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Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Gefitinibe , Indóis , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Quinolinas , Humanos , Gefitinibe/administração & dosagem , Gefitinibe/efeitos adversos , Gefitinibe/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Indóis/administração & dosagem , Indóis/uso terapêutico , Indóis/efeitos adversos , Masculino , Feminino , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Idoso de 80 Anos ou maisRESUMO
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.
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Antibacterianos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Plasmídeos , Tetraciclinas , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Tetraciclinas/farmacologia , Plasmídeos/genética , Humanos , Antibacterianos/farmacologia , Infecções por Klebsiella/microbiologia , China , Tigeciclina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Resistência a Tetraciclina/genética , Fezes/microbiologiaRESUMO
OBJECTIVE: To investigate the correlations between the expressions of proto-oncogenes C-myc and B-cell-specific Moloney leukemia virus integration site-1 (BMI-1), vaginal microecology, and human papillomavirus-DNA (HPV-DNA) load in patients with different cervical lesions. METHODS: A total of 51 patients with cervix squamous cell carcinoma (CSCC), 72 patients with cervical intraepithelial neoplasia (CIN) and 50 patients with normal cervix (NC) who were diagnosed or admitted between Jan. 1st 2020 and Dec. 31st 2022 at the Suzhou Hospital of Integrated Traditional Chinese and Western Medicine were selected and divided into three groups, i.e., the CSCC group, the CIN group and the NC group, for a retrospective analysis. Hybrid capture 2 (hc2) was used to detect the HPV-DNA load in each group. Immunohistochemistry was performed to detect C-myc and BMI-1 expressions in each group. The indicators of vaginal microecology in patients were compared among groups to analyze the correlations between C-myc, BMI-1 expressions, vaginal microecology and HPV-DNA load. RESULTS: The HPV-DNA load and expression levels of positive C-myc and BMI-1 in the CSCC group were all higher than those of the CIN and NC groups (P<0.05). The detection rate of lactobacillus in the CSCC group was lower than that of the CIN and NC groups. The percentages of leukocyte esterase (LE) positivity and pH ≥4.6 were higher in the CSCC group than those in the CIN and NC groups (P<0.05). The difference in the detection rate of spores among the three groups was not significant (P>0.05). Both C-myc and BMI-1 scores were positively correlated with HPV-DNA load in the 173 samples. CONCLUSION: The proto-oncogenes C-myc and BMI-1 were highly expressed in the cervical tissues of CIN and CSCC patients, whose vaginal microecology was also altered. Both may play an important role in the progression of cervical lesions.
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Atypical L858R or other L858X mutations in the epidermal growth factor receptor (EGFR) gene, beyond the classical EGFRL858R mutation caused by c.2573 T > G, have been identified in non-small cell lung cancer (NSCLC), yet their genomic features and survival benefits with EGFR tyrosine kinase inhibitor (TKI) treatment have not been fully explored. We retrospectively enrolled 489 NSCLC patients with baseline tumor tissue/plasma samples carrying uncommon EGFRL858R (N = 124), EGFRL858Q/M (N = 17), or classical EGFRL858R mutations (N = 348). The comparison of molecular features was performed using treatment-naïve tumor tissues. Survival benefits and resistance mechanisms of first-line EGFR TKI treatment were studied in an advanced disease subcohort. NSCLCs harboring uncommon EGFRL858R had lower TP53 mutation prevalence (p = 0.04) and chromosome instability scores (p = 0.02) than those with classical EGFRL858R. Concomitant EGFRL861Q mutations were enriched in NSCLCs with EGFRL858Q/M (p < 0.01), with cooccurrence in those carrying EGFRL858M. Patients with uncommon EGFRL858R experienced improved progression-free survival (PFS) compared to those with classical EGFRL858R (median: 13.0 vs. 10.0 months, hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.41-0.80). The association remained significant when adjusting for sex, age, histological subtype, TKI category, and anti-vascular therapy (HR: 0.55, 95% CI: 0.39-0.77). Furthermore, EGFRL858Q/M patients showed enhanced first-line PFS (vs. classical EGFRL858R, HR: 0.26, 95% CI: 0.10-0.67), potentially benefiting more from afatinib. Additionally, NSCLCs with uncommon EGFRL858R and classical EGFRL858R had similar resistance profiles to EGFR TKIs. In conclusion, NSCLCs carrying atypical EGFR L858 aberrations, which had fewer TP53 mutations and higher chromosome stability, exhibited improved PFS under first-line EGFR TKIs than those with the classical EGFRL858R.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Resultado do Tratamento , /uso terapêuticoRESUMO
Background: In China, most of the citizens experienced SARS-CoV-2 infection since the end of 2022. The Coronavirus disease 2019 (COVID-19) pandemic affected people's physical health and also had a significant impact on mental well-being. The present study aims to discover if the experience of SARS-CoV-2 infection influences patients' anxiety toward third molar surgery in the Chinese population. Materials and methods: The present study took the form of a questionnaire survey. From January 1, 2023, to June 30, 2023, patients who went to the Stomatology Center of China-Japan Friendship Hospital (Beijing, China) for the third molar extraction were included according to the inclusion criteria. The information on COVID-19 infection and the Modified Dental Anxiety Scale (MDAS) was collected. The software SPSS 22.0 was used for the statistical analyses. Results: A total of 574 survey results were harvested in the present study. The infection rate of COVID-19 was 86.6% (p > 0.05). The Average MDAS scores between patients who had been infected with COVID-19 and patients who were never infected were not significantly different (11.65 ± 4.41 vs. 11.42 ± 4.41, p > 0.05). The subgroup analysis was conducted according to the length of time after the recovery of COVID-19 (Model 1), and the highest temperature during the infection (Model 2). In Model 1 and Model 2, the one-way ANOVA test did not find statistical significance between the groups (Model 1 p = 0.114; Model 2 p = 0.481). The MDAS scores in female patients were significantly higher than in male patients (12.29 ± 4.53 vs. 9.91 ± 3.80, p < 0.001). Patients who extracted double teeth got significantly higher MDAS scores than those who extracted single teeth before the surgery (12.03 ± 4.74 vs. 11.24 ± 4.18, p = 0.037). Conclusion: The present study did not establish a significant impact of SARS-CoV-2 infection on the anxiety levels associated with third molar surgery among Chinese patients. The potential long-term biopsychological effects of the virus warrant further investigation.
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OBJECTIVE: To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens. METHODS: This large-scale multicentre prospective study performed in 8 hospitals across China from April to October 2022. Hospitalised patients with a diagnosis of pneumonia at admission were included. Complete clinical data were collected, and bronchoalveolar lavage fluid were obtained from each patient. These samples underwent simultaneous testing using conventional microbial testing, metagenomic next-generation sequencing, and nanopore targeted sequencing. RESULTS: A total of 218 patients were included. Among the 168 cases of pulmonary infection, 246 strains of pathogens were confirmed. Nanopore targeted sequencing outperformed conventional microbial testing, identifying more pathogens with a sensitivity increase of 47.9% (77.2% vs. 29.3%). Metagenomic next-generation sequencing had a sensitivity of 82.9%. Total of 70.1% patients had consistent results in both metagenomic next-generation sequencing and nanopore targeted sequencing. Nanopore targeted sequencing exhibited significantly higher sensitivity in detecting Pneumocystis jiroveci, cytomegalovirus, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Streptococcus pneumoniae, and Mycoplasma pneumoniae compared to conventional microbial testing. However, metagenomic next-generation sequencing demonstrated higher sensitivity than nanopore targeted sequencing for Aspergillus (88.5% vs. 53.8%). Regarding the detection of co-infections, nanopore targeted sequencing displayed significantly higher sensitivity than conventional microbial testing (76.7% vs. 28.7%) and was on par with metagenomic next-generation sequencing (76.7% vs. 82.9%). CONCLUSION: Nanopore targeted sequencing performs equally well as metagenomic next-generation sequencing in bronchoalveolar lavage fluid for pathogen diagnosis in pneumonia, both methods showing higher sensitivity than conventional microbial testing. Nanopore targeted sequencing can be considered a reliable method for diagnosing pathogens in pneumonia.
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Nanoporos , Pneumonia , Humanos , Líquido da Lavagem Broncoalveolar , Estudos Prospectivos , Pneumonia/diagnóstico , Streptococcus pneumoniae , Sequenciamento de Nucleotídeos em Larga Escala , Sensibilidade e EspecificidadeRESUMO
Cancer remains the most common lethal disease in the world. Although the treatment choices for cancer are still limited, significant progress has been made over the past few years. By improving targeted drug therapy, drug delivery systems promoted the therapeutic effects of anti-cancer medications. Exosome is a kind of natural nanoscale delivery system with natural substance transport properties, good biocompatibility, and high tumor targeting, which shows great potential in drug carriers, thereby providing novel strategies for cancer therapy. In this review, we present the formation, distribution, and characteristics of exosomes. Besides, extraction and isolation techniques are discussed. We focus on the recent progress and application of exosomes in cancer therapy in four aspects: exosome-mediated gene therapy, chemotherapy, photothermal therapy, and combination therapy. The current challenges and future developments of exosome-mediated cancer therapy are also discussed. Finally, the latest advances in the application of exosomes as drug delivery carriers in cancer therapy are summarized, which provide practical value and guidance for the development of cancer therapy.
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Exossomos , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Terapia CombinadaRESUMO
OBJECTIVE: Periodontitis is a common inflammatory disease associated with systemic factors. Visfatin is a pleiotropic adipokine that exerts metabolic and immune functions. Studies have shown visfatin played roles in the development of periodontitis. The present study aims to compare the levels of visfatin in body fluids including serum, saliva, and gingival crevicular fluid (GCF) between periodontitis patients and healthy individuals, and to elucidate the alteration of visfatin levels after periodontal treatments. MATERIALS AND METHODS: The database searched included Pubmed, Embase, Web of Science, and Cochrane Library. According to the Eligibility criteria, the records were screened and the eligible studies were included. The methodological qualities of the included case-controlled studies were assessed according to the Newcastle-Ottawa scale (NOS). The Methodological Index for Nonrandomized Studies (MINORS) was applied for assessing the qualities of the included clinical trials. The statistical analyses were processed using STATA 15.0. RESULTS: Twenty-three studies were included in the statistical analyses. The meta-analysis showed significantly elevated visfatin levels of GCF, serum, and saliva in the periodontitis population compared with the controls (GCF: SMD = 5.201, 95% CI: 3.886-6.516, Z = 7.75, P < 0.05; Serum: SMD = 7.417, 95% CI: 3.068-11.767, Z = 3.34, P = P < 0.05; Saliva: SMD = 2.683, 95% CI: 1.202-4.163, Z = 3.34, P < 0.05). Visfatin levels of saliva serum and GCF were significantly decreased after periodontal treatment. (Saliva: SMD = -1.338, 95% CI: -2.289-0.487, Z = 39.77, P < 0.05; Serum: SMD = -2.890, 95% CI: -5.300-0.480, Z = 2.35, P < 0.05; GCF: SMD = -6.075, 95% CI: -11.032-1.117, Z = 2.40, P = 0.016; I 2 = 95.9%, P < 0.05). CONCLUSIONS: Periodontitis elevated the visfatin levels in GCF, serum, and saliva. Additionally, GCF, serum, and saliva visfatin levels could be reduced after periodontal treatment.
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Periodontite Crônica , Periodontite , Humanos , Nicotinamida Fosforribosiltransferase/análise , Nicotinamida Fosforribosiltransferase/metabolismo , Periodontite/terapia , Periodontite/metabolismo , Saliva/química , Líquido do Sulco Gengival/química , Estudos de Casos e Controles , Periodontite Crônica/terapiaRESUMO
The Characterization and anticancer effects of extracellular polysaccharide (EPS) from DHA-producing microalga Crypthecodinium sp. SUN were studied in the present research. Results showed that EPS from C. sp. SUN have a molecular weight of 1.118 × 106 g/mol. EPS significantly inhibited the proliferation and migration of LA795 lung adenocarcinoma cells, and the apoptosis rate decreased in a concentration-dependent manner, reached 52 % at 15 mg/mL. C. sp. SUN EPS also significantly decreased reactive oxygen species (ROS) level by over 50 %, superoxide dismutase (SOD) activity by 76 %, and catalase (CAT) activity by 34 % at 10 mg/mL, indicating that EPS may inhibit tumor cell growth instead of killing tumor cells. Additionally, C. sp. SUN EPS suppressed cell proliferation by downregulating the expression of adhesion proteins and cyclin D1 in LA795 cells. In vivo experiments demonstrated that C. sp. SUN EPS inhibited the growth of lung adenocarcinoma tumors without affecting the normal body weight of nude mice. Collectively, the present study showed that C. sp. SUN EPS could be a potential substance for cancer treatment, which provided a research basis for future study on EPS and expanded the application of Crypthecodinium.
