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1.
J Immunother Cancer ; 12(5)2024 May 09.
Article in English | MEDLINE | ID: mdl-38724465

ABSTRACT

BACKGROUND: CD276 (B7-H3), a pivotal immune checkpoint, facilitates tumorigenicity, invasiveness, and metastasis by escaping immune surveillance in a variety of tumors; however, the underlying mechanisms facilitating immune escape in esophageal squamous cell carcinoma (ESCC) remain enigmatic. METHODS: We investigated the expression of CD276 in ESCC tissues from patients by using immunohistochemistry (IHC) assays. In vivo, we established a 4-nitroquinoline 1-oxide (4NQO)-induced CD276 knockout (CD276wKO) and K14cre; CD276 conditional knockout (CD276cKO) mouse model of ESCC to study the functional role of CD276 in ESCC. Furthermore, we used the 4NQO-induced mouse model to evaluate the effects of anti-CXCL1 antibodies, anti-Ly6G antibodies, anti-NK1.1 antibodies, and GSK484 inhibitors on tumor growth. Moreover, IHC, flow cytometry, and immunofluorescence techniques were employed to measure immune cell proportions in ESCC. In addition, we conducted single-cell RNA sequencing analysis to examine the alterations in tumor microenvironment following CD276 depletion. RESULTS: In this study, we elucidate that CD276 is markedly upregulated in ESCC, correlating with poor prognosis. In vivo, our results indicate that depletion of CD276 inhibits tumorigenesis and progression of ESCC. Furthermore, conditional knockout of CD276 in epithelial cells engenders a significant downregulation of CXCL1, consequently reducing the formation of neutrophil extracellular trap networks (NETs) via the CXCL1-CXCR2 signaling axis, while simultaneously augmenting natural killer (NK) cells. In addition, overexpression of CD276 promotes tumorigenesis via increasing NETs' formation and reducing NK cells in vivo. CONCLUSIONS: This study successfully elucidates the functional role of CD276 in ESCC. Our comprehensive analysis uncovers the significant role of CD276 in modulating immune surveillance mechanisms in ESCC, thereby suggesting that targeting CD276 might serve as a potential therapeutic approach for ESCC treatment.


Subject(s)
B7 Antigens , Chemokine CXCL1 , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Receptors, Interleukin-8B , Animals , Esophageal Squamous Cell Carcinoma/immunology , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/metabolism , Mice , Humans , Receptors, Interleukin-8B/metabolism , Esophageal Neoplasms/immunology , Esophageal Neoplasms/pathology , B7 Antigens/metabolism , Chemokine CXCL1/metabolism , Extracellular Traps/metabolism , Tumor Escape , Female , Male , Mice, Knockout , Tumor Microenvironment
2.
J Org Chem ; 89(8): 5442-5457, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38567881

ABSTRACT

In this study, concise, efficient, and modular hydrophosphinylation and hydroamidation of gem-difluorocyclopropenes were disclosed in a mild and transition-metal-free pattern. Through this approach, phosphorus, and nitrogen-containing gem-difluorocyclopropanes were produced in moderate to good yields with excellent regio- and diastereoselectivity. Readily available gem-difluorocyclopropenes and nucleophilic reagents, along with inexpensive inorganic bases, were employed. Multiple synthetic applications, including gram-scale and derivatization reactions and modification of bioactive molecules, were subsequently elaborated.

3.
Microorganisms ; 12(4)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38674616

ABSTRACT

In our previous microbiome profiling analysis, Lactobacillus (L.) johnsonii was suggested to contribute to resistance against chronic heat stress-induced diarrhea in weaned piglets. Forty-nine L. johnsonii strains were isolated from these heat stress-resistant piglets, and their probiotic properties were assessed. Strains N5 and N7 exhibited a high survival rate in acidic and bile environments, along with an antagonistic effect against Salmonella. To identify genes potentially involved in these observed probiotic properties, the complete genome sequences of N5 and N7 were determined using a combination of Illumina and nanopore sequencing. The genomes of strains N5 and N7 were found to be highly conserved, with two N5-specific and four N7-specific genes identified. Multiple genes involved in gastrointestinal environment adaptation and probiotic properties, including acidic and bile stress tolerance, anti-inflammation, CAZymes, and utilization and biosynthesis of carbohydrate compounds, were identified in both genomes. Comparative genome analysis of the two genomes and 17 available complete L. johnsonii genomes revealed 101 genes specifically harbored by strains N5 and N7, several of which were implicated in potential probiotic properties. Overall, this study provides novel insights into the genetic basis of niche adaptation and probiotic properties, as well as the genome diversity of L. johnsonii.

