Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 840
Filter
1.
Int Immunopharmacol ; 140: 112790, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39088920

ABSTRACT

Tertiary lymphoid structures (TLSs) are ectopic lymphocyte aggregates formed in non-lymphoid tissues, including cancers, and are loci for the generation of in situ anti-tumor immune responses, which play a crucial role in cancer control. The state of TLS presence in cancer and its composition can significantly impact the treatment response and prognosis of patients. TLSs have the potential to serve as predictive and prognostic biomarkers for cancer. However, the mechanisms underlying TLS formation in cancer and how the essential components of TLSs affect cancer are not fully understood. In this review, we summarized TLS formation in cancer, the value of the TLS in different states of existence, and its key constituents for cancer prediction and prognosis. Finally, we discussed the impact of cancer treatment on TLSs.

2.
Trends Cancer ; 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39097431

ABSTRACT

The evolution of antitumor therapies has significantly improved cancer prognosis but has concurrently resulted in cardiovascular toxicities. Understanding the biological mechanisms behind these toxicities is crucial for effective management. Immunotherapy-related cardiovascular toxicities are primarily mediated by immune cells and secreted cytokines. Chemotherapy may cause cardiovascular damage through autophagy disruption and mitochondrial dysfunction. Targeted therapies can induce toxicity through endothelin-1 (ET-1) production and cardiac signaling disruption. Radiotherapy may lead to cardiomyopathy and myocardial fibrosis by affecting endothelial cells, triggering inflammatory responses and accelerating atherosclerosis. This review provides insights into these mechanisms and strategies, aiming to enhance the clinical prevention and treatment of cardiovascular toxicities.

3.
Infect Drug Resist ; 17: 3273-3287, 2024.
Article in English | MEDLINE | ID: mdl-39104458

ABSTRACT

Purpose: This study aimed to investigate the microbiological characteristics of clinically isolated Staphylococcus aureus with different hemolytic phenotypes in China. Materials and Methods: Using the three-point inoculation method, the hemolytic phenotypes of 1295 clinically isolated S. aureus strains were detected and categorized. Antimicrobial susceptibility testing of all strains was performed using a VITEK 2 Compact System. After sample size matching, plasma coagulase activity, catalase activity, mRNA expression of hemolysin genes (hla, hlb, hlc, and hld), biofilm formation, growth kinetics, inflammatory response of macrophages and cytotoxicity of S. aureus with different hemolytic phenotypes using the rabbit plasma kit, the catalase test on slides, qRT-PCR, crystal violet staining, the microcultivation assay, the ELISA kits, and the CCK-8 assay, respectively. Results: Seven categories of hemolytic phenotypes were identified. Accordingly, strains were categorized into seven different groups, including S. aureus with complete hemolytic phenotype (SCHP), S. aureus with weak hemolytic phenotype (SWHP), S. aureus with incomplete hemolytic phenotype 1 (SIHP-1), SIHP-2, SIHP-3, SIHP-4 and SIHP-5, the last three of which were reported for the first time. Except for the hemolytic phenotype, all seven groups differed in clinical isolation rates, antibiotic resistance profile, plasma coagulase activity, mRNA expression of hemolysin genes, biofilm formation, growth kinetics, inflammatory response of macrophages, and cytotoxicity. Conclusion: S. aureus with different hemolytic phenotypes have distinctive microbiological characteristics. Clinical microbiologists need to be vigilant about the hemolytic phenotypes when culturing S. aureus strains, and actively enhance communication with clinicians to optimize the treatment of infection.