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Adenocarcinoma de Pulmão , Microalgas , Animais , Camundongos , Microalgas/metabolismo , Camundongos Nus , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Proliferação de CélulasRESUMO
Chemodynamic therapy (CDT) is a highly tumor-specific treatment, while its efficacy is compromised by the intratumoral Fenton reaction efficiency, which is determined by the following reaction factors, including the availability of Fenton ions (e.g., Fe2+), the amount of H2O2, and the degree of acidity. Synchronous optimization of these factors is a big challenge for efficient CDT. Herein, a strategy of comprehensively optimizing Fenton reaction factors was developed for traceable multistage augmented CDT by charge-reversal theranostics. The customized pH-responsive poly(ethylene)glycol-poly(ß-amino esters) (PEG-PAE) micelle (PM) was prepared as the carrier. Glucose oxidase (GOx), Fe2+, and pH-responsive second near-infrared (NIR-II) LET-1052 probe were coloaded by PM to obtain the final theranostics. The activity of metastable Fe2+ remained by the unsaturated coordination with PEG-PAE. Then tumor accumulation and exposure of Fe2+ were achieved by charge-reversal cationization of PEG-PAE, which was further enhanced by a GOx catalysis-triggered pH decrease. Together with the abundant H2O2 generation and pH decrease through GOx catalysis, the limiting factors of the Fenton reaction were comprehensively optimized, achieving the enhanced CDT both in vitro and in vivo. These findings provide a strategy for comprehensively optimizing intratumoral Fenton reaction factors to overcome the intrinsic drawbacks of current CDT.
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Peróxido de Hidrogênio , Medicina de Precisão , Catálise , Ésteres , Glucose OxidaseRESUMO
KRAS mutation is the most frequent type of genetic mutation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma. However, KRAS mutation can affect many biological processes and the mechanisms underlying KRAS mutation-mediate carcinogenesis in NSCLC have not been fully understood. In this research, we found that KRASG12C mutation was associated with the upregulation of T-LAK cell-originated protein kinase (TOPK), which is a well-known serine/threonine MAPK-like protein kinase implicated in tumorigenesis. The overexpression of TOPK significantly promoted the malignant phenotype of A549 cells, and TOPK silencing impaired the malignant phenotype with KRASG12C mutation. Moreover, we demonstrated that TOPK level was regulated by MAPK/ERK signalling and the transcription factor Elk1. TOPK was also found to promote the activation of NF-κB signalling in A549 cells with KRASG12C mutation via facilitating the phosphorylation of TAK1. In the in vivo tumorigenesis model, the administration of TOPK inhibitor OTS514 enhanced the anticancer effect of 5-FU, and the combinatory use of OTS514 and KRASG12C inhibitor AMG510 showed synergistic anti-tumour effect. These results suggest that KRAS-TOPK axis contributes to the progression of NSCLC and targeting this axis could synergize with anticancer effect of the existing chemotherapeutics.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células Matadoras Ativadas por Linfocina/metabolismo , Células Matadoras Ativadas por Linfocina/patologia , Neoplasias Pulmonares/patologia , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismoRESUMO
Heptamethine cyanines (Cy7) are one of the most important dyes in bioimaging and phototherapy, but they often suffer from poor photostability or limited photothermal conversion efficiency. Here, a facile molecular engineering approach to regulating the photophysical properties of Cy7 by metal ions is demonstrated. By innovatively modifying the nitrogen with functional groups, a novel terpyridine-grafted nitrogen-terminated Cy7 scaffold (denoted as CydtPy) was synthesized and exhibited tunable photophysical properties when chelating with various metal ions (Mn2+, Fe2+, etc.). In comparison with metal-ion-free PEGylated CydtPy (LET-11), Mn2+-chelated LET-11 (namely, LET-11-Mn) exhibited the increased fluorescence emission intensity, and Fe2+-chelated LET-11 (namely, LET-11-Fe) showed the enhanced photostability with ~2-fold increase in photothermal conversion efficiency. By simply switching the chelated metal ion species, LET-11-Mn or LET-11-Fe could be used for near-infrared fluorescence imaging, magnetic resonance imaging, or photoacoustic imaging. Furthermore, LET-11-Fe displayed superior synergistic efficacy of photothermal therapy and chemodynamic therapy both in vitro and in vivo. This work not only provides a new strategy for regulating the photophysical properties of cyanine dyes but also establishes a versatile nanoplatform for cancer theranostics.
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Cancer is one of the acute life-threatening diseases endangering the whole of humanity. The treatment modalities for cancer are various. However, in most cases, a single treatment choice provides multiple side effects, poor targeting, and ineffective treatment. In recent years, the physiological regulatory function of carbon monoxide (CO) in the cancer process has been reported gradually, and CO-related nano-drugs have been explored. It shows better application prospects in cancer treatment and provides new ideas for treatment. The present review introduces the pathophysiological role of CO. The recent advances in cancer therapy, such as CO-mediated gas therapy, combined application of CO chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and immunotherapy, are described. Current challenges and future developments in CO-based treatment are also discussed. This review provides comprehensive information on recent advances in CO therapy and also some valuable guidance for promoting the progress of gas therapy nanomedicine.
