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1.
Eur J Pharmacol ; 976: 176696, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38821160

RESUMO

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD+/NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI.


Assuntos
Injúria Renal Aguda , Ácidos Cafeicos , Lipopolissacarídeos , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sepse , Succinatos , Animais , Sepse/complicações , Sepse/tratamento farmacológico , Camundongos , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Masculino , Succinatos/farmacologia , Succinatos/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células RAW 264.7 , Estresse Oxidativo/efeitos dos fármacos , Inflamassomos/metabolismo , Camundongos Endogâmicos C57BL , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Glicólise/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ativação de Macrófagos/efeitos dos fármacos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38487885

RESUMO

OBJECTIVES: In this study, we employed a multi-dimensional data mining approach to examine the clinical instances where Professor Xu Zhiyin treated thyroid nodules. Our aim is to understand the patterns of symptoms, underlying causes, and treatment approaches used for thyroid nodules. By doing so, the intention is to distill the essential aspects, compile Professor Xu Zhiyin's clinical insights, and investigate his scholarly perspectives. METHODS: Professor Xu Zhiyin's clinical diagnoses and treatments spanning from 2009 to 2019 were entered into Microsoft Excel. Subsequently, the collected data was imported into the Medcase V5.2 system to facilitate data mining. Various techniques, such as frequency-based method, association rule analysis, and clustering, including a decentralized system clustering approach, were employed on a set of 346 cases involving patients with thyroid nodules that conformed to the specified criteria. The primary focus was on extracting insights regarding symptoms and the underlying causes from the medical records. By integrating these findings with Professor Xu Zhiyin's clinical expertise, we examined and summarized the outcomes of the data mining process. RESULTS: The fundamental prescriptions were successfully extracted using the techniques for mining across multiple dimensions. Utilizing the scattered grouping of these prescriptions and with reference to the cluster analysis of the frequency-linked system, the fundamental prescriptions proposed by Professor Xu Zhiyin for addressing thyroid nodules encompass the following ingredients: Glycyrrhiza uralensis Fisch, Cortex Moutan, Paeoniae radix rubra, Curcuma longa L., Radix Curcumae, persica seed, Citri Reticulatae Viride Pericarpium, Pinellia ternata, Spica Prunellae, Ostreae concha, Gleditsia sinensis spine, Tuckahoe and Radix Codonopsis. CONCLUSION: The fundamental prescriptions were acquired using the frequency approach, association rule technique, k-means clustering approach, and systematic clustering approach. The research findings corroborate one another, demonstrating that Professor Xu Zhiyin's approach to distinguishing and treating thyroid nodules is embodied in distinct prescriptions tailored to specific diseases.


Assuntos
Mineração de Dados , Medicamentos de Ervas Chinesas , Nódulo da Glândula Tireoide , Humanos , Mineração de Dados/métodos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Medicina Tradicional Chinesa/métodos , Prescrições de Medicamentos/estatística & dados numéricos , Idoso , História do Século XXI
3.
Phytomedicine ; 123: 155175, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37951150

RESUMO

BACKGROUND: Sepsis-related cardiac dysfunction is believed to be a primary cause of high morbidity and mortality. Metabolic reprogramming is closely linked to NLRP3 inflammasome activation and dysregulated glycolysis in activated macrophages, leading to inflammatory responses in septic cardiomyopathy. Succinate dehydrogenase (SDH) and succinate play critical roles in the progression of metabolic reprogramming in macrophages. Inhibition of SDH may be postulated as an effective strategy to attenuate macrophage activation and sepsis-induced cardiac injury. PURPOSE: This investigation was designed to examine the role of potential compounds that target SDH in septic cardiomyopathy and the underlying mechanisms involved. METHODS/RESULTS: From a small molecule pool containing about 179 phenolic compounds, we found that chicoric acid (CA) had the strongest ability to inhibit SDH activity in macrophages. Lipopolysaccharide (LPS) exposure stimulated SDH activity, succinate accumulation and superoxide anion production, promoted mitochondrial dysfunction, and induced the expression of hypoxia-inducible factor-1α (HIF-1α) in macrophages, while CA ameliorated these changes. CA pretreatment reduced glycolysis by elevating the NAD+/NADH ratio in activated macrophages. In addition, CA promoted the dissociation of K(lysine) acetyltransferase 2A (KAT2A) from α-tubulin, and thus reducing α-tubulin acetylation, a critical event in the assembly and activation of NLRP3 inflammasome. Overexpression of KAT2A neutralized the effects of CA, indicating that CA inactivated NLRP3 inflammasome in a specific manner that depended on KAT2A inhibition. Importantly, CA protected the heart against endotoxin insult and improved sepsis-induced cardiac mitochondrial structure and function disruption. Collectively, CA downregulated HIF-1α expression via SDH inactivation and glycolysis downregulation in macrophages, leading to NLRP3 inflammasome inactivation and the improvement of sepsis-induced myocardial injury. CONCLUSION: These results highlight the therapeutic role of CA in the resolution of sepsis-induced cardiac inflammation.


