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1.
Int Dent J ; 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39307671

ABSTRACT

INTRODUCTION: The aim of this study was to explore the causal relationship between telomere length and Oral and oropharyngeal cancers by using Mendelian randomization (MR) analysis. METHODS: We carried out a 2-sample MR to examine the causal association between telomere length and Oral and oropharyngeal cancers. Two large genome-wide association studies (GWAS) were employed to identify single nucleotide polymorphisms (SNPs) as instrumental variables through statistical and biological approaches. The data on SNP-oral and oropharyngeal cancer risk factor associations were sourced from various consortia/UK Biobank. The inverse variance weighted (IVW) method was employed as the primary approach for overall causal estimation in MR, with sensitivity analyses conducted to assess potential confounding by pleiotropy, heterogeneity, and the leave-one-out analysis. RESULTS: The statistically driven approach indicates limited evidence of a genetically causal effect of telomere length on the risk of oral cavity cancer (OR = 0.999, 95% CI 0.998-1.000, P = .100), oropharyngeal cancer (OR = 0.999, 95% CI 0.998-1.001, P = .650), combined oral and oropharyngeal cancer (OR = 0.999, 95% CI 0.998-1.000, P = .119) in Europeans. The biologically driven approach demonstrated consistent causal effects across all MR methods, thereby further strengthening the reliability of the results. Moreover, the MR-Egger (Q [df] 170.816 [130], P = .009) and inverse variance weighted methods (Q [df] 171.656 [131], P = .010) identified considerable heterogeneity among instrumental variable estimates in Oral cavity cancer, and no evidence of horizontal pleiotropy was detected. CONCLUSIONS: No significant causal associations between telomere length and Oral and oropharyngeal cancers were found in this study.

2.
Sci Rep ; 14(1): 20183, 2024 08 30.
Article in English | MEDLINE | ID: mdl-39215189

ABSTRACT

It is not clear whether different radiation methods have different effects on enamel. The purpose of this study was to compare the effects of single and fractionated radiation on enamel and caries susceptibility and to provide an experimental basis for further study of radiation­related caries. Thirty-six caries-free human third molars were collected and randomly divided into three groups (n = 12). Group1 (control group) was not exposed to radiation. Group 2 received single radiation with a cumulative dose of 70 Gy. Group 3 underwent fractionated radiation, receiving 2 Gy/day for 5 days followed by a 2-day rest period, for a total of 7 weeks with a cumulative dose of 70 Gy. Changes in microhardness, roughness, surface morphology, bacterial adhesion and ability of acid resistance of each group were tested. Scanning electron microscope revealed that the enamel surface in both radiation groups exhibited unevenness and cracks. Compared with the control group, microhardness and acid resistance of enamel decreased, while roughness and bacterial adhesion increased in both the single radiation and fractionated radiation groups. Compared with the single radiation group, the enamel surface microhardness and acid resistance decreased in the fractionated radiation group, while roughness and bacterial adhesion increased. Both single radiation and fractionated radiation resulting in changes in the physical and biological properties of enamel, with these changes being more pronounced in the fractionated radiation group. Therefore, fractionated radiation is recommended as a more suitable method for constructing a radiation­related caries model in vitro.


Subject(s)
Bacterial Adhesion , Dental Caries , Dental Enamel , Surface Properties , Humans , Dental Enamel/radiation effects , Dental Enamel/microbiology , Dental Caries/microbiology , Dental Caries/pathology , Bacterial Adhesion/radiation effects , Surface Properties/radiation effects , Microscopy, Electron, Scanning , Dental Caries Susceptibility , Hardness
3.
Cell Death Dis ; 15(8): 591, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39143050

ABSTRACT

Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.


Subject(s)
Mitochondria , Mitophagy , Neurons , Receptors, G-Protein-Coupled , Animals , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Neurons/metabolism , Mitochondria/metabolism , Mice , Humans , Oxidative Phosphorylation , Microtubule-Associated Proteins/metabolism , Microtubule-Associated Proteins/genetics , Reactive Oxygen Species/metabolism , Mice, Knockout , Neurogenesis
4.
Br J Radiol ; 97(1162): 1706-1712, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39177575

ABSTRACT

OBJECTIVE: CA125 is recommended by many countries as the primary screening test for ovarian cancer. But there are patients with ovarian cancer having normal CA125. We hope to identify the types of EOC with normal CA125 levels better by building a refined model based on the ultrasound radiomics, thus providing precise medical treatment for patients. METHODS: We included 58 patients with EOC with normal CA125 from 2 centres, who were confirmed by preoperative ultrasound and pathology. We extracted 1130 radiomics features based on the tumour's region of interest from the most typical ultrasound image of each patient. We selected radiomics and clinical features by LASSO and logistic regression to construct Rad-score and clinical models, respectively. Receiver operating characteristic curves judged their test efficacy. On the basis of the combined model, we developed a nomogram. RESULTS: Area under the curves (AUCs) of 0.93 and 0.83 were achieved in both the training and test groups for the combined model. There were similar AUCs between the Rad-score and clinical models of 0.82 and 0.80, respectively. By analysing the calibration curves, it was determined that the nomogram matched actual observations in the training cohort. CONCLUSION: Ultrasound radiomics can differentiate type I and type II EOC with normal CA125 levels. ADVANCES IN KNOWLEDGE: This study is the first to focus on EOC cases with normal level of CA125. The subset of patients constituting 20% of the disease population may require more refined radiomics models.


Subject(s)
CA-125 Antigen , Carcinoma, Ovarian Epithelial , Ovarian Neoplasms , Ultrasonography , Humans , Female , CA-125 Antigen/blood , Carcinoma, Ovarian Epithelial/diagnostic imaging , Carcinoma, Ovarian Epithelial/blood , Middle Aged , Ultrasonography/methods , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/blood , Adult , Aged , Nomograms , Retrospective Studies , ROC Curve , Radiomics
5.
J Med Imaging (Bellingham) ; 11(4): 044505, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39114540

ABSTRACT

Purpose: Segmentation of ovarian/adnexal masses from surrounding tissue on ultrasound images is a challenging task. The separation of masses into different components may also be important for radiomic feature extraction. Our study aimed to develop an artificial intelligence-based automatic segmentation method for transvaginal ultrasound images that (1) outlines the exterior boundary of adnexal masses and (2) separates internal components. Approach: A retrospective ultrasound imaging database of adnexal masses was reviewed for exclusion criteria at the patient, mass, and image levels, with one image per mass. The resulting 54 adnexal masses (36 benign/18 malignant) from 53 patients were separated by patient into training (26 benign/12 malignant) and independent test (10 benign/6 malignant) sets. U-net segmentation performance on test images compared to expert detailed outlines was measured using the Dice similarity coefficient (DSC) and the ratio of the Hausdorff distance to the effective diameter of the outline ( R HD - D ) for each mass. Subsequently, in discovery mode, a two-level fuzzy c-means (FCM) unsupervised clustering approach was used to separate the pixels within masses belonging to hypoechoic or hyperechoic components. Results: The DSC (median [95% confidence interval]) was 0.91 [0.78, 0.96], and R HD - D was 0.04 [0.01, 0.12], indicating strong agreement with expert outlines. Clinical review of the internal separation of masses into echogenic components demonstrated a strong association with mass characteristics. Conclusion: A combined U-net and FCM algorithm for automatic segmentation of adnexal masses and their internal components achieved excellent results compared with expert outlines and review, supporting future radiomic feature-based classification of the masses by components.

6.
Nat Commun ; 15(1): 7081, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39152168

ABSTRACT

DSS1, essential for BRCA2-RAD51 dependent homologous recombination (HR), associates with the helical domain (HD) and OB fold 1 (OB1) of the BRCA2 DSS1/DNA-binding domain (DBD) which is frequently targeted by cancer-associated pathogenic variants. Herein, we reveal robust ss/dsDNA binding abilities in HD-OB1 subdomains and find that DSS1 shuts down HD-OB1's DNA binding to enable ssDNA targeting of the BRCA2-RAD51 complex. We show that C-terminal helix mutations of DSS1, including the cancer-associated R57Q mutation, disrupt this DSS1 regulation and permit dsDNA binding of HD-OB1/BRCA2-DBD. Importantly, these DSS1 mutations impair BRCA2/RAD51 ssDNA loading and focus formation and cause decreased HR efficiency, destabilization of stalled forks and R-loop accumulation, and hypersensitize cells to DNA-damaging agents. We propose that DSS1 restrains the intrinsic dsDNA binding of BRCA2-DBD to ensure BRCA2/RAD51 targeting to ssDNA, thereby promoting optimal execution of HR, and potentially replication fork protection and R-loop suppression.


Subject(s)
BRCA2 Protein , DNA Replication , DNA, Single-Stranded , DNA , Homologous Recombination , Mutation , Rad51 Recombinase , BRCA2 Protein/metabolism , BRCA2 Protein/genetics , BRCA2 Protein/chemistry , Humans , DNA/metabolism , Rad51 Recombinase/metabolism , Rad51 Recombinase/genetics , DNA, Single-Stranded/metabolism , DNA, Single-Stranded/genetics , Homeostasis , Protein Binding , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Protein Domains , Cell Line, Tumor , DNA Damage , Proteasome Endopeptidase Complex
7.
Front Surg ; 11: 1360982, 2024.
Article in English | MEDLINE | ID: mdl-38966233

ABSTRACT

Background: Oblique lateral interbody fusion (OLIF) combined with transpedicular screw fixation has been practiced for degenerative spinal diseases of elderly patients for years. However, overweight patients have been shown to have longer operative times and more complications from surgery. The effect on clinical outcome is still uncertified. The objective of this study was to determine is overweight a risk factor to clinical outcome of OLIF combined with transpedicular screw fixation technique. Material and methods: A retrospective study in patients submitted to OLIF combined with transpedicular screw fixation from January 2018 to August 2019 was conducted. VAS score, ODI score and EQ5D were measured before the operation and one year after the operation. Results: A total of 111 patients were included with 48 patients in the non-obese group and 55 patients in the overweight/obese group. There was no significant difference between the two groups in gender, age, smoking history, hypertension, chronic kidney disease and diabetes mellitus. Overweight/obese group has higher BMI (28.4 vs. 22.7, p < 0.001) than non-obese group. There was no difference between the two groups in pre-operative VAS score, ODI score and EQ5D score. However, the healthy weight group improved much more than the overweight score in VAS score, ODI score and EQ5D score. Conclusion: The overweight/obese patient group had clinical outcomes worse than the non-obese group in terms of pain relief and life functions.

8.
New Phytol ; 243(4): 1329-1346, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38898642

ABSTRACT

Drought-induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked. We quantified the vulnerability to drought-induced embolism, pressure-volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads. Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads. Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits - particularly vessels - may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads.


Subject(s)
Cycadopsida , Droughts , Plant Leaves , Water , Xylem , Xylem/physiology , Xylem/anatomy & histology , Plant Leaves/anatomy & histology , Plant Leaves/physiology , Cycadopsida/physiology , Cycadopsida/anatomy & histology , Species Specificity
9.
FEBS Lett ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813713

ABSTRACT

Elevated oxidative stress, which threatens genome stability, has been detected in almost all types of cancers. Cells employ various DNA repair pathways to cope with DNA damage induced by oxidative stress. Recently, a lot of studies have provided insights into DNA damage response upon oxidative stress, specifically in the context of transcriptionally active genomes. Here, we summarize recent studies to help understand how the transcription is regulated upon DNA double strand breaks (DSB) and how DNA repair pathways are selectively activated at the damage sites coupling with transcription. The role of RNA molecules, especially R-loops and RNA modifications during the DNA repair process, is critical for protecting genome stability. This review provides an update on how cells protect transcribed genome loci via transcription-coupled repair pathways.

11.
Sleep Med Rev ; 75: 101928, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38614049

ABSTRACT

The sleep quality of lowlanders in hypoxic environments has become increasingly important with an increase in highland and alpine activities. This study aimed to identify the effects of acute exposure to hypoxia on the sleep structure of lowlanders and to analyze the changes in sleep indicators at varying levels of hypoxia. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-three studies were screened and included in the quantitative analysis. The results showed that acute exposure to hypoxia reduced sleep quality in lowlanders. Post-sleep arousal events and the percentage of N1 were significantly increased, whereas total sleep time, sleep efficiency, and the percentage of N3 and rapid eye movement sleep were significantly decreased in hypoxic environments. Acute exposure to hypoxia had the greatest negative impact on wakefulness after sleep onset (WASO). In addition, a larger decrease in sleep efficiency and higher increase in the percentages of N1 and WASO were observed when lowlanders were exposed to higher levels of hypoxia. This study clarifies the quantitative effects of acute hypoxic exposure on sleep in lowlanders based on original studies and explains the sleep disorders faced by lowlanders in hypoxic environments.


Subject(s)
Hypoxia , Adult , Humans , Altitude , Arousal/physiology , Hypoxia/physiopathology , Sleep/physiology , Sleep Quality , Sleep Stages/physiology , Sleep, REM/physiology , Wakefulness/physiology
12.
Sci Rep ; 14(1): 7065, 2024 03 25.
Article in English | MEDLINE | ID: mdl-38528001

ABSTRACT

In the future, novel and highly pathogenic viruses may re-emerge, leading to a surge in healthcare demand. It is essential for urban epidemic control to investigate different cities' spatiotemporal spread characteristics and medical carrying capacity during the early stages of COVID-19. This study employed textual analysis, mathematical statistics, and spatial analysis methods to examine the situation in six highly affected Chinese cities. The findings reveal that these cities experienced three phases during the initial outbreak of COVID-19: "unknown-origin incubation", "Wuhan-related outbreak", and "local exposure outbreak". Cities with a high number of confirmed cases exhibited a multicore pattern, while those with fewer cases displayed a single-core pattern. The cores were distributed hierarchically in the central built-up areas of cities' economic, political, or transportation centers. The radii of these cores shrank as the central built-up area's level decreased, indicating a hierarchical decay and a core-edge structure. It suggests that decentralized built environments (non-clustered economies and populations) are less likely to facilitate large-scale epidemic clusters. Additionally, the deployment of designated hospitals in these cities was consistent with the spatial distribution of the epidemic; however, their carrying capacity requires urgent improvement. Ultimately, the essence of prevention and control is the governance of human activities and the efficient management of limited resources about individuals, places, and materials through leveraging IT and GIS technologies to address supply-demand contradictions.


Subject(s)
COVID-19 , Epidemics , Humans , COVID-19/epidemiology , Cities/epidemiology , SARS-CoV-2 , Disease Outbreaks , China/epidemiology
13.
Huan Jing Ke Xue ; 45(2): 744-754, 2024 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-38471914

ABSTRACT

As one of the important paths for China to achieve the "dual carbon" strategy, developing hydrogen fuel cell vehicles is currently being promoted in various regions across the country, including passenger cars, coaches, and heavy-duty trucks. Quantifying the carbon reduction potential of hydrogen fuel cell vehicles for different vehicle types and regions has become a hot research topic. Using a life cycle assessment method that considers future vehicle fuel economy, power generation carbon emission factors, hydrogen production carbon emission factors, and regional differences in the scale and hydrogen production methods, this study quantitatively evaluated the life cycle carbon emissions of different types of vehicles, including fuel cell vehicles (FCV), traditional fuel vehicles (ICEV), and battery electric vehicles (BEV). We compared and analyzed the carbon reduction potential of hydrogen fuel cell vehicles at different times and in different regions and conducted an uncertainty analysis on hydrogen consumption per hundred kilometers. The results showed that by 2025, the life cycle carbon emissions of hydrogen fuel cell coaches would decrease by 36.0% compared to that of traditional fuel coaches, but the reduction in carbon emissions for hydrogen fuel cell heavy-duty trucks was not significant. By 2035, as the hydrogen energy source structure in China continues to improve, the life cycle carbon emissions of hydrogen fuel cell heavy-duty trucks were predicted to decrease by 36.5% compared to that of traditional fuel heavy-duty trucks. The decarbonization potential was most significant for heavy-duty trucks compared to that of passenger cars and coaches. Taking the Beijing-Tianjin-Hebei demonstration group as an example in 2035, as the hydrogen consumption per hundred kilometers decreases by 20%, the carbon reduction potential of FCV passenger cars, coaches, and heavy-duty trucks would increase by 7.29%, 9.93%, and 19.57%, respectively. Therefore, it is recommended to prioritize the promotion of hydrogen fuel cell coaches in the short term, heavy-duty trucks in the long term, and passenger cars as a supplement. Promoting hydrogen fuel cell vehicles in different regions and stages will help advance the low-carbon development of the automotive industry in China.

14.
Nat Commun ; 15(1): 1568, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383600

ABSTRACT

Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). SYCP2 promotes R-loop formation at DSBs and facilitates RAD51 recruitment independently of BRCA1. SYCP2 loss impairs RAD51 localization, reduces TC-HR, and renders tumors sensitive to PARP and topoisomerase I (TOP1) inhibitors. Furthermore, our studies of two clinical cohorts find that SYCP2 overexpression correlates with breast cancer resistance to antibody-conjugated TOP1 inhibitor and ovarian cancer resistance to platinum treatment. Collectively, our data suggest that SYCP2 confers cancer cell resistance to DNA-damaging agents by stimulating R-loop-mediated DSB repair, offering opportunities to improve DDR therapy.


Subject(s)
DNA Repair , R-Loop Structures , DNA Breaks, Double-Stranded , Homologous Recombination , BRCA1 Protein/genetics , BRCA1 Protein/metabolism , DNA , Rad51 Recombinase/genetics , Rad51 Recombinase/metabolism , Recombinational DNA Repair
15.
Nat Commun ; 15(1): 1254, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38341424

ABSTRACT

It has been extensively studied that the gut microbiome provides animals flexibility to adapt to food variability. Yet, how gut phageome responds to diet variation of wild animals remains unexplored. Here, we analyze the eco-evolutionary dynamics of gut phageome in six wild gibbons (Hoolock tianxing) by collecting individually-resolved fresh fecal samples and parallel feeding behavior data for 15 consecutive months. Application of complementary viral and microbial metagenomics recovers 39,198 virulent and temperate phage genomes from the feces. Hierarchical cluster analyses show remarkable seasonal diet variations in gibbons. From high-fruit to high-leaf feeding period, the abundances of phage populations are seasonally fluctuated, especially driven by the increased abundance of virulent phages that kill the Lachnospiraceae hosts, and a decreased abundance of temperate phages that piggyback the Bacteroidaceae hosts. Functional profiling reveals an enrichment through horizontal gene transfers of toxin-antitoxin genes on temperate phage genomes in high-leaf season, potentially conferring benefits to their prokaryotic hosts. The phage-host ecological dynamics are driven by the coevolutionary processes which select for tail fiber and DNA primase genes on virulent and temperate phage genomes, respectively. Our results highlight complex phageome-microbiome interactions as a key feature of the gibbon gut microbial ecosystem responding to the seasonal diet.


Subject(s)
Bacteriophages , Hylobates , Hylobatidae , Animals , Seasons , Ecosystem , Virome , Diet , Bacteriophages/genetics , Fruit
16.
Cell Rep ; 43(1): 113610, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38165804

ABSTRACT

Fanconi anemia (FA) is characterized by congenital abnormalities, bone marrow failure, and cancer susceptibility. The central FA protein complex FANCI/FANCD2 (ID2) is activated by monoubiquitination and recruits DNA repair proteins for interstrand crosslink (ICL) repair and replication fork protection. Defects in the FA pathway lead to R-loop accumulation, which contributes to genomic instability. Here, we report that the splicing factor SRSF1 and FANCD2 interact physically and act together to suppress R-loop formation via mRNA export regulation. We show that SRSF1 stimulates FANCD2 monoubiquitination in an RNA-dependent fashion. In turn, FANCD2 monoubiquitination proves crucial for the assembly of the SRSF1-NXF1 nuclear export complex and mRNA export. Importantly, several SRSF1 cancer-associated mutants fail to interact with FANCD2, leading to inefficient FANCD2 monoubiquitination, decreased mRNA export, and R-loop accumulation. We propose a model wherein SRSF1 and FANCD2 interaction links DNA damage response to the avoidance of pathogenic R-loops via regulation of mRNA export.


Subject(s)
Fanconi Anemia , Neoplasms , Humans , R-Loop Structures , Active Transport, Cell Nucleus , Fanconi Anemia/metabolism , Fanconi Anemia Complementation Group Proteins/metabolism , Fanconi Anemia Complementation Group D2 Protein/genetics , Fanconi Anemia Complementation Group D2 Protein/metabolism , Ubiquitination , DNA Repair , RNA, Messenger/genetics , RNA, Messenger/metabolism , DNA Damage , Serine-Arginine Splicing Factors/genetics , Serine-Arginine Splicing Factors/metabolism
17.
Virol J ; 21(1): 4, 2024 01 04.
Article in English | MEDLINE | ID: mdl-38178220

ABSTRACT

BACKGROUND: Cross-species transmission of zoonotic IAVs to humans is potentially widespread and lethal, posing a great threat to human health, and their cross-species transmission mechanism has attracted much attention. miRNAs have been shown to be involved in the regulation of IAVs infection and immunity, however, few studies have focused on the molecular mechanisms underlying miRNAs and mRNAs expression after IAVs cross-species infection. METHODS: We used tree shrews, a close relative of primates, as a model and used RNA-Seq and bioinformatics tools to analyze the expression profiles of DEMs and DEGs in the nasal turbinate tissue at different time points after the newly emerged swine influenza A virus SW2783 cross-species infection with tree shrews, and miRNA-mRNA interaction maps were constructed and verified by RT-qPCR, miRNA transfection and luciferase reporter assay. RESULTS: 14 DEMs were screened based on functional analysis and interaction map, miR-760-3p, miR-449b-2, miR-30e-3p, and miR-429 were involved in the signal transduction process of replication and proliferation after infection, miR-324-3p, miR-1301-1, miR-103-1, miR-134-5p, miR-29a, miR-31, miR-16b, miR-34a, and miR-125b participate in negative feedback regulation of genes related to the immune function of the body to activate the antiviral immune response, and miR-106b-3p may be related to the cross-species infection potential of SW2783, and the expression level of these miRNAs varies in different days after infection. CONCLUSIONS: The miRNA regulatory networks were constructed and 14 DEMs were identified, some of them can affect the replication and proliferation of viruses by regulating signal transduction, while others can play an antiviral role by regulating the immune response. It indicates that abnormal expression of miRNAs plays a crucial role in the regulation of cross-species IAVs infection, which lays a solid foundation for further exploration of the molecular regulatory mechanism of miRNAs in IAVs cross-species infection and anti-influenza virus targets.


Subject(s)
MicroRNAs , Animals , Humans , Swine , MicroRNAs/genetics , MicroRNAs/metabolism , Influenza A Virus, H3N2 Subtype/genetics , Tupaia , Gene Expression Profiling , Tupaiidae/genetics , Shrews , RNA, Messenger
18.
Med Res Rev ; 44(2): 686-706, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37983866

ABSTRACT

Cancer continues to be a major health concern globally, although the advent of targeted therapy has revolutionized treatment options. Aurora Kinase B is a serine-threonine kinase that has been explored as an oncology therapeutic target for more than two decades. Aurora Kinase B inhibitors show promising biological results in in-vitro and in-vivo experiments. However, there are no inhibitors approved yet for clinical use, primarily because of the side effects associated with Aurora B inhibitors. Several studies demonstrate that Aurora B inhibitors show excellent synergy with various chemotherapeutic agents, radiation therapy, and targeted therapies. This makes it an excellent choice as an adjuvant therapy to first-line therapies, which greatly improves the therapeutic window and side effect profile. Recent studies indicate the role of Aurora B in some deadly cancers with limited therapeutic options, like triple-negative breast cancer and glioblastoma. Herein, we review the latest developments in Aurora Kinase B targeted research, with emphasis on its potential as an adjuvant therapy and its role in some of the most difficult-to-treat cancers.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Aurora Kinase B/therapeutic use , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein Serine-Threonine Kinases/therapeutic use , Neoplasms/drug therapy , Aurora Kinase A/therapeutic use , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1024361