4.
BMC Neurosci ; 25(1): 35, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095700

ABSTRACT

BACKGROUND: There are currently no effective prediction methods for evaluating the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD). AIMS: To investigate the risk factors for cognitive dysfunction in patients with CSVD and to construct a risk prediction model. METHODS: A retrospective study was conducted on 227 patients with CSVD. All patients were assessed by brain magnetic resonance imaging (MRI), and the Montreal Cognitive Assessment (MoCA) was used to assess cognitive status. In addition, the patient's medical records were also recorded. The clinical data were divided into a normal cognitive function group and a cognitive impairment group. A MoCA score < 26 (an additional 1 point for education < 12 years) is defined as cognitive dysfunction. RESULTS: A total of 227 patients (mean age 66.7 ± 6.99 years) with CSVD were included in this study, of whom 68.7% were male and 100 patients (44.1%) developed cognitive impairment. Age (OR = 1.070; 95% CI = 1.015 ~ 1.128, p < 0.05), hypertension (OR = 2.863; 95% CI = 1.438 ~ 5.699, p < 0.05), homocysteine(HCY) (OR = 1.065; 95% CI = 1.005 ~ 1.127, p < 0.05), lacunar infarct score(Lac_score) (OR = 2.732; 95% CI = 1.094 ~ 6.825, P < 0.05), and CSVD total burden (CSVD_score) (OR = 3.823; 95% CI = 1.496 ~ 9.768, P < 0.05) were found to be independent risk factors for cognitive decline in the present study. The above 5 variables were used to construct a nomogram, and the model was internally validated by using bootstrapping with a C-index of 0.839. The external model validation C-index was 0.867. CONCLUSIONS: The nomogram model based on brain MR images and clinical data helps in individualizing the probability of cognitive impairment progression in patients with CSVD.


Subject(s)
Cerebral Small Vessel Diseases , Cognitive Dysfunction , Magnetic Resonance Imaging , Humans , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/diagnostic imaging , Male , Female , Aged , Cognitive Dysfunction/etiology , Cognitive Dysfunction/diagnostic imaging , Retrospective Studies , Middle Aged , Risk Factors , Magnetic Resonance Imaging/methods , Mental Status and Dementia Tests , Brain/diagnostic imaging , Brain/pathology
5.
Article in English | MEDLINE | ID: mdl-38973223

ABSTRACT

INTRODUCTION: Treatment of oligohydramnios in the mid-trimester is challenging, because of the high incidence of adverse perinatal outcomes mainly due to bronchopulmonary dysplasia. Antenatal amnioinfusion has been proposed as a possible treatment for oligohydramnios with intact amnions, but there are few relevant studies. This study aimed to evaluate the effectiveness of transabdominal amnioinfusion in the management of oligohydramnios without fetal lethal malformations in the second and early third trimesters. MATERIAL AND METHODS: It is a historical cohort study. A total of 79 patients diagnosed with oligohydramnios at 18-32 weeks gestation were enrolled. In the amnioinfusion group (n = 39), patients received transabdominal amnioinfusion with the assistance of real-time ultrasound guidance. In the expectant group (n = 41), patients were treated with 3000 mL of intravenous isotonic fluids daily. The perioperative complications and perinatal outcomes were analyzed. RESULTS: Compared with the expectant group, the delivery latency was significantly prolonged, and the rate of cesarean delivery was significantly reduced in the amnioinfusion group (p < 0.05). Although the rate of intrauterine fetal death was significantly reduced, the incidence of spontaneous miscarriage, premature rupture of membranes (PROMs), and threatened preterm labor were significantly higher in the amnioinfusion group than in the expectant group (p < 0.05). There was no significant difference in terms of perinatal mortality (28.9% vs. 41.4%, p > 0.05). Multivariate logistic regression revealed that amnioinfusion (odds ratio [OR] 0.162, 95% confidence interval [CI] 0.04-0.61, p = 0.008) and gestational age at diagnosis (OR 0.185, 95% CI 0.04-0.73, p = 0.016) were independently associated with neonatal adverse outcomes. Further subgrouping showed that amnioinfusion significantly reduced the frequency of bronchopulmonary hypoplasia for patients ≤26 weeks (26.7% vs. 75.0%, p = 0.021). The rates of other neonatal complications were similar in both groups. CONCLUSIONS: Amnioinfusion has no significant effect on improving the perinatal mortality of oligohydramnios in the second and early third trimesters. It may lead to a relatively high rate of PROM and spontaneous abortion. However, amnioinfusion may significantly improve the latency period, the rate of cesarean delivery, and neonatal outcomes of oligohydramnios, especially for women ≤26 weeks with high risk of neonatal bronchopulmonary hypoplasia.

6.
Int J Sports Med ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39084326

ABSTRACT

This study investigates the biomechanical adaptations of the longitudinal arch (LA) in long-distance runners, focusing on changes in stiffness, angle, and moment during a 60-minute run. Twenty runners participated in this experiment, and were asked to run at a speed of 2.7 m·s-1 for 60 minutes. The kinematic and kinetic data collected at five-minute intervals during running were calculated, including the stiffness of LA in the loading phase (k load ) and the stiffness of LA in the unloading phase (k unload ), the maximum LA moment (M max ), the range of LA angle change (∆θ range ), and the maximum LA angle change (∆θ max ). Foot morphology was also scanned before and after running. Variations of kinematic and kinetic data were analyzed throughout the running activity, as well as variations of foot morphology pre- and post-run. Results showed that there was a significant decrease in k load (p<0.001), coupled with increases in ∆θ range (p=0.002) and ∆θ max (p<0.001), during the first 15 minutes of running, which was followed by a period of mechanical stability. No differences were found in k unload and M max throughout the running process and the foot morphology remained unchanged after running. These results highlight a critical adaptation phase that may be pivotal for improving running economy and performance.

7.
Discov Oncol ; 15(1): 274, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980474

ABSTRACT

BACKGROUND: The level of tumor abnormal protein (TAP) level has a significant impact on tumor growth, recurrence, and metastasis. Previous studies have highlighted the influence of the mutations in exons 19 and 21 of the epidermal growth factor receptor (EGFR), particularly the sensitivity displayed by tumor cells to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Our study is centered on exploring the clinical relevance of TAP and EGFR mutations in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: In this study, tissue samples were collected from a total of 176 patients diagnosed with non-small cell lung cancer (NSCLC). Real-time PCR technology was utilized to detect mutations within exons 19 and 21 of the epidermal growth factor receptor (EGFR) gene in these samples. This approach enables precise identification of EGFR mutations associated with NSCLC. Furthermore, the study investigated the impact of various tumor markers, including tumor abnormal protein (TAP) and carcinoembryonic antigen (CEA), on EGFR mutation status. Established assays were employed to evaluate TAP and CEA levels, aiming to ascertain their potential correlation with EGFR mutation in NSCLC patients. RESULTS: EGFR exhibited mutation rates of 23.86% and 12.50% in exons 19 and 21, respectively. EGFR mutations were more prevalent in younger women (< 60 years old) and in cases with pleural invasion, vessel invasion, CEA > 6.5 ng/mL, and TAP > 228 µm2 for both genders. Increased TAP levels independently predicted EGFR mutations (P = 0.001 for males; P = 0.000 for females). An area under the curve (AUC) of 0.833 indecated EGFR mutation prediction with sensitivity and specificity of 79.7% and 87.0%, respectively. For females, the sensitivity increased to 89.7% and specificity increased to 93.8%. CONCLUSIONS: TAP effectively predicts EGFR mutations in NSCLC patients with moderate accuracy, particularly benefiting diagnosis in females with high sensitivity and specificity. Integrating TAP assessment into EGFR mutation testing can significantly enhance diagnostic precision, especially in female NSCLC cases.

8.
J Pediatr Nurs ; 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39085008

ABSTRACT

PROBLEM: Virtual reality (VR) is used as a novel intervention technique to alleviate uncomfortable experiences such as anxiety and pain in children. Recently, VR distraction has gained prominence in pediatric medical procedures. However, no studies have yet conducted a further quantitative analysis of the intervention effects of virtual reality exposure (VRE). This systematic review aims to analyse the effect of VRE on anxiety and pain levels in paediatric patients undergoing medical procedures. ELIGIBILITY CRITERIA: Relevant studies were searched from four databases, including PubMed, Cochrane Library, Embase, and Web of Science. This systematic review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). RESULTS: The meta-analysis incorporated a total of 11 articles, encompassing 1,099 pediatric patients. The results showed that VRE relieved children's anxiety [SMD = -0.61, 95% CI (-0.93, -0.28), p < 0.001], but there was no significant difference in alleviating pain in children [SMD = -1.48, 95% CI (-3.40, 0.44), p = 0.131]. CONCLUSIONS: The results suggest that VRE is effective in reducing children's anxiety during medical procedures. However, 7 of the 11 original studies included in this review were from the same research project, which may increase the risk of reporting bias. Also, more high-quality studies are needed in the future to verify its effectiveness for pain levels. IMPLICATIONS: VRE can help children become familiar with the medical environment, overcome anxiety and fear, and learn about medical procedures in advance. This can enhance their cooperation during medical process, leading to a more positive medical experience.