4.
Aging (Albany NY) ; 16(7): 6445-6454, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38575312

ABSTRACT

PURPOSE: The aim of this study was to investigate whether young patients with endometrial carcinoma can preserve adnexa and lymph nodes to improve their quality of life without compromising their prognosis. METHODS: A total of 319 patients with type I endometrial carcinoma (high or moderate differentiation and less than 1/2 myometrial invasion) hospitalized in the First Affiliated Hospital of Zhengzhou University from May 2012 to July 2021 were included. The patients were divided into four groups: high differentiation without myometrial invasion group (G1MI-), high differentiation with superficial myometrial invasion group (G1MI+), moderate differentiation without myometrial invasion group (G2MI-), and moderate differentiation with superficial myometrial invasion group (G2MI+). Logistic regression analysis was conducted to identify risk factors for extra-uterine involvement. Kaplan-Meier method was used to draw the survival curve to compare the prognosis in subgroups and rates of extra-uterine involvement were also compared using Chi-square test or Fisher's exact test. RESULTS: Multivariable logistic regression revealed that differentiation (HR = 14.590, 95%CI = 1.778-119.754, p = 0.013) and myometrial invasion (HR = 10.732, 95%CI = 0.912-92.780, p = 0.037) were the independent risk factors for extra-uterine involvement. The overall difference was statistically significant (p < 0.001). In the subgroups analysis, both adnexal metastasis and lymph node metastasis were statistically significant in the G2MI+ group compared with G1MI- (p = 0.007, p = 0.008). There were no significant differences in the overall survival (OS) rate and progression free survival (PFS) rate among the four subgroups (p > 0.05). CONCLUSIONS: Surgery with adnexal preservation and without systematic lymphadenectomy could be employed for the patients who are high differentiation with less than 1/2 myometrial invasion or moderate differentiation without myometrial invasion, but not recommended to the patients with moderate differentiation and superficial myometrial invasion.


Subject(s)
Endometrial Neoplasms , Myometrium , Neoplasm Invasiveness , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/mortality , Myometrium/pathology , Prognosis , Middle Aged , Adult , Risk Assessment , Risk Factors , Cell Differentiation , Lymphatic Metastasis/pathology
5.
Cancer Immunol Immunother ; 73(6): 97, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38619620

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity with various immune cell infiltration patterns, which have been associated with therapeutic sensitivity and resistance. In particular, dendritic cells (DCs) are recently discovered to be associated with prognosis and survival in cancer. However, how DCs differ among ESCC patients has not been fully comprehended. Recently, the advance of single-cell RNA sequencing (scRNA-seq) enables us to profile the cell types, states, and lineages in the heterogeneous ESCC tissues. Here, we dissect the ESCC tumor microenvironment at high resolution by integrating 192,078 single cells from 60 patients, including 4379 DCs. We then used Scissor, a method that identifies cell subpopulations from single-cell data that are associated bulk samples with genomic and clinical information, to stratify DCs into Scissorhi and Scissorlow subtypes. We applied the Scissorhi gene signature to stratify ESCC scRNAseq patient, and we found that PD-L1, TIGIT, PVR and IL6 ligand-receptor-mediated cell interactions existed mainly in Scissorhi patients. Finally, based on the Scissor results, we successfully developed a validated prognostic risk model for ESCC and further validated the reliability of the risk prediction model by recruiting 40 ESCC clinical patients. This information highlights the importance of these genes in assessing patient prognosis and may help in the development of targeted or personalized therapies for ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Prognosis , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Neoplasms/genetics , Reproducibility of Results , Immunity , Dendritic Cells , Tumor Microenvironment/genetics
6.
Int J Surg ; 110(5): 3072-3080, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38445439

