ABSTRACT
Cancer-induced bone pain (CIBP) is one of the most common and feared symptoms in patients with advanced tumors. The X-C motif chemokine ligand 12 (CXCL12) and the CXCR4 receptor have been associated with glial cell activation in bone cancer pain. Moreover, mitogen-activated protein kinases (MAPKs), as downstream CXCL12/CXCR4 signals, and c-Jun, as activator protein AP-1 components, contribute to the development of various types of pain. However, the specific CIBP mechanisms remain unknown. Esketamine is a non-selective N-methyl-d-aspartic acid receptor (NMDA) inhibitor commonly used as an analgesic in the clinic, but its analgesic mechanism in bone cancer pain remains unclear. We used a tumor cell implantation (TCI) model and explored that CXCL12/CXCR4, p-MAPKs, and p-c-Jun were stably up-regulated in the spinal cord. Immunofluorescence images showed activated microglia in the spinal cord on day 14 after TCI and co-expression of CXCL12/CXCR4, p-MAPKs (p-JNK, p-ERK, p-p38 MAPK), and p-c-Jun in microglia. Intrathecal injection of the CXCR4 inhibitor AMD3100 reduced JNK and c-Jun phosphorylations, and intrathecal injection of the JNK inhibitor SP600125 and esketamine also alleviated TCI-induced pain and reduced the expression of p-JNK and p-c-Jun in microglia. Overall, our data suggest that the CXCL12/CXCR4-JNK-c-Jun signaling pathway of microglia in the spinal cord mediates neuronal sensitization and pain hypersensitivity in cancer-induced bone pain and that esketamine exerts its analgesic effect by inhibiting the JNK-c-Jun pathway.
Subject(s)
Bone Neoplasms , Cancer Pain , Ketamine , Humans , Rats , Animals , Cancer Pain/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Rats, Sprague-Dawley , Pain/metabolism , Bone Neoplasms/complications , Spinal Cord/metabolism , Mitogen-Activated Protein Kinases/metabolism , Spinal Cord Dorsal Horn/metabolism , Analgesics/pharmacology , Hyperalgesia/metabolismABSTRACT
Phytophthora capsici deploys effector proteins to manipulate host immunity and facilitate its colonization. However, the underlying mechanisms remain largely unclear. In this study, we demonstrated that a Sne-like (Snel) RxLR effector gene PcSnel4 is highly expressed at the early stages of P. capsici infection in Nicotiana benthamiana. Knocking out both alleles of PcSnel4 attenuated the virulence of P. capsici, while expression of PcSnel4 promoted its colonization in N. benthamiana. PcSnel4B could suppress the hypersensitive reaction (HR) induced by Avr3a-R3a and RESISTANCE TO PSEUDOMONAS SYRINGAE 2 (AtRPS2), but it did not suppress cell death elicited by Phytophthora infestin 1 (INF1) and Crinkler 4 (CRN4). COP9 signalosome 5 (CSN5) in N. benthamiana was identified as a host target of PcSnel4. Silencing NbCSN5 compromised the cell death induced by AtRPS2. PcSnel4B impaired the interaction and colocalization of Cullin1 (CUL1) and CSN5 in vivo. Expression of AtCUL1 promoted the degradation of AtRPS2 and disrupted HR, while AtCSN5a stabilized AtRPS2 and promoted HR, regardless of the expression of AtCUL1. PcSnel4 counteracted the effect of AtCSN5 and enhanced the degradation of AtRPS2, resulting in HR suppression. This study deciphered the underlying mechanism of PcSnel4-mediated suppression of HR induced by AtRPS2.
Subject(s)
Phytophthora infestans , Plant Immunity/genetics , Proteins/metabolism , Virulence , Cell Death/genetics , Plant Diseases , Nicotiana/metabolismABSTRACT
BACKGROUND: Ovarian cancer (OC) has the highest mortality rate among all gynecological malignancies. A hypoxic microenvironment is a common feature of solid tumors, including ovarian cancer, and an important driving factor of tumor cell survival and chemo- and radiotherapy resistance. Previous research identified the hypoxia-associated gene angiopoietin-like 4 (ANGPTL4) as both a pro-angiogenic and pro-metastatic factor in tumors. Hence, this work aimed to further elucidate the contribution of ANGPTL4 to OC progression. METHODS: The expression of hypoxia-associated ANGPTL4 in human ovarian cancer was examined by bioinformatics analysis of TCGA and GEO datasets. The CIBERSORT tool was used to analyze the distribution of tumor-infiltrating immune cells in ovarian cancer cases in TCGA. The effect of ANGPTL4 silencing and overexpression on the proliferation and migration of OVCAR3 and A2780 OC cells was studied in vitro, using CCK-8, colony formation, and Transwell assays, and in vivo, through subcutaneous tumorigenesis assays in nude mice. GO enrichment analysis and WGCNA were performed to explore biological processes and genetic networks associated with ANGPTL4. The results obtained were corroborated in OC cells in vitro by western blotting. RESULTS: Screening of hypoxia-associated genes in OC-related TCGA and GEO datasets revealed a significant negative association between ANGPTL4 expression and patient survival. Based on CIBERSORT analysis, differential representation of 14 distinct tumor-infiltrating immune cell types was detected between low- and high-risk patient groups. Silencing of ANGPTL4 inhibited OVCAR3 and A2780 cell proliferation and migration in vitro and reduced the growth rate of xenografted OVCAR3 cells in vivo. Based on results from WGCNA and previous studies, western blot assays in cultured OC cells demonstrated that ANGPTL4 activates the Extracellular signal-related kinases 1 and 2 (ERK1/2) pathway and this results in upregulation of c-Myc, Cyclin D1, and MMP2 expression. Suggesting that the above mechanism mediates the pro-oncogenic actions of ANGPTL4T in OC, the pro-survival effects of ANGPTL4 were largely abolished upon inhibition of ERK1/2 signaling with PD98059. CONCLUSIONS: Our work suggests that the hypoxia-associated gene ANGPTL4 stimulates OC progression through activation of the ERK1/2 pathway. These findings may offer a new prospect for targeted therapies for the treatment of OC.
ABSTRACT
Ubiquitination is the most common post-translational modification and is essential for various cellular regulatory processes. RNF187, which is known as RING domain AP1 coactivator-1, is a member of the RING finger family. RNF187 can promote the proliferation and migration of various tumor cells. However, whether it has a similar role in regulating spermatogonia is not clear. This study explored the role and molecular mechanism of RNF187 in a mouse spermatogonia cell line (GC-1). We found that RNF187 knockdown reduced the proliferation and migration of GC-1 cells and promoted their apoptosis. RNF187 overexpression significantly increased the proliferation and migration of GC-1 cells. In addition, we identified Keratin36/Keratin84 (KRT36/KRT84) as interactors with RNF187 by co-immunoprecipitation and mass spectrometry analyses. RNF187 promoted GC-1 cell growth by degrading KRT36/KRT84 via lysine 48-linked polyubiquitination. Subsequently, we found that KRT36 or KRT84 overexpression significantly attenuated proliferation and migration of RNF187-overexpressing GC-1 cells. In summary, our study explored the involvement of RNF187 in regulating the growth of spermatogonia via lysine 48-linked polyubiquitination-mediated degradation of KRT36/KRT84. This may provide a promising new strategy for treating infertility caused by abnormal spermatogonia development.
Subject(s)
Lysine , Spermatogonia , Ubiquitin-Protein Ligases , Animals , Male , Mice , Ubiquitin-Protein Ligases/genetics , UbiquitinationABSTRACT
The aging process of microplastics (MPs) could significantly change their physical and chemical characteristics and impact their migration behavior in soil. However, the complex effects of different cations and humic acids (HA) on the migration of aged MPs through saturated media are not clear. In this research, the migration and retention of pristine/aged PSMPs (polystyrene microplastics) under combined effects of cations (Na+, Ca2+) (ionic strength = 10 mM) and HA (0, 5, 15 mg/L) were investigated and analyzed in conjunction with the two-site kinetic retention model and DLVO theory. The findings showed that the aging process accelerated PSMPs migration under all tested conditions. Aged PSMPs were less susceptible to Ca2+ than pristine PSMPs. Under Ca2+ conditions, pristine/aged PSMPs showed higher retention than under Na+ conditions in the absence of HA. Furthermore, under Na+ conditions, the migration of aged PSMPs significantly increased at higher concentrations of HA. However, under Ca2+ conditions, the migration of aged PSMPs decreased significantly at higher concentrations of HA. In higher HA conditions, HA, Ca2+, and PSMPs interact to cause larger aggregations, resulting in the sedimentation of aged PSMPs. The DLVO calculations and two-site kinetic retention models' results showed the detention of PSMPs was irreversible under higher HA conditions (15 mg/L) with Ca2+, and aged PSMPs were more susceptible to clogging. These findings may help to understand the potential risk of migration behavior of PSMPs in the soil-groundwater environment.
