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1.
Nitric Oxide ; 152: 19-30, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39260562

RESUMO

The mutual regulation between hydrogen sulfide (H2S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H2S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H2S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H2S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H2S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H2S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H2S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases.

2.
Cell Signal ; 124: 111406, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39270916

RESUMO

Cystathionine ß-synthase (CBS) occupies a key position as the initiating and rate-limiting enzyme in the sulfur transfer pathway and plays a vital role in health and disease. CBS is responsible for regulating the metabolism of cysteine, the precursor of glutathione (GSH), an important antioxidant in the body. Additionally, CBS is one of the three enzymes that produce hydrogen sulfide (H2S) in mammals through a variety of mechanisms. The dysregulation of CBS expression in cancer cells affects H2S production through direct or indirect pathways, thereby influencing cancer growth and metastasis by inducing angiogenesis, facilitating proliferation, migration, and invasion, modulating cellular energy metabolism, promoting cell cycle progression, and inhibiting apoptosis. It is noteworthy that CBS expression exhibits complex changes in different cancer models. In this paper, we focus on the CBS synthesis and metabolism, tissue distribution, potential mechanisms influencing tumor growth, and relevant signaling pathways. We also discuss the impact of pharmacological CBS inhibitors and silencing CBS in preclinical cancer models, supporting their potential as targeted cancer therapies.

3.
Lancet Reg Health West Pac ; 51: 101172, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39247209

RESUMO

Background: Evidence on the long-term benefits and cost-effectiveness of colorectal cancer (CRC) screening strategies in China remains limited. This modelling study aims to address this issue for various CRC screening strategies in China between 2020 and 2060. Methods: Using a previously developed microsimulation model (MIMIC-CRC) with Chinese epidemiological data, we evaluated four CRC screening strategies targeting population aged 45-74 years: no screening, colonoscopy every 10 years, biennial faecal immunochemical testing (FIT), and a roll-out FIT screening strategy. Screening coverage (invitation) rates from 5% to 100% were analysed. Single-cohort analysis of 100,000 individuals was conducted to estimate the relative cost-effectiveness of each strategy. A multiple-cohort analysis of 100,000 people aged 40+ over 2020-2060 was conducted to project nation-wide long-term benefits and cost-effectiveness. Findings: In single-cohort analysis, all strategies yielded reductions in CRC incidence and mortality compared to no screening, with colonoscopy outperforming FIT-based strategies at the same invitation rates. In multiple-cohort analysis, among people over 40 years of age in China over 2020-2060, compared to no screening, at invitation rate of 5%, screening by colonoscopy, biennial FIT and roll-out FIT-based approach were estimated to avert 1.2, 0.4, and 0.3 million incident CRCs and 0.2, 0.1, and 0.1 million CRC-related deaths, respectively, compared to no screening (25.4 million incident CRCs and 4.4 million CRC-related deaths), and this preventive effect enlarged as the screening coverage rate increased. At full coverage, colonoscopy achieved the largest reductions (38.2% lower incidence and 43.2% lower mortality) but required the most resources. Biennial FIT and roll-out FIT-based approach screening was slightly less effective but had significant reduced colonoscopy needs (reduction of 83.8% and 85.2%, respectively) and overall cost (reduction of 23.4% and 37.8%, respectively) compared to colonoscopy screening. Interpretation: Nation-wide implementation of screening would be effective in reducing the burden of CRC in China. Biennial FIT and roll-out FIT-based screening strategies could prevent incident CRC cases and CRC-related deaths with considerably fewer resources than colonoscopy screening. Efforts should be made to increase the screening coverage in China. Funding: Chinese Academy of Medical Science Innovation Fund for Medical Science (2022-I2M-1-0031); National Natural Science Foundation of China (82173606; 82273726); Beijing Nova Program of Science and Technology (20230484397).