ABSTRACT

Objective To analyze the clinical efficacy of non-inflatable transaxillary approach and transthoracic approach surgery for thyroid cancer,and analyze the occurrence of postoperative complications in patients.Methods The clinical data of 88 patients with thyroid cancer who underwent surgical treatment in our hospital from October 2019 to November 2022 were analyzed.They were divided into group A and B according to the surgical method.Forty-five patients in group A received complete endoscopic thyroidectomy through the non-inflatable axillary approach,while 43 patients in group B received endoscopic thyroidectomy through the thoracic approach.The perioperative indicators,satisfaction with surgical incision,postoperative pain,and incidence of complications of patients in the two groups were compared.And the main influence factors for the occurrence of complications were analyzed.Results The total satisfaction rate for surgical incision of patients in group A was significantly higher than that in group B(P<0.05);while the intraoperative bleeding volume and postoperative drainage volume of patients in group A were significantly lower than those in group B(P<0.05).The VAS score 3 and 5 days after surgery were significantly lower than that 1 day after surgery(P<0.05),and the VAS score 5 days after surgery was lower than that 3 days after surgery(P<0.05).The incidence of postoperative complications in group A was significantly lower than that in group B(P<0.05).Logistic regression results showed that intraoperative bleeding volume was the independent influencing factor for postoperative complications(P<0.05).Conclusion Both non-inflatable transaxillary approach and transthoracic approach surgery are effective for thyroid cancer,but the non-inflatable transaxillary approach surgery has the advantages of concealed incision,higher postoperative aesthetics,and less intraoperative bleeding volume,postoperative drainage volume and postoperative complications.Excessive intraoperative bleeding is the main factor leading to postoperative complications.

20.
Journal of Chinese Physician ; (12): 172-175, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1026097

ABSTRACT

Objective:To explore the correlation between the ratio of C-reactive protein (CRP) to albumin (CAR) and the syndrome type of Wei-Qi-Ying-Xue in patients with severe coronavirus disease 2019 (COVID-19).Methods:A case-control study was conducted to select 63 severe patients with COVID-19 admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2022 to December 2023, including 50 severe cases and 13 critical cases. The clinical data of the patients were collected. According to the syndrome differentiation of Wei-Qi-Ying-Xue, there were 21 cases of Qi syndrome, 20 cases of Ying syndrome and 22 cases of Xue syndrome. The differences of CRP, ALB and CAR levels in patients with different Wei-Qi-Ying-Xue syndromes were compared. Spearman correlation test was used to test the correlation between CRP, ALB, CAR and the Wei-Qi-Ying-Xue syndrome type, and the receiver operating characteristic (ROC) curve was used to detect the diagnostic efficacy of CRP, ALB and CAR on the Wei-Qi-Ying-Xue syndrome type.Results:There was a statistically significant difference in the clinical classification of Western medicine among the three groups ( P<0.05). The CAR of the Ying group and the Xue group was higher than that of the Qi group ( P<0.05), while there was no statistically significant difference in age and comorbidities (all P>0.05). The CRP of the Xue group was higher than that of the Qi group ( P<0.05), and the ALB of the Ying group and the Xue group was lower than that of the Qi group (all P<0.05). Correlation analysis showed that there was a correlation between the Wei-Qi-Ying-Xue syndrome type and CRP, ALB and CAR ( P<0.05), among which CAR changed most significantly with the change of Wei-Qi-Ying-Xue syndrome type. ROC curve analysis showed that CRP, ALB and CAR had good diagnostic value for Qi syndrome and Xue syndrome ( P<0.05). The critical values of the diagnosis of Qi syndrome were 48.57 mg/L, 34.20 g/L and 2.97. The critical values of the diagnosis of Xue syndrome were 28.30 mg/L, 26.6 g/L and 5.96. Conclusions:CAR ratio is correlated with the Wei-Qi-Ying-Xue syndrome type of severe COVID-19 patients, and its level changes are in line with the evolution law of Wei-Qi-Ying-Xue syndrome. CAR≤2.97 is contributed to the diagnosis of Qi syndrome, and CAR>5.96 is contributed to the diagnosis of Xue syndrome. CAR may be an objective index related to the Wei-Qi-Ying-Xue syndrome type of severe COVID-19 patients.

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