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1.
Int Dent J ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39358172

ABSTRACT

BACKGROUND: The gap between theoretical knowledge and clinical skills highlights the need for clinical reasoning training curriculum in periodontal education, especially in periodontal internships. This study aims to develop a Chief Complaint-Based Clinical Reasoning Training (CCB-CRT) program and evaluate its impact on periodontal interns' clinical reasoning abilities and overall performance. METHODS: The CCB-CRT program was developed based on eight common chief complaints (CCs) identified through surveys of periodontal specialists and an analysis of patient visit data from a university-affiliated hospital's periodontal clinic. The study involved a comparison between a control group of fifth-year dental students (2021) and a CCB-CRT group (2022). Both groups completed an 8-week training course. The CCB-CRT group received additional training focused on the 8 common CCs, using student-led discussions, flipped classroom, mind mapping, and presentations. Evaluation criteria included overall performance, disease diagnosis and treatment plan, misdiagnosis rates, and students' satisfaction. RESULTS: After 1 year of CCB-CRT implementation, participants in the CCB-CRT group showed substantial improvements in overall performance, diagnostic accuracy, and satisfaction compared to traditional teaching methods. The program enhanced students' understanding of theoretical knowledge, improved their interpretation of clinical manifestations and examination results, and enhanced their clinical reasoning skills and diagnostic accuracy. CONCLUSIONS: The successful application of the CCB-CRT program in periodontology education demonstrates its efficacy in improving clinical reasoning skills and diagnostic efficiency among students. The structured approach facilitates the transition from theoretical knowledge to practical application, contributing to better patient care in periodontal practice.

2.
Ther Adv Hematol ; 15: 20406207241277549, 2024.
Article in English | MEDLINE | ID: mdl-39372558

ABSTRACT

Background: There is limited data on third-party umbilical cord blood (UCB) or mesenchymal stem cell (MSC) transplantation-assisted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients. Objective: To evaluate the efficacy and safety of UCB and MSC transplantation-assisted haplo-HSCT in pediatric patients with acute leukemia (AL). Design: Observational study. Methods: Clinical data of 152 children with AL undergoing haplo-HSCT at the Children's Hospital of Soochow University between January 2020 and June 2022 were collected. The patients were divided into the haplo-HSCT + UCB group (n = 76), haplo-HSCT + MSC group (n = 31), and haplo-HSCT group (n = 45). Hematopoietic reconstruction time, complications within 30 days after transplantation, and survival and recurrence at 3 years after transplantation were compared among the groups. Results: Multivariate analysis revealed that haplo-HSCT with MSC and human leukocyte antigen (HLA) matching ⩾6/10 were independent factors reducing engraftment syndrome (ES) incidence. There were no significant differences among the groups in the hematopoietic reconstruction time or incidence of complications within 30 days after transplantation (p > 0.05). Overall survival, relapse-free survival, cumulative incidence of relapse, cumulative incidence of hematological relapse, and 3-year transplant-related mortality were not significantly different (p > 0.05). The incidence of adverse reactions in the haplo-HSCT + UCB group was 97.3% within 4 h after UCB infusion, with a particularly high occurrence rate of 94.7% for hypertension. No transfusion-related adverse reactions occurred after the transfusion of umbilical cord MSC in the haplo-HSCT + MSC group. Conclusion: MSC-assisted haplo-HSCT can reduce ES incidence after transplantation in pediatric patients with AL. UCB infusion is associated with a high incidence of reversible hypertension. However, no adverse reactions were observed in umbilical cord MSC transfusion.

4.
Int J Mol Sci ; 25(18)2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39337460

ABSTRACT

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4+ Effective Memory T Cell (CD4+ TEM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4+ TEM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10-15) and LAG3 (rs67706382, p = 6.16× 10-16). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4+ TEM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4+ TEM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find.


Subject(s)
Antigens, CD , CD4-Positive T-Lymphocytes , COVID-19 , Lymphocyte Activation Gene 3 Protein , Mendelian Randomization Analysis , Quantitative Trait Loci , SARS-CoV-2 , Humans , COVID-19/genetics , COVID-19/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Risk Factors , Antigens, CD/genetics , Antigens, CD/metabolism , Single-Cell Analysis/methods , GTP-Binding Proteins/genetics , Memory T Cells/immunology , Memory T Cells/metabolism , Biomarkers , Polymorphism, Single Nucleotide , Male , Female , Genetic Predisposition to Disease , Genome-Wide Association Study
5.
Microbiol Spectr ; 12(10): e0340623, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39240085

ABSTRACT

Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE: Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.


Subject(s)
COVID-19 , Coinfection , Disease Outbreaks , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Male , Female , Middle Aged , Coinfection/epidemiology , Coinfection/virology , Coinfection/microbiology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Adult , Retrospective Studies , Aged
6.
Int J Biol Macromol ; 279(Pt 4): 135525, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39260650

ABSTRACT

E26-transforming specific (ETS) variant 6 (ETV6) is a transcription factor regulating the expression of interferon stimulating genes (ISGs) and involved in the embryonic development and hematopoietic regulation, but the role of ETV6 in host response to virus infection is not clear. In this study, we show that ETV6 was upregulated in DF-1 cells with poly(I:C) stimulation or IBDV, AIV and ARV infection via engagement of dsRNA by MDA5. Overexpression of ETV6 in DF-1 cells markedly inhibited IBDV-induced type I interferon (IFN-I) and ISGs expressions. In contrast, knockdown, or knockout of ETV6 remarkably inhibited IBDV replication via promoting IFN-I response. Furthermore, our data show that ETV6 negatively regulated host antiviral response to IBDV infection by interaction with TANK binding kinase 1 (TBK1) and subsequently inhibited its phosphorylation. These results uncovered a novel role of ETV6 as a pro-viral factor in host response by inhibiting TBK1 phosphorylation, furthering our understandings of RNA virus immunosuppression and providing a valuable clue to the development of antiviral reagents for the control of avian RNA virus infection.

7.
World J Clin Cases ; 12(26): 5901-5907, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39286375

ABSTRACT

BACKGROUND: Being too light at birth can increase the risk of various diseases during infancy. AIM: To explore the effect of perinatal factors on term low-birth-weight (LBW) infants and build a predictive model. This model aims to guide the clinical management of pregnant women's healthcare during pregnancy and support the healthy growth of newborns. METHODS: A retrospective analysis was conducted on data from 1794 single full-term pregnant women who gave birth. Newborns were grouped based on birth weight: Those with birth weight < 2.5 kg were classified as the low-weight group, and those with birth weight between 2.5 kg and 4 kg were included in the normal group. Multiple logistic regression analysis was used to identify the factors influencing the occurrence of full-term LBW. A risk prediction model was established based on the analysis results. The effectiveness of the model was analyzed using the Hosmer-Leme show test and receiver operating characteristic (ROC) curve to verify the accuracy of the predictions. RESULTS: Among the 1794 pregnant women, there were 62 cases of neonatal weight < 2.5 kg, resulting in an LBW incidence rate of 3.46%. The factors influencing full-term LBW included low maternal education level [odds ratio (OR) = 1.416], fewer prenatal examinations (OR = 2.907), insufficient weight gain during pregnancy (OR = 3.695), irregular calcium supplementation during pregnancy (OR = 1.756), and pregnancy hypertension syndrome (OR = 2.192). The prediction model equation was obtained as follows: Logit (P) = 0.348 × maternal education level + 1.067 × number of prenatal examinations + 1.307 × insufficient weight gain during pregnancy + 0.563 × irregular calcium supplementation during pregnancy + 0.785 × pregnancy hypertension syndrome - 29.164. The area under the ROC curve for this model was 0.853, with a sensitivity of 0.852 and a specificity of 0.821. The Hosmer-Leme show test yielded χ 2 = 2.185, P = 0.449, indicating a good fit. The overall accuracy of the clinical validation model was 81.67%. CONCLUSION: The occurrence of full-term LBW is related to maternal education, the number of prenatal examinations, weight gain during pregnancy, calcium supplementation during pregnancy, and pregnancy-induced hypertension. The constructed predictive model can effectively predict the risk of full-term LBW.

8.
Int J Ophthalmol ; 17(9): 1743-1751, 2024.
Article in English | MEDLINE | ID: mdl-39296568

ABSTRACT

Ophthalmology is a subject that highly depends on imaging examination. Artificial intelligence (AI) technology has great potential in medical imaging analysis, including image diagnosis, classification, grading, guiding treatment and evaluating prognosis. The combination of the two can realize mass screening of grass-roots eye health, making it possible to seek medical treatment in the mode of "first treatment at the grass-roots level, two-way referral, emergency and slow treatment, and linkage between the upper and lower levels". On the basis of summarizing the AI technology carried out by scholars and their teams all over the world in the field of ophthalmology, quite a lot of studies have confirmed that machine learning can assist in diagnosis, grading, providing optimal treatment plans and evaluating prognosis in corneal and conjunctival diseases, ametropia, lens diseases, glaucoma, iris diseases, etc. This paper systematically shows the application and progress of AI technology in common anterior segment ocular diseases, the current limitations, and prospects for the future.

9.
Transpl Immunol ; 87: 102130, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39278332

ABSTRACT

Toxoplasmosis, caused by the parasite Toxoplasma gondii, is a life-threatening infection that may occur following hematopoietic stem cell transplantation (HSCT). Toxoplasmic encephalitis (TE) is one of the most severe manifestations of this infection and often results in unsatisfactory therapeutic outcomes, especially regarding neurological damage. Recent studies have demonstrated that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can significantly aid in neural repair and remodeling. Furthermore, hUC-MSCs have been shown to reduce the risk of graft-versus-host disease (GVHD) associated with the reduction or discontinuation of immunosuppressive therapy. In this case report, we present a pediatric patient who developed TE as a complication of haploidentical HSCT. The patient received a combined treatment regimen of standard anti-Toxoplasma therapy and adjunctive hUC-MSC therapy. The outcomes were satisfactory. The patient regained consciousness, maintained a stable body temperature, and regained the ability to perform daily activities independently. Additionally, next-generation sequencing revealed a decrease in Toxoplasma DNA sequences in the blood and cerebrospinal fluid to undetectable levels. This case report underscores the potential of hUC-MSCs as a promising therapeutic modality for TE.

10.
Front Vet Sci ; 11: 1461116, 2024.
Article in English | MEDLINE | ID: mdl-39301286

ABSTRACT

Avian reoviruses (ARVs) cause viral arthritis or tenosynovitis, resulting in poor weight gain and increased feed conversion ratios in chickens. In this study, we generated three Marek's disease virus (MDV) recombinants, namely, rMDV-ARV-σB, rMDV-ARV-σC, and rMDV-ARV-σB + C, expressing ARV σB, σC, and both σB and σC, respectively. In rMDV-ARV-σB and rMDV-ARV-σC, the σB or σC gene was inserted into the US2 gene of MDV vaccine strain 814 using a fosmid-based rescue system. In rMDV-ARV-σB + C, the σB and σC genes were cloned into different expression cassettes, which were co-inserted into the US2 gene of the MDV 814 strain. In infected chicken embryo fibroblasts (CEFs), the recombinant virus rMDV-ARV-σB expressed σB, rMDV-ARV-σC expressed σC, and the rMDV-ARV-σB + C virus simultaneously expressed σB and σC. These recombinant viruses exhibited growth kinetics in CEFs similar to those of the parent MDV, and the inserted genes were stably maintained and expressed in the recombinant MDVs after 20 passages in cell cultures. These recombinant MDVs expressing σB and σC will provide potential vaccines against ARV infection in chickens.

11.
Interdiscip Sci ; 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39222258

ABSTRACT

As a common disease, cardiovascular and cerebrovascular diseases pose a great harm threat to human wellness. Even using advanced and comprehensive treatment methods, there is still a high mortality rate. Arteriosclerosis, as an important factor reflecting the severity of cardiovascular and cerebrovascular diseases, is imperative to detect the arteriosclerotic retinopathy. However, the detection of arteriosclerosis retinopathy requires expensive and time-consuming manual evaluation, while end-to-end deep learning detection methods also need interpretable design to high light task-related features. Considering the importance of automatic arteriosclerotic retinopathy grading, we propose a segmentation and classification interaction network (SCINet). We propose a segmentation and classification interaction architecture for grading arteriosclerotic retinopathy. After IterNet is used to segment retinal vessel from original fundus images, the backbone feature extractor roughly extracts features from the segmented and original fundus arteriosclerosis images and further enhances them through the vessel aware module. The last classifier module generates fundus arteriosclerosis grading results. Specifically, the vessel aware module is designed to highlight the important areal vessel features segmented from original images by attention mechanism, thereby achieving information interaction. The attention mechanism selectively learns the vessel features of segmentation region information under the proposed interactive architecture, which leads to reweighting the extracted features and enhances significant feature information. Extensive experiments have confirmed the effect of our model. SCINet has the best performance on the task of arteriosclerotic retinopathy grading. Additionally, the CNN method is scalable to similar tasks by incorporating segmented images as auxiliary information.

12.
Nat Prod Bioprospect ; 14(1): 53, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39276287

ABSTRACT

Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline's additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures.

13.
BMC Microbiol ; 24(1): 318, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39223464

ABSTRACT

BACKGROUND: The role of microbes in diseases, especially cancer, has garnered significant attention. However, research on the oral microbiota in oral potentially malignant disorders (OPMDs) remains limited. Our study investigates microbial communities in OPMDs. MATERIALS AND METHODS: Oral biopsies from19 oral leukoplakia (OLK) patients, 19 proliferative verrucous leukoplakia (PVL) patients, 19 oral lichen planus (OLP) patients, and 19 oral lichenoid lesions (OLL) patients were obtained. 15 SCC specimens were also collected from PVL patients. Healthy individuals served as controls, and DNA was extracted from their paraffin-embedded tissues. 2bRAD-M sequencing generated taxonomic profiles. Alpha and beta diversity analyses, along with Linear Discriminant Analysis effect size analysis, were conducted. RESULTS: Our results showed the microbial richness and diversity were significantly different among groups, with PVL-SCC resembling controls, while OLK exhibited the highest richness. Each disease group displayed unique microbial compositions, with distinct dominant bacterial species. Noteworthy alterations during PVL-SCC progression included a decline in Fusobacterium periodonticum and an elevation in Prevotella oris. CONCLUSIONS: Different disease groups exhibited distinct dominant bacterial species and microbial compositions. These findings offer promise in elucidating the underlying mechanisms of this disease.


Subject(s)
Bacteria , Carcinoma, Squamous Cell , Leukoplakia, Oral , Microbiota , Mouth Neoplasms , Humans , Male , Female , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Middle Aged , Microbiota/genetics , Mouth Neoplasms/microbiology , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/microbiology , Carcinoma, Squamous Cell/pathology , Aged , Leukoplakia, Oral/microbiology , Leukoplakia, Oral/pathology , Adult , Lichen Planus, Oral/microbiology , Lichen Planus, Oral/pathology , Mouth/microbiology , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics
14.
Nat Commun ; 15(1): 7654, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227578

ABSTRACT

Citrullination plays an essential role in various physiological or pathological processes, however, whether citrullination is involved in regulating tumour progression and the potential therapeutic significance have not been well explored. Here, we find that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization. Mechanistically, PADI4-mediated HIF-1αR698 citrullination blocks von Hippel-Lindau (VHL) binding, thereby antagonizing HIF-1α ubiquitination and subsequent proteasome degradation. We also show that citrullinated HIF-1αR698, HIF-1α and PADI4 are highly expressed in hepatocellular carcinoma (HCC) tumour tissues, suggesting a potential correlation between PADI4-mediated HIF-1αR698 citrullination and cancer development. Furthermore, we identify that dihydroergotamine mesylate (DHE) acts as an antagonist of PADI4, which ultimately suppresses tumour progression. Collectively, our results reveal citrullination as a posttranslational modification related to HIF-1α stability, and suggest that targeting PADI4-mediated HIF-1α citrullination is a promising therapeutic strategy for cancers with aberrant HIF-1α expression.


Subject(s)
Carcinoma, Hepatocellular , Citrullination , Disease Progression , Hypoxia-Inducible Factor 1, alpha Subunit , Liver Neoplasms , Protein-Arginine Deiminase Type 4 , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Protein-Arginine Deiminase Type 4/metabolism , Animals , Cell Line, Tumor , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Ubiquitination , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Mice , HEK293 Cells , Protein Stability/drug effects , Protein-Arginine Deiminases/metabolism , Protein-Arginine Deiminases/genetics , Mice, Nude , Male
15.
J Reprod Immunol ; 166: 104326, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39265316