4.
Medicine (Baltimore) ; 103(22): e38322, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-39259123

RESUMO

BACKGROUND: Recent studies have found that ferroptosis-related genes (FRGs) have broad applications in tumor therapy. However, the predictive potential of these genes in lung adenocarcinoma (LUAD) remains to be fully characterized. We aimed to investigate the FRGs that might be potential targets for LUAD. METHODS: We screened the RNA sequencing samples from LUAD patients from the GEO database and analyzed the ferroptosis-related differentially expressed genes (DEGs). A functional analysis of DEGs was performed. The risk model was constructed to evaluation and validation FRGs. We explored the immune landscape of LUAD and controls. The value of FRGs in diagnosing LUAD was tested in the GSE30219, GSE37745, GSE0081 datasets, and qPCR was used to verify their diagnostic value in LUAD patients in our hospital. RESULTS: A total of 1327 DEGs in quantitative proteomics were obtained, of which ferroptosis-related DEGs were 259. Enrichment analysis showed significant enrichment in the absorption and metabolism of fatty acids and arachidonic acid. The upregulated genes (GCLC, RRM2, AURKA, SLC7A5, and SLC2A1) and downregulated genes (ANGPTL7, ALOX15, ALOX15B, HSD17B11, IL33, TSC22D3, and DUOX1) were selected as core genes in tissue samples from 62 patients by qPCR. DUOX1 and HSD17B11 were obtained by bioinformatics analysis, both of which showed similar expression trends at the RNA and protein levels. The Kaplan-Meier method showed that DUOX1 and HSD17B11 were closely related to the overall survival (OS) of LUAD patients. CONCLUSION SUBSECTIONS: Ferroptosis-related genes DUOX1 and HSD17B11 are of considerable value in the diagnosis of LUAD patients. Their low expression suggests an increased recurrence rate and leads to a decrease in the patient quality of life.


Assuntos
Adenocarcinoma de Pulmão , Oxidases Duais , Ferroptose , Neoplasias Pulmonares , Microambiente Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , 20-Hidroxiesteroide Desidrogenases , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Oxidases Duais/genética , Estradiol Desidrogenases/genética , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Prognóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
5.
J Gastrointest Oncol ; 15(4): 1698-1711, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39279966

RESUMO

Background: The optimal timing to discontinue immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC) patients with clinical benefits remains unclear. This study aimed to assess the outcomes of HCC patients after ICI discontinuation. Methods: Patients with HCC were retrospectively screened and those discontinued ICI therapy in the absence of progressive disease (PD) were included. Responses at discontinuation were evaluated per response evaluation criteria in solid tumors (RECIST) version 1.1 and modified RECIST (mRECIST). Patients were classified into five subgroups according to the cause of discontinuation: complete response (CR), partial response (PR), stable disease (SD) per RESICT version 1.1, adverse event (AE), or others. Progression-free survival (PFS) and overall survival (OS) since ICI start or after ICI discontinuation were assessed. Results: A total of 66 patients were included. The median follow-up was 29.33 months. The median PFS since ICI start was 30.83 months [95% confidence interval (CI): 24.93-36.72], and the median OS was not reached. The median PFS after discontinuation was 20.6 months (95% CI: 7.63-33.56), and the median OS after discontinuation was not reached. Univariate analysis showed that age, treatment after discontinuation, Response (RECIST version 1.1) at discontinuation and modified response (mResponse per mRECIST) at discontinuation were significantly associated with PFS after discontinuation, while age and mResponse at discontinuation were significantly associated with OS after discontinuation. Multivariate analysis further demonstrated that mResponse at discontinuation and treatment after discontinuation were independently associated with PFS after discontinuation, while age was independently associated with OS after discontinuation. Conclusions: ICIs might be discontinued in HCC patients with a response of CR per mRECIST. Patients with a response of PR/SD per mRECIST or elder age could continue ICI therapy after achieving clinical benefits. Tyrosine kinase inhibitor (TKI) maintenance therapy might help to prevent progression after ICI discontinuation.

6.
Chem Biol Interact ; 403: 111226, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39237072

RESUMO

Hydrogen sulfide (H2S), an endogenous gasotransmitter, plays a key role in several critical physiological and pathological processes in vivo, including vasodilation, anti-infection, anti-tumor, anti-inflammation, and angiogenesis. In colorectal cancer (CRC), aberrant overexpression of H2S-producing enzymes has been observed. Due to the important role of H2S in the proliferation, growth, and death of cancer cells, H2S can serve as a potential target for cancer therapy. In this review, we thoroughly analyzed the underlying mechanism of action of H2S in CRC from the following aspects: the synthesis and catabolism of H2S in CRC cells and its effect on cell signal transduction pathways; the inhibition effects of exogenous H2S donors with different concentrations on the growth of CRC cells and the underlying mechanism of H2S in garlic and other natural products. Furthermore, we elucidate the expression characteristics of H2S in CRC and construct a comprehensive H2S-related signaling pathway network, which has important basic and practical significance for promoting the clinical research of H2S-related drugs.

7.
Heliyon ; 10(15): e35587, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170472

RESUMO

Background: This study was conducted to investigate whether baseline creatinine-cystatin C ratio is associated with all-cause mortality in adult Chinese patients hospitalized with coronavirus disease 2019. Methods: This study included 933 patients with coronavirus disease 2019 who were admitted to The Affiliated Hospital of Guangdong Medical University between December 2022 and March 2023. All-cause mortality was determined by telephone follow-up after 28 days. Multivariate Cox proportional risk models were used to investigate the relationship between baseline creatinine-cystatin C ratio and all-cause mortality. Restricted cubic spline and two-piecewise Cox proportional hazards risk models were used to identify non-linear correlations. Results: Of the 933 patients, 128 died during the 28 days follow-up. The restricted cubic spline analysis of hospitalized patients with coronavirus disease 2019 revealed an L-shaped association between baseline creatinine-cystatin C ratio and all-cause mortality, with a threshold creatinine-cystatin C ratio of ≤0.93 predicting all-cause mortality. Specifically, a baseline creatinine-cystatin C ratio below this threshold value was negatively correlated with mortality (hazard ratio 0.12, 95 % confidence interval 0.03-0.48), but a creatinine-cystatin C ratio >0.93 was not correlated with mortality (hazard ratio 1.29, 95 % confidence interval 0.65-2.55). Conclusions: In Chinese adult patients hospitalized with coronavirus disease 2019, an L-shaped relationship was observed between the baseline creatinine-cystatin C ratio and all-cause mortality.

8.
J Environ Manage ; 369: 122286, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39213849

RESUMO

Active iron oxides, especially poorly crystalline forms, benefit soil organic carbon (SOC) accumulation via directly bounding and indirectly promoting aggregation. However, it remains unclear on the impacts of active iron oxides on SOC accumulation in paddy and upland soils under long-term fertilization regimes. Here, we attempted to clarify the underlying mechanisms of amorphous (FeO) and organically complexed (FeP) iron oxides mediating SOC accumulation in paddy and upland soils based on two long-term fertilization experiments (both including no fertilization [CK]; chemical nitrogen, phosphorus and potassium [NPK] and NPK plus manure [NPKM] treatments). Results showed that compared to upland soil, Fe-bound organic carbon (Fe-bound OC) content in paddy soil, occupying 21-30% of SOC, was 77% higher on average, due to larger amounts of FeO (+31%) and FeP (+224%). The FeO and FeP were positively related to mean weight diameter (MWD) of soil aggregates across paddy and upland soils. Compared to NPK treatment, NPKM treatment strongly increased FeO (+41%), FeP (+60%) and associated Fe-bound OC (+19%) in paddy soil, and increased FeO (+17%) and FeP (+25%) while decreasing Fe-bound OC (-9%) in upland soil. These combined findings indicated the importance of poorly crystalline iron oxides facilitating Fe-bound OC formation and its contribution to SOC accumulation in paddy soil rather than upland soil. Moreover, long-term manure amendment could enhance SOC accumulation by increasing Fe-bound OC and aggregation stability in paddy soil and enhancing physical protection in upland soil, largely attributed to increased poorly crystalline iron oxides. Overall, these results highlight the potential mechanisms through which active iron oxides regulate SOC accumulation and guide fertilization management in paddy and upland soils.


