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1.
Artigo em Inglês | MEDLINE | ID: mdl-35029165

RESUMO

INTRODUCTION: Antibiotic use has emerged as a risk factor for colorectal neoplasia and is hypothesized as a contributor to the rising incidence of colorectal cancer under age 50 years or early-onset colorectal cancer (EOCRC). However, the impact of antibiotic use and risk of EOCRC is unknown. METHODS: We conducted a population-based case-control study of CRC among individuals aged ≥18 years in the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort (2006-2016). The primary outcome was EOCRC. A secondary outcome was CRC at any age. Incident CRC was pathologically confirmed, and for each, up to 5 population-based controls were matched on age, sex, county of residence, and calendar year. We assessed prescriptions until 6 months before CRC diagnosis. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: We identified 54,804 cases of CRC (2,557 EOCRCs) and 261,089 controls. Compared with none, previous antibiotic use was not associated with EOCRC risk after adjustment for potential confounders (aOR 1.06, 95% CI: 0.96, 1.17) with similarly null findings when stratified by anatomic tumor site. In contrast, previous antibiotic use was weakly associated with elevated risk for CRC at any age (aOR 1.05, 95% CI: 1.02, 1.07). A potential but modest link between broad-spectrum antibiotic use and EOCRC was observed (aOR 1.13, 95% CI: 1.02, 1.26). DISCUSSION: We found no conclusive evidence that antibiotics are associated with EOCRC risk. Although antibiotic use was weakly associated with risk of CRC at any age, the magnitude of association was modest, and the study period was relatively short.

2.
Chembiochem ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34989090

RESUMO

The isothermal exponential amplification technology have rarely been fabricated as the universal sensing platform for the detection of various proteins. To broaden its application, we here developed a strategy named protein recognition-initiated exponential amplification reaction (PRIEAR) using protein recognition to induce the DNA assembly which converts protein recognition events into ssDNA amplicons and combining two-stage amplification to achieve exponential amplification technology. Taking advantage of this principle, diverse biomarkers can be quantified at sub-picomolar concentrations in the homogenous manner, making the PRIEAR suitable for clinical practice. Therefore, this strategy can expand the powerful isothermal exponential amplification technology to protein targets and thus provide a new toolbox into the clinical and biomedical applications.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34980677

RESUMO

Prospective data examining the association of aspirin use, according to dose and duration, with long-term risk of gastric adenocarcinoma in non-Asian cohorts are lacking. We evaluated the association between aspirin use and risk of gastric adenocarcinoma in two large prospective U.S. cohort studies, the Nurses' Health Study and the Health Professionals Follow-up Study. Cox proportional hazards regression models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CI). Among the 159,116 participants, we documented 316 gastric adenocarcinoma cases (176 women, 140 men) over 34 years encompassing 4.5 million person-years. Among women, regular aspirin use (at least 2 times or more per week) was significantly associated with lower risk of gastric adenocarcinoma (multivariable HR 0.52, 95% CI 0.37-0.73) compared with nonregular use. However, regular aspirin use was not associated with gastric adenocarcinoma risk among men (multivariable HR 1.08, 95% CI 0.77-1.52) (P-heterogeneity for sex = 0.003). Among women, the lower risk of gastric adenocarcinoma was more apparent with increasing duration of aspirin use (P for trend <.001) and more than 5 tablets per week (multivariable HR, 0.51; 95% CI 0.31-0.84). Regular, long-term aspirin use was associated with lower risk of gastric adenocarcinoma among women, but not men. The benefit appeared after at least 10 years of use and was maximized at higher doses among women. The heterogeneity by sex in the association of aspirin use with risk of gastric adenocarcinoma requires further investigation.

4.
J Hazard Mater ; 422: 126901, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34419849

RESUMO

With increased industrial development, vast heavy metals are inevitably discharged into wastewater. Cu2+ is one of the most hazardous heavy metals in biotreatment. However, the potential effect of Cu2+ on denitrifying granular sludge is still unknown. This work assesses the response of denitrifying granular sludge to Cu2+ stress from multiple aspects. The denitrifying granular sludge could tolerate 5 mg L-1 Cu2+, while the nitrogen removal efficiency decreased to 48.5% under 10 mg L-1 Cu2+. Enzyme activity and carbohydrate metabolism were inhibited, and the denitrifying bacteria were washed out under Cu2+ stress. The resulting deteriorated state was reversed by phosphