3 expression.
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Hepatectomia/métodos , Regeneração Hepática/fisiologia , Fígado/fisiologia , Fígado/cirurgia , Fatores de Transcrição/fisiologia , Animais , Linhagem Celular , Proliferação de Células , Glipicanas/fisiologia , Hepatócitos/patologia , Proteínas de Homeodomínio/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , RNA Interferente Pequeno/farmacologia , Fatores de Tempo , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/genética , Transfecção , alfa-Fetoproteínas/fisiologiaRESUMO
Animal cell culture technology in the production of slaughter-free meat offers ethical advantages with regards to animal welfare, rendering it a more socially acceptable approach for dog meat production. In this study, edible plant-derived scaffold was used as a platform for cell expansion to construct cell-cultured dog meat slices. Primary dog skeletal muscle satellite cells (MSCs) and adipose stem cells (ASCs) were isolated and cultured as seed cells, and 3D spheroid culture in vitro promoted MSCs and ASCs myogenic and adipogenic differentiation, respectively. Natural leaf veins (NLV) were produced as edible mesh scaffolds to create 3D engineered dog muscle and fat tissues. After MSCs and ASCs adhered, proliferated and differentiated on the NLV scaffolds, and muscle and fat slices were produced with cultured dog muscle fibers and adipocytes, respectively. These findings demonstrate the potential of plant-derived NLV scaffolds in the production of cultured dog meat.
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Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS typically present with thymomas, reduced or absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity. We report the case of a 67-year-old woman diagnosed with GS following the development of a progressive, severe, refractory pulmonary infection and diffuse panbronchiolitis (DPB). She also had diabetes, characterized by anti-glutamic acid decarboxylase antibody positivity, leading to a diagnosis of latent autoimmune diabetes in adults (LADA). A thorough review of existing literature revealed that GS is often confirmed after multiple episodes of opportunistic infections or autoimmune diseases post-thymoma surgery. Due to their immunodeficiency, GS patients frequently suffer from recurrent infections over extended periods, and some succumb to severe infections. Regular immunoglobulin infusions may be effective in treating GS.
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Altrenogest (ALT), a synthetic progestogen, serves a critical role in estrus synchronization among animals like gilts and mares. However, its practical application in animal husbandry is hampered due to its poor solubility and limited oral bioavailability. To address this challenge, a solvent evaporation method was employed to create an inclusion complex of ALT with hydroxypropyl-ß-cyclodextrin (ALT/HP-ß-CD). The formation of this inclusion complex was confirmed by scanning electron microscopy, power X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and docking calculations. In addition, we further conducted pharmacokinetic investigation involving gilts, comparing ALT/HP-ß-CD inclusion complex to an ALT oral solution. The physicochemical characterization results unveiled a transformation of ALT's crystal morphology into an amorphous state, with ALT effectively entering the cavity of HP-ß-CD. Compared with ALT, the solubility of ALT/HP-ß-CD inclusion complex increased by 1026.51-fold, and its dissolution rate demonstrated significant improvement. Pharmacokinetic assessments further revealed that the oral bioavailability of ALT/HP-ß-CD inclusion complex surpassed that of the ALT oral solution, with a relative bioavailability of 114.08 %. In conclusion, complexation with HP-ß-CD represents a highly effective approach to improve both the solubility and oral bioavailability of ALT.
