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1.
Cell Mol Immunol ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839915

ABSTRACT

Acute systemic inflammation critically alters the function of the immune system, often promoting myelopoiesis at the expense of lymphopoiesis. In the thymus, systemic inflammation results in acute thymic atrophy and, consequently, impaired T-lymphopoiesis. The mechanism by which systemic inflammation impacts the thymus beyond suppressing T-cell development is still unclear. Here, we describe how the synergism between TL1A and IL-18 suppresses T-lymphopoiesis to promote thymic myelopoiesis. The protein levels of these two cytokines were elevated in the thymus during viral-induced thymus atrophy infection with murine cytomegalovirus (MCMV) or pneumonia virus of mice (PVM). In vivo administration of TL1A and IL-18 induced acute thymic atrophy, while thymic neutrophils expanded. Fate mapping with Ms4a3-Cre mice demonstrated that thymic neutrophils emerge from thymic granulocyte-monocyte progenitors (GMPs), while Rag1-Cre fate mapping revealed a common developmental path with lymphocytes. These effects could be modeled ex vivo using neonatal thymic organ cultures (NTOCs), where TL1A and IL-18 synergistically enhanced neutrophil production and egress. NOTCH blockade by the LY411575 inhibitor increased the number of neutrophils in the culture, indicating that NOTCH restricted steady-state thymic granulopoiesis. To promote myelopoiesis, TL1A, and IL-18 synergistically increased GM-CSF levels in the NTOC, which was mainly produced by thymic ILC1s. In support, TL1A- and IL-18-induced granulopoiesis was completely prevented in NTOCs derived from Csf2rb-/- mice and by GM-CSFR antibody blockade, revealing that GM-CSF is the essential factor driving thymic granulopoiesis. Taken together, our findings reveal that TL1A and IL-18 synergism induce acute thymus atrophy while  promoting extramedullary thymic granulopoiesis in a NOTCH and GM-CSF-controlled manner.

2.
Nat Cell Biol ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839978

ABSTRACT

Dynamic epigenomic reprogramming occurs during mammalian oocyte maturation and early development. However, the underlying transcription circuitry remains poorly characterized. By mapping cis-regulatory elements using H3K27ac, we identified putative enhancers in mouse oocytes and early embryos distinct from those in adult tissues, enabling global transitions of regulatory landscapes around fertilization and implantation. Gene deserts harbour prevalent putative enhancers in fully grown oocytes linked to oocyte-specific genes and repeat activation. Embryo-specific enhancers are primed before zygotic genome activation and are restricted by oocyte-inherited H3K27me3. Putative enhancers in oocytes often manifest H3K4me3, bidirectional transcription, Pol II binding and can drive transcription in STARR-seq and a reporter assay. Finally, motif analysis of these elements identified crucial regulators of oogenesis, TCF3 and TCF12, the deficiency of which impairs activation of key oocyte genes and folliculogenesis. These data reveal distinctive regulatory landscapes and their interacting transcription factors that underpin the development of mammalian oocytes and early embryos.

3.
Angew Chem Int Ed Engl ; : e202409656, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837290

ABSTRACT

Perovskite quantum dots (QDs) have shown attractive prospects in the field of visible photocatalysis, especially in the synthesis of high value-added chemicals. However, under aerobic conditions, the stable operation of QD catalysts has been limited by the reactive oxygen species (ROS) generated by photoexcitation, especially superoxide species. Here, we propose a strategy of Ce3+ doping in perovskite QDs to guide superoxide species for photocatalytic oxidation reactions. In C(sp3)-H bond oxidation of hydrocarbons, superoxide species were rapidly generated and efficiently utilized on the surface of perovskite QDs, which achieves the stable operation of the catalytic system and obtains a high product conversion rate (15.3 mmol/g/h for benzaldehydes). The mechanism studies show that the strong Ce-oxygen affinity accelerates the relaxation process of photoinduced exciton transfer to superoxide species and inhibits the radiative recombination pathway. This work provides a new idea of utilizing oxygen species on perovskite surface and broadens the design strategy of high-performance QD photocatalysts.

