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1.
Int J Mol Sci ; 25(17)2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39273439

ABSTRACT

Mycorrhizal fungi, a category of fungi that form symbiotic relationships with plant roots, can participate in the induction of plant disease resistance by secreting phosphatase enzymes. While extensive research exists on the mechanisms by which mycorrhizal fungi induce resistance, the specific contributions of phosphatases to these processes require further elucidation. This article reviews the spectrum of mycorrhizal fungi-induced resistance mechanisms and synthesizes a current understanding of how phosphatases mediate these effects, such as the induction of defense structures in plants, the negative regulation of plant immune responses, and the limitation of pathogen invasion and spread. It explores the role of phosphatases in the resistance induced by mycorrhizal fungi and provides prospective future research directions in this field.


Subject(s)
Disease Resistance , Mycorrhizae , Plant Diseases , Mycorrhizae/physiology , Plant Diseases/microbiology , Plant Diseases/immunology , Plant Diseases/genetics , Phosphoric Monoester Hydrolases/metabolism , Plants/microbiology , Plants/immunology , Symbiosis , Plant Roots/microbiology , Plant Immunity
2.
Front Immunol ; 15: 1439485, 2024.
Article in English | MEDLINE | ID: mdl-39229278

ABSTRACT

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with a poor prognosis. The molecular mechanisms underlying its development remain unclear. Recent studies have highlighted the crucial role of RNA modifications in HCC progression, which indicates their potential as therapeutic targets and biomarkers for managing HCC. In this review, we discuss the functional role and molecular mechanisms of RNA modifications in HCC through a review and summary of relevant literature, to explore the potential therapeutic agents and biomarkers for diagnostic and prognostic of HCC. This review indicates that specific RNA modification pathways, such as N6-methyladenosine, 5-methylcytosine, N7-methylguanosine, and N1-methyladenosine, are erroneously regulated and are involved in the proliferation, autophagy, innate immunity, invasion, metastasis, immune cell infiltration, and drug resistance of HCC. These findings provide a new perspective for understanding the molecular mechanisms of HCC, as well as potential targets for the diagnosis and treatment of HCC by targeting specific RNA-modifying enzymes or recognition proteins. More than ten RNA-modifying regulators showed the potential for use for the diagnosis, prognosis and treatment decision utility biomarkers of HCC. Their application value for HCC biomarkers necessitates extensive multi-center sample validation in the future. A growing number of RNA modifier inhibitors are being developed, but the lack of preclinical experiments and clinical studies targeting RNA modification in HCC poses a significant obstacle, and further research is needed to evaluate their application value in HCC treatment. In conclusion, this review provides an in-depth understanding of the complex interplay between RNA modifications and HCC while emphasizing the promising potential of RNA modifications as therapeutic targets and biomarkers for managing HCC.


Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular , Liver Neoplasms , RNA Processing, Post-Transcriptional , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/therapy , Liver Neoplasms/diagnosis , Biomarkers, Tumor/metabolism , Animals , Gene Expression Regulation, Neoplastic , Prognosis , RNA/genetics , RNA/metabolism
4.
J Photochem Photobiol B ; 259: 113005, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39126797

ABSTRACT

Light exposure significantly impacted the coloration and metabolism of Auricularia cornea, although the underlying mechanisms remain unclear. This study aimed to test the apparent color and pigment metabolic profiles of A. cornea in response to red (λp = 630 nm) and blue (λp = 463 nm) visible light exposure. Colorimeter analysis showed that fruiting bodies appeared bright-white under red-light and deeper-red under blue-light, both with a yellow tinge. On the 40th day of light-exposure, bodies were collected for metabolite detection. A total of 481 metabolites were targeted analysis, resulting in 18 carotenoids and 11 anthocyanins. Under red and blue light exposure, the total carotenoids levels were 1.1652 µg/g and 1.1576 µg/g, the total anthocyanins levels were 0.0799 µg/g and 0.1286 µg/g, respectively. Four differential metabolites and three putative gene linked to the visual coloration of A. cornea were identified. This pioneering study provides new insights into the role of light in regulating A. cornea pigmentation and metabolic profile.


Subject(s)
Anthocyanins , Carotenoids , Light , Tandem Mass Spectrometry , Anthocyanins/metabolism , Carotenoids/metabolism , Basidiomycota/metabolism , Basidiomycota/chemistry , Chromatography, Liquid , Metabolome/radiation effects , Liquid Chromatography-Mass Spectrometry
5.
BMC Neurol ; 24(1): 300, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39198773

ABSTRACT

BACKGROUND: Motor neuron disease (MND) is a chronic and progressive neurodegenerative disorder with an unknown cause. The development of amyotrophic lateral sclerosis (ALS) is believed to be linked to an immune response. Monocytes/macrophages and T cells are key players in the disease's advancement. Monitoring levels of cytokines in the blood can help forecast patient outcomes, while immunotherapy shows promise in alleviating symptoms for certain individuals. CASE PRESENTATION: A 56-year-old male patient was admitted to the hospital due to progressive limb weakness persisting for eight months. The neurological examination revealed impairments in both upper and lower motor neurons, as well as sensory anomalies, without corresponding signs. Electrophysiological examination results indicated extensive neuronal damage and multiple peripheral nerve impairments, thereby the diagnosis was ALS. One month ago, the patient began experiencing symptoms of dry mouth and a bitter taste. Following tests for rheumatic immune-related antibodies and a lip gland biopsy, a diagnosis of Sjögren's syndrome (SS) was proposed. Despite treatment with medications such as hormones (methylprednisolone), immunosuppressants (hydroxychloroquine sulfate), and riluzole, the symptoms did not significantly improve, but also did not worsen. CONCLUSION: It is recommended to include screening for SS in the standard assessment of ALS. Furthermore, research should focus on understanding the immune mechanisms involved in ALS, providing new insights for the diagnosis and treatment of ALS in conjunction with SS.


Subject(s)
Amyotrophic Lateral Sclerosis , Sjogren's Syndrome , Humans , Male , Middle Aged , Amyotrophic Lateral Sclerosis/complications , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/drug therapy , Amyotrophic Lateral Sclerosis/pathology , Sjogren's Syndrome/complications , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/drug therapy , Sjogren's Syndrome/pathology
6.
Chem Commun (Camb) ; 60(68): 9058-9061, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39101215

ABSTRACT

Here, we propose a piperidine-based ionic liquid additive. The electrostatic shielding effect of the piperidine cation (PP13+) effectively inhibits the growth of lithium dendrites. Simultaneously, the redox activity of the bromine anion synergistically reduces the overpotential. This approach significantly improves the cycling performance of lithium-oxygen batteries.

7.
Chemosphere ; 364: 143065, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39128778

ABSTRACT

In this study, a novel strain Burkholderia stabilis TF-2 capable of assimilatory and co-metabolic degradation of chlorobenzenes was obtained. The interaction between chlorobenzene (CB) and target enzymes, as well as the metabolic pathways in TF-2, were elucidated using multi-omics and molecular docking techniques. Results of degradation experiments indicated that TF-2 assimilated CB at a rate of 0.22-0.66 mg·gcell-1·h-1 in concentrations of 20-200 mg L-1. Additionally, TF-2 also used sodium succinate and sodium citrate as substrates to co-metabolize CB, with degradation rates of 0.26-2.00 and 0.31-1.72 mol·gcell-1·h-1, respectively. Whole-genome sequencing revealed over 18 novel genes associated with aromatic hydrocarbon degradation in TF-2. Transcriptomic analysis showed that CB induced the high expression of 119 genes involved in CB metabolism and late mineralization. The significant up-regulation of the bedC1 (encoding a ring-hydroxylated dioxygenase), CatA (chlorocatechol 1,2-dioxygenase), pcaJ (3-oxoadipate CoA-transferase alpha subunit) and fadA (acetyl-CoA acyltransferase) genes facilitated CB metabolism. Based on these findings, a metabolic pathway for CB was constructed, with the key step involving ortho cleavage of the aromatic ring under the action of the catA gene. Furthermore, molecular docking revealed that CB bound to bedC1 with -4.5 kcal mol-1 through hydrophobic bonds, π-stacking, and a halogen bond. These results provide strong support for development of efficient strains to enhance the removal of chlorinated organic compounds.

8.
Microb Pathog ; : 106840, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39153577

ABSTRACT

Staphylococcus aureus (S. aureus) is a kind of gram-positive bacteria, and its virulence factors can cause many kinds of infections. Traditional antibiotics can not only kill bacteria, but also easily lead to bacterial resistance. Jingfang Mixture (JFM) is commonly used in clinic to prevent and treat epidemic diseases and infectious diseases. The main purpose of this study is to explore the inhibitory effect of JFM on alpha-hemolysin (Hla) of S. aureus and to alleviate the damage caused by Hla. We found that JFM could inhibit the hemolytic activity, gene and protein level and neutralizing activity of Hla in a dose-dependent manner at the concentrations of 125, 250 and 500 µg/mL, without affecting the growth of bacteria. In addition, JFM reduced the damage of Hla to A549 cells and the release of lactate dehydrogenase (LDH). We also observed that in the S. aureus - induced pneumonia mouse model, JFM could significantly prolong the life of mice, reduce the bacterial load in the lungs, significantly improve the pathological state of the lungs and alleviate the damage caused by inflammatory factors, and the pathogenicity of gene deletion strain DU 1090 of S. aureus to pneumonia mice was also significantly reduced. In conclusion, this study proved that JFM is a potential drug against S. aureus infection, and this study provided a preliminary study for better guidance of clinical drug use.

10.
Microbiol Spectr ; 12(9): e0049624, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39041815

ABSTRACT

Omadacycline and eravacycline are gradually being used as new tetracycline antibiotics for the clinical treatment of Gram-negative pathogens. Affected by various tetracycline-inactivating enzymes, there have been reports of resistance to eravacycline and omadacycline in recent years. We isolated a strain carrying the mobile tigecycline resistance gene tet(X4) from the feces of a patient in Zhejiang Province, China. The strain belongs to the rare ST485 sequence type. The isolate was identified as Klebsiella pneumoniae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The MICs of antimicrobial agents were determined using either the agar dilution method or the micro broth dilution method. The result showed that the isolate was resistant to eravacycline (MIC = 32 mg/L), omadacycline (MIC > 64 mg/L), and tigecycline (MIC > 32 mg/L). Whole-genome sequencing revealed that the tet(X4) resistance gene is located on the IncFII(pCRY) conjugative plasmid. tet(X4) is flanked by ISVsa3, and we hypothesize that this association contributes to the spread of the resistance gene. Plasmids were analyzed by S1-nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blotting, and electrotransformation experiment. We successfully transferred the plasmid carrying tet(X4) to the recipient bacteria by electrotransformation experiment. Compared with the DH-5α, the MICs of the transformant L3995-DH5α were increased by eight-fold for eravacycline and two-fold higher for omadacycline. Overall, the emergence of plasmid-borne tet(X4) resistance gene in a clinical isolate of K. pneumoniae ST485 underscores the essential requirement for the ongoing monitoring of tet(X4) to prevent and control its further dissemination in China.IMPORTANCEThere are still limited reports on Klebsiella pneumoniae strains harboring tetracycline-resistant genes in China, and K. pneumoniae L3995hy adds a new example to those positive for the tet(X4) gene. Importantly, our study raises concerns that plasmid-mediated resistance to omadacycline and eravacycline may spread further to a variety of ecological and clinical pathogens, limiting the choice of medication for extensively drug-resistant bacterial infections. Therefore, it is important to continue to monitor the prevalence and spread of tet(X4) and other tetracyclines resistance genes in K. pneumoniae and diverse bacterial populations.


Subject(s)
Anti-Bacterial Agents , Klebsiella Infections , Klebsiella pneumoniae , Plasmids , Tetracyclines , Humans , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , China , Drug Resistance, Multiple, Bacterial/genetics , Feces/microbiology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Microbial Sensitivity Tests , Plasmids/genetics , Tetracycline Resistance/genetics , Tetracyclines/pharmacology , Tigecycline/pharmacology
11.
Rev Cardiovasc Med ; 25(3): 96, 2024 Mar.
Article in English | MEDLINE | ID: mdl-39076962

ABSTRACT

Background: Atrial fibrillation (AF), which occurs four to six times more frequently in hypertrophic cardiomyopathy (HCM) patients than in the general population, is the most common persistent arrhythmia and has a substantial therapeutic consequence. In HCM patients, there are currently no discovered signs that could be utilized to identify AF. Methods: From 2018 to 2022, 493 individuals with a continuous diagnosis of HCM were examined at Beijing Anzhen Hospital. AF was proven using routine electrocardiography (ECG), 24-hour Holter ECGs, or bedside ECGs. Echocardiography and blood tests were performed for all patients. Analysis and comparison of the traits were performed in HCM patients with AF (n = 77) and without AF (n = 416). Results: Age (p < 0.001), prevalence of ventricular tachycardia (VT, p < 0.001), prevalence of pulmonary artery hypertension (p = 0.027), and albumin-to-globulin ratio (AGR, p = 0.046) were all significantly higher in patients with AF, compared to patients without AF. In multivariate logistic analysis, age (odds ratio [OR], 1.063; 95% confidence interval [CI], 1.032-1.095; p < 0.001), history of VT (OR, 2.702; 95% CI, 1.007-7.255; p = 0.048), AGR (OR, 3.477; 95% CI, 1.417-8.536; p = 0.007), left atrial diameter (OR, 1.132; 95% CI, 1.073-1.194; p < 0.001), left ventricular end-diastolic diameter (OR, 0.861; 95% CI, 0.762-0.974; p = 0.017), left ventricular end-systolic diameter (OR, 1.239; 95% CI, 1.083-1.417; p = 0.002), and peak A wave velocity (OR, 0.983; 95% CI, 0.972-0.994; p = 0.002) were independently associated with AF in HCM patients. In the receiver operating characteristic curve analysis, the area under the curve for the established model was 0.819 (95% CI, 0.755-0.883, p = 0.033), with a sensitivity and specificity of 0.763 and 0.816, respectively, for AF occurrence in HCM patients. Conclusions: In individuals with HCM, a history of VT and a higher AGR are independently linked to AF. Further investigation is necessary to determine whether increased AGR represents a risk factor for embolic stroke or cardiovascular death.

12.
Anal Bioanal Chem ; 416(20): 4435-4445, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38981911

ABSTRACT

Rapid, efficient, versatile, easy-to-use, and non-expensive analytical approaches are globally demanded for food analysis. Many ambient ionization approaches based on electrospray ionization (ESI) have been developed recently for the rapid molecular characterization of food products. However, those approaches mainly suffer from insufficient signal duration for comprehensive chemical characterization by tandem MS analysis. Here, a commercially available disposable gel loading tip is used as a low-cost emitter for the direct ionization of untreated food samples. The most important advantages of our approach include high stability, and durability of the signal (> 10 min), low cost (ca. 0.1 USD per run), low sample and solvent consumption, prevention of tip clogging and discharge, operational simplicity, and potential for automation. Quantitative analysis of sulfapyridine, HMF (hydroxymethylfurfural), and chloramphenicol in real sample shows the limit-of-detection 0.1 µg mL-1, 0.005 µg mL-1, 0.01 µg mL-1; the linearity range 0.1-5 µg mL-1, 0.005-0.25 µg mL-1, 0.01-1 µg mL-1; and the linear fits R2 ≥ 0.980, 0.991, 0.986. Moreover, we show that tip-ESI can also afford sequential molecular ionization of untreated viscous samples, which is difficult to achieve by conventional ESI. We conclude that tip-ESI-MS is a versatile analytical approach for the rapid chemical analysis of untreated food samples.


Subject(s)
Food Analysis , Limit of Detection , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Electrospray Ionization/methods , Food Analysis/methods , Gels/chemistry , Chloramphenicol/analysis , Food Contamination/analysis , Furaldehyde/analysis , Furaldehyde/analogs & derivatives
13.
Nat Commun ; 15(1): 5881, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-38997250

ABSTRACT

Carbon chain elongation (CCE) is normally carried out using either chemical catalysts or bioenzymes. Herein we demonstrate a catalyst-free approach to promote demethylation C-C coupling reactions for advanced CCE constructed with functional groups under ambient conditions. Accelerated by the electric field, two organic cations containing a methyl group (e.g., ketones, acids, and aldehydes) approach each other with such proximity that the energy of the repulsive Coulomb interaction between these two cations exceeds the bond energy of the methyl group. This results in the elimination of a methyl cation and the coupling of the residual carbonyl carbon groups. As confirmed by high-resolution mass spectrometry and isotope-labeling experiments, the C-C coupling reactions (yields up to 76.5%) were commonly observed in the gas phase or liquid phase, for which the mechanism was further studied using molecular dynamics simulations and stationary-point calculations, revealing deep insights and perspectives of chemistry.

14.
Food Res Int ; 191: 114704, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39059912

ABSTRACT

This study investigates the metabolic responses of Auricularia cornea when cultured on de-oiled leaves of Cinnamomum longepaniculatum (DeCL), an underutilized waste product. The metabolic profiles of A. cornea cultured with four different quality ratios of DeCL substrate (0 %, 14 %, 28 % and 42 %) were analyzed by UHPLC-MS/MS-based metabolomics. A total of 516 metabolites were identified and classified into 78 categories, with phenols, alkaloids and flavonoids accounting for 26.7 % of the total. In addition, 32 metabolite biomarkers associated with eight major metabolic pathways were identified. This pioneering research provides valuable insights into the utilization of DeCL, and expands our knowledge of the metabolic dynamics underlying the growth of A. cornea on alternative substrates.


Subject(s)
Biomarkers , Camphor , Metabolome , Metabolomics , Plant Leaves , Tandem Mass Spectrometry , Plant Leaves/metabolism , Plant Leaves/chemistry , Biomarkers/metabolism , Biomarkers/analysis , Metabolomics/methods , Camphor/metabolism , Camphor/analysis , Chromatography, High Pressure Liquid , Cinnamomum/chemistry , Cinnamomum/metabolism , Phenols/analysis , Phenols/metabolism , Flavonoids/analysis , Flavonoids/metabolism , Alkaloids/analysis , Alkaloids/metabolism
15.
Sci Rep ; 14(1): 15346, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961201

ABSTRACT

Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.

16.
Genomics ; 116(5): 110902, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39053612

ABSTRACT

A pioneering pink cultivar of Auricularia cornea, first commercially cultivated in 2022, lacks genomic data, hindering research in genetic breeding, gene discovery, and product development. Here, we report the de novo assembly of the pink A. cornea Fen-A1 genome and provide a detailed functional annotation. The genome is 73.17 Mb in size, contains 86 scaffolds (N50 âˆ¼ 5.49 Mb), 59.09% GC content and encodes 19,120 predicted genes with a BUSCO completeness of 92.60%. Comparative genomic analysis reveals the phylogenetic relatedness of Fen-A1 and remarkable gene family dynamics. Putative genes were found mapped to 3 antibiotic-related, 36 light-dependent and 25 terpene metabolites. In addition, 789 CAZymes genes were classified, revealing the dynamics of quality loss due to postharvest refrigeration. Overall, our work is the first report on a pink A. cornea genome and provides a comprehensive insight into its complex functions.

17.
Plants (Basel) ; 13(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38999601

ABSTRACT

The ramet system is a typical structural type in the life history of clonal plants. This massive structure is formed by many similar ramets connected by underground rhizomes, which are independent and mutually influential. Therefore, the ramet system is unique to bamboo forests, and its role in the construction, maintenance, and productivity of bamboo populations is irreplaceable. Mulch management is a high-level cultivation model for bamboo forests that is used to cultivate bamboo shoots. However, the basic conditions of bamboo ramet systems in this managed model are poorly understood. This study analyzed the underground rhizome morphology, bud bank, and branching of bamboo ramets in a Phyllostachys praecox C.D. Chu et C.S. Chao 'Prevernalis' forest to explore the growth patterns of bamboo ramets in high-level management fields. In mulched bamboo forests, the bamboo rhizomes, distributed in intermediate positions of the bamboo ramet system, were long with many lateral buds and branches, and those at the initial and distal ends were short with few lateral buds and branches. The initial end of the ramet system reduced the ramet system, the intermediate part expanded the ramet system, and the distal end promoted ramet system regeneration. Owing to the continuous reduction, expansion, and renewal of ramet systems, the bamboo rhizome system demonstrates mobility and adaptability. This study found that a higher level of bamboo forest management increased the possibility of artificial fragmentation of the ramet system and that improving the efficiency of the ramet system was beneficial for maintaining its high vitality. Thus, this study provides a crucial reference for guiding the precise regulation of bamboo ramet systems in artificial bamboo forests.

18.
Cell Death Dis ; 15(7): 520, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039052

ABSTRACT

Aldehyde dehydrogenases superfamily (ALDHs), which are ubiquitously present in various organisms with diverse subcellular localizations, play a crucial role in regulating malignant tumor progression; Nevertheless, their involvement in clear cell renal cell carcinoma (ccRCC) has not been elucidated. In this study, we performed comprehensive bioinformatics analyses on the 19 ALDHs genes, and identified ALDH9A1 as a key contributor in ccRCC. Expression patterns and clinical relevance of ALDH9A1 were determined using bioinformatics analyses, real-time PCR, western blotting, and immunohistochemistry. To explore the underlying mechanism behind the tumor suppressor role of ALDH9A1, RNA sequencing, methylated RNA immunoprecipitation, luciferase reporter assay, mass spectroscopy, immunoprecipitation, mutational studies and immunofluorescence were employed. The impact of ALDH9A1 in ccRCC progression and metabolic programming was assessed through both in vitro and in vivo. Here, this study revealed ALDH9A1 as a tumor suppressor gene in ccRCC. The fat mass and obesity associated protein (FTO) was identified as a demethylase for ALDH9A1 mRNA, resulting in its reduced stability and expression levels in ccRCC. Functional experiments demonstrated that the deficiency of ALDH9A1 in ccRCC promoted tumor proliferation, invasion, migration and lipid accumulation. Mechanistic insights illustrated that the diminished levels of ALDH9A1 resulted in the failure to sequester nucleophosmin 1 (NPM1) within cytoplasm, thereby suppressing the transcription of IQ motif containing the GTPase-activating protein 2 (IQGAP2), subsequently activating the AKT-mTOR signaling, ultimately fostering tumor progression and lipid accumulation. In conclusion, the present study highlights the robust prognostic significance of ALDH9A1 and delivers a comprehensive understanding of ALDH9A1-NPM1-IQGAP2-AKT axis in ccRCC. These findings established a solid research foundation for novel therapeutic strategies for ccRCC patients.


Subject(s)
Adenosine , Carcinoma, Renal Cell , Kidney Neoplasms , Nucleophosmin , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Female , Humans , Male , Mice , Adenosine/analogs & derivatives , Adenosine/metabolism , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , GTPase-Activating Proteins/metabolism , GTPase-Activating Proteins/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Mice, Nude , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Proto-Oncogene Proteins c-akt/metabolism
19.
Cancer Lett ; 598: 217118, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39002690

ABSTRACT

Recent studies have highlighted palmitoylation, a novel protein post-translational modification, as a key player in various signaling pathways that contribute to tumorigenesis and drug resistance. Despite this, its role in bladder cancer (BCa) development remains inadequately understood. In this study, ZDHHC9 emerged as a significantly upregulated oncogene in BCa. Functionally, ZDHHC9 knockdown markedly inhibited tumor proliferation, promoted tumor cell apoptosis, and enhanced the efficacy of gemcitabine (GEM) and cisplatin (CDDP). Mechanistically, SP1 was found to transcriptionally activate ZDHHC9 expression. ZDHHC9 subsequently bound to and palmitoylated the Bip protein at cysteine 420 (Cys420), thereby inhibiting the unfolded protein response (UPR). This palmitoylation at Cys420 enhanced Bip's protein stability and preserved its localization within the endoplasmic reticulum (ER). ZDHHC9 might become a novel therapeutic target for BCa and could also contribute to combination therapy with GEM and CDDP.


Subject(s)
Acyltransferases , Apoptosis , Cell Proliferation , Endoplasmic Reticulum Chaperone BiP , Lipoylation , Unfolded Protein Response , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/metabolism , Acyltransferases/genetics , Endoplasmic Reticulum Chaperone BiP/metabolism , Unfolded Protein Response/drug effects , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Apoptosis/drug effects , Cisplatin/pharmacology , Mice , Heat-Shock Proteins/metabolism , Heat-Shock Proteins/genetics , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Disease Progression , Gemcitabine , Gene Expression Regulation, Neoplastic/drug effects , Xenograft Model Antitumor Assays , Mice, Nude , Male
20.
World J Microbiol Biotechnol ; 40(9): 286, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39083107

ABSTRACT

Staphylococcus aureus is a gram-positive bacteria, and its virulence factors can cause many kinds of infections, such as pneumonia, sepsis, enteritis and osteomyelitis. Traditional antibiotics can not only kill bacteria, but also easily lead to bacterial resistance. Jingfang Mixture (JFM) has the effects of inducing sweating and relieving the exterior, dispelling wind and eliminating dampness, and is commonly used in clinic to prevent and treat epidemic diseases and infectious diseases. The main purpose of this study is to explore the inhibitory effect of JFM on alpha-hemolysin (Hla) of S. aureus and to alleviate the damage caused by Hla. We found that JFM could inhibit the hemolytic activity, transcription level and neutralizing activity of Hla in a dose-dependent manner at the concentrations of 125, 250 and 500 µg/mL, without affecting the growth of bacteria. In addition, JFM reduced the damage of Hla to A549 cells and the release of lactate dehydrogenase (LDH). We also observed that in the S. aureus - induced pneumonia mouse model, JFM could significantly prolong the life of mice, reduce the bacterial load in the lungs, significantly improve the pathological state of the lungs and alleviate the damage caused by inflammatory factors, and the pathogenicity of gene deletion strain DU 1090 of S. aureus to pneumonia mice was also significantly reduced. In conclusion, this study proved that JFM is a potential drug against S. aureus infection, and this study provided a preliminary study for better guidance of clinical drug use.


Subject(s)
Anti-Bacterial Agents , Hemolysin Proteins , Staphylococcal Infections , Staphylococcus aureus , Animals , Female , Humans , Mice , A549 Cells , Anti-Bacterial Agents/pharmacology , Bacterial Load/drug effects , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Hemolysin Proteins/metabolism , Hemolysis/drug effects , Lung/microbiology , Lung/drug effects , Mice, Inbred BALB C , Pneumonia, Staphylococcal/drug therapy , Pneumonia, Staphylococcal/microbiology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Virulence Factors/genetics
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