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Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Monóxido de Carbono , Fototerapia , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: This systematic review aims to investigate possible connections between the oral microbiome and the onset and carcinogenesis of oral epithelial dysplasia (OED). METHODS: A systematic search was performed on PubMed, Embase, Cochrane Database, and SCOPUS by two authors independently, addressing the focused question- "Has oral microbiome dysbiosis been involved in the onset and carcinogenesis of oral epithelial dysplasia?" We used the Newcastle-Ottawa scale to assess the quality of studies included in the review. RESULTS: Out of 580 references screened, ten studies were found eligible for inclusion. All studies were case-control studies, and only qualitative analysis was conducted due to heterogeneous characteristics. The overall risk of bias in the eligible studies was considered as high. Microbiome diversity indices showed inconsistent evidence among studies. A significant increase of phylum Bacteroidetes in OED patients was reported in five studies. Five studies reported an increase of genus Fusobacterium in both the OED and oral squamous cell carcinoma (OSCC) patients and six different studies respectively reported a reduction of genus Streptococcus in both the OED and OSCC groups when compared to normal controls. Other predominant bacteria that were specific to different patient groups varied in each study. CONCLUSIONS: The results of the included studies showed that the composition of the oral microbiome in patients with OED compared to healthy controls and OSCC patients was inconsistent. However, all ten studies showed non-negligible heterogeneity in the type and size of the sample, and the comparability between groups, which strongly limited the external validity of results. Further studies are strongly recommended.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/metabolismo , Disbiose/complicações , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , CarcinogêneseRESUMO
The Pearson and likelihood ratio statistics are commonly used to test goodness of fit for models applied to data from a multinomial distribution. The goodness-of-fit test based on Pearson's Chi-squared statistic is sometimes considered to be a global test that gives little guidance to the source of poor fit when the null hypothesis is rejected, and it has also been recognized that the global test can often be outperformed in terms of power by focused or directional tests. For the cross-classification of a large number of manifest variables, the GFfit statistic focused on second-order marginals for variable pairs i, j has been proposed as a diagnostic to aid in finding the source of lack of fit after the model has been rejected based on a more global test. When data are from a table formed by the cross-classification of a large number of variables, the common global statistics may also have low power and inaccurate Type I error level due to sparseness in the cells of the table. The sparseness problem is rarely encountered with the GFfit statistic because it is focused on the lower-order marginals. In this paper, a new and extended version of the GFfit statistic is proposed by decomposing the Pearson statistic from the full table into orthogonal components defined on marginal distributions and then defining the new version, [Formula: see text], as a partial sum of these orthogonal components. While the emphasis is on lower-order marginals, the new version of [Formula: see text] is also extended to higher-order tables so that the [Formula: see text] statistics sum to the Pearson statistic. As orthogonal components of the Pearson [Formula: see text] statistic, [Formula: see text] statistics have advantages over other lack-of-fit diagnostics that are currently available for cross-classified tables: the [Formula: see text] generally have higher power to detect lack of fit while maintaining good Type I error control even if the joint frequencies are very sparse, as will be shown in simulation results; theoretical results will establish that [Formula: see text] statistics have known degrees of freedom and are asymptotically independent with known joint distribution, a property which facilitates less conservative control of false discovery rate (FDR) or familywise error rate (FWER) in a high-dimensional table which would produce a large number of bivariate lack-of-fit diagnostics. Computation of [Formula: see text] statistics is also computationally stable. The extended [Formula: see text] statistic can be applied to a variety of models for cross-classified tables. An application of the new GFfit statistic as a diagnostic for a latent variable model is presented.