Subject(s)
Cations , Humic Substances , Microplastics , Polystyrenes , Polystyrenes/chemistry , Microplastics/toxicity , Cations/chemistry , Porosity , Kinetics , Soil/chemistryABSTRACT
Previous research has predominantly relied on single-informant reports to establish the association between parental control and children's anxiety. However, there remains ambiguity regarding the extent to which discrepancies in parent-child reports of parental control are related to children anxiety. This study examined parent-child perceived discrepancies in parental control and their association with children's anxiety, along with the moderated effect of parent-child closeness through cross-sectional and prospective analysis. The sample consisted of 790 children (Mage = 11.34, SD = 6.73, 45.60% for girls), with 741 father-child dyads and 760 mother-child dyads included. Data were analyzed using polynomial regressions with response surface analysis. The results indicated that children tended to perceive higher levels of parental psychological control and lower levels of behavioral control compared to their parents' perceptions. In the cross-sectional analysis, a significant association between greater incongruence in psychological/behavioral control and higher levels of children's anxiety at T1 was observed exclusively in father-child dyads. In prospective analysis, for both father-child and mother-child dyads, congruence in higher levels of psychological control was associated with higher levels of children's anxiety at T2, while congruence in higher levels of behavioral control was associated with lower levels of children's anxiety at T2. Additionally, greater incongruence in psychological/behavioral control was linked to higher levels of children's anxiety at T2. Furthermore, mother-child closeness emerged as a significant moderator such that perceived incongruence in psychological/behavioral control could not affect children's anxiety at T2 in the high mother-child closeness condition. These findings highlight the significance of considering parent-child congruence and incongruence when examining the impact of parental control on children's anxiety.
ABSTRACT
RESEARCH QUESTION: What is the molecular function of hsa_circ_0001550 in decidualization? DESIGN: Human endometrial stromal cells (HESC) were isolated from the endometrium tissues to build an in-vitro decidualization model. Different concentrations of medroxyprogesterone acetate (MPA) were used to observe whether the expression level of hsa_circ_0001550 was related to progesterone. Biological characteristics and distribution of hsa_circ_0001550 were determined by RNase R, actinomycin D (Act D) assay and cytoplasmic/nuclear fraction assay. Then the overexpression of hsa_circ_0001550 was achieved by adenovirus vector. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assays. The cell cycle was assessed by flow cytometry analyses. Cell apoptosis was determined by annexin-V/propidium iodide double staining experiment and western blotting. RESULTS: The expression of hsa_circ_0001550 was decreased in decidua and decidualized HESC (P < 0.001, Pâ¯=â¯0.014). Hsa_circ_0001550 is a covalently closed RNA molecule that was verified by RNase R assay and Act D assay (Pâ¯=â¯0.012). Nuclear and cytoplasmic separation experiments confirmed that hsa_circ_0001550 was mainly distributed in the cytoplasm. Overexpression of hsa_circ_0001550 inhibited decidualization of HESC (P < 0.0001). Furthermore, overexpression of hsa_circ_0001550 inhibited proliferation by decreasing the number of S phase cells (Pâ¯=â¯0.033). Annexin-V/propidium iodide double staining experiment and western blotting revealed that overexpression of hsa_circ_0001550 promoted HESC apoptosis (P < 0.001, Pâ¯=â¯0.0139). CONCLUSIONS: Hsa_circ_0001550 impairs decidualization of HESC. Progesterone decreases the expression of hsa_circ_0001550. The results may provide new insights into the cause of decidualization.
Subject(s)
Decidua , MicroRNAs , RNA, Circular , Female , Humans , Annexins/metabolism , Apoptosis , Cell Proliferation , Decidua/metabolism , Endometrium/metabolism , MicroRNAs/metabolism , Progesterone/pharmacology , Progesterone/metabolism , Propidium/metabolism , Stromal Cells/metabolism , RNA, Circular/metabolism , Embryo ImplantationABSTRACT
Background: The pathogenesis of ankylosing spondylitis (AS) is still not clear, and immune-related genes have not been systematically explored in AS. The purpose of this paper was to identify the potential early biomarkers most related to immunity in AS and develop a predictive disease risk model with bioinformatic methods and the Gene Expression Omnibus database (GEO) to improve diagnostic and therapeutic efficiency. Methods: To identify differentially expressed genes and create a gene coexpression network between AS and healthy samples, we downloaded the AS-related datasets GSE25101 and GSE73754 from the GEO database and employed weighted gene coexpression network analysis (WGCNA). We used the GSVA, GSEABase, limma, ggpubr, and reshape2 packages to score immune data and investigated the links between immune cells and immunological functions by using single-sample gene set enrichment analysis (ssGSEA). The value of the core gene set and constructed model for early AS diagnosis was investigated by using receiver operating characteristic (ROC) curve analysis. Results: Biological function and immune score analyses identified central genes related to immunity, key immune cells, key related pathways, gene modules, and the coexpression network in AS. Granulysin (GNLY), Granulysin (GZMK), CX3CR1, IL2RB, dysferlin (DYSF), and S100A12 may participate in AS development through NK cells, CD8+ T cells, Th1 cells, and other immune cells and represent potential biomarkers for the early diagnosis of AS occurrence and progression. Furthermore, the T cell coinhibitory pathway may be involved in AS pathogenesis. Conclusion: The AS disease risk model constructed based on immune-related genes can guide clinical diagnosis and treatment and may help in the development of personalized immunotherapy.
Subject(s)
CD8-Positive T-Lymphocytes , Spondylitis, Ankylosing , Humans , Spondylitis, Ankylosing/genetics , Biomarkers , Computational Biology , Databases, FactualABSTRACT
Non-coding RNA (ncRNA) refers to RNA that lack the ability to encode protein. Based on their distinct biological characteristics, ncRNA are mainly classified into microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). NcRNA plays a crucial regulatory role in various biological processes. Pregnancy is a highly intricate physiological process that requires successful completion of multiple steps. Embryo implantation, as a key event of pregnancy, which is regulated by numerous factors, including embryo development, endometrial changes, and the maternal-embryo crosstalk. A diverse array of regulatory mechanisms ensures the accomplishment of embryo localization, adhesion, invasion, and ultimately successful implantation. MiRNA, lncRNA, and circRNA are extensively studied ncRNA molecules at present, which play an important role in the physiological and pathological processes associated with embryo implantation through targeting and regulating the expression of multiple cytokine and genes. With advancements in molecular biology technology, it is anticipated that ncRNA will contribute to the prediction and enhancement of clinical pregnancy outcomes from a molecular perspective.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Pregnancy , Female , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Circular , Embryo Implantation/genetics , RNA, Untranslated/genetics , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung fibrosis with a high mortality rate. This study aimed to uncover the underlying molecular features for different types of IPF. IPF microarray datasets were retrieved from GEO databases. Weighted gene co-expression analysis (WGCNA) was used and identified subgroup-specific WGCNA modules. Infiltration-level immune cells in different subgroups of microenvironments were analyzed with CIBERSORT algorithms. The result is we classified 173 IPF cases into two subgroups based on gene expression profiles, which were retrieved from the GEO databases. The SGRQ score and age were significantly higher in C2 than in C1. Using WGCNA, five subgroup-specific modules were identified. M4 was mainly enriched by MAPK signaling, which was mainly expressed in C2; M1, M2, and M3 were mainly enriched by metabolic pathways and Chemokine signaling, and the pathway of M5 was phagosome inflammation; M1, M2, M3, and M5 were mainly expressed in C1. Utilizing the CIBERSORT, we showed that the number of M1 macrophage cells, CD8 T cells, regulatory T cells (Tregs), and Plasma cells was significantly different between C1 and C2. We found the molecular subgroups of IPF revealed that cases from different subgroups may have their unique patterns and provide novel information to understand the mechanisms of IPF itself.