Assuntos
Carbono , Compostos Férricos , Fertilizantes , Solo , Solo/química , Carbono/metabolismo , Agricultura , Fósforo/análise , Nitrogênio/metabolismo , Nitrogênio/análise , Oryza/metabolismo , Oryza/crescimento & desenvolvimento
9.
Biomedicines ; 12(8)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39200279

RESUMO

Breath analysis, despite being an overlooked biomatrix, has a rich history in disease diagnosis. However, volatile organic compounds (VOCs) have yet to establish themselves as clinically validated biomarkers for specific diseases. As focusing solely on late-stage or malignant disease biomarkers may have limited relevance in clinical practice, the objective of this review is to explore the potential of VOC breath tests for the diagnosis of non-cancer diseases: (1) Precancerous conditions like gastro-esophageal reflux disease (GERD) and Barrett's esophagus (BE), where breath tests can complement endoscopic screening; (2) endoluminal diseases associated with autoinflammation and dysbiosis, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease, which currently rely on biopsy and symptom-based diagnosis; (3) chronic liver diseases like cirrhosis, hepatic encephalopathy, and non-alcoholic fatty liver disease, which lack non-invasive diagnostic tools for disease progression monitoring and prognostic assessment. A literature search was conducted through EMBASE, MEDLINE, and Cochrane databases, leading to an overview of 24 studies. The characteristics of these studies, including analytical platforms, disorder type and stage, group size, and performance evaluation parameters for diagnostic tests are discussed. Furthermore, how VOCs can be utilized as non-invasive diagnostic tools to complement existing gold standards is explored. By refining study designs, sampling procedures, and comparing VOCs in urine and blood, we can gain a deeper understanding of the metabolic pathways underlying VOCs. This will establish breath analysis as an effective non-invasive method for differential diagnosis and disease monitoring.

10.
Surg Endosc ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164437

RESUMO

OBJECTIVE: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. METHODS: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. RESULTS: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. CONCLUSION: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.

11.
MedComm (2020) ; 5(9): e661, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39156767

RESUMO

In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S-catalyzing enzymes, such as cystathionine-ß-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia-reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.

12.
EJHaem ; 5(4): 757-767, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39157627

RESUMO

Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS-IB-1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, p = 0.045; HR = 3.64, 95%CI 1.40-9.44, p = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

13.
Cell Rep Med ; 5(7): 101645, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39019012

RESUMO

Fms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g., gilteritinib) are effective, they face challenges such as drug resistance, relapse, and high costs. Here, we report that metformin, a cheap, safe, and widely used anti-diabetic agent, exhibits a striking synergistic effect with gilteritinib in treating FLT3-ITD AML. Metformin significantly sensitizes FLT3-ITD AML cells (including TKI-resistant ones) to gilteritinib. Metformin plus gilteritinib (low dose) dramatically suppresses leukemia progression and prolongs survival in FLT3-ITD AML mouse models. Mechanistically, the combinational treatment cooperatively suppresses polo-like kinase 1 (PLK1) expression and phosphorylation of FLT3/STAT5/ERK/mTOR. Clinical analysis also shows improved survival rates in patients with FLT3-ITD AML taking metformin. Thus, the metformin/gilteritinib combination represents a promising and cost-effective treatment for patients with FLT3-mutated AML, particularly for those with low income/affordability.


Assuntos
Compostos de Anilina , Proteínas de Ciclo Celular , Sinergismo Farmacológico , Leucemia Mieloide Aguda , Metformina , Mutação , Quinase 1 Polo-Like , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas , Pirazinas , Transdução de Sinais , Tirosina Quinase 3 Semelhante a fms , Metformina/farmacologia , Metformina/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Humanos , Animais , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Transdução de Sinais/efeitos dos fármacos , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Camundongos , Mutação/genética , Linhagem Celular Tumoral , Tiofenos/farmacologia , Tiofenos/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Fator de Transcrição STAT5/metabolismo , Fator de Transcrição STAT5/genética , Feminino , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Serina-Treonina Quinases TOR/metabolismo
14.
J Exp Clin Cancer Res ; 43(1): 200, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39030638