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Modelos Teóricos , Psicometria , Simulação por ComputadorRESUMO
PURPOSE: The present meta-analysis aimed to evaluate quantitively the recent scientific evidence regarding the association between obstructive sleep apnea (OSA) and periodontitis. METHODS: Databases searched were PubMed, EMBASE, Scopus, and Web of Science. Publications were included according to the inclusion criteria. The following outcomes were evaluated: the prevalence of periodontitis, probing depth (PD), clinical attachment loss (CAL), the percentage of sites with bleeding on probing (BOP), plaque index (PI), and gingival index (GI). The statistical analysis was processed using the software STATA. RESULTS: Thirteen eligible studies comprising a total of 31,800 patients were included. The meta-analysis showed an increased prevalence of periodontitis in OSA populations compared to controls. Both PD and CAL were increased in OSA populations compared with controls. (Prevalence of periodontitis: OR 2.348; 95%CI 2.221-2.482; PD: SMD = 0.681, 95% CI: 0.062-1.301, Z = 2.61, P = 0.031; CAL: SMD = 0.694, 95% CI: 0.167-1.22, Z = 2.58, P = 0.01). The study also found significantly increased BOP in patients with OSA after heterogeneity was clarified. (SMD = 0.357, 95% CI: 0.079-0.635, Z = 2.52, P = 0.012). CONCLUSIONS: The findings suggest that OSA was associated with an increased prevalence of periodontitis.
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Periodontite , Apneia Obstrutiva do Sono , Humanos , Periodontite/diagnóstico , Periodontite/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Índice Periodontal , PrevalênciaRESUMO
OBJECTIVE: The long non-coding RNA Growth-arrest-specific transcript 5 (GAS5) has been extensively linked with the ability of cancer cells to resist chemotherapeutic interventions. This prospective study aimed to investigate the role of GAS5 in oral squamous cell carcinoma (OSCC), which has been poorly characterized to date. METHODS: GAS5 and miR-196a expression levels were detected by quantitative real-time PCR analysis. Cisplatin (DDP) sensitivity and apoptosis levels were determined using Cell Counting Kit 8 and flow cytometry, respectively. Luciferase reporter and RNA immunoprecipitation assays were performed to confirm target miRNAs of GAS5. RESULTS: We found that GAS5 was expressed at low levels in DDP-resistant OSCC cell lines and tissues, and that GAS5 levels were intricately linked to the survival rates of OSCC patients. GAS5 overexpression led to the recovery of DDP sensitivity in CAL27/DDP cells. Additionally, in both DDP-resistant and -sensitive lines, GAS5 showed a cytoplasmic distribution and downregulated miR-196a in OSCC tissues. Exogenous transfection of miR-196a alleviated the effects of GAS5 on DDP sensitivity, confirming this as the mechanism of chemoresistance. CONCLUSIONS: These findings may provide new targets for the treatment of chemotherapy-resistant OSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Circular RNAs (circRNAs) are involved in the carcinogenesis of lung cancer. Human MYC gene is highly expressed in melanoma, multiple myeloma, and nasopharyngeal carcinoma. We aimed to investigate the role of circMYC in small cell lung cancer (SCLC). The expression of cirMYC in SCLC tissues and cells were examined. Functional studies were performed to evaluate the roles of circMYC in SCLC cells. Luciferase reporter gene assay, RNA pull-down assay, and rescue experiments were performed to evaluate the regulatory relationship between circMYC and miR-145, and MiR-145 and MMP2 mRNA. We found that CirMYC was highly expressed in SCLC tissues and cells. Knockdown of circMYC could inhibit cell proliferation, migration, invasion, and induce apoptosis. CircMYC targeted miR-145 and miR-145 targeted MMP2 (Matrix Metallopeptidase 2) mRNA. Our data indicated that circMYC upregulates the expression of MMP-2 by inhibiting miR-145, which functions to promote the proliferation, migration, and invasion and inhibit the apoptosis of SCLC. These findings suggest that targeting circMYC/miR-145/MMP-2 could serve as a potential therapeutic strategy for SCLC treatment.
Assuntos
Neoplasias Pulmonares , MicroRNAs , Neoplasias Nasofaríngeas , Carcinoma de Pequenas Células do Pulmão , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Neoplasias Pulmonares/patologia , Metaloproteinase 2 da Matriz/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro , Carcinoma de Pequenas Células do Pulmão/metabolismoRESUMO
Reported here is a new [Cu4I4] cluster-based coordination polymer, namely [Cu4I4(bib)2]n·n(DMF) (1, bib = 1,4-bis(imidazolyl)butane, DMF = N,N'-dimethylformamide), which was synthesized by the self-assemble reaction of CuI, bib and KI under solvothermal conditions. Remarkably, compound 1 shows promising photocatalytic performance toward to the degradation of MB solution under visible light irradiation. For the COPD treatment, the ELISA detection kit was conducted to determine the content of INF-γ released by the respiratory tract mucosal epithelial cells. In addition to this, the activation levels of the NF-κB signaling pathway were still need to be assessed by the real time RT-PCR after the compound treatment.