ABSTRACT

Clinical observational studies have suggested hyperlipidemia may disturb embryo implantation through endometrium; however, the mechanism has been unclear. With its profound implications for reproductive health, the present study aims to investigate whether hyperlipidemia affects endometrial epithelial cell tight junctions for implantation failures. By constructing hyperlipidemia mice model, the number and distribution of embryo implantation status were investigated after both natural mating and in vitro fertilization and embryo transfer (IVF-ET). Transmission electron microscopy (TEM) was used to compare the ultrastructure of tight junctions in endometrial endothelial cells. Western blot and immunofluorescence were used to explore the expression and localization of tight junction proteins, such as Claudin (CDLN)3, CLDN4, occludin (OCLN), and zonula occludens-1 (ZO1). For women with reproductive failure, mid-luteal phase endometrial tissues were collected, and gene expression of tight junction proteins was investigated using RNA sequencing and qRT-PCR. In hyperlipidemic mice, the number of embryo implantation sites significantly decreased with uneven distribution after natural mating and IVF-ET. Disrupted tight junctions were found, characterized by a decreased number of tight junctions by TEM, downregulated expressions of CDLN4, OCLN, and ZO1, and an increased expression of CLDN3 by western blot. In hyperlipidemic women with reproductive failure, the dysregulated expression of CLDN3 and CLDN4 was also present in the luteal phase endometrium. In this study, evaluation of both animal models and infertile women in vivo demonstrated that hyperlipidemia reduced female fertility, accompanied by disruption of tight junction structures and dysregulation of CLDN3 and CLDN4 expression in the endothelial cells of luteal phase endometrium.

16.
Placenta ; 156: 46-54, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39265375

ABSTRACT

INTRODUCTION: Placental dysfunction is the primary cause of selective fetal growth restriction (sFGR), and the specific role of mitochondria remains unclear. This study aims to elucidate mitochondrial functional defects in sFGR placentas and explore the roles of mitochondrial genomic and epigenetic alterations in its pathogenesis. METHODS: The placental villi of MCDA twins with sFGR were collected and the morphology and number of mitochondria were observed by transmission electron microscopy. Meanwhile, the levels of reactive oxygen species (ROS), ATP and oxidative damage markers were assessed. Mitochondrial DNA (mtDNA) copy number detection, targeted sequencing and methylation sequencing were performed. The expression of placental cytochrome c oxidase subunit I (COX I) and mitochondrial long non-coding RNAs (lncRNAs) were evaluated by Western blotting and qPCR. RESULTS: Compared with placentae from normal fetuses, pronounced mitochondrial damage within cytotrophoblast was revealed in sFGR placentae, alongside augmented mitochondrial number in syncytiotrophoblast. Enhanced oxidative stress in these placentae was evidenced by elevated markers of oxidative damage, accompanied by increased ROS production and diminished ATP generation. In sFGR placentae, a notable rise in mitochondrial copy number and one heterozygous mutation in the MT-RNR2 gene were observed, along with decreased COX Ⅰ levels, increased lncND5, lncND6, lncCyt b, and MDL1 synthesis, and decreased RMRP synthesis. DISCUSSION: Findings collectively confirmed an exacerbation of oxidative stress within sFGR placentae, coinciding with mitochondrial dysfunction, compromised energy production, and ultimately the failure of compensatory mechanisms to restore energy balance, which may result from mutations in the mitochondrial genome and abnormal expression of epigenetic regulatory genes.

17.
Gastrointest Endosc ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39265743

ABSTRACT

BACKGROUND AND AIMS: Hemostatic powder (HP) is a novel hemostasis modality for nonvariceal gastrointestinal (GI) bleeding. The meta-analysis was performed to evaluate the efficacy of HP monotherapy versus conventional endoscopic treatment (CET) for nonvariceal GI bleeding. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched from inception to October 16, 2023. The primary outcomes were the initial hemostatic rate and the 30-day rebleeding rate. After the meta-analysis, the trial sequential analysis (TSA) was also conducted to decrease the risk of random errors and validate the result. RESULTS: The meta-analysis included eight studies, incorporating 653 patients in total. Given significant heterogeneity, all analyses were segregated into malignancy-related and non-malignancy-related GI bleeding lesions. For the former, HP monotherapy significantly improved the initial hemostasis rate and 30-day rebleeding rate compared to CET (Relative risk [RR] 1.50, 95% confidence interval [CI] 1.28 - 1.75, P < .001; RR .32, 95% CI .12 - .86, P = .02), and TSA supported the above results. For non-malignancy-related GI bleeding, HP monotherapy and CET have similar initial hemostasis and 30-day rebleeding rates (RR 1.08, 95% CI .98 - 1.19, P = .11; RR 1.15, 95% CI .46 - 2.90, P = .76), but the TSA failed to confirm the above results. CONCLUSIONS: In conclusion, HP monotherapy surpassed CET in terms of the initial hemostasis rate and 30-day rebleeding rate for patients with malignancy-related GI bleeding. However, their relative efficacy for non-malignancy-related GI bleeding remains unresolved.