RESUMO

BACKGROUND: The progression of non-small cell lung cancer (NSCLC) is significantly influenced by circular RNAs (circRNAs), especially in tumor hypoxia microenvironment. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC remain largely unexplored. METHODS: Differentially expressed circRNAs in NSCLC tissues were identified through high-throughput RNA sequencing. The characteristics of circ_0007386 were rigorously confirmed via Sanger sequencing, RNase R treatment and actinomycin D treatment. The effects of circ_0007386 on proliferation and apoptosis were investigated using CCK8, cloning formation assays, TUNEL staining, and flow cytometry assays in vitro. In vivo, xenograft tumor models were used to evaluate its impact on proliferation. Mechanistically, the regulatory relationships of circ_0007386, miR-383-5p and CIRBP were examined through dual luciferase reporter assays and rescue experiments. Additionally, we detected the binding of EIF4A3 to CRIM1 pre-mRNA by RNA immunoprecipitation and the interaction between YAP1 and EIF4A3 under hypoxic conditions by co-immunoprecipitation. RESULTS: Our investigation revealed a novel circRNA, designated as circ_0007386, that was upregulated in NSCLC tissues and cell lines. Circ_0007386 modulated proliferation and apoptosis in NSCLC both in vitro and in vivo. Functionally, circ_0007386 acted as a sponge for miR-383-5p, targeting CIRBP, which influenced NSCLC cell proliferation and apoptosis via the PI3K/AKT signaling pathway. Furthermore, under hypoxic conditions, the interaction between YAP1 and EIF4A3 was enhanced, leading to the displacement of EIF4A4 from binding to CRIM1 pre-mRNA. This facilitated the back-splicing of CRIM1 pre-mRNA, increasing the formation of circ_0007386. The circ_0007386/miR-383-5p/CIRBP axis was significantly associated with the clinical features and prognosis of NSCLC patients. CONCLUSIONS: Circ_0007386, regulated by YAP1-EIF4A3 interaction under hypoxia conditions, plays an oncogenic role in NSCLC progression via the miR-383-5p/CIRBP axis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Progressão da Doença , Fator de Iniciação 4A em Eucariotos , Neoplasias Pulmonares , RNA Circular , Proteínas de Sinalização YAP , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Animais , Proteínas de Sinalização YAP/metabolismo , Camundongos , Fator de Iniciação 4A em Eucariotos/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Feminino , Linhagem Celular Tumoral , Proliferação de Células , Precursores de RNA/metabolismo , Precursores de RNA/genética , Masculino , Splicing de RNA , Apoptose , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , RNA Helicases DEAD-box
15.
NPJ Digit Med ; 7(1): 182, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971937

RESUMO

Computer-aided implant surgery has undergone continuous development in recent years. In this study, active and passive systems of dynamic navigation were divided into active dynamic navigation system group and passive dynamic navigation system group (ADG and PDG), respectively. Active, passive and semi-active implant robots were divided into active robot group, passive robot group and semi-active robot group (ARG, PRG and SRG), respectively. Each group placed two implants (FDI tooth positions 31 and 36) in a model 12 times. The accuracy of 216 implants in 108 models were analysed. The coronal deviations of ADG, PDG, ARG, PRG and SRG were 0.85 ± 0.17 mm, 1.05 ± 0.42 mm, 0.29 ± 0.15 mm, 0.40 ± 0.16 mm and 0.33 ± 0.14 mm, respectively. The apical deviations of the five groups were 1.11 ± 0.23 mm, 1.07 ± 0.38 mm, 0.29 ± 0.15 mm, 0.50 ± 0.19 mm and 0.36 ± 0.16 mm, respectively. The axial deviations of the five groups were 1.78 ± 0.73°, 1.99 ± 1.20°, 0.61 ± 0.25°, 1.04 ± 0.37° and 0.42 ± 0.18°, respectively. The coronal, apical and axial deviations of ADG were higher than those of ARG, PRG and SRG (all P < 0.001). Similarly, the coronal, apical and axial deviations of PDG were higher than those of ARG, PRG, and SRG (all P < 0.001). Dynamic and robotic computer-aided implant surgery may show good implant accuracy in vitro. However, the accuracy and stability of implant robots are higher than those of dynamic navigation systems.