4.
J Dig Dis ; 25(4): 255-265, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38837552

ABSTRACT

OBJECTIVES: In this study we aimed to assess the impact of acetylation of hepatocyte nuclear factor 4α (HNF4α) on lysine 458 on the differentiation therapy of hepatocellular carcinoma (HCC). METHODS: Periodic acid-Schiff (PAS) staining, Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake, and senescence-associated ß-galactosidase (SA-ß-gal) activity analysis were performed to assess the differentiation of HCC cells. HNF4α protein was detected by western blot and immunohistochemistry (IHC). The effects of HNF4α-K458 acetylation on HCC malignancy were evaluated in HCC cell lines, a Huh-7 xenograft mouse model, and an orthotopic model. The differential expression genes in Huh-7 xenograft tumors were screened by RNA-sequencing analysis. RESULTS: K458R significantly enhanced the inhibitory effect of HNF4α on the malignancy of HCC cells, whereas K458Q reduced the inhibitory effects of HNF4α. Moreover, K458R promoted, while K458Q decreased, HNF4α-induced HCC cell differentiation. K458R stabilized HNF4α, while K458Q accelerated the degradation of HNF4α via the ubiquitin proteasome system. K458R also enhanced the ability of HNF4α to inhibit cell growth of HCC in the Huh-7 xenograft mouse model and the orthotopic model. RNA-sequencing analysis revealed that inhibiting K458 acetylation enhanced the transcriptional activity of HNF4α without altering the transcriptome induced by HNF4α in HCC. CONCLUSION: Our data revealed that inhibiting K458 acetylation of HNF4α might provide a more promising candidate for differential therapy of HCC.


Subject(s)
Carcinoma, Hepatocellular , Cell Differentiation , Hepatocyte Nuclear Factor 4 , Liver Neoplasms , Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 4/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Acetylation , Animals , Humans , Mice , Cell Line, Tumor , Lysine/metabolism , Xenograft Model Antitumor Assays
5.
Appl Environ Microbiol ; : e0054024, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829054

ABSTRACT

Halophilic archaea are promising microbial cell factories for bacterioruberin (BR) production. BR is a natural product with multi-bioactivities, allowing potential application in many fields. In the previous work, a haloarchaeon Halorubrum sp. HRM-150 with a high proportion of BR (about 85%) was isolated, but the low yield impeded its large-scale production. This work figured out BR synthesis characteristics and mechanisms, and proposed strategies for yield improvement. First, glucose (10 g/L) and tryptone (15 g/L) were tested to be better sources for BR production. Besides, the combination of glucose and starch achieved the diauxic growth, and the biomass and BR productivity increased by 85% and 54% than using glucose. Additionally, this work first proposed the BR synthesis pattern, which differs from that of other carotenoids. As a structural component of cell membranes, the BR synthesis is highly coupled with growth, which was most active in the logarithm phase. Meanwhile, the osmotic down shock at the logarithm phase could increase the BR productivity without sacrificing the biomass. Moreover, the de-novo pathway for BR synthesis with a key gene of lyeJ, and its competitive pathways (notably tetraether lipids and retinal) were revealed through genome, transcriptome, and osmotic down shock. Therefore, the BR yield is expected to be improved through mutant construction, such as the overexpression of key gene lyeJ and the knockout of competitive genes, which need to be further explored. The findings will contribute to a better understanding of the metabolism mechanism in haloarchaea and the development of haloarchaea as microbial cell factories. IMPORTANCE: Recent studies have revealed that halophilic microorganism is a promising microbial factory for the next-generation industrialization. Among them, halophilic archaea are advantageous as microbial factories due to their low contamination risk and low freshwater consumption. The halophilic archaea usually accumulate long chain C50 carotenoids, which are barely found in other organisms. Bacterioruberin (BR), the major C50 carotenoid, has multi-bioactivities, allowing potential application in food, cosmetic, and biomedical industries. However, the low yield impedes its large-scale application. This work figured out the BR synthesis characteristics and mechanism, and proposed several strategies for BR yield improvement, encouraging halophilic archaea to function as microbial factories for BR production. Meanwhile, the archaea have special evolutionary status and unique characteristics in taxonomy, the revelation of BR biosynthesis mechanism is beneficial for a better understanding of archaea.

6.
Chem Commun (Camb) ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829288

ABSTRACT

Herein, a covalent organic framework (SO3-COF) containing sulfonic acid groups has been developed on the surface of alumina by a one-step method, labeled as SO3-COF@Al2O3. The experimental results show that SO3-COF@Al2O3 can effectively inhibit the shuttle effect of soluble lithium polysulfide (LiPSs) in LSBs after loading the active material sulfur, and exhibits better cycling behavior than the initial polymer SO3-COF. The initial discharge specific capacity of this electrode material at 0.05C is as high as 1141 mA h g-1, and the capacity can be maintained at 466 mA h g-1 after 500 cycles with a capacity decay rate of 0.08% per cycle.

7.
Cell Metab ; 36(6): 1269-1286.e9, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38838640

ABSTRACT

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD), especially advanced metabolic dysfunction-associated steatohepatitis (MASH), have an increased risk of cardiovascular diseases (CVDs). Whether CVD events will, in turn, influence the pathogenesis of MASLD remains unknown. Here, we show that myocardial infarction (MI) accelerates hepatic pathological progression of MASLD. Patients with MASLD who experience CVD events after their diagnosis exhibit accelerated liver fibrosis progression. MI promotes hepatic fibrosis in mice with MASH, accompanied by elevated circulating Ly6Chi monocytes and their recruitment to damaged liver tissues. These adverse effects are significantly abrogated when deleting these cells. Meanwhile, MI substantially increases circulating and cardiac periostin levels, which act on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis, finally exacerbating hepatic pathological progression of MASH. These preclinical and clinical results demonstrate that MI alters systemic homeostasis and upregulates pro-fibrotic factor production, triggering cross-disease communication that accelerates hepatic pathological progression of MASLD.


Subject(s)
Disease Progression , Mice, Inbred C57BL , Myocardial Infarction , Animals , Myocardial Infarction/pathology , Myocardial Infarction/metabolism , Humans , Mice , Male , Liver Cirrhosis/pathology , Liver Cirrhosis/metabolism , Monocytes/metabolism , Female , Middle Aged , Inflammation/pathology , Inflammation/metabolism , Hepatocytes/metabolism , Hepatocytes/pathology , Liver/pathology , Liver/metabolism , Cell Adhesion Molecules/metabolism
8.
J Neurochem ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822659

ABSTRACT

The relationship between peripheral inflammatory markers, their dynamic changes, and the disease severity of myasthenia gravis (MG) is still not fully understood. Besides, the possibility of using it to predict the short-term poor outcome of MG patients have not been demonstrated. This study aims to investigate the relationship between peripheral inflammatory markers and their dynamic changes with Myasthenia Gravis Foundation of America (MGFA) classification (primary outcome) and predict the short-term poor outcome (secondary outcome) in MG patients. The study retrospectively enrolled 154 MG patients from June 2016 to December 2021. The logistic regression was used to investigate the relationship of inflammatory markers with MGFA classification and determine the factors for model construction presented in a nomogram. Finally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were utilized to evaluate the incremental capacity. Logistic regression revealed significant associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI) and MGFA classification (p = 0.013, p = 0.032, p = 0.017, respectively). Incorporating dynamic changes of inflammatory markers into multivariable models improved their discriminatory capacity of disease severity, with significant improvements observed for NLR, systemic immune-inflammation index (SII) and AISI in NRI and IDI. Additionally, AISI was statistically associated with short-term poor outcome and a prediction model incorporating dynamic changes of inflammatory markers was constructed with the area under curve (AUC) of 0.953, presented in a nomograph. The inflammatory markers demonstrate significant associations with disease severity and AISI could be regarded as a possible and easily available predictive biomarker for short-term poor outcome in MG patients.

9.
Neural Netw ; 178: 106402, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38823067

ABSTRACT

This paper investigates a sliding mode control method for a class of uncertain delayed fractional-order reaction-diffusion memristor neural networks. Different from most existing literature on sliding mode control for fractional-order reaction-diffusion systems, this study constructs a linear sliding mode switching function and designs the corresponding sliding mode control law. The sufficient theory for the globally asymptotic stability of the sliding mode dynamics are provided, and it is proven that the sliding mode surface is finite-time reachable under the proposed control law, with an estimate of the maximum reaching time. Finally, a numerical test is presented to validate the effectiveness of the theoretical analysis.

10.
Reprod Biomed Online ; 49(2): 103947, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38810315

ABSTRACT

RESEARCH QUESTION: What are the efficacy, safety and reproductive outcomes of intrauterine balloon stent placement for 4 or 6 weeks after hysteroscopic adhesiolysis? DESIGN: This retrospective cohort study was conducted at a university-affiliated hospital, and included 155 women with moderate to severe intrauterine adhesions who underwent hysteroscopic adhesiolysis between March 2016 and December 2019. Participants were divided according to whether the heart-shaped balloon stent was left in place for 4 (group 1) or 6 (group 2) weeks after surgery. Stents removed at the second-look hysteroscopy 4 or 6 weeks after surgery were sent for culturing of common bacteria. The incidence of adhesion reformation, adhesion score reduction, bacterial colonization of the intrauterine balloon stent, live birth rate and time to live birth were analysed. RESULTS: Group 2 had a significantly lower adhesion reformation rate (45.7% versus 28.2%, P = 0.024) and a more significant reduction in adhesion score (5.2 ± 2.1 versus 6.3 ± 2.2, P = 0.003) compared with group 1. However, no statistical difference was observed in the percentage of bacterial colonization of the intrauterine balloon stent (55.9% versus 66.7%, P = 0.174), live birth rate (52.4% versus 42.3%, P = 0.331) or time to live birth (hazard ratio 1.09, 95% confidence interval 0.60-1.96, P = 0.778) between the two groups. CONCLUSIONS: Extending intrauterine balloon stent use from 4 to 6 weeks further reduces the adhesion reformation rate after hysteroscopic adhesiolysis in patients with moderate to severe intrauterine adhesion. No increase in bacterial colonization of the balloon stent was observed. Extending the duration of intrauterine balloon stent placement did not significantly affect live birth rates.

11.
Cell Rep ; 43(6): 114277, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38805397

ABSTRACT

Affective empathy enables social mammals to learn and transfer emotion to conspecifics, but an understanding of the neural circuitry and genetics underlying affective empathy is still very limited. Here, using the naive observational fear between cagemates as a paradigm similar to human affective empathy and chemo/optogenetic neuroactivity manipulation in mouse brain, we investigate the roles of multiple brain regions in mouse affective empathy. Remarkably, two neural circuits originating from the ventral hippocampus, previously unknown to function in empathy, are revealed to regulate naive observational fear. One is from ventral hippocampal pyramidal neurons to lateral septum GABAergic neurons, and the other is from ventral hippocampus pyramidal neurons to nucleus accumbens dopamine-receptor-expressing neurons. Furthermore, we identify the naive observational-fear-encoding neurons in the ventral hippocampus. Our findings highlight the potentially diverse regulatory pathways of empathy in social animals, shedding light on the mechanisms underlying empathy circuity and its disorders.

12.
Article in English | MEDLINE | ID: mdl-38776048

ABSTRACT

Exosomes, nano-sized small extracellular vesicles, have been shown to serve as mediators between intercellular communications by transferring bioactive molecules, such as non-coding RNA, proteins, and lipids from secretory to recipient cells, modulating a variety of physiological and pathophysiological processes. Recent studies have gradually demonstrated that altered exosome charges may represent a key mechanism driving the pathological process of ferroptosis. This review summarizes the potential mechanisms and signal pathways relevant to ferroptosis and then discusses the roles of exosome in ferroptosis. As well as transporting iron, exosomes may also indirectly convey factors related to ferroptosis. Furthermore, ferroptosis may be transmitted to adjacent cells through exosomes, resulting in cascading effects. It is expected that further research on exosomes will be conducted to explore their potential in ferroptosis and will lead to the creation of new therapeutic avenues for clinical diseases.

13.
FASEB J ; 38(10): e23685, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38780518

ABSTRACT

BACKGROUND: Cervical cancer (CC), closely linked to persistent human papillomavirus infection, represents a major health problem for women worldwide. The objective of this study is to elucidate KIF23's role in the development of CC and its regulatory mechanism. METHODS: The bioinformatics methods were utilized to extract pyroptosis-associated differentially expressed genes (DEGs) and pivot genes from the GSE9750 and GSE63678 datasets, followed by immune infiltration analysis and quantification of these genes' expression. The effects of kinesin family member 23 (KIF23) were verified through functional experiments in vitro and a mouse xenograft model. The NLPR3 activator, nigericin, was applied for further analyzing the potential regulatory mechanism of KIF23 in CC. RESULTS: A total of 8 pyroptosis-related DEGs were screened out, among which 4 candidate core genes were identified as candidate hub genes and confirmed upregulation in CC tissues and cells. These genes respectively showed a positive correlation with the infiltration of distinct immune cells or tumor purity. Downregulation of KIF23 could suppress the proliferation, migration, and invasion abilities in CC cells and tumorigenesis through enhancing pyroptosis. Conversely, KIF23 overexpression accelerated the malignant phenotypes of CC cells and inhibited pyroptosis activation, which was blocked by nigericin treatment. CONCLUSIONS: KIF23 may play an oncogenic role in CC progression via inhibition of the NLRP3-mediated pyroptosis pathway.


Subject(s)
Gene Expression Regulation, Neoplastic , NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis , Uterine Cervical Neoplasms , Pyroptosis/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Humans , Female , Animals , Mice , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Mice, Nude , Kinesins/genetics , Kinesins/metabolism , Cell Proliferation , Cell Line, Tumor , Disease Progression , Mice, Inbred BALB C , Microtubule-Associated Proteins
14.
Front Allergy ; 5: 1345929, 2024.
Article in English | MEDLINE | ID: mdl-38774588

ABSTRACT

Background: Oral immunotherapy (OIT) is a promising allergen-specific approach in the management of food allergy; however, studies on OIT for allergic rhinitis (AR) have rarely been reported. The purpose of this study is to evaluate the efficacy and safety of OIT using enteric-coated capsules for AR induced by house dust mites. Methods: A total of 49 patients with AR were enrolled, including 25 who received subcutaneous immunotherapy (SCIT) and 24 who received OIT. The clinical efficacy and safety in both groups were evaluated. Results: After 1 year of treatment, both SCIT and OIT demonstrated significant therapeutic effects. OIT was found to be more effective than SCIT in reducing the total AR symptom score and improving the results of nasal provocation tests. Local and systemic adverse reactions were observed in the SCIT group, while none were reported in the OIT group. Conclusion: OIT is an effective and safe treatment for mite-induced AR.

15.
Pharm Biol ; 62(1): 404-422, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38739082

ABSTRACT

CONTEXT: Traditional Chinese medicines (TCMs) have emerged as potential adjuvant therapies to treat non-small cell lung cancer. More direct comparative studies must be conducted among various oral TCMs. OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of seven oral TCMs combined with chemotherapy in treating NSCLC. METHODS: The analysis included Zilongjin, Banmao, Hongdoushan, Huachansu, Kanglaite, Xihuang, and Pingxiao TCMs. Randomized-controlled trials (RCTs) were identified from the following databases: China National Infrastructure, Wanfang, PubMed, Embase, and the Cochrane Library up to April 2023. Two researchers independently extracted data. RESULTS: Sixty-eight RCTs (5,099 patients) were included. Compared to chemotherapy, Banmao capsules [odds ratio (OR) = 2.69, 95% confidence interval (CI) 1.96-3.69)] and Huachansu tablets [OR = 2.35, 95%CI (1.81, 3.05)] ranked in the top two in terms of increasing disease control rate. The two main TCMs to improve the objective response rate were Banmao capsules [OR = 3.49, 95%CI (2.17, 5.60)] and Zilongjin tablets [OR = 2.62, 95%CI (1.92, 3.57)]. Zilongjin tablets [OR = 3.47, 95%CI (2.14, 5.63)] and Huachansu tablets [OR = 3.30, 95%CI (1.65, 6.60)] were ranked as the top two in improving Karnofsky performance status. Hongdoushan capsules (SUCRA = 18.8%) and Banmao capsules (SUCRA = 19.8%) were the top two in reducing gastrointestinal toxicity. Zilongjin tablets (SUCRA = 18.9%) and Banmao capsules (SUCRA = 26.6%) were the top two to reduce liver and kidney toxicity. Hongdoushan capsules (SUCRA = 15.7%) and Huachansu tablets (SUCRA = 16.8%) ranked the top two in reducing thrombocytopenia. Banmao capsules (SUCRA = 14.3%) and Zilongjin tablets (SUCRA = 26.3%) were the top two decreasing leukopenia. CONCLUSIONS: Combining oral TCMs with platinum-based chemotherapy has shown superior efficacy compared to platinum-based chemotherapy alone in treating NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Drugs, Chinese Herbal , Lung Neoplasms , Medicine, Chinese Traditional , Network Meta-Analysis , Randomized Controlled Trials as Topic , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional/methods , Administration, Oral , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Treatment Outcome
16.
J Chromatogr A ; 1728: 464987, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38821034

ABSTRACT

In this work, we proposed an indirect phase-conversion strategy to construct a new approach for accurately and efficiently determining the permanganate index in water samples via headspace GC measurement. After the reducible substances in water reacted with excess potassium permanganate, the remaining potassium permanganate underwent a reaction with sodium oxalate under acidic conditions. The carbon dioxide generated from the gas-evolving reaction was then analyzed by headspace GC. Our findings showed that this new approach boasts high precision (relative standard deviation ≤ 2.18%) and accuracy for permanganate index analysis, thus validating the effectiveness of this new method in analyzing permanganate index. The introduction of the indirect phase-conversion strategy in this study is expected to set a precedent for further advancements in methodologies designed to indirectly evaluate substances capable of undergoing gas-producing reactions.

17.
BMC Cancer ; 24(1): 551, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693472

ABSTRACT

OBJECTIVE: We aimed to screen novel gene signatures for ovarian cancer (OC) and explore the role of biomarkers in OC via regulating pyroptosis using bioinformatics analysis. METHODS: Differentially expressed genes (DEGs) of OC were screened from GSE12470 and GSE16709 datasets. Hub genes were determined from protein-protein interaction networks after bioinformatics analysis. The role of Centromeric protein M (CENPM) in OC was assessed by subcutaneous tumor experiment using hematoxylin-eosin and immunohistochemical staining. Tumor metastasis was evaluated by detecting epithelial-mesenchymal transition-related proteins. The proliferation, migration, and invasion were determined using cell counting kit and transwell assay. Enzyme-linked immunosorbent assay was applied to measure inflammatory factors. The mRNA and protein expression were detected using real-time quantitative PCR and western blot. RESULTS: We determined 9 hub genes (KIFC1, PCLAF, CDCA5, KNTC1, MCM3, OIP5, CENPM, KIF15, and ASF1B) with high prediction value for OC. In SKOV3 and A2780 cells, the expression levels of hub genes were significantly up-regulated, compared with normal ovarian cells. CENPM was selected as a key gene. Knockdown of CENPM suppressed proliferation, migration, and invasion of OC cells. Subcutaneous tumor experiment revealed that CENPM knockdown significantly suppressed tumor growth and metastasis. Additionally, pyroptosis was promoted in OC cells and xenograft tumors after CENPM knockdown. Furthermore, CENPM knockdown activated cGAS-STING pathway and the pathway inhibitor reversed the inhibitory effect of CENPM knockdown on viability, migration, and invasion of OC cells. CONCLUSION: CENPM was a novel biomarker of OC, and knockdown of CENPM inhibited OC progression by promoting pyroptosis and activating cGAS-STING pathway.


Subject(s)
Membrane Proteins , Nucleotidyltransferases , Ovarian Neoplasms , Pyroptosis , Signal Transduction , Humans , Female , Pyroptosis/genetics , Membrane Proteins/genetics , Membrane Proteins/metabolism , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Animals , Mice , Nucleotidyltransferases/metabolism , Nucleotidyltransferases/genetics , Cell Line, Tumor , Gene Knockdown Techniques , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Chromosomal Proteins, Non-Histone/metabolism , Chromosomal Proteins, Non-Histone/genetics , Cell Movement/genetics , Xenograft Model Antitumor Assays , Mice, Nude
18.
Cell Death Discov ; 10(1): 251, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789412

ABSTRACT

Damage to the ribosome or an imbalance in protein biosynthesis can lead to some human diseases, such as diabetic retinopathy (DR) and other eye diseases. Here, we reported that the kri1l gene was responsible for retinal development. The kri1l gene encodes an essential component of the rRNA small subunit processome. The retinal structure was disrupted in kri1l mutants, which resulted in small eyes. The boundaries of each layer of cells in the retina were blurred, and each layer of cells was narrowed and decreased. The photoreceptor cells and Müller glia cells almost disappeared in kri1l mutants. The lack of photoreceptor cells caused a fear of light response. The development of the retina started without abnormalities, and the abnormalities began two days after fertilization. In the kri1l mutant, retinal cell differentiation was defective, resulting in the disappearance of cone cells and Müller cells. The proliferation of retinal cells was increased, while apoptosis was also enhanced in kri1l mutants. γ-H2AX upregulation indicated the accumulation of DNA damage, which resulted in cell cycle arrest and apoptosis. The kri1l mutation reduced the expression of some opsin genes and key retinal genes, which are also essential for retinal development.

19.
Int J Mol Sci ; 25(10)2024 May 11.
Article in English | MEDLINE | ID: mdl-38791295

ABSTRACT

To achieve the environmentally friendly and rapid green synthesis of efficient and stable AgNPs for drug-resistant bacterial infection, this study optimized the green synthesis process of silver nanoparticles (AgNPs) using Dihydromyricetin (DMY). Then, we assessed the impact of AgNPs on zebrafish embryo development, as well as their therapeutic efficacy on zebrafish infected with Methicillin-resistant Staphylococcus aureus (MRSA). Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) analyses revealed that AgNPs possessed an average size of 23.6 nm, a polymer dispersity index (PDI) of 0.197 ± 0.0196, and a zeta potential of -18.1 ± 1.18 mV. Compared to other published green synthesis products, the optimized DMY-AgNPs exhibited smaller sizes, narrower size distributions, and enhanced stability. Furthermore, the minimum concentration of DMY-AgNPs required to affect zebrafish hatching and survival was determined to be 25.0 µg/mL, indicating the low toxicity of DMY-AgNPs. Following a 5-day feeding regimen with DMY-AgNP-containing food, significant improvements were observed in the recovery of the gills, intestines, and livers in MRSA-infected zebrafish. These results suggested that optimized DMY-AgNPs hold promise for application in aquacultures and offer potential for further clinical use against drug-resistant bacteria.


Subject(s)
Anti-Bacterial Agents , Flavonols , Green Chemistry Technology , Metal Nanoparticles , Methicillin-Resistant Staphylococcus aureus , Silver , Zebrafish , Animals , Methicillin-Resistant Staphylococcus aureus/drug effects , Metal Nanoparticles/chemistry , Silver/chemistry , Silver/pharmacology , Flavonols/pharmacology , Flavonols/chemistry , Green Chemistry Technology/methods , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Staphylococcal Infections/drug therapy , Microbial Sensitivity Tests
20.
Heliyon ; 10(9): e30190, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707361

ABSTRACT

Background: The severity of white matter hyperintensities (WMH) has been shown to be an independent predictor of poor stroke outcome, but the effect of sex on this correlation has not been investigated further. Therefore, the purpose of our study was to assess whether there was a sex difference between the severity of WMH and poor stroke outcome. Methods: This retrospective study included 449 patients with acute ischemic stroke (AIS) who received intravenous thrombolysis. WMH severity was graded based on the Fazekas scale. The association between WMH severity and stroke outcome was explored through multivariable regression analyses in men and women. Results: Among women, when dividing WMH severity into tertiles, T3 (Fazekas scale >3) had a 5.334 times higher risk for unfavorable outcomes than T1 (Fazekas scale <2) (p-trend = 0.026) in the adjusted model. In addition, moderate-severe WMH (Fazekas scale 3-6) had a 3.391 (1.151-9.991) times higher risk than none-mild WMH (Fazekas scale 0-2) (p = 0.027). Conclusions: The risk of unfavorable outcomes increased proportionally with the enlargement of the WMH severity in females, suggesting the sex-specific value of the WMH severity in optimizing the risk stratification of stroke.

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