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2-Hidroxipropil-beta-Ciclodextrina , Acetato de Trembolona/análogos & derivados , Animais , Feminino , Cavalos , Suínos , 2-Hidroxipropil-beta-Ciclodextrina/química , Solubilidade , Disponibilidade Biológica , Espectroscopia de Infravermelho com Transformada de Fourier , Varredura Diferencial de Calorimetria , Difração de Raios XRESUMO
Parthenogenetic embryonic stem cells (pESCs) have been generated in several mammalian species from parthenogenetic embryos that would otherwise die around mid-gestation. However, previous reports suggest that pESCs derived from in vivo ovulated (IVO) mature oocytes show limited pluripotency, as evidenced by low chimera production, high tissue preference and especially deficiency in germline competence, a critical test for genetic integrity and pluripotency of ESCs. Here, we report efficient generation of germline-competent pESC lines (named as IVM pESCs) from parthenogenetic embryos developed from immature oocytes of adult mouse ovaries following in vitro maturation (IVM) and artificial activation. In contrast, pESCs derived from IVO oocytes show defective germline competence, consistent with previous reports. Further, IVM pESCs resemble more ESCs from fertilized embryos (fESCs) than do IVO pESCs on genome-wide DNA methylation and global protein profiles. In addition, IVM pESCs express higher levels of Blimp1, Lin28 and Stella, relative to fESCs, and in their embryoid bodies following differentiation. This may indicate differences in differentiation potentially to the germline. The mechanisms for acquisition of pluripotency and germline competency of IVM pESCs from immature oocytes remain to be determined.
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Antígenos de Diferenciação/biossíntese , Células-Tronco Embrionárias , Oócitos , Ovário , Partenogênese , Células-Tronco Pluripotentes , Animais , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Feminino , Camundongos , Oócitos/citologia , Oócitos/metabolismo , Ovário/citologia , Ovário/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismoRESUMO
In the global war for talent, traditional recruiting methods are failing to cope with the talent competition, so employers need the right recruiting tools to fill open positions. First, we explore how talent acquisition has transitioned from digital 1.0 to 3.0 (AI-enabled) as the digital tool redesigns business. The technology of artificial intelligence has facilitated the daily work of recruiters and improved recruitment efficiency. Further, the study analyzes that AI plays an important role in each stage of recruitment, such as recruitment promotion, job search, application, screening, assessment, and coordination. Next, after interviewing with AI recruitment stakeholders (recruiters, managers, and applicants), the study discusses their acceptance criteria for each recruitment stage; stakeholders also raised concerns about AI recruitment. Finally, we suggest that managers need to be concerned about the cost of AI recruitment, legal privacy, recruitment bias, and the possibility of replacing recruiters. Overall, the study answers the following questions: (1) How artificial intelligence is used in various stages of the recruitment process. (2) Stakeholder (applicants, recruiters, managers) perceptions of AI application in recruitment. (3) Suggestions for managers to adopt AI in recruitment. In general, the discussion will contribute to the study of the use of AI in recruitment, as well as providing recommendations for implementing AI recruitment in practice.
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A phosphorylcholine polymer (poly(MPC-co-BMA-co-TSMA), PMBT) was prepared by free radical polymerization and coated on the surface of the polymethylpentene hollow fiber membrane (PMP-HFM). ATR-FTIR and SEM analyses showed that the PMBT polymer containing phosphorylcholine groups was uniformly coated on the surface of the PMP-HFM. Thermogravimetric analysis showed that the PMBT had the best stability when the molar percentage of MPC monomer in the polymer was 35%. The swelling test and static contact angle test indicated that the coating had excellent hydrophilic properties. The fluorescence test results showed that the coating could resist dissolution with 90% (v/v%) ethanol solution and 1% (w/v%) SDS solution. The PMBT coating was shown to be able to decrease platelet adherence to the surface of the hollow fiber membrane, and lower the risk of blood clotting; it had good blood compatibility in tests of whole blood contact and platelet adhesion. These results show that the PMBT polymer may be coated on the surface of the PMP-HFM, and is helpful for improving the blood compatibility of membrane oxygenation.