Assuntos
Ácidos Cafeicos , Cardiomiopatias , Sepse , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Tubulina (Proteína)/metabolismo , Reprogramação Metabólica , Macrófagos/metabolismo , Succinatos/efeitos adversos , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/etiologia , Sepse/complicações , Sepse/tratamento farmacológico , Ácido Succínico/efeitos adversos , Lipopolissacarídeos/efeitos adversos
4.
Cancer Biol Ther ; 25(1): 2284849, 2024 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-38051132

RESUMO

OBJECTIVE: This study aims to investigate the effect of red ginseng polysaccharide (RGP) on gastric cancer (GC) development and explore its mechanism. METHODS: GC cell lines AGS were treated with varying concentrations of RGP (50, 100, and 200 µg/mL). AGS cells treated with 200 µg/mL RGP were transfected with aquaporin 3 (AQP3) overexpression vector. Cell proliferation, viability, and apoptosis were evaluated by MTT, colony formation assay, and flow cytometry, respectively. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression of AQP3. The levels of Fe2+, malondialdehyde, and lactate dehydrogenase were measured using their respective detection kits, and the reactive oxygen species levels was determined by probe 2',7'-dichlorodihydrofluorescein diacetate. The expression of ferroptosis-related protein and PI3K/Akt pathway-related protein were assessed by western blot. In vivo experiments in nude mice were performed and the mice were divided into four groups (n = 5/group) which gavage administrated with 150 mg/kg normal saline, and 75, 150, 300 mg/kg RGP, respectively. Their tumor weight and volume were recorded. RESULTS: RGP treatment effectively inhibited the proliferation and viability of AGS cells in a dosage-dependent manner and induced apoptosis. It induced ferroptosis in AGS cells, as well as inhibiting the expression of PI3K/Akt-related proteins. AQP3 overexpression could reversed the effect of RGP treatment on ferroptosis. Confirmatory in vivo experiments showed that RGP could reduce the growth of implanted tumor, with increased RGP concentration resulting in greater tumor inhibitory effects. CONCLUSION: RGP might have therapeutic potential against GC, effectively inhibiting the proliferation and viability of AGS cells.


Assuntos
Ferroptose , Panax , Neoplasias Gástricas , Animais , Camundongos , Neoplasias Gástricas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Regulação para Baixo , Aquaporina 3/genética , Aquaporina 3/metabolismo , Camundongos Nus , Proliferação de Células , Panax/metabolismo , Linhagem Celular Tumoral
5.
Huan Jing Ke Xue ; 44(12): 6700-6709, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098396

RESUMO

Organophosphate esters(OPEs), as a substitute for brominated flame retardants, are widely used in production and life, and their environmental pollution and toxic effects have attracted widespread attention. In this study, the concentrations and distribution characteristics of OPEs in seven major drainage basins of China were sorted out. The average daily dose of OPEs in Chinese adults, adolescents, and children was calculated to assess the health risks, and the reliability of the results was evaluated using Monte Carlo simulation. The toxic effect concentrations of 12 OPEs on aquatic organisms were investigated, and the species sensitivity distribution(SSD) curve was constructed to assess the ecological risk. The results showed that the 5th percentile concentration of ΣOPEs in the seven drainage basins was 52.61 ng·L-1 under the low exposure scenario. The median concentration of ΣOPEs in the seven basins was 499.74 ng·L-1, with trichloroethyl phosphate(TCEP), triethyl phosphate(TEP), and triethyl phosphate(1,3-dichloro-2-propyl) esters(TDCP) as the main contaminants. Under the high exposure scenario, the 95th percentile concentration of ΣOPEs in the seven basins was 1904.4 ng·L-1, 3.8 times that of the intermediate exposure scenario, and the Yangtze River Basin had the highest ΣOPEs concentration under the high exposure scenario. The health risk assessment showed that the non-carcinogenic risk of OPEs exposure through drinking water was within acceptable limits for different populations. Trimethyl phosphate(TMP), triisobutyl phosphate(TiBP), and TCEP were the main contributors to cancer risk. The results of ecological risk assessment showed that TCEP had medium ecological risk at the high exposure level, tributyl phosphate(TnBP) had medium ecological risk under the intermediate exposure scenario, and there was higher ecological risk under the high exposure scenario. Triphenyl phosphate(TPhP) had a risk quotient greater than 1 under the low, intermediate, and high exposure scenarios, and there was a high ecological risk, which requires special attention.


Assuntos
Monitoramento Ambiental , Retardadores de Chama , Criança , Humanos , Adolescente , Monitoramento Ambiental/métodos , Rios , Reprodutibilidade dos Testes , Organofosfatos , Poluição Ambiental , Medição de Risco , China , Ésteres , Fosfatos , Retardadores de Chama/análise
6.
Nat Commun ; 14(1): 7264, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945658

RESUMO

Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.


Assuntos
Artrópodes , Hemípteros , Animais , Artrópodes/genética , Hemípteros/genética , Retroviridae
7.
World J Clin Cases ; 11(28): 6864-6870, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37901002

RESUMO

BACKGROUND: Congenital agenesis of the gallbladder (CAGB) is a rare condition often misdiagnosed as cholecystolithiasis, leading to unnecessary surgeries. Accurate diagnosis and surgical exploration are crucial in patients with suspected CAGB or atypical gallbladder stone symptoms. Preoperative imaging, such as magnetic resonance cholangiopancreatography (MRCP), plays a vital role in confirming the diagnosis. Careful intraoperative dissection is necessary to avoid iatrogenic injuries and misdiagnosis. Multidisciplinary consultations and collaboration, along with the use of various diagnostic methods, can minimize associated risks. CASE SUMMARY: We present the case of a 34-year-old female with suspected gallbladder stones, ultimately diagnosed with CAGB through surgical exploration. The patient underwent laparoscopic examination followed by open exploratory surgery, which confirmed absence of the gallbladder. Subsequent imaging studies supported the diagnosis. The patient received appropriate postoperative care and experienced a successful recovery. CONCLUSION: This case highlights the rarity of CAGB and the importance of considering this condition in the differential diagnosis of patients with gallbladder stone symptoms. Accurate diagnosis using preoperative imaging, such as MRCP, is crucial to prevent unnecessary surgeries. Surgeons should exercise caution and conduct meticulous dissection during surgery to avoid iatrogenic injuries and ensure accurate diagnosis. Multidisciplinary collaboration and utilization of various diagnostic methods are essential to minimize the risk of misdiagnosis. Selection of the optimal treatment strategy should prioritize minimizing trauma and maintaining open communication with the patient and their family members.

8.
Int Immunopharmacol ; 125(Pt A): 111108, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37890380

RESUMO

Currently, there are no effective therapeutic targets for the treatment of chronic cerebral hypoperfusion(CCH)-induced cerebral ischemic injury. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are discovered as the inducers of neurogenesis and angiogenesis. We previously made a nanofiber membrane (NFM), maintaining a long-term release of VEGF and bFGF up to 35 days, which might make VEGF and bFGF NFM as the potential protective agents against cerebral ischemic insult. In this study, the effects of VEGF and bFGF delivered by NFM into brain were investigated as well as their underlying mechanismsin a rat model of CCH. VEGF + bFGF NFM application increased the expressions of tight junction proteins, maintained BBB integrity, and alleviated vasogenic cerebral edema. Furthermore, VEGF + bFGF NFM sticking enhanced angiogenesis and elevated CBF. Besides, VEGF + bFGF NFM treatment inhibited neuronal apoptosis and decreased neuronal loss. Moreover, roofing of VEGF + bFGF NFM attenuated microglial activation and blocked the launch of NLRP3/caspase-1/IL-1ß pathway. In addition, VEGF + bFGF NFM administration prevented disruption to the pre/postsynaptic membranes and loss of myelin sheath, relieving synaptic injury and demyelination. Oligodendrogenesis, neurogenesis and PI3K/AKT/mTOR pathway were involved in the treatment of VEGF + bFGF NFM against CCH-induced neuronal injury and hypomyelination. These findings supported that VEGF + bFGF NFM application constitutes a neuroprotective strategy for the treatment of CCH, which may be worth further clinical translational research as a novel neuroprotective approach, benifiting indirect surgical revascularization.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Nanofibras , Ratos , Animais , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Fosfatidilinositol 3-Quinases , Nanofibras/uso terapêutico , Fatores de Crescimento do Endotélio Vascular , Isquemia Encefálica/metabolismo , Isquemia
9.
Mol Biol Evol ; 40(10)2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37804524

RESUMO

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.


Assuntos
Afídeos , Hemípteros , Animais , Ferredoxinas/metabolismo , Plantas/metabolismo , Hemípteros/genética , Nicotiana/genética , Nicotiana/metabolismo , Afídeos/metabolismo , Proteínas e Peptídeos Salivares/genética
10.
Genes (Basel) ; 14(8)2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37628691

RESUMO

The whitefly Bemisia tabaci is one of the most destructive pests worldwide, and causes tremendous economic losses. Tobacco Nicotiana tabacum serves as a model organism for studying fundamental biological processes and is severely damaged by whiteflies. Hitherto, our knowledge of how tobacco perceives and defends itself against whiteflies has been scare. In this study, we analyze the gene expression patterns of tobacco in response to whitefly infestation. A total of 244 and 2417 differentially expressed genes (DEGs) were identified at 12 h and 24 h post whitefly infestation, respectively. Enrichment analysis demonstrates that whitefly infestation activates plant defense at both time points, with genes involved in plant pattern recognition, transcription factors, and hormonal regulation significantly upregulated. Notably, defense genes are more intensely upregulated at 24 h post infestation than at 12 h, indicating an increased immunity induced by whitefly infestation. In contrast, genes associated with energy metabolism, carbohydrate metabolism, ribosomes, and photosynthesis are suppressed, suggesting impaired plant development. Taken together, our study provides comprehensive insights into how plants respond to phloem-feeding insects, and offers a theoretical basis for better research on plant-insect interactions.


Assuntos
Hemípteros , Nicotiana , Animais , Nicotiana/genética , Hemípteros/genética , Transcriptoma/genética , Metabolismo Energético , Medo
11.
Curr Opin Insect Sci ; 59: 101106, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37625640

RESUMO

Planthoppers possess an impressive ability to exhibit phenotypic plasticity, which allows them to adjust their morphology for migration, overwintering, and adaptation to different environmental conditions. The wing and color polyphenism are the two most outward morphologies. Wing polyphenism serves as a classic illustration of a life history trade-off between reproduction and migration, while color polyphenism is potentially correlated with the insect development and immunity. In this review, we present the important contributions that link environment cues to wing and color polyphenism, and highlight recent advances in insulin/insulin-like growth factor signaling-forkhead transcription factor subgroup O (FoxO) pathway-mediated wing development and tyrosine-melanin pathway-mediated coloration. Further work, particularly in the identification of the genes that FoxO regulates and in the elucidation of the intracellular signals that link the stimuli to the tyrosine-melanin pathway, is required.

12.
Front Cell Infect Microbiol ; 13: 1206393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448774

RESUMO

Objective: Surgical site infection (SSI) are a serious complication that can occur after open reduction and internal fixation (ORIF) of tibial fractures, leading to severe consequences. This study aimed to develop a machine learning (ML)-based predictive model to screen high-risk patients of SSI following ORIF of tibial fractures, thereby aiding in personalized prevention and treatment. Methods: Patients who underwent ORIF of tibial fractures between January 2018 and October 2022 at the Department of Emergency Trauma Surgery at Ganzhou People's Hospital were retrospectively included. The demographic characteristics, surgery-related variables and laboratory indicators of patients were collected in the inpatient electronic medical records. Ten different machine learning algorithms were employed to develop the prediction model, and the performance of the models was evaluated to select the best predictive model. Ten-fold cross validation for the training set and ROC curves for the test set were used to evaluate model performance. The decision curve and calibration curve analysis were used to verify the clinical value of the model, and the relative importance of features in the model was analyzed. Results: A total of 351 patients who underwent ORIF of tibia fractures were included in this study, among whom 51 (14.53%) had SSI and 300 (85.47%) did not. Of the patients with SSI, 15 cases were of deep infection, and 36 cases were of superficial infection. Given the initial parameters, the ET, LR and RF are the top three algorithms with excellent performance. Ten-fold cross-validation on the training set and ROC curves on the test set revealed that the ET model had the best performance, with AUC values of 0.853 and 0.866, respectively. The decision curve analysis and calibration curves also showed that the ET model had the best clinical utility. Finally, the performance of the ET model was further tested, and the relative importance of features in the model was analyzed. Conclusion: In this study, we constructed a multivariate prediction model for SSI after ORIF of tibial fracture through ML, and the strength of this study was the use of multiple indicators to establish an infection prediction model, which can better reflect the real situation of patients, and the model show great clinical prediction performance.


Assuntos
Infecção da Ferida Cirúrgica , Fraturas da Tíbia , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Estudos Retrospectivos , Tíbia/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fraturas da Tíbia/complicações , Fraturas da Tíbia/cirurgia , Aprendizado de Máquina , Fatores de Risco
13.
Neoplasma ; 70(3): 443-450, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37498067

RESUMO

The 5-year survival rate for patients with lung cancer, the world's second most frequent malignant tumor, is less than 20%, and its prognosis cannot be clearly predicted. Our aim was to analyze the epidermal growth factor receptor (EGFR) rs763317 (G>A) single nucleotide polymorphism and its association with prognosis in Chinese Han lung cancer patients. 839 patients with primary lung cancer were recruited, and genomic DNA was extracted and genotyped by SNPscan. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the association between prognosis and EGFR polymorphism rs763317. A significant association after stratification by age, significantly increased lung cancer risk was associated with the AA homozygous genotype of rs763317 (adjusted hazard ratio = 2.53, 95% CI: 1.31-4.88, p=0.005), and conferred a poor survival for lung cancer patients (MST: median survival time: 13.6 months) compared with GG genotype (MST: 41.5 months), and in the recessive model AA genotype (AA vs. GG + GA; adjusted hazard ratio = 2.57, 95% CI: 1.34-4.93, p=0.004) who were young (<60 years) had a significantly increased risk of death. The EGFR polymorphism rs763617 might serve as a significant genetic marker for predicting the prognosis of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , População do Leste Asiático , Receptores ErbB/genética , Predisposição Genética para Doença , Genótipo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico
14.
Front Oncol ; 13: 1048485, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37274230

RESUMO

Purpose: To provide reference method for the treatment of thyroid follicular carcinoma by studing the clinical imaging, pathological features and multimodal treatment of a case of thyroid follicular carcinoma with bone metastasis. Methods: By identifying the case's clinical, imaging, pathological features of a case of thyroid follicular carcinoma with bone metastasis, reflecting on the case's diagnosis and treatment process, and referring to literature about the characteristics of thyroid follicular carcinoma, the study aims to provide reference for the treatment of this kind of disease. Result: A 67-year-old male patient was admitted to the hospital with clinical symptoms of left pelvic pain. The biopsy pathology showed well-differentiated thyroid tissue. Considering his medical history, conclusion of thyroid follicular carcinoma metastasis could be made.The patient was stable and no tumor progression was observed after a combination of therapies including 131I and topical and targeted agents. Conclusions: Thyroid follicular carcinoma are prone to bone metastasis, and bone metastasis is the first symptom in some cases. Clinical imaging and pathology are needed for correct diagnosis, and a successful treatment requires a combination of multiple approaches including 131I, which is a Radioactive Iodine Therapy(RAI), local therapy and targeted drug therapy.

15.
Metabolism ; 145: 155579, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37127227

RESUMO

BACKGROUND: Na+/K+-ATPase (NKA), an ion pumping enzyme ubiquitously expressed in various cells, is critically involved in cellular ion homeostasis and signal transduction. However, the role of NKA in hepatic lipid homeostasis has yet to be fully characterized. METHODS: The activity of NKA and NKAα1 expression were determined in steatotic cells, mice and patients. The roles of NKAα1 in hepatosteatosis were detected using hepatocyte knockout or specific overexpression of NKAα1 in mice. RESULTS: Herein, we demonstrated that the expression and activity of α1 subunit of NKA (NKAα1) were lowered in the livers of nonalcoholic fatty liver disease (NAFLD) patients, high-fat diet (HFD)-induced obese mice, and genetically obese (ob/ob, db/db) mice, as well as oleic acid-induced hepatocytes. Hepatic deficiency of NKAα1 exacerbated, while adeno-associated virus-mediated liver specific overexpression of NKAα1 alleviated hepatic steatosis through regulation of fatty acid oxidation (FAO) and lipogenesis. Mechanistically, we revealed that NKAα1 upregulated sirtuin 1 (SIRT1) via interacting with ubiquitin specific peptidase 22 (USP22), a deubiquitinating enzyme for the stabilization and deubiquitination of SIRT1, thus activating the downstream autophagy signaling. Blockade of the SIRT1/autophagy signaling pathway eliminated the protective effects of NKAα1 against lipid deposition in hepatocytes. Importantly, we found that an antibody against the DR region (897DVEDSYGQQWTYEQR911) of NKAα1 subunit (DR-Ab) ameliorated hepatic steatosis through maintaining the membrane density of NKAα1 and inducing its activation. CONCLUSIONS: Collectively, this study renews the functions of NKAα1 in liver lipid metabolism and provides a new clue for gene therapy or antibody treatment of hepatic lipid metabolism disturbance by targeting NKAα1.


Assuntos
Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Camundongos Obesos , Sirtuína 1/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatócitos/metabolismo , Ácido Oleico/metabolismo , Ácido Oleico/farmacologia , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL
16.
Am J Physiol Cell Physiol ; 324(4): C856-C877, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36878842

RESUMO

Hydrogen sulfide (H2S) is previously described as a potentially lethal toxic gas. However, this gasotransmitter is also endogenously generated by the actions of cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) in mammalian systems, thus belonging to the family of gasotransmitters after nitric oxide (NO) and carbon monoxide (CO). The physiological or pathological significance of H2S has been extensively expanded for decades. Growing evidence has revealed that H2S exerts cytoprotective functions in the cardiovascular, nervous, and gastrointestinal systems by modulating numerous signaling pathways. With the continuous advancement of microarray and next-generation sequencing technologies, noncoding RNAs (ncRNAs) have gained recognition as key players in human health and diseases due to their considerable potential as predictive biomarkers and therapeutic targets. Coincidentally, H2S and ncRNAs are not independent regulators but interact with each other during the development and progression of human diseases. Specifically, ncRNAs might serve as downstream mediators of H2S or act on H2S-generating enzymes to govern endogenous H2S production. The purpose of this review is to summarize the interactive regulatory roles of H2S and ncRNAs in the initiation and development of various diseases and explore their potential health and therapeutic benefits. This review will also highlight the importance of cross talk between H2S and ncRNAs in disease therapy.


Assuntos
Gasotransmissores , Sulfeto de Hidrogênio , Animais , Humanos , Sulfeto de Hidrogênio/metabolismo , Cistationina , Transdução de Sinais , Óxido Nítrico , Cistationina gama-Liase , Mamíferos/metabolismo
18.
PLoS Pathog ; 19(3): e1011266, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36928081

RESUMO

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved signaling pathway that can regulate various biological processes. However, the role of JAK-STAT pathway in the persistent viral infection in insect vectors has rarely been investigated. Here, using a system that comprised two different plant viruses, Rice stripe virus (RSV) and Rice black-streaked dwarf virus (RBSDV), as well as their insect vector small brown planthopper, we elucidated the regulatory mechanism of JAK-STAT pathway in persistent viral infection. Both RSV and RBSDV infection activated the JAK-STAT pathway and promoted the accumulation of suppressor of cytokine signaling 5 (SOCS5), an E3 ubiquitin ligase regulated by the transcription factor STAT5B. Interestingly, the virus-induced SOCS5 directly interacted with the anti-apoptotic B-cell lymphoma-2 (BCL2) to accelerate the BCL2 degradation through the 26S proteasome pathway. As a result, the activation of apoptosis facilitated persistent viral infection in their vector. Furthermore, STAT5B activation promoted virus amplification, whereas STAT5B suppression inhibited apoptosis and reduced virus accumulation. In summary, our results reveal that virus-induced JAK-STAT pathway regulates apoptosis to promote viral infection, and uncover a new regulatory mechanism of the JAK-STAT pathway in the persistent plant virus transmission by arthropod vectors.


Assuntos
Tenuivirus , Viroses , Animais , Janus Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Tenuivirus/metabolismo , Insetos Vetores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
19.
Int J Mol Sci ; 24(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36902225

RESUMO

Low-color-temperature light-emitting diodes (LEDs) (called 1900 K LEDs for short) have the potential to become a healthy light source due to their blue-free property. Our previous research demonstrated that these LEDs posed no harm to retinal cells and even protected the ocular surface. Treatment targeting the retinal pigment epithelium (RPE) is a promising direction for age-related macular degeneration (AMD). Nevertheless, no study has evaluated the protective effects of these LEDs on RPE. Therefore, we used the ARPE-19 cell line and zebrafish to explore the protective effects of 1900 K LEDs. Our results showed that the 1900 K LEDs could increase the cell vitality of ARPE-19 cells at different irradiances, with the most pronounced effect at 10 W/m2. Moreover, the protective effect increased with time. Pretreatment with 1900 K LEDs could protect the RPE from death after hydrogen peroxide (H2O2) damage by reducing reactive oxygen species (ROS) generation and mitochondrial damage caused by H2O2. In addition, we preliminarily demonstrated that irradiation with 1900 K LEDs in zebrafish did not cause retinal damage. To sum up, we provide evidence for the protective effects of 1900 K LEDs on the RPE, laying the foundation for future light therapy using these LEDs.


Assuntos
Antioxidantes , Epitélio Pigmentado da Retina , Animais , Epitélio Pigmentado da Retina/metabolismo , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos da radiação , Peixe-Zebra/metabolismo , Peróxido de Hidrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Luz
20.
Br J Neurosurg ; 37(3): 254-257, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32476503

RESUMO

OBJECTIVE: Data about postoperative infections in male adults with spinal cord injury are scarce. We aimed to evaluate the association between prior exposure to pressure ulcers (PU) and the risk of postoperative infections in male adults with spinal cord injury (SCI). METHODS: We conducted a prospective study of male adults receiving surgery of SCI from January 2007 to December 2019. Postoperative infection included septicemia, pneumonia, surgical incision infection and urinary tract infection. A logistic regression analysis was applied. Risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were calculated. RESULTS: There were 408 patients with SCI in this study, which comprised 204 patients with prior PU and 204 patients without. The rate of postoperative infections within 14 days in patients with PU was 23.5%, which was higher than that of patients without PU (6.9%). The amounts to a 4.18-folds elevated risk of any postoperative infections with 14 days in patients with PU (RR: 4.18, 95% CI: 2.30-7.60, p-value: <0.001). With respect to specific infections, positive associations in pneumonia (RR: 4.18, 95% CI: 2.30-7.60, p-value: <0.001), surgical incision infection (RR: 4.18, 95% CI: 2.30-7.60, p-value: <0.001), and urinary tract infection (RR: 4.18, 95% CI: 2.30-7.60, p-value: <0.001) were also statistically significant. These results did not materially alter adjustment for potential risk factors. CONCLUSIONS: The study suggests an elevated risk of postoperative infections after surgery for SCI in male patients with prior exposure to pressure ulcers.


Assuntos
Pneumonia , Úlcera por Pressão , Traumatismos da Medula Espinal , Ferida Cirúrgica , Infecções Urinárias , Humanos , Adulto , Masculino , Úlcera por Pressão/etiologia , Úlcera por Pressão/complicações , Estudos Prospectivos , Ferida Cirúrgica/complicações , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/cirurgia , Fatores de Risco , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Pneumonia/complicações , Pneumonia/epidemiologia
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