ABSTRACT

PURPOSE: Endometrial cancer arising in adenomyosis (EC-AIA) is frequently detected accidentally following a general hysterectomy for adenomyosis. Whether supplemental lymphadenectomy in patients with EC-AIA can improve the survival outcome remains inconclusive. Herein, the authors summarized the data of patients with EC-AIA and further explored the impact of lymphadenectomy on the prognosis of these patients. METHODS: Five electronic databases, namely MEDLINE, Web of Science, PubMed, Embase, and the Cochrane Library were employed for searching articles from inception to May 2023. RESULTS: In total, 38 eligible studies enrolling 56 patients were included. Of these, 44 patients had a traceable prognosis. Kaplan-Meier curves demonstrated that patients who had undergone lymphadenectomy had a better progression-free survival (PFS) compared with those who had not undergone lymphadenectomy ( P =0.016), but there was no difference in overall survival. Univariable ( P =0.025, HR=0.25, 95% CI=0.08-0.84) and multivariable ( P =0.042, HR=0.13, 95% CI=0.020-0.930) Cox regression analyses revealed that lymphadenectomy was an independent protective factor for PFS. CONCLUSION: For patients diagnosed with EC-AIA following hysterectomy for benign disease, further supplementary lymphadenectomy is recommended to improve PFS.


Subject(s)
Adenomyosis , Endometrial Neoplasms , Hysterectomy , Lymph Node Excision , Humans , Female , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology , Endometrial Neoplasms/mortality , Adenomyosis/surgery , Adenomyosis/complications , Prognosis
7.
iScience ; 27(3): 109327, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38487015

ABSTRACT

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

8.
Nat Commun ; 15(1): 2449, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38503771

ABSTRACT

Wheat powdery mildew is one of the most destructive diseases threatening global wheat production. The wild relatives of wheat constitute rich sources of diversity for powdery mildew resistance. Here, we report the map-based cloning of the powdery mildew resistance gene Pm13 from the wild wheat species Aegilops longissima. Pm13 encodes a mixed lineage kinase domain-like (MLKL) protein that contains an N-terminal-domain of MLKL (MLKL_NTD) domain in its N-terminus and a C-terminal serine/threonine kinase (STK) domain. The resistance function of Pm13 is validated by mutagenesis, gene silencing, transgenic assay, and allelic association analyses. The development of introgression lines with significantly reduced chromosome segments of Ae. longissima encompassing Pm13 enables widespread deployment of this gene into wheat cultivars. The cloning of Pm13 may provide valuable insights into the molecular mechanisms underlying Pm13-mediated powdery mildew resistance and highlight the important roles of kinase fusion proteins (KFPs) in wheat immunity.


Subject(s)
Aegilops , Ascomycota , Triticum/genetics , Genes, Plant , Disease Resistance/genetics , Ascomycota/genetics , Aegilops/genetics , Protein Kinases/genetics , Plant Diseases/genetics
9.
Plant Cell ; 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38552172

ABSTRACT

S-acylation is a reversible post-translational modification catalyzed by protein S-acyltransferases (PATs), and acyl protein thioesterases (APTs) mediate de-S-acylation. Although many proteins are S-acylated, how the S-acylation cycle modulates specific biological functions in plants is poorly understood. In this study, we report that the S-acylation cycle of transcription factor MtNAC80 is involved in the Medicago truncatula cold stress response. Under normal conditions, MtNAC80 localized to membranes through MtPAT9-induced S-acylation. In contrast, under cold stress conditions, MtNAC80 translocated to the nucleus through de-S-acylation mediated by thioesterases such as MtAPT1. MtNAC80 functions in the nucleus by directly binding the promoter of the glutathione S-transferase gene MtGSTU1 and promoting its expression, which enables plants to survive under cold stress by removing excess malondialdehyde and H2O2. Our findings reveal an important function of the S-acylation cycle in plants and provide insight into stress response and tolerance mechanisms.

10.
Eur J Surg Oncol ; 50(4): 108260, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38484492

ABSTRACT

PURPOSE: The aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC). METHODS: A total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM. RESULTS: Univariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558-7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327-5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919-8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344-6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1-1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056-16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933-12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003-17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly. CONCLUSIONS: Cervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.


Subject(s)
Endometrial Neoplasms , Lymph Node Excision , Female , Humans , Lymphatic Metastasis/pathology , Retrospective Studies , Endometrial Neoplasms/pathology , Lymph Nodes/pathology , Risk Factors , Neoplasm Staging , Neoplasm Invasiveness/pathology
11.
Chemistry ; : e202400157, 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38520385

ABSTRACT

Up to now, the mainstream adoption of renewable energy has brought about substantial transformations in the electricity and energy sector. This shift has garnered considerable attention within the scientific community. Supercapacitors, known for their exceptional performance metrics like good charge/discharge capability, strong power density, as well as extended cycle longevity, have gained widespread traction across various sectors, including transportation and aviation. Metal-organic frameworks (MOFs) with unique traits including adaptable structure, highly customizable synthetic methods, and high specific surface area, have emerged as strong candidates for electrode materials. For enhancing the performance, MOFs are commonly compounded with other conducting materials to increase capacitance. This paper provides a detailed analysis of various common preparation strategies and characteristics of MOFs. It summarizes the recent application of MOFs and their derivatives as supercapacitor electrodes alongside other carbon materials, metal compounds, and conductive polymers. Additionally, the challenges encountered by MOFs in the realm of supercapacitor applications are thoroughly discussed. Compared to previous reviews, the content of this paper is more comprehensive, offering readers a deeper understanding of the diverse applications of MOFs. Furthermore, it provides valuable suggestions and guidance for future progress and development in the field of MOFs.

12.
Cell Rep Med ; 5(2): 101414, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38330942

ABSTRACT

ADG106, a ligand-blocking agonistic antibody targeting CD137 (4-1BB), exhibits promising results in preclinical studies, demonstrating tumor suppression in various animal models and showing a balanced profile between safety and efficacy. This phase 1 study enrolls 62 patients with advanced malignancies, revealing favorable tolerability up to the 5.0 mg/kg dose level. Dose-limiting toxicity occurs in only one patient (6.3%) at 10.0 mg/kg, resulting in grade 4 neutropenia. The most frequent treatment-related adverse events include leukopenia (22.6%), neutropenia (22.6%), elevated alanine aminotransferase (22.6%), rash (21.0%), itching (17.7%), and elevated aspartate aminotransferase (17.7%). The overall disease control rates are 47.1% for advanced solid tumors and 54.5% for non-Hodgkin's lymphoma. Circulating biomarkers suggest target engagement by ADG106 and immune modulation of circulating T, B, and natural killer cells and cytokines interferon γ and interleukin-6, which may affect the probability of clinical efficacy. ADG106 has a manageable safety profile and preliminary anti-tumor efficacy in patients with advanced cancers (this study was registered at ClinicalTrials.gov: NCT03802955).


Subject(s)
Lymphoma, Non-Hodgkin , Neoplasms , Neutropenia , Humans , Lymphoma, Non-Hodgkin/drug therapy , Antibodies, Monoclonal , Treatment Outcome
13.
Biomed Pharmacother ; 172: 116288, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38377739

ABSTRACT

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.


Subject(s)
Neoplasms , Synthetic Lethal Mutations , Cell Death , DNA Repair , Neoplasms/drug therapy , Neoplasms/genetics
14.
Plant Commun ; 5(1): 100663, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-37496271

ABSTRACT

Membraneless biomolecular condensates play important roles in both normal biological activities and responses to environmental stimuli in living organisms. Liquid‒liquid phase separation (LLPS) is an organizational mechanism that has emerged in recent years to explain the formation of biomolecular condensates. In the past decade, advances in LLPS research have contributed to breakthroughs in disease fields. By contrast, although LLPS research in plants has progressed over the past 5 years, it has been concentrated on the model plant Arabidopsis, which has limited relevance to agricultural production. In this review, we provide an overview of recently reported advances in LLPS in plants, with a particular focus on photomorphogenesis, flowering, and abiotic and biotic stress responses. We propose that many potential LLPS proteins also exist in crops and may affect crop growth, development, and stress resistance. This possibility presents a great challenge as well as an opportunity for rigorous scientific research on the biological functions and applications of LLPS in crops.


Subject(s)
Intrinsically Disordered Proteins , Intrinsically Disordered Proteins/metabolism , Phase Separation
15.
J Adolesc ; 96(1): 5-17, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37718625

ABSTRACT

INTRODUCTION: The present study sought to investigate whether the relationship between childhood trauma, childhood socioeconomic (SES), and adolescents' altruism were mediated by their life history strategies and different adverse childhood experiences may function diversely on altruism, with two waves of data collected 6 months apart in a longitudinal design among Chinese adolescents. METHODS: A total of 658 adolescents (Mage = 13.51, SD = 0.73 at T1) were recruited and completed the online survey; their life history strategies were measured by the Mini-K, the Delayed of Gratification Questionnaire (DOG), and the Chinese version of the Adolescent Risk-Taking Questionnaire (ARQ-RB) together, and their altruism was collected again after six months. RESULTS: After controlling for gender and their altruism at T1, the results showed that childhood trauma (i.e., emotional maltreatment, physical maltreatment), as well as low SES and fast life history strategy, were significantly negatively correlated with adolescents' altruism at T2. Importantly, life history strategy at T1 mediated the relationship between T1 emotional maltreatment, T1 low SES, and adolescents' altruism at T2. However, the effect of physical maltreatment on altruism was not mediated by life history strategy. CONCLUSIONS: This study indicated that emotional maltreatment and low SES can affect adolescents' altruism by influencing the formation of adolescents' life history strategies. The findings revealed the different influences of adverse childhood experiences on adolescents' altruism, which supplied new empirical evidence for the life history theory and provided certain reference values for cultivating adolescents' altruism.


Subject(s)
Adverse Childhood Experiences , Child Abuse , Life History Traits , Humans , Adolescent , Child , Altruism , Emotions , Surveys and Questionnaires , Child Abuse/psychology
16.
Int J Surg ; 110(1): 332-341, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37916933

ABSTRACT

BACKGROUND: After radical surgery, patients with esophageal cancer should undergo long-term surveillance of disease relapse. However, the optimal follow-up strategy remains to be explored. METHOD: A total of 4688 patients were recruited. Recursive partition analysis was applied to develop recurrence risk stratification for patients. The follow-up strategies of each stratification were developed based on monthly recurrence probability and validated by bootstrap validation and an external dataset. A Markov decision-analytic model was constructed to evaluate the cost-effectiveness of the follow-up strategies. RESULTS: Patients were stratified into four groups according to four pathological features. The authors applied a random survival forest to calculate the monthly recurrence probability of each group. Based on the temporal distribution of recurrences, the authors further established surveillance strategies for four groups. The strategies were validated as optimal protocols by bootstrap resampling and another dataset. Markov cost-effective analysis indicated that our recommended strategies outperformed the mainstream protocols from guidelines. Using less than 12 visits across the first 5 years on average, our follow-up strategies were more efficient than the NCCN recommended strategies (14 visits average). Our results also supported the computerized tomography from the neck to the upper abdomen as a routine examination and PETCT of distant metastasis for some groups with high risks. CONCLUSION: Our study provided data-driven evidence of personalized and economic follow-up strategies for esophageal cancer patients and shed light on follow-up optimization for other cancer types.


Subject(s)
Esophageal Neoplasms , Neoplasm Recurrence, Local , Humans , Cohort Studies , Follow-Up Studies , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Probability , Cost-Benefit Analysis
17.
Cancer Chemother Pharmacol ; 93(4): 295-306, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37938423

ABSTRACT

PURPOSE: CUDC-907 is a promising dual-target inhibitor of the HDAC and PI3K signaling pathways, with demonstrated therapeutic effects in a range of malignant tumors. However, its potential application in ovarian cancer (OC) has not been fully explored yet. In this study, we sought to investigate the efficacy of CUDC-907 in treating OC, both in vitro and in vivo. METHODS: Here, we examined the correlation between PI3K or HDAC expression and the prognosis of OC patients using the GEPIA database. RNA-Seq analysis was performed on OC cells treated with CUDC-907.To assess various cellular processes, including proliferation, migration, invasion, apoptosis, and cell cycle, we performed a series of assays, including the CCK8, EDU, wound healing, cell invasion, and flow cytometry assays. Real-time quantitative PCR and western blotting were performed to measure the expressions of target genes. Additionally, we utilized the SKOV3 xenograft tumor model to investigate the inhibitory effects of CUDC-907 on tumor growth in vivo. RESULTS: Bioinformatics analyses revealed that up-regulated HDAC and PI3K were significantly correlated with patients' poor survival in OC. In vivo and in vitro experiments have demonstrated that CUDC-907 could inhibit the proliferation of OC cells by inhibiting the PI3K and HDAC pathways to down-regulate the expression of c-Myc, and induce cell apoptosis by inhibiting the PI3K/AKT/Bcl-2 pathway, and up-regulate p21 to induce G2 /M phase arrest. CONCLUSION: Our results showed that CUDC-907 had powerful anti-tumor effects on OC, which could provide a theoretical and experimental basis for the application of CUDC-907 in the therapy of OC.