10.
Foods ; 13(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38998563

ABSTRACT

Deoxynivalenol (DON) is a global contaminant found in crop residues, grains, feed, and animal and human food. Biodegradation is currently the best solution for addressing DON pollution. However, efficient detoxification bacteria or enzymes that can be applied in complex matrices are lacking. The aim of this study was to isolate a DON-detoxifying probiotic strain with a high degradation rate, a good safety profile, and a clear genetic background. One hundred and eight bacterial strains were isolated from 300 samples collected from a school farm and surrounding livestock farms. A new DON-degrading strain, Lactobacillus rhamnosus MY-1 (L. rhamnosus MY-1), with a degradation rate of 93.34% after 48 h and a comprehensive degradation method, was identified. Then, MY-1 at a concentration of 1 × 108 CFU/mL was administered to mice in a chronic intoxication experiment for 28 days. The experimental group showed significantly higher weight gain and exhibited good production performance compared to the control group. The length of the ileal villi in the experimental group was significantly longer than that in the control group. The expression of pro-inflammatory cytokines decreased, while the expression of anti-inflammatory factors increased in the experimental group. Whole-genome analysis revealed that most of the MY-1 genes were involved in carbohydrate metabolism and membrane transport, with a cluster of secondary metabolite genes encoding antimicrobial properties. In summary, this study successfully identified a Lactobacillus strain with good safety performance, high DON degradation efficiency, and a clear genetic background, providing a new approach for the treatment of DON contamination.

11.
BMJ Open ; 14(7): e084228, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013642

ABSTRACT

PURPOSE: Evidence about the associations of migraine features with cardiovascular risk profiles in Chinese population is lacking. The Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK) cohort was constructed to investigate longitudinal migraine features and their cardiovascular implications in Hong Kong Chinese women. PARTICIPANTS: We enrolled 4221 Hong Kong Chinese women aged 30 years or above from October 2019 to December 2020. Demographics, reproductive information, lifestyle factors, disease history, blood lipids and glucose, anthropometrics and body compositions were measured during baseline and follow-up. Migraine diagnosis followed the International Classification of Headache Disorders-3 criteria. Migraine features were longitudinally tracked using a migraine diary and summarised by a wide range of epidemiological metrics. Cardiovascular health was assessed using the Framingham risk score (FRS). FINDINGS TO DATE: From October 2021 to June 2023, 3455 women completed the first follow-up measurement. The retention rate was 81.9%. The average age at baseline was 54.40 years. The mean blood glucose, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were 6.44 mmol/L, 65.06 mg/dL and 102.40 mg/dL, respectively. The average FRS was 0.06. Participants had a 10.3% prevalence of migraine or probable migraine. After 1.27 years of follow-up, the median migraine attack frequency was 0.99 attacks/month, with an incidence rate of 2.55 attacks/person-month and a median duration of 7.70 hours/attack. Sleep problems (64.7%) and stress (54.0%) were the top triggers, while prevalent accompanying symptoms were nausea (67.4%), photophobia (39.9%), phonophobia (30.0%) and vomiting (26.2%). Migraine auras included blurred visions (59.6%), flashing lights (41.3%), blind spots (33.0%), pins and needles (6.4%) and halo (1.8%). FUTURE PLANS: The follow-up for the cohort will be implemented every 2 years. MECH-HK will provide unique longitudinal data on migraine features in Hong Kong women. The linkage between migraine features and cardiovascular disease risk progression will be identified by a long-term observation.


Subject(s)
Cardiovascular Diseases , Migraine Disorders , Humans , Female , Migraine Disorders/epidemiology , Hong Kong/epidemiology , Middle Aged , Cardiovascular Diseases/epidemiology , Adult , Cohort Studies , Prevalence , Longitudinal Studies , Risk Factors , Heart Disease Risk Factors , East Asian People
12.
Front Immunol ; 15: 1413067, 2024.
Article in English | MEDLINE | ID: mdl-39026670

ABSTRACT

Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.


Subject(s)
Neoplasms , Tertiary Lymphoid Structures , Tumor Microenvironment , Humans , Tertiary Lymphoid Structures/immunology , Tertiary Lymphoid Structures/pathology , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/pathology , Tumor Microenvironment/immunology , Animals , Immunotherapy/methods , B-Lymphocytes/immunology , T-Lymphocytes/immunology
13.
Front Plant Sci ; 15: 1368885, 2024.
Article in English | MEDLINE | ID: mdl-39006957