17.
Diagnostics (Basel) ; 14(14)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39061700

RESUMO

Volatile organic compounds have drawn significant attention in recent years as a novel tool for non-invasive detection of a wide range of diseases, including gastrointestinal cancers, for which the need for effective, affordable, and non-invasive screening methods is substantial. Sample preparation is a fundamental step that greatly influences the quality of results and the feasibility of wide-range applications. This review summarizes sampling methods used in studies aiming at testing the diagnostic value of volatile organic compounds in gastrointestinal cancers, discussing in detail some of the recent advancements in automated sampling techniques. Finally, we propose some directions in which sample collection and processing can improve for VOC analysis to be popularized in clinical settings.

18.
Exp Cell Res ; 441(2): 114172, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39053869

RESUMO

In recent years, the impact of age-related diseases on human health has become increasingly severe, and developing effective drugs to deal with these diseases has become an urgent task. Considering the essential regulatory role of hydrogen sulfide (H2S) in these diseases, it is regarded as a promising target for treatment. H2S is a novel gaseous transmitter involved in many critical physiological activities, including anti-oxidation, anti-inflammation, and angiogenesis. H2S also regulates cell activities such as cell proliferation, migration, invasion, apoptosis, and autophagy. These regulatory effects of H2S contribute to relieving and treating age-related diseases. In this review, we mainly focus on the pathogenesis and treatment prospects of H2S in regulating age-related diseases.


Assuntos
Envelhecimento , Sulfeto de Hidrogênio , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Humanos , Envelhecimento/metabolismo , Animais , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
19.
Nitric Oxide ; 150: 18-26, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38971520

RESUMO

Hydrogen sulfide (H2S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H2S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H2S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H2S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H2S in normal skin, the role of altering H2S metabolism in dermatological diseases, and the therapeutic potential of diverse H2S donors for the treatment of dermatological diseases.


Assuntos
Sulfeto de Hidrogênio , Dermatopatias , Sulfeto de Hidrogênio/metabolismo , Humanos , Dermatopatias/tratamento farmacológico , Dermatopatias/metabolismo , Animais , Pele/metabolismo
20.
Chin Med J (Engl) ; 137(16): 1957-1964, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38958046

RESUMO

BACKGROUND: Digestive system cancers constitute a significant number of cancer cases, but their burden is not uniform. As Global Cancer Observatory (GLOBOCAN) 2022 has recently updated its estimates of cancer burden, we aimed to investigate the burden of six major digestive system cancers both worldwide and in China, along with geographical and temporal variations in cancer-specific incidence and mortality. METHODS: We extracted data on primary cancers of the esophagus, stomach, colorectum, liver, pancreas, and gallbladder from the GLOBOCAN database for 2022. Age-standardized incidence and mortality rates were calculated and stratified by sex, country, region, and human development index (HDI). We used the 2022 revision of the World Population Prospects (United Nations) to obtain demographic data for various age groups in China from 1988 to 2012 and used the joinpoint model and the average annual percentage change (AAPC) to analyze cancer incidence trends in China. RESULTS: In 2022, the estimated global incidence of digestive system cancers reached 4,905,882, with an estimated 3,324,774 cancer-related deaths. Colorectal cancer was most prevalent in terms of incidence and mortality. There was a significant correlation between the burden of gastrointestinal cancers and country HDI. From 1988 to 2012, the incidence of esophageal, gastric, and liver cancers declined in China, whereas colorectal and pancreatic cancer incidences continued to increase. By 2050, colorectal and liver cancers are projected to remain the leading cancer types in China in terms of incidence and mortality, respectively. CONCLUSIONS: Digestive system cancers remain a significant public health challenge globally and in China. Although progress has been made in the prevention and control of some cancers, the burden of digestive system cancers persists. The implementation of tertiary prevention strategies must be intensified to reduce the incidence and mortality of digestive system cancers, mitigating their impact on public health.


Assuntos
Neoplasias do Sistema Digestório , Humanos , China/epidemiologia , Neoplasias do Sistema Digestório/epidemiologia , Incidência , Masculino , Feminino , Neoplasias Pancreáticas/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias da Vesícula Biliar/epidemiologia
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