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Glioblastoma is the most common glioma with high mortality and poor prognosis. Radiation resistance is one of the large challenges in the treatment of glioma. The study aimed to identify whether DNA polymerase ζ affects glioma cell radiosensitivity. The mRNA and protein levels of REV3L and REV7 were examined using quantitative real-time PCR and western blot. After REV3L and REV7 knockdown in a GBM cell line (A172), we assessed cell viability, colonies, apoptosis, and immune escape. The underlying mechanisms were evaluated using western blot and were confirmed using rescue experiments. The results showed that REV3L and REV7 levels were increased in glioma and related to poor survival. γ-ray treatment inhibited cell viability, survival fraction, and immune escape, and induced apoptosis of glioma cells from a GBM cell line, whereas knockdown of REV3L or REV7 enhanced these effects. Mechanically, silencing of REV3L or REV7 inactivated the PI3K/AKT/mTOR pathway. IGF-1 treatment abrogated the effects on cell viability, colonies, and apoptosis induced by REV3L or REV7 knocking down. Taken together, silencing of REV3L and REV7 inhibited radiation resistance via inactivating the PI3K/AKT/mTOR pathway, suggesting that targeting DNA polymerase ζ may be a new strategy to reduce the radiotherapy resistance of glioma.
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Glioma , Proteínas Proto-Oncogênicas c-akt , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Glioma/genética , Glioma/radioterapia , Serina-Treonina Quinases TOR/metabolismo , Tolerância a Radiação/genética , Linhagem Celular Tumoral , Apoptose/genética , Proliferação de Células , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/farmacologia , Proteínas de Ligação a DNARESUMO
[This corrects the article DOI: 10.3389/fmed.2022.996442.].
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PURPOSE: This article explores the workplace stresses faced by home working (HW) employees in the COVID-19 outbreak; what strategies human resource manager (HRM) may deal with the present circumstances. DESIGN/ METHODOLOGY/APPROACH: We refer to the views and perceptions of HRM and review the current state of stress faced by home-based workers and their responses through the lens of HRM. FINDINGS: (1) The types as eustress, acute stress, and chronic stress and the stressors as work, family, and psychological were analyzed. (2) HW brought more adverse effects caused by work-related stress than benefits. (3) HRM can provide stress mitigation from job support, work-family balance, and psychological relief. ORIGINALITY/VALUE: By focusing on those employees who are most vulnerable to pandemic fatigue and work-related stress, HRM can build better organizations for all employees. HRM practices may consider measures related to job itself, family, or psychology to reduce the stress of HW under the COVID-19 crisis.
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COVID-19 , Estresse Ocupacional , COVID-19/epidemiologia , Humanos , Estresse Ocupacional/epidemiologia , Pandemias , Estresse Psicológico/epidemiologia , Teletrabalho , Local de Trabalho/psicologiaRESUMO
Objective: The objective of the present study was to describe and analyze the clinical characteristics of nocardiosis. Materials and methods: We described and analyzed the clinical characteristics of nocardiosis cases from two centers over the past 5 years from the following aspects: age and sex, Nocardia species, sites of Nocardia infection, test specimens, detection methods, concurrent pathogens, symptoms, imaging features, co-conditions, drug susceptibility tests, antibiotic therapy/duration, outcomes, and follow-up. Results: The median age of the 19 cases was 64 years, with an interquartile range (IQR) of 56-68 years. Eight cases (42.1%) were immunocompromised [those who had been on corticosteroid use (62.5%), those who had used immunosuppressants (50.0%), or those who had suffered from chronic nephrosis (37.5%) or diabetes mellitus (DM) (25.0%)]. The plethora of comorbidities of these cases included diabetes (10.5%), chronic kidney disease (CDK) (15.8%), chronic lung disease (36.8%), and rheumatic diseases (10.5%). Cough and expectoration (73.7%) was the most common symptom of nocardiosis. The respiratory tract (89.5%) was the most common site of the clinical disease. Nearly half (9 cases, 47.3%) of these patients had concurrent infections. The most common Nocardia isolation site was the respiratory tract (73.7%). All patients were given antibiotic therapies, out of whom as many as 63.6% of patients were treated with two concurrent antimicrobial agents, 15.8% of patients were treated under monotherapy and 21.1% of patients were treated with three or more concurrent antimicrobial agents. Conclusions: An uncommon life-threatening infection, nocardiosis, affects those patients with structural lung disease or immunosuppression. Although nocardiosis is capable of progressing into a serious and metastatic disease, early recognition and prompt treatment usually result in successful outcomes benefitting the patient.