ABSTRACT

Introduction: Global illegal trade in timbers is a major cause of the loss of tree species diversity. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) has been developed to combat the illegal international timber trade. Its implementation relies on accurate wood identification techniques for field screening. However, meeting the demand for timber field screening at the species level using the traditional wood identification method depending on wood anatomy is complicated, time-consuming, and challenging for enforcement officials who did not major in wood science. Methods: This study constructed a CITES-28 macroscopic image dataset, including 9,437 original images of 279 xylarium wood specimens from 14 CITES-listed commonly traded tree species and 14 look-alike species. We evaluated a suitable wood image preprocessing method and developed a highly effective computer vision classification model, SE-ResNet, on the enhanced image dataset. The model incorporated attention mechanism modules [squeeze-and-excitation networks (SENet)] into a convolutional neural network (ResNet) to identify 28 wood species. Results: The results showed that the SE-ResNet model achieved a remarkable 99.65% accuracy. Additionally, image cropping and rotation were proven effective image preprocessing methods for data enhancement. This study also conducted real-world identification using images of new specimens from the timber market to test the model and achieved 82.3% accuracy. Conclusion: This study presents a convolutional neural network model coupled with the SENet module to discriminate CITES-listed species with their look-alikes and investigates a standard guideline for enhancing wood transverse image data, providing a practical computer vision method tool to protect endangered tree species and highlighting its substantial potential for CITES implementation.

14.
Genet Test Mol Biomarkers ; 28(7): 267-274, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39034913

ABSTRACT

Background: A high-altitude environment has inhibitory effects on obesity. Tibetans are not a high-risk population for obesity, but there are still obese individuals within that population. Obesity has become a worldwide health problem, and previous studies have found that obesity is closely associated with hereditary factors. Few studies have investigated obesity in Tibetans, and the association between gene polymorphisms and obesity in Tibetans remains unclear. Methods: Our study investigated the fat mass of 140 native Tibetan individuals (70 men and 70 women) from Lhasa and analyzed the associations between polymorphisms of melanocortin 4 receptor (MC4R), Src homology 2B adapter protein 1 (SH2B1), and neuronal growth regulator 1 (NEGR1) and obesity. Result: Among Tibetan individuals, there were differences in genotype and allele frequencies between those in the obesity group and those in the healthy group at MC4R (rs17782313) and SH2B1 (rs7359397). The polymorphisms of MC4R (rs17782313) were associated with fat mass and obesity in Tibetan men and women, and there was an association between SH2B1 (rs7359397) polymorphisms and fat mass and obesity in Tibetan men. However, polymorphisms of NEGR1 (rs3101336) were not associated with fat mass or obesity in Tibetan individuals. Conclusion: Among Tibetan individuals, polymorphisms of MC4R (rs17782313) and SH2B1 (rs7359397) were associated with obesity, but NEGR1 (rs3101336) polymorphisms were not associated with obesity.


Subject(s)
Adaptor Proteins, Signal Transducing , Gene Frequency , Genetic Predisposition to Disease , Obesity , Polymorphism, Single Nucleotide , Receptor, Melanocortin, Type 4 , Humans , Receptor, Melanocortin, Type 4/genetics , Male , Female , Obesity/genetics , Tibet , Adult , Polymorphism, Single Nucleotide/genetics , Adaptor Proteins, Signal Transducing/genetics , Middle Aged , Gene Frequency/genetics , Asian People/genetics , Genotype , Alleles , Case-Control Studies , East Asian People , Cell Adhesion Molecules, Neuronal , GPI-Linked Proteins
15.
JAMA Netw Open ; 7(6): e2413835, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38869902

ABSTRACT

Importance: Few studies have directly and objectively measured the individual and combined effects of multifaceted hand hygiene education programs. Objective: To evaluate the individual and combined immediate effects of an instructional video and hand scan images on handwashing quality, decontamination, and knowledge improvement. Design, Setting, and Participants: This cluster randomized clinical trial was conducted in June to July 2023 among first-year nursing students at a university in Hong Kong. The study used an intention-to-treat analysis. Intervention: Hand hygiene education sessions featuring an instructional video, hand scan images, or both. Main Outcomes and Measures: The primary outcome was the change in residue from fluorescent lotion remaining on participants' hands after handwashing before and after the intervention. The secondary outcomes included handwashing quality and knowledge of hand hygiene. Results: A total of 270 of 280 students (mean [SD] age, 19 [1] years; 182 [67.4%] female) participated in the trial (96.4% participation rate). Participants were randomized to a control group (66 participants), hand scan image group (68 participants), instructional video group (67 participants), and hand scan image with instructional video group (69 participants). All intervention groups had greater reductions in residue after the intervention compared with the control group, although none reached statistical significance (hand scan image group: 3.9 [95% CI, 2.0-5.8] percentage points; instructional video group: 4.8 [95% CI, 2.9-6.7] percentage points; hand scan image with instructional video: 3.5 [95% CI, 1.6-5.4] percentage points; control group: 3.2 [95% CI, 1.3-5.2] percentage points). The instructional video group showed a significant improvement in their handwashing performance, with a higher percentage of participants correctly performing all 7 steps compared with the control group (22.4% [95% CI, 13.1% to 31.6%] vs 1.5% [-7.9% to 10.9%]; P < .001). Hand scan images revealed that wrists, fingertips, and finger webs were the most commonly ignored areas in handwashing. Conclusions and Relevance: In this cluster randomized clinical trial of an education program for hand hygiene, a handwashing instructional video and hand scan images did not enhance the level of decontamination. The intervention group had improved handwashing techniques compared with the control group, a secondary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT05872581.