Subject(s)
Idiopathic Pulmonary Fibrosis , Gene Expression Profiling , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/metabolism , Inflammation/metabolism , Lung/metabolism , Metabolic Networks and Pathways , Transcriptome/geneticsABSTRACT
The difficulty in maintaining the balance between oxides and antioxidants causes a phenomenon named oxidative stress. Oxidative stress often leads to tissue damage and participates in the pathogenesis of a series of diseases. Decidua provides the 'soil' for embryo implantation, and the normal decidualization shows the characteristics of strong antioxidation. Once the mechanism of antioxidant stress goes awry, it will lead to a series of pregnancy-related diseases. In recent years, more and more studies have shown that oxidative stress is involved in pregnancy-related diseases caused by abnormal decidualization of the endometrium. In order to have a more comprehensive understanding of the role of oxidative stress in decidual defect diseases, this paper reviews the common decidual defect diseases in conjunction with relevant regulatory molecules, in order to arouse thinking about the importance of oxidative stress, and to provide more theoretical basis for the aetiology of decidual defects.
Subject(s)
Decidua , Pregnancy Complications , Pregnancy , Female , Humans , Endometrium/pathology , Embryo Implantation , Pregnancy Complications/pathology , Oxidative Stress , Stromal CellsABSTRACT
The Waveflex semi-rigid-dynamic-internal-fixation system shows good short-term effects in the treatment of lumbar degenerative diseases, but there are few long-term follow-up studies, especially for recovery of sagittal balance. Fifty patients with lumbar degenerative diseases treated from January 2016 to October 2017 were retrospectively analysed: 25 patients treated with Waveflex semi-rigid-dynamic-internal-fixation system (Waveflex group) and 25 patients treated with double-segment PLIF (PLIF group). Clinical efficacy was evaluated by Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). Imaging data before surgery and at 3 months, 1 year, and 5 years postoperatively was used for imaging indicator assessment. Local disc degeneration of the cephalic adjacent segment (including disc height index (DHI), intervertebral foramen height (IFH), and range of motion (ROM)) and overall spinal motor function (including lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and |PI-LL|) were analysed. Regarding clinical efficacy, comparison of VAS and ODI scores between the Waveflex and PLIF groups showed no significant preoperative or postoperative differences. The comparison of the objective imaging indicators showed no significant differences in the DHI, IFH, LL, |PI-LL|, and SS values between the Waveflex and PLIF groups preoperatively and 3 months postoperatively (P > 0.05). These values were significantly different at 1 and 5 years postoperatively (P < 0.05), and the Waveflex group showed better ROM values than those of the PLIF group (P < 0.05). PI values were not significantly different between the groups, but PT showed a significant improvement in the Waveflex group 5 years postoperatively (P < 0.05). The Waveflex semi-rigid dynamic fixation system can effectively reduce the probability of intervertebral disc degeneration in upper adjacent segments. Simultaneously, patients in the Waveflex group showed postoperative improvements in LL, spinal sagittal imbalance, and quality of life.
Subject(s)
Intervertebral Disc Degeneration , Lumbar Vertebrae , Humans , Male , Female , Intervertebral Disc Degeneration/surgery , Intervertebral Disc Degeneration/diagnostic imaging , Middle Aged , Retrospective Studies , Lumbar Vertebrae/surgery , Lumbar Vertebrae/diagnostic imaging , Treatment Outcome , Adult , Range of Motion, Articular , Spinal Fusion/methods , Aged , Internal Fixators , Lordosis/diagnostic imaging , Lordosis/surgeryABSTRACT
BACKGROUND: F-box-only protein 22 (FBXO22), an important substrate receptor of the SKP1-Cullin-F-box (SCF) ubiquitin ligases, has been reported to be involved in many biological processes, including tumorigenesis, neurological disorders, cellular senescence, and DNA damage. However, the specific role of FBXO22 during spermatogenesis is poorly understood. METHODS: We produced Fbxo22 conditional knockout (cKO) and global knockout (KO) mice and assessed their sperm masurements using a computer-assisted sperm analysis (CASA) system. Additionally, we conducted histologic staining and immunostaining to examine the impact of Fbxo22 loss on spermatogenesis. RESULTS: Our results revealed that there were no notable differences in semen quality, fertility test results, or histologic findings in Fbxo22-KO and Fbxo22-cKO mice compared to the control group. CONCLUSIONS: Our study demonstrated that Fbxo22 is not significant for spermatogenesis or male fertility in mice. These findings will help researchers avoid redundant efforts and serve as a foundational resource for genetic studies on human fertility.