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In mammals, oxidative stress-induced apoptosis of granulosa cells is one of the major causes of follicular atresia, affecting ovarian physiological function. Protegrin-1 (PG-1) is an antimicrobial peptide with effective antimicrobial activity, immunomodulatory function, and porcine growth-promoting effects. PG-1 has been detected in porcine ovaries follicles. This study aimed to investigate the effect of PG-1 on oxidative stress-induced apoptosis of porcine ovarian granulosa cells and the underlying molecular mechanism. Granulosa cells were obtained from porcine follicles and treated with H2O2 to establish the oxidative stress model, and then treated with or without PG-1 (10 µg/mL). PG-1 significantly suppressed H2O2-induced apoptosis in granulosa cells after 24 h of treatment. Furthermore, these results revealed that PG-1 increased the mRNA and protein expression of anti-apoptotic B cell lymphoma/leukemia 2 (BCL2) and the BCL2/Bcl-2-associated X protein (BAX) ratio while decreasing the expression of pro-apoptotic BAX and active caspase-3. Using Western blot analysis, it was found that PG-1 decreased the phosphorylation of RNA-like endoplasmic reticulum kinase (PERK) and the α-subunit of eukaryotic initiation factor 2 (eIF2α) as well as the protein expression level of CCAAT enhancer-binding protein homologous protein (CHOP), all of which were increased by H2O2. Moreover, inhibitors against PERK and phospho-eIF2É both suppressed the H2O2-induced granulosa cells apoptosis and enhanced the anti-apoptosis effect of PG-1. Taken together, our findings demonstrated that PG-1 inhibited porcine ovarian granulosa cell apoptosis from oxidative stress via the PERK/eIF2α/CHOP signaling pathway in vitro, which suggests the novel regulatory function of the antimicrobial peptide in the ovary.
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Fator de Iniciação 2 em Eucariotos , Ovário , Animais , Peptídeos Catiônicos Antimicrobianos , Peptídeos Antimicrobianos , Apoptose , Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Fator de Iniciação 2 em Eucariotos/metabolismo , Feminino , Atresia Folicular , Células da Granulosa/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Ovário/metabolismo , Estresse Oxidativo , Fosforilação , RNA/metabolismo , Transdução de Sinais , Suínos , eIF-2 Quinase/metabolismoRESUMO
Aim: The aim of this study is to evaluate the association between serum sodium concentrations at hospital admission and all-cause mortality within 365 days post-discharge in patients with atrial fibrillation (AF) without heart failure (HF). Methods: The prospective cohort study enrolled 1,446 patients with AF without HF between November 2018 and October 2020. A follow-up was performed 30, 90, 180, and 365 days after enrollment through outpatient visits or telephone interviews. All-cause mortality was estimated in three groups according to serum sodium concentrations: hyponatremia (< 135 mmol/L), normonatremia (135-145 mmol/L), and hypernatremia (> 145 mmol/L). We estimated the risk of all-cause mortalities using univariable and multivariable Cox proportional hazards models with normonatremia as the reference. Results: The all-cause mortalities of hyponatremia, normonatremia, and hypernatremia were 20.6, 9.4, and 33.3% within 365 days post-discharge, respectively. In the univariable analysis, hyponatremia (HR: 2.19, CI 1.5-3.2) and hypernatremia (HR: 4.03, CI 2.32-7.02) increased the risk of all-cause mortality. The HRs for hyponatremia and hypernatremia were 1.55 (CI 1.05-2.28) and 2.55 (CI 1.45-4.46) after adjustment for age, diabetes mellitus, loop diuretics, antisterone, antiplatelet drugs, and anticoagulants in the patients with AF without HF. The association between serum sodium concentrations and the HRs of all-cause mortality was U-shaped. Conclusion: Dysnatremia at hospital admission was an independent factor for all-cause mortality in patients with AF without HF within 365 days post-discharge.