Subject(s)
Hand Hygiene , Students, Nursing , Humans , Female , Male , Students, Nursing/statistics & numerical data , Hong Kong , Young Adult , Hand Hygiene/methods , Hand Hygiene/statistics & numerical data , Hand Disinfection/methods , Health Knowledge, Attitudes, Practice , Adolescent
16.
Front Immunol ; 15: 1369406, 2024.
Article in English | MEDLINE | ID: mdl-38835760

ABSTRACT

Epigenetic mechanisms are involved in several cellular functions, and their role in the immune system is of prime importance. Histone deacetylases (HDACs) are an important set of enzymes that regulate and catalyze the deacetylation process. HDACs have been proven beneficial targets for improving the efficacy of immunotherapies. HDAC11 is an enzyme involved in the negative regulation of T cell functions. Here, we investigated the potential of HDAC11 downregulation using RNA interference in CAR-T cells to improve immunotherapeutic outcomes against prostate cancer. We designed and tested four distinct short hairpin RNA (shRNA) sequences targeting HDAC11 to identify the most effective one for subsequent analyses. HDAC11-deficient CAR-T cells (shD-NKG2D-CAR-T) displayed better cytotoxicity than wild-type CAR-T cells against prostate cancer cell lines. This effect was attributed to enhanced activation, degranulation, and cytokine release ability of shD-NKG2D-CAR-T when co-cultured with prostate cancer cell lines. Our findings reveal that HDAC11 interference significantly enhances CAR-T cell proliferation, diminishes exhaustion markers PD-1 and TIM3, and promotes the formation of T central memory TCM populations. Further exploration into the underlying molecular mechanisms reveals increased expression of transcription factor Eomes, providing insight into the regulation of CAR-T cell differentiation. Finally, the shD-NKG2D-CAR-T cells provided efficient tumor control leading to improved survival of tumor-bearing mice in vivo as compared to their wild-type counterparts. The current study highlights the potential of HDAC11 downregulation in improving CAR-T cell therapy. The study will pave the way for further investigations focused on understanding and exploiting epigenetic mechanisms for immunotherapeutic outcomes.


Subject(s)
Histone Deacetylases , Immunotherapy, Adoptive , Prostatic Neoplasms , RNA, Small Interfering , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapy , Prostatic Neoplasms/immunology , Humans , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Animals , Mice , RNA, Small Interfering/genetics , Cell Line, Tumor , Immunotherapy, Adoptive/methods , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Gene Silencing , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Xenograft Model Antitumor Assays
17.
Mikrochim Acta ; 191(7): 415, 2024 06 22.
Article in English | MEDLINE | ID: mdl-38907752

ABSTRACT

A novel approach is proposed leveraging surface-enhanced Raman spectroscopy (SERS) combined with machine learning (ML) techniques, principal component analysis (PCA)-centroid displacement-based nearest neighbor (CDNN). This label-free approach can identify slight abnormalities between SERS spectra of gastric lesions at different stages, offering a promising avenue for detection and prevention of precancerous lesion of gastric cancer (PLGC). The agaric-shaped nanoarray substrate was prepared using gas-liquid interface self-assembly and reactive ion etching (RIE) technology to measure SERS spectra of serum from mice model with gastric lesions at different stages, and then a SERS spectral recognition model was trained and constructed using the PCA-CDNN algorithm. The results showed that the agaric-shaped nanoarray substrate has good uniformity, stability, cleanliness, and SERS enhancement effect. The trained PCA-CDNN model not only found the most important features of PLGC, but also achieved satisfactory classification results with accuracy, area under curve (AUC), sensitivity, and specificity up to 100%. This demonstrated the enormous potential of this analysis platform in the diagnosis of PLGC.