ABSTRACT
RING finger 187 (RNF187), a ubiquitin-ligating (E3) enzyme, plays a crucial role in the proliferation of cancer cells. However, it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells. To investigate the potential involvement of RNF187 in germ cell development, we conducted interference and overexpression assays using GC-2 cells, a mouse spermatocyte-derived cell line. Our findings reveal that the interaction between RNF187 and histone H3 increases the viability, proliferation, and migratory capacity of GC-2 cells. Moreover, we provide evidence demonstrating that RNF187 interacts with H3 and mediates the ubiquitination of H3 at lysine 57 (K57) or lysine 80 (K80), directly or indirectly resulting in increased cellular transcription. This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediating histone H3 ubiquitination, thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of gene transcription. These discoveries provide a new theoretical foundation for further comprehensive investigations into the function of RNF187 in the reproductive system.
Subject(s)
Cell Proliferation , Histones , Ubiquitin-Protein Ligases , Ubiquitination , Animals , Histones/metabolism , Mice , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Male , Cell Proliferation/physiology , Cell Proliferation/genetics , Cell Line , Spermatocytes/metabolism , Cell Movement/genetics , Cell Movement/physiology , Lysine/metabolism , Cell Survival/physiology , Cell Survival/geneticsABSTRACT
BACKGROUND: Ovarian cancer is a common gynecological tumor with high malignant potential and poor prognosis. TRIM8, is involved in the development of various tumors, but its precise regulatory role in ovarian cancer is still unknown. AIMS: The aim of this study was to explore the specific mechanism by which TRIM8 regulates ovarian cancer. MATERIALS AND METHODS: We used bioinformatics analysis to screen for high expression of TRIM8 in ovarian cancer. The expression of TRIM8 in healthy and cancerous ovarian tissues was assessed by immunofluorescence. TRIM8 was silenced or overexpressed in ovarian cancer cell lines, with cell proliferation and migration evaluated by CCK8, transwell and clonal formation assays. The effect of TRIM8 on ovarian cancer cells in vivo was assessed by subcutaneous tumor formation experiments in nude mice. The potential interacting protein VDAC2 was identified by mass spectrometry. The mechanism underlying TRIM8 regulation of VDAC2 was evaluated by co-immunoprecipitation and western blotting. RESULTS: TRIM8 was overexpressed in ovarian cancer. TRIM8 promoted the proliferation and migration of ovarian cancer cells in vitro and the growth of subcutaneous tumors in mice in vivo. TRIM8 interacted with VDAC2, weakened the stability of the protein, and promoted its polyubiquitination and subsequent degradation. Knockdown of VDAC2 increased the resistance of ovarian cancer cells to iron death, whereas overexpression of VDAC2 attenuated ovarian cancer progression induced by TRIM8 overexpression. DISCUSSION: TRIM8 promotes ovarian cancer proliferation and migration by targeting VDAC2 for ubiquitination and degradation, these finding may provide new targets for the treatment of ovarian cancer. CONCLUSION: TRIM8 degraded VDAC2 through the ubiquitination pathway, increased the resistance of ovarian cancer cells to iron death, and promoted the proliferation and migration of ovarian cancer.
Subject(s)
Cell Movement , Cell Proliferation , Mice, Nude , Ovarian Neoplasms , Ubiquitination , Voltage-Dependent Anion Channel 2 , Humans , Female , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Ovarian Neoplasms/genetics , Animals , Mice , Voltage-Dependent Anion Channel 2/metabolism , Voltage-Dependent Anion Channel 2/genetics , Cell Line, Tumor , Proteolysis , Gene Expression Regulation, Neoplastic , Xenograft Model Antitumor AssaysABSTRACT
The molecular mechanisms underlying unexplained recurrent implantation failure (RIF) remain unclear. This study aimed at identifying potential biomarkers, exploring relevant signaling pathways, and analyzing the contribution of immune cell infiltration in RIF. Microarray expression datasets were extracted from the Gene Expression Omnibus database to perform bioinformatic analyses. The results showed that ten hub genes may predict RIF with high specificity and sensitivity (area under the curve = 1.000). Protein-protein interaction analysis revealed close interactions between the hub genes and the endometrial receptivity array. The real-time quantitative polymerase chain reaction further validated three potential biomarkers (RAB32, TRIB2, and FAM155B). Functional enrichment analyses indicated that immune pathways were significantly downregulated and lipid metabolism pathways were significantly upregulated in RIF compared with the controls. Significant negative correlations were observed between fatty acid biosynthesis and the immune pathways. Immune cell infiltration, including those in CD56dim natural killer, dendritic, Th1, Th2, and regulatory T cells, as well as macrophages, was significantly reduced in RIF compared with the controls used herein. This study may provide a novel perspective on the diagnosis and treatment of RIF.
Subject(s)
Embryo Implantation , Endometrium , Female , Humans , Endometrium/metabolism , Proteins/metabolism , Microarray Analysis , Biomarkers/metabolismABSTRACT
OBJECTIVE: New vertebral compression fracture (NVCF) occurring after bone cement injection in middle-aged and elderly patients with vertebral compression fracture is very common. Preoperative baseline characteristics and surgical treatment parameters have been widely studied as a risk factor, but the importance of the patients' laboratory indicators has not been thoroughly explored. We aimed to explore the relationship between laboratory indicators and NVCF, and attempt to construct a clinical prediction model of NVCF together with other risk factors. METHODS: Retrospective analysis was performed for 200 patients who underwent bone cement injection (percutaneous kyphoplasty or vertebroplasty) for vertebral compression fractures between January 2019 and January 2020. We consulted the relevant literature and collated the factors affecting the occurrence of NVCF. Feature selection of patients with NVCF was optimized using the least absolute shrinkage and selection operator regression model, which was used to conduct multivariable logistic regression analysis, to create a predictive model incorporating the selected features. The discrimination, calibration, and clinical feasibility of the predictive model were assessed using the concordance index (C-index), calibration plots, and decision curve analysis. Internal validation was performed using Bootstrap resampling verification. RESULTS: Time from injury to surgery exceeding 7 days, low osteocalcin levels, elevated homocysteine levels, osteoporosis, mode of operation (percutaneous vertebroplasty), lack of postoperative anti-osteoporosis treatment, and poor diffusion of bone cement were independent risk factors for NVCF in middle-aged and elderly patients with vertebral compression fracture after bone cement injection. The C-index of the nomogram constructed using these seven factors was 0.895, indicating good discriminatory ability. The calibration plot showed that the model was well calibrated. Bootstrap resampling verification yielded a significant C-index of 0.866. Decision curve analysis demonstrated that the greatest clinical net benefit for predicting NVCF after bone cement injection could be achieved with a threshold of 1%-91%. CONCLUSION: This nomogram can effectively predict NVCF incidence after bone cement injection in middle-aged and elderly patients with vertebral compression fracture, thus aiding clinical decision-making and postoperative management, promoting effective postoperative rehabilitation, and improving the quality of life.
Subject(s)
Fractures, Compression , Kyphoplasty , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Aged , Middle Aged , Humans , Fractures, Compression/surgery , Spinal Fractures/surgery , Spinal Fractures/etiology , Bone Cements/adverse effects , Osteoporotic Fractures/surgery , Osteoporotic Fractures/etiology , Retrospective Studies , Models, Statistical , Nomograms , Quality of Life , Treatment Outcome , Prognosis , Vertebroplasty/adverse effects , Kyphoplasty/adverse effectsABSTRACT
Objective: To explore the influence and potential factors of the bone cement dispersion state on residual pain after vertebral augmentation. Methods: The cases included in this retrospective cohort study were patients treated with vertebral augmentation (VA) for osteoporotic vertebral compression fractures (OVCFs) between July 2018 and June 2021. According to the type of cement diffusion distribution, the patients were divided into a sufficient diffusion group (Group A) and an insufficient diffusion group (Group B). The differences in the baseline data, visual analog scale (VAS), Oswestry disability index score (ODI), injured vertebral height (IVH), and local kyphosis angle (LKA) between the two groups were analyzed. Assessments were performed preoperatively on the 2nd day postoperation and at the last follow-up. The imaging data of injured vertebrae were accurately reconstructed by a GE AW4.7 workstation, and the differences in the vertebral body volume, bone cement volume, and bone cement volume ratio were compared between the groups. Result: After screening, 36 patients were included. (1) The postoperative VAS and ODI scores of the two groups were significantly improved compared with the preoperative scores. (2) On the 2nd day postoperation and the last follow-up, the VAS and ODI scores of Group A were significantly different from those of Group B, and Group A outperformed Group B. (3) The IVH and LKA of the two groups were improved after the operation, and no significant difference was found between the groups. (4) Significant differences were found in the bone cement volume and bone cement volume ratio between the groups, and Group A was larger than Group B. Conclusions: Sufficient bone cement diffusion can reduce residual pain after vertebral augmentation.
Subject(s)
Fractures, Compression , Osteoporotic Fractures , Spinal Fractures , Vertebroplasty , Humans , Bone Cements/therapeutic use , Fractures, Compression/diagnostic imaging , Fractures, Compression/surgery , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Retrospective Studies , Treatment Outcome , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/surgery , Spine , PainABSTRACT
As a destructive plant pathogen, Phytophthora infestans secretes diverse host-entering RxLR effectors to facilitate infection. One critical RxLR effector, PiAvr3b, not only induces effector-triggered immunity (ETI), which is associated with the potato resistance protein StR3b, but also suppresses pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). To date, the molecular basis underlying such dual activities remains unknown. Based on phylogenetic analysis of global P. infestans isolates, we found two PiAvr3b isoforms that differ by three amino acids. Despite this sequence variation, the two isoforms retain the same properties in activating the StR3b-mediated hypersensitive response (HR) and inhibiting necrosis induced by three PAMPs (PiNpp, PiINF1, and PsXeg1) and an RxLR effector (Pi10232). Using a combined mutagenesis approach, we found that the dual activities of PiAvr3b were tightly linked and determined by 88 amino acids at the C-terminus. We further determined that either the W60 or the E134 residue of PiAvr3b was essential for triggering StR3b-associated HR and inhibiting PiNpp- and Pi10232-associated necrosis, while the S99 residue partially contributed to PTI suppression. Additionally, nuclear localization of PiAvr3b was required to stimulate HR and suppress PTI, but not to inhibit Pi10232-associated cell death. Our study revealed that PiAvr3b suppresses the plant immune response at different subcellular locations and provides an example in which a single amino acid of an RxLR effector links ETI induction and cell death suppression.
Subject(s)
Phytophthora infestans , Phylogeny , Cell Death , Plants , Plant Immunity , Necrosis , Amino Acids/metabolism , Plant DiseasesABSTRACT
Thousands of genes are expressed in the testis of mice. However, the details about their roles during spermatogenesis have not been well-clarified for most genes. The purpose of this study was to examine the effect of Slc26a1 deficiency on mouse spermatogenesis and male fertility. Slc26a1-knockout (KO) mice were generated using CRISPR/Cas9 technology on C57BL/6J background. We found no obvious differences between Slc26a1-KO and Slc26a1-WT mice in fertility tests, testicular weight, sperm concentrations, or morphology. Histological analysis found that Slc26a1-KO mouse testes had normal germ cell types and mature sperm. These findings indicated that Slc26a1 was dispensable for male fertility in mice. Our results may save time and resources by allowing other researchers to focus on genes that are more meaningful for fertility studies. We also found that mRNAs of two Slc26a family members (Slc26a5 and Slc26a11) were expressed on higher mean levels in Slc26a1-KO total mouse testes, compared to Slc26a1-WT mice. This effect was not found in mouse GC-1 and GC-2 germ cell lines with the Slc26a1 gene transiently knocked down. This result may indicate that a gene compensation phenomenon was present in the testes of Slc26a1-KO mice.