18.
Technol Health Care ; 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39331118

ABSTRACT

BACKGROUND: The human oral cavity contains over 700 types of bacteria that may protect the body against colonization by exogenous pathogens and maintain relative homeostasis. However, alterations in the immune status can disrupt the balance between microorganisms and the host, inducing various diseases such as oral cancer and diabetes mellitus. The mechanism underlying this process is not clearly understood. OBJECTIVE: The purpose of this study was to investigate the relationships between subgingival bacteria, T-cell receptor ß-chain complementarity-determining region 3 (TCRß CDR3), and the development oforal squamous cell carcinoma (OSCC). METHODS: We grouped patients as "healthy periodontal" (H), "moderate-to-severe chronic periodontitis" (C), and "moderate-to-severe chronic periodontitis with OSCC" (T). Bacterial groups were "subgingival plaque" (bp) and "gingival/tumor tissue" (g). We also recorded patients' age, gender, attachment level (AL), bleeding on probing (BOP), and probing depth (PD). We extracted and sequenced RNA from plaques, gingival tissues, tumors, and teeth. We performed high-throughput sequencing on TCRß CDR3 and plaque bacteria. RESULTS: Synergistetes and Veillonella parvula were more abundant in the H group than in the T group. Granulicatella, Peptostreptococcus, and Streptococcus infantis were enriched in the T-bp group. AL, BOP, and PD were positively correlated with Granulicatella, Peptostreptococcus, and Pseudomonas but negatively correlated with Prevotella nigrescens and V. parvula. TCRß CDR3 diversity was C > H > T. TCR ß-chain Variable gene (TRBV)20-1 usage varied among the H, C, and T groups. TRBV2 and TRBV5-1 usage was greater in the T group than in the C group. TRBJ1-1, TRBJ1-2, TRBJ2-2, TRBJ2-7, and TRBJ2-5 were most frequently used. CONCLUSIONS: These trends and the reduction of gingival Synergistetes were correlated with OSCC. TCRß CDR3 diversity was the lowest in patients in the T group, and there were considerable changes in the expression of TRBV2 and TRBJ. Therefore, plaque bacterial composition can influence TCRß CDR3.

19.
Food Chem ; 463(Pt 2): 141328, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39305673

ABSTRACT

We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressive-like behaviour. Molecular docking and molecular dynamics simulations revealed an inter-molecular interaction between NOB and the pyruvate kinase isozyme M1/M2 (PKM2) protein. We then used compound 3 k to construct a zebrafish model in which PKM2 was inhibited. Our analysis of this model suggested that NOB alleviated depression-like behaviour via inhibition of PKM2. In summary, NOB alleviated depressive-like behaviour induced by ALAN in zebrafish via targeting of PKM2 and activation of the glycolytic signalling pathway.

20.
Mar Pollut Bull ; 208: 116999, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39305843

ABSTRACT

During the spring and summer of 2021, two investigations were conducted in the northern Chinese sea by using the high-performance liquid chromatography with the pigment-based chemotaxonomic tool PIGMENTUM. Results showed that the average chlorophyll a (Chl a) concentration during spring was significantly higher (p < 0.01) than that during summer. 19'-hexanoyloxyfucoxanthin-containing algae, alloxanthin-containing algae (ACA), and fucoxanthin-containing algae (FCA) were the main pigment groups in spring, whereas zeaxanthin-containing algae (ZCA) and peridinin-containing algae (PeCA) were dominated in summer. Five ecological provinces were divided, and the phytoplankton biomass (Chl a) in Province V was the lowest. Redundancy analysis showed that ACA, FCA, and PeCA were positively correlated with nutrients; in comparison, ZCA preferred high salinity. The PIGMENTUM estimates were significantly positively correlated (p < 0.01) with CHEMTAX for all phytoplankton assemblages. Nevertheless, the coefficients of determination and slope by regression analysis between two methods showed large differences for several phytoplankton groups.

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