Subject(s)
Machine Learning , Precancerous Conditions , Spectrum Analysis, Raman , Stomach Neoplasms , Stomach Neoplasms/diagnosis , Spectrum Analysis, Raman/methods , Animals , Precancerous Conditions/diagnosis , Precancerous Conditions/blood , Mice , Principal Component Analysis
18.
J Arthroplasty ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38851406

ABSTRACT

BACKGROUND: The present study aimed to identify the risk factors of periprosthetic femoral fracture (PFF) after cementless total hip arthroplasty and rank them based on importance. METHODS: The age, sex, body mass index (BMI), osteoporosis, canal flare index (CFI), canal bone ratio (CBR), canal calcar ratio (CCR), stem design, and stem canal fill ratio (P1, P2, P3, and P4) of the proximal femoral medullary cavity of 111 total hip arthroplasty patients who had PFF and 388 who did not have PFF were analyzed. Independent-samples student t-tests were used for continuous variables, and Chi-square tests were used for categorical variables. The importance rankings of influencing factors were assessed using a random forest algorithm. Dimensionally reduced variables were then incorporated into a binary logistic regression model to determine the PFF-related risk factors. RESULTS: The mean age, BMI, CBR, CCR, and incidence of osteoporosis were higher in cases of PFF (all P < .001), while the mean CFI, P1, P2, P3, and P4 were lower in cases of PFF (P < .001, P = .033, P = .008, P < .001, and P < .001, respectively). Additionally, the stem design was also statistically associated with PFF (P < .001). Multivariate logistic regression revealed that advanced age, higher BMI, osteoporosis, stem design, lower CFI, higher CBR, higher CCR, lower P1, lower P2, lower P3, and lower P4 were the risk factors of PFF (P < .001, P < .001, P < .001, P < .001, P < .001, P = .010, P < .001, P = .002, P < .001, P < .001, and P = .007, respectively). The ranked importance of the risk factors for PFF was P3, CFI, osteoporosis, CBR, age, P4, P1, stem design, CCR, BMI, and P2. CONCLUSIONS: Lower P3, lower CFI, osteoporosis, higher CBR, advanced age, lower P4, lower P1, stem design, higher CCR, higher BMI, and lower P2 increased the risk of PFF.

19.
Dev Cell ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38848718

ABSTRACT

Characterizing cellular features during seed germination is crucial for understanding the complex biological functions of different embryonic cells in regulating seed vigor and seedling establishment. We performed spatially enhanced resolution omics sequencing (Stereo-seq) and single-cell RNA sequencing (scRNA-seq) to capture spatially resolved single-cell transcriptomes of germinating rice embryos. An automated cell-segmentation model, employing deep learning, was developed to accommodate the analysis requirements. The spatial transcriptomes of 6, 24, 36, and 48 h after imbibition unveiled both known and previously unreported embryo cell types, including two unreported scutellum cell types, corroborated by in situ hybridization and functional exploration of marker genes. Temporal transcriptomic profiling delineated gene expression dynamics in distinct embryonic cell types during seed germination, highlighting key genes involved in nutrient metabolism, biosynthesis, and signaling of phytohormones, reprogrammed in a cell-type-specific manner. Our study provides a detailed spatiotemporal transcriptome of rice embryo and presents a previously undescribed methodology for exploring the roles of different embryonic cells in seed germination.

20.
Heliyon ; 10(10): e31673, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38831837

ABSTRACT

Mucoepidermoid carcinoma (MEC) typically manifests in the salivary glands, but occurrences in the pancreatic gland are exceedingly rare. Surgical resection proves effective; however, pancreatic MEC is prone to metastasis, and lacking a standardized postoperative treatment. We discussed the experience of a 51-year-old female patient with pancreatic MEC who received paclitaxel and gemcitabine as postoperative care. Within a predetermined amount of time, this regimen successfully stopped the spread of metastatic tumors and returned tumor markers to normal. A Stable Disease status was achieved within 6 months after chemotherapy. In summary, gemcitabine and paclitaxel display efficacy in treating pancreatic MEC.

SELECTION OF CITATIONS
SEARCH DETAIL