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1.
Methods Mol Biol ; 2782: 39-63, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38622391

RESUMO

T cells are a heterogeneous group of cells that can be classified into different subtypes according to different classification methods. The body's immune system has a highly complex and effective regulatory network that allows for the relative stability of immune system function. Maintaining proper T cell homeostasis is essential for promoting protective immunity and limiting autoimmunity and tumor formation. Among the T cell family members, more and more T cell subsets have gradually been characterized. In this chapter, we summarize the functions of some key T cell subsets and their impact on immune homeostasis.


Assuntos
Neoplasias , Linfócitos T Reguladores , Humanos , Subpopulações de Linfócitos T , Autoimunidade , Homeostase
2.
Plant Mol Biol ; 114(3): 47, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632206

RESUMO

Natural Antisense Transcripts (NATs) are a kind of complex regulatory RNAs that play crucial roles in gene expression and regulation. However, the NATs in Cannabis Sativa L., a widely economic and medicinal plant rich in cannabinoids remain unknown. In this study, we comprehensively predicted C. sativa NATs genome-wide using strand-specific RNA sequencing (ssRNA-Seq) data, and validated the expression profiles by strand-specific quantitative reverse transcription PCR (ssRT-qPCR). Consequently, a total of 307 NATs were predicted in C. sativa, including 104 cis- and 203 trans- NATs. Functional enrichment analysis demonstrated the potential involvement of the C. sativa NATs in DNA polymerase activity, RNA-DNA hybrid ribonuclease activity, and nucleic acid binding. Finally, 18 cis- and 376 trans- NAT-ST pairs were predicted to produce 621 cis- and 5,679 trans- small interfering RNA (nat-siRNAs), respectively. These nat-siRNAs were potentially involved in the biosynthesis of cannabinoids and cellulose. All these results will shed light on the regulation of NATs and nat-siRNAs in C. sativa.

3.
Environ Geochem Health ; 46(5): 149, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578493

RESUMO

There is limited evidence linking exposure to heavy metals, especially mixed metals, to stress urinary incontinence (SUI). This study aimed to explore the relationship between multiple metals exposure and SUI in women. The data were derived from the National Health and Nutrition Examination Survey (NHANES), 2007-2020. In the study, a total of 13 metals were analyzed in blood and urine. In addition, 5155 adult women were included, of whom 2123 (41.2%) suffered from SUI. The logistic regression model and restricted cubic spline (RCS) were conducted to assess the association of single metal exposure with SUI risk. The Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) were used to estimate the combined effect of multiple metals exposure on SUI. First, we observed that blood Pb, Hg and urinary Pb, Cd were positively related to SUI risk, whereas urinary W was inversely related by multivariate logistic regression (all p-FDR < 0.05). Additionally, a significant non-linear relationship between blood Hg and SUI risk was observed by RCS analysis. In the co-exposure models, WQS model showed that exposure to metal mixtures in blood [OR (95%CI) = 1.18 (1.06, 1.31)] and urine [OR (95%CI) = 1.18 (1.03, 1.34)] was positively associated with SUI risk, which was consistent with the results of BKMR model. A potential interaction was identified between Hg and Cd in urine. Hg and Cd were the main contributors to the combined effects. In summary, our study indicates that exposure to heavy metal mixtures may increase SUI risk in women.


Assuntos
Mercúrio , Metais Pesados , Incontinência Urinária por Estresse , Adulto , Feminino , Humanos , Inquéritos Nutricionais , Teorema de Bayes , Cádmio/toxicidade , Chumbo , Incontinência Urinária por Estresse/induzido quimicamente , Incontinência Urinária por Estresse/epidemiologia , Metais Pesados/toxicidade
4.
PeerJ ; 12: e17176, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560479