Subject(s)
Morpholines , Ovarian Neoplasms , Phosphatidylinositol 3-Kinases , Pyrimidines , Humans , Female , Phosphatidylinositol 3-Kinases/metabolism , Histone Deacetylase Inhibitors/pharmacology , Cell Line, Tumor , Cell Proliferation , Ovarian Neoplasms/drug therapy , Apoptosis
18.
Heliyon ; 10(1): e23318, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38148826

ABSTRACT

Mechanosensitive ion channels are a class of membrane-integrated proteins that convert externalmechanical forces, including stretching, pressure, gravity, and osmotic pressure changes, some of which can be caused by pathogen invasion, into electrical and chemical signals transmitted to the cytoplasm. In recent years, with the identification of many of these channels, their roles in the initiation and progression of many diseases have been gradually revealed. Multiple studies have shown that mechanosensitive ion channels regulate the proliferation, activation, and inflammatory responses of immune cells by being expressed on the surface of immune cells and further responding to mechanical forces. Nonetheless, further clarification is required regarding the signaling pathways of immune-cell pattern-recognition receptors and on the impact of microenvironmental changes and mechanical forces on immune cells. This review summarizes the roles of mechanosensitive ion channels in immune cells.

19.
iScience ; 26(10): 107752, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37954141

ABSTRACT

Symbiotic nitrogen fixation is a complex process in which legumes interact with rhizobia under nitrogen starvation. In this study, we found that myotubularin phosphatase (MtMP) is mainly expressed in roots and nodules in Medicago truncatula. MtMP promotes autophagy by dephosphorylating PtdIns3P on autophagosomes. The mp mutants inoculated with rhizobia showed a significant reduction in nitrogenase activity and significantly higher number of mitochondria than those of wild-type plants under nitrogen starvation, indicating that MtMP is involved in mitophagy of the infection zone. Mitophagy may provide carbon skeletons and nitrogen for the development of bacteroids and the reprogramming of infected cells. In conclusion, we found, for the first time, that myotubularin phosphatase is involved in autophagy in plants. MtMP-involved autophagy plays an active role in symbiotic nitrogen fixation. These results deepen our understanding of symbiotic nitrogen fixation.

20.
World J Surg Oncol ; 21(1): 357, 2023 Nov 21.
Article in English | MEDLINE | ID: mdl-37986077

ABSTRACT

BACKGROUND: Endometrial carcinoma (EC) is the second most common gynecological malignancy, and the differences between different pathological types are not entirely clear. Here, we retrospectively collected eligible EC patients to explore their differences regarding clinical characteristics and prognosis. METHODS: Five hundred seventy EC patients from the First Affiliated Hospital of Zhengzhou University were included. Prognostic factors were measured using the univariate/multivariate Cox models. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. RESULTS: In total, 396 patients with uterine endometrioid carcinoma (UEC), 106 patients with uterine serous carcinoma (USC), 34 patients with uterine mixed carcinoma (UMC), and 34 patients with uterine clear cell carcinoma (UCCC) were included. Comparison of baseline characteristics revealed patients diagnosed with UEC were younger, had more early clinical stage, and had lower incidence of menopause and lymph node metastasis. Compared to UEC, other pathological EC obtained more unfavorable OS (UCCC: HR = 12.944, 95%CI = 4.231-39.599, P < 0.001; USC: HR = 5.958, 95%CI = 2.404-14.765, P < 0.001; UMC: HR = 1.777, 95%CI = 0.209-15.114, P = 0.599) and PFS (UCCC: HR = 8.696, 95%CI = 1.972-38.354, P = 0.004; USC: HR = 4.131, 95%CI = 1.243-13.729, P = 0.021; UMC: HR = 5.356, 95%CI = 0.935-30.692, P = 0.060). Compared with UEC patients, the OS of UCCC patients in stage I-II and USC patients in stage III-IV were significantly worse, while UMC patients in stage I-II favored poorer PFS. The OS of UCCC patients receiving no postoperative adjuvant therapy or chemotherapy alone were significantly worse. CONCLUSIONS: The baseline characteristics of UEC and other rare EC types varied greatly, and the prognostic significance of different pathological types on EC patients depended on clinical tumor stages and therapeutic options.


Subject(s)
Carcinoma , Endometrial Neoplasms , Uterine Neoplasms , Female , Humans , Retrospective Studies , Neoplasm Staging , Prognosis , Endometrial Neoplasms/therapy , Endometrial Neoplasms/pathology , Uterine Neoplasms/pathology , Carcinoma/pathology
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