RESUMO

The effects of nitrogen application or earthworms on soil respiration in the Huang-Huai-Hai Plain of China have received increasing attention. However, the response of soil carbon dioxide (CO2) emission to nitrogen application and earthworm addition is still unclear. A field experiment with nitrogen application frequency and earthworm addition was conducted in the Huang-Huai-Hai Plain. Results showed nitrogen application frequency had a significant effect on soil respiration, but neither earthworms nor their interaction with nitrogen application frequency were significant. Low-frequency nitrogen application (NL) significantly increased soil respiration by 25%, while high-frequency nitrogen application (NH), earthworm addition (E), earthworm and high-frequency nitrogen application (E*NH), and earthworm and low-frequency nitrogen application (E*NL) also increased soil respiration by 21%, 21%, 12%, and 11%, respectively. The main reason for the rise in soil respiration was alterations in the bacterial richness and keystone taxa (Myxococcales). The NH resulted in higher soil nitrogen levels compared to NL, but NL had the highest bacterial richness. The abundance of Corynebacteriales and Gammaproteobacteria were positively connected with the CO2 emissions, while Myxococcales, Thermoleophilia, and Verrucomicrobia were negatively correlated. Our findings indicate the ecological importance of bacterial communities in regulating the carbon cycle in the Huang-Huai-Hai Plain.


Assuntos
Myxococcales , Oligoquetos , Animais , Dióxido de Carbono , Soja , Nitrogênio/farmacologia , Solo , Produtos Agrícolas
5.
Plant Physiol Biochem ; 210: 108570, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38560957

RESUMO

The WUSCHEL-related homeobox (WOX) gene family is vital for plant development and stress response. In this study, we conducted a comprehensive analysis of WOX genes in Cunninghamia lanceolata (C. lanceolata) and subsequently explored the potential roles of two ClWOX genes within the WUS clade. In total, six ClWOX genes were identified through a full-length transcriptome analysis. These genes, exhibiting conserved structural and functional motifs, were assigned to the ancient clade and Modern/WUS clade, respectively, through a phylogenetic analysis. Our expression analysis indicated that these ClWOX genes were highly expressed in the middle and late developmental stages of zygotic embryos in C. lanceolata. Moreover, only ClWOX5 and ClWOX6 within the Modern/WUS clade exhibited transcriptional activity, and their expressions were also induced in response to auxin and wounding. Overexpression of ClWOX5 and ClWOX6 in Arabidopsis caused a partially sterile phenotype, resulting in a very low seed setting rate. Transcriptomic analysis revealed that expressions of many embryo-defective (EMB) genes, phytohormone-related genes, and transcription factors (TFs) were dramatically altered in ClWOX5 and ClWOX6 transgenic plants, which suggested that ClWOX5 and ClWOX6 may play specific important roles in embryo development via complex gene networks. In addition, overexpression of ClWOX5 and ClWOX6 in leaf segments promoted shoot regeneration in tobacco, indicating that ClWOX5 and ClWOX6 can promote plant regeneration and could be used to improve genetic transformation. In conclusion, these results help to elucidate the function of the WOX gene and provide a valuable basis for future studies of the developmental regulation and applications of WOX genes in C. lanceolata.

6.
Stem Cell Res ; 77: 103390, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38507880

RESUMO

Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinopathy resulting in irreversible loss of vision. Mutations in RAX2 gene has been related to RP with mechanisms unclear. Here, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a RP patient carrying c.77C > T mutation in RAX2 gene. This cell line was induced by integration-free episomal vectors and validated for pluripotency and differentiation capacity, which may serve as a model to study the role of RAX2 in RP pathogenesis.

7.
Brain Stimul ; 17(2): 382-391, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38499287

RESUMO

BACKGROUND: Vagus nerve stimulation (VNS) at low frequencies (≤30 Hz) has been an established treatment for drug-resistant epilepsy (DRE) for over 25 years. OBJECTIVE: To examine the initial safety and efficacy performance of an investigational, high-frequency (≥250 Hz) VNS paradigm herein called "Microburst VNS" (µVNS). µVNS consists of short, high-frequency bursts of electrical pulses believed to preferentially modulate certain brain regions. METHODS: Thirty-three (33) participants were enrolled into an exploratory feasibility study, 21 with focal-onset seizures and 12 with generalized-onset seizures. Participants were titrated to a personalized target dose of µVNS using an investigational fMRI protocol. Participants were then followed for up to 12 months, with visits every 3 months, and monitored for side-effects at all time points. This study was registered as NCT03446664 on February 27th, 2018. RESULTS: The device was well-tolerated. Reported adverse events were consistent with typical low frequency VNS outcomes and tended to diminish in severity over time, including dysphonia, cough, dyspnea, and implant site pain. After 12 months of µVNS, the mean seizure frequency reduction for all seizures was 61.3% (median reduction: 70.4%; 90% CI of median: 48.9%-83.3%). The 12-month responder rate (≥50% reduction) was 63.3% (90% CI: 46.7%-77.9%) and the super-responder rate (≥80% reduction) was 40% (90% CI: 25.0%-56.6%). Participants with focal-onset seizures appeared to benefit similarly to participants with generalized-onset seizures (mean reduction in seizures at 12 months: 62.6% focal [n = 19], versus 59.0% generalized [n = 11]). CONCLUSION: Overall, µVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.

8.
Crit Rev Oncol Hematol ; 196: 104323, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462148

RESUMO

BACKGROUND: Smoking history is a heterogeneous situation for different populations, and numerous studies suggest that smoking cessation is conducive to reduce the mortality of lung cancer. However, no quantitative meta-analysis regarding smoking cessation duration based on different populations has demonstrated it clearly. METHODS: We systematically searched four electronic databases (PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Scoups) till February 2023. Eligible studies reported the association between lung cancer survival and duration of smoking cessation. Additionally, we stratified the study population according to whether they had lung cancer at the time they quit smoking. Studies were pooled with the random-effects model. RESULTS: Out of the 11,361 potential studies initially identified, we included 24 studies involving 969,560 individuals in our analysis. Lung cancer mortality varied across two groups: general quitters and peri-diagnosis quitters. For general quitters, those who had quit smoking for less than 10 years exhibited an RR of 0.64 (95% CI [0.55-0.76]), while those who quit for 10-20 years had an RR of 0.33 (0.25-0.43), over 20 years had an RR of 0.16 (0.11-0.24), and never-smokers had an RR at 0.11 (0.07-0.15). Among peri-diagnosis quitters, the 1-year Overall Survival (OS) showed an RR of 0.80 (0.67-0.96), the 2-year OS had an RR of 0.89 (0.80-0.98), the 3-year OS had an RR of 0.93 (0.84-1.03), and the 5-year OS had an RR of 0.85 (0.76-0.96). CONCLUSIONS: Earlier and longer smoking cessation is associated with reduced lung cancer mortality, no matter in which cessation stage for two different populations.


Assuntos
Neoplasias Pulmonares , Abandono do Hábito de Fumar , Humanos , Neoplasias Pulmonares/etiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Fumar Tabaco
9.
J Clin Ultrasound ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538081

RESUMO

PURPOSE: To assess the predictive value of an ultrasound-based radiomics-clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients. METHODS: This retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram. RESULTS: A total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound-based radiomics-clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort. CONCLUSIONS: Ultrasound-based radiomics-clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients.

10.
JMIR Public Health Surveill ; 10: e47453, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315527

RESUMO

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.


Assuntos
Asma , COVID-19 , Doença das Coronárias , Diabetes Mellitus , Refluxo Gastroesofágico , Feminino , Humanos , Lactente , Masculino , SARS-CoV-2 , Estudos Transversais , Vacinas contra COVID-19 , COVID-19/complicações , COVID-19/epidemiologia , Tosse/epidemiologia , Fatores de Risco , 60521 , China/epidemiologia , Asma/complicações , Asma/epidemiologia
11.
J Thorac Dis ; 16(1): 379-390, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38410578

RESUMO

Background: Reference equations for forced expiratory flow at 50% and 75% of forced vital capacity (FVC) (FEF50 and FEF75) in the Chinese population are lacking. It is of great importance to establish equations covering most age groups and to study their applicability in clinical practice. Methods: Using the lambda-mu-sigma (LMS) method, reference equations for FEF50 and FEF75 were constructed based on pulmonary function data from healthy subjects collected from January 2007 to June 2010 at 24 centers throughout China. Differences between the established equations and extraneous equations were compared using standardized means (Z values) and percentage errors (PE). The proportion of small airway dysfunction (SAD) defined by the present equations was calculated. The Fisher precision probability test and the Mann-Whitney test were used to analyze the magnitude of changes in small and large airway indices after bronchodilator inhalation in patients with suspected asthma and chronic obstructive pulmonary disease (COPD). Results: Reference equations for FEF50 and FEF75 were established based on data from 7,115 healthy individuals (aged 4 to 80 years, 50.9% female, height between 95 and 190 cm). The present equations (all Z values were -0.0 and PE ranged from 2.0% to 4.2%) showed advantages over the European Community for Steel and Coal (ECSC) equations in 1993 (with Z values ranging from -0.7 to -0.2 and PE ranged from -23.4% to -4.5%). A total of 4,356 patients with suspected asthma (51.1% female; a mean age of 45.4 years) and 6,558 patients with suspected COPD (10.1% female; a mean age of 65.0 years) were included. The present equations defined 95.7% and 99.9% of SAD in these patients. After bronchodilator inhalation, greater mean improvement rates in small airway indices were observed both in patients with suspected asthma [mean ± standard deviation (SD) =48%±47%] and in patients with suspected COPD (mean ± SD =20%±30%) (P<0.05). Conclusions: The reference equations for FEF50 and FEF75 established in this study should be considered for use in China. Further studies are needed to validate their value in the diagnosis of some chronic respiratory diseases.

12.
Am J Hematol ; 99(5): 1005-1007, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38410879

RESUMO

IRF2BP1 breaked in the middle of exon 1 at the c.322 position and fused with RARA intron 2 which is located at 3717 bp upstream of its exon 3. The fusion produced a new intron by forming a paired splicing donor GT at 9 bp downstream of RARA breakpoint and acceptor AG at the 5' end of RARA exon 3. The IRF2BP1::RARA fusion gene leads a fusion transcript involving IRF2BP1 exon 1 and RARA exon 3, linked by a 9-bp fragment derived from RARA intron 2. The patient with IRF2BP1::RARA has same clinical features of APL.


Assuntos
Leucemia Promielocítica Aguda , Humanos , Cromossomos Humanos Par 17 , Éxons/genética , Leucemia Promielocítica Aguda/genética , Proteínas de Fusão Oncogênica/genética , Receptores do Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/genética , Translocação Genética
13.
Eur J Obstet Gynecol Reprod Biol ; 295: 219-227, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387304

RESUMO

INTRODUCTION: Premature menopause is a major complication of primary ovarian insufficiency (POI), and this loss is closely relates to bone mineral density (BMD). Previous research has indicated potential associations between BMD and POI. This study set out to provide the first systematic literature review and meta-analysison account of BMD content among women with POI. METHODS: Studies including women with POI and controls were eligible from PubMed, Embase, Cochrane Library and Web of Science databases (from their inception to April 2022). Two reviewers independently evaluated study eligibility. The meta-analysis was performed using the DerSimonian and Laird random effects model. RESULTS: Ten studies featuring 578 women with POI and 480 controls were selected. BMD content of femur neck (SMD:-0.76; 95 % CI: -1.20 to -0.31; P = 0.0008), the BMD content of nondominating forearm (SMD:-0.67; 95 % CI: -1.15 to -0.18; P = 0.007) were significantly decreased in women with POI. However, no differences were seen in other regions (lumbar spine, total hip, hipneck). DISCUSSION: The results of this study indicate that BMD content altered in patients with primary ovarian insufficiency. An implication of this is the possibility that hormone replacement therapy to minimize the prevalence of fracture morbidity and mortality associated with osteopenia in patients with POI.


Assuntos
Fraturas Ósseas , Osteoporose Pós-Menopausa , Insuficiência Ovariana Primária , Humanos , Feminino , Densidade Óssea , Insuficiência Ovariana Primária/complicações , Terapia de Reposição Hormonal
14.
Head Neck ; 46(5): 1189-1200, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38366691

RESUMO

BACKGROUND: The effect of radiotherapy waiting time after last induction chemotherapy (IC-RT) on prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC) needs further discussion. METHODS: Three hundred and six patients with LANPC diagnosed pathologically by induction chemotherapy (IC) and radiotherapy (RT) from 2013 to 2018 were selected for this study. RESULTS: The IC-RT was a risk factor for the post-treatment progression of LANPC (OR = 1.017 95%CI: 1.003-1.031), For patients with LANPC, the IC-RT > 40 days significantly reduced 5-year PFS (70% vs. 55%; p = 0.0012), 5-year OS (84% vs. 73%; p = 0.028), 5-year DMFS (80% vs. 66%; p = 0.003), 5-year LRFS (77% vs. 67%; p = 0.012). Indicating that patients with stage IVa who IC-RT > 40 days were found to be a significant predictor of aggravated PFS (HR = 2.69; 95%CI: 1.57-4.6), OS (HR = 2.55; 95%CI: 1.29-5.03), DMFS (HR = 3.07; 95%CI: 1.64-5.76) and LRFS (HR = 2.26; 95%CI: 1.21-4.21). CONCLUSION: The prognosis of patients will be adversely affected if the IC-RT exceeds 40 days, especially for stage IVa patients.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Quimioterapia de Indução , Listas de Espera , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Quimiorradioterapia/efeitos adversos , Carcinoma/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
15.
J Addict Med ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408186

RESUMO

OBJECTIVES: To provide valuable insights for targeted cancer screening among high-risk patients, we analyzed the global and regional burden of neoplasms resulting from alcohol consumption between 1990 and 2019. METHODS: The information used in this study was collected from the Global Burden of Disease 2019 dataset. Initially, the database was used to extract details of mortality rates, disability-adjusted life years (DALYs), and the number of individuals affected by alcohol-related neoplasms (ARNs). Subsequently, the data were compared by cancer type, sex, age, region, and sociodemographic index. Furthermore, the study involved the calculation and comparison of estimated annual percentage changes in age-standardized DALYs rates (ASDRs) and mortality rates. RESULTS: The impact of alcohol on the burden of cancer varied by type of cancer, sex, age, and geographical location. Notably, males exhibited significantly higher ASDRs compared with females. Specifically, in 2019, alcohol emerged as the primary contributor to the number of DALYs associated with esophageal cancer, followed by liver cancer and colorectal cancer in men. Patients aged 50+ years exhibited a heightened rate of DALYs associated with ARNs. From 1990 to 2019, ASDRs among individuals with ARNs did not exhibit a decline in low-middle and low sociodemographic index regions. CONCLUSIONS: Alcohol consumption represents a significant risk factor for the burden of cancer, particularly within the realm of digestive system malignancies. Consequently, targeted cancer screening efforts should be directed toward the population that engages in alcohol drinking, with a particular focus on men aged 50 years and older, residing in economically disadvantaged areas.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38189805

RESUMO

The laboratory practice "Primary culture and directional differentiation of rat bone marrow mesenchymal stem cells (BMSCs)" is part of a required course for sophomore medical students at Tongji university, which has been conducted since 2012. Blended learning has been widely applied in medical courses. Based on a student-centered teaching philosophy, we reconstructed a comprehensive stem cell laboratory module with blended learning in 2021, aiming to facilitate students in enhancing their understanding of the multi-lineage differentiation potential of stem cells and improve their experimental skills, self-directed learning ability, and innovative thinking. First, we constructed in-depth online study resources, including videos demonstrating laboratory procedures, a PowerPoint slide deck, and published literature on student self-learning before class. In class, students performed a primary culture of BMSCs, freely chose among adipogenic, osteogenic, or chondrogenic differentiation, and used cytochemical or immunofluorescence staining for identification. After class, the extracurricular part involved performing quantitative polymerase chain reaction to examine the expression of multi-lineage differentiation marker genes, which was designed as an elective. After 2 years of practice, positive feedback was obtained from both students and faculty members who achieved, the learning goal as expected. The reconstructed stem cell laboratory module provides comprehensive practice opportunities for students. Students have a better understanding of BMSC at the molecular, cellular, and functional levels and have improved their experimental skills, which forms a basis for scientific research for medical students. Introducing blended learning into other medical laboratory practices thus seems valuable.

17.
EClinicalMedicine ; 67: 102359, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38188690

RESUMO

Background: Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Findings: Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95-428.68 h]) than that of Placebo (271.33 h [IQR 219.00-529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07-1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. Interpretation: Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. Funding: This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.

18.
Bioorg Chem ; 144: 107114, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224637

RESUMO

Acute myelogenous leukemia (AML) is the most common form of acute leukemia in adults. PDE1 (Phosphodiesterase 1) is a subfamily of the PDE super-enzyme families that can hydrolyze the second messengers cAMP and cGMP simultaneously. Previous research has shown that suppressing the gene expression of PDE1 can trigger apoptosis of human leukemia cells. However, no selective PDE1 inhibitors have been used to explore whether PDE1 is a potential target for treating AML. Based on our previously reported PDE9/PDE1 dual inhibitor 11a, a series of novel pyrazolopyrimidinone derivatives were designed in this study. The lead compound 6c showed an IC50 of 7.5 nM against PDE1, excellent selectivity over other PDEs and good metabolic stability. In AML cells, compound 6c significantly inhibited the proliferation and induced apoptosis. Further experiments indicated that the apoptosis induced by 6c was through a mitochondria-dependent pathway by decreasing the ratio of Bcl-2/Bax and increasing the cleavage of caspase-3, 7, 9, and PARP. All these results suggested that PDE1 might be a novel target for AML.


Assuntos
Leucemia Mieloide Aguda , Inibidores de Fosfodiesterase , Pirazóis , Pirimidinonas , Adulto , Humanos , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , GMP Cíclico/metabolismo
19.
Biochim Biophys Acta Mol Cell Res ; 1871(3): 119657, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38176443

RESUMO

Choroidal neovascularization (CNV) is a devastating pathology of numerous ocular diseases, such as wet age-related macular degeneration (wAMD), which causes irreversible vision loss. Although anti-vascular endothelial growth factor (VEGF) therapy has been widely used, poor response or no response still exists in some cases, suggesting that there are other components involved in the angiogenic process. Therefore, the underlying mechanism needs to be clarified and new target of anti-angiogenic therapy is urgently needed. It has been demonstrated that damaged retinal pigment epithelium (RPE) cells can activate inflammasome, driving a degenerative tissue environment and an enhanced pro-angiogenic response, which implies that RPE dysfunction may be a hallmark of the pathogenesis. Previously, we have shown that DNA damage can induce RPE dysfunction, triggering senescence-associated secretory phenotype (SASP) and local inflammation. In this study, we identify that chrysin can reduce DNA damage, especially telomere erosion in vitro, thus compromise the dysfunction of RPE and the decreased expression of SASP factor. Importantly, we find that DNA damage of RPE cells is remarkable in laser-induced CNV lesion, resulting in inflammatory response, which can be ameliorated by chrysin, mainly through IL-17 signaling pathway and its downstream signal transducer and activator of transcription 3 (STAT3) activities. In summary, our results indicate the interplay between DNA damage, perturbed RPE homeostasis, inflammatory response and angiogenesis in laser-induced CNV, and more importantly, chrysin may be an effective therapeutic supplement for CNV.


Assuntos
Neovascularização de Coroide , Flavonoides , Epitélio Pigmentado da Retina , Humanos , Fator A de Crescimento do Endotélio Vascular/genética , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/genética , Dano ao DNA , Lasers
20.
Anim Biosci ; 37(1): 95-104, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37905322

RESUMO

OBJECTIVE: In the present study, we aimed to investigate the effects of enzymolysis fermentation of Chinese herbal medicines (CHMs) on egg production performance, egg quality, lipid metabolism, serum reproductive hormone levels, and the mRNA expression of the ovarian hormone receptor of laying hens in the late-laying stage. METHODS: A total of 360 Hy-Line Brown laying hens (age, 390 days) were randomly categorized into four groups. Hens in the control (C) group were fed a basic diet devoid of CHMs, the crushed CHM (CT), fermented CHM (FC), and enzymatically fermented CHM (EFT) groups received diets containing 2% crushed CHM, 2% fermented CHM, and 2% enzymatically fermented CHM, respectively. RESULTS: Compared with crushed CHM, the acid detergent fiber, total flavonoids, and total saponins contents of fermented CHM showed improvement (p<0.05); furthermore, the neutral and acid detergent fiber, total flavonoids, and total saponins contents of enzymatically fermented CHM improved (p<0.05). At 5 to 8 weeks, hens in the FC and EFT groups showed increased laying rates, haugh unit, albumin height, yolk color, shell thickness, and shell strength compared with those in the C group (p<0.05). Compared with the FC group, the laying rate, albumin height, and Shell thickness in the EFT group was increased (p<0.05). Compared with the C, CT, and FC groups, the EFT group showed reduced serum total cholesterol and increased serum luteinizing hormone levels and mRNA expressions of follicle stimulating hormone receptor and luteinizing hormone receptor (p<0.05). CONCLUSION: These results indicated that the ETF group improved the laying rate and egg quality and regulated the lipid metabolism in aged hens. The mechanism underlying this effect was likely related to cell wall degradation of CHM and increased serum levels of luteinizing hormone and mRNA expression of the ovarian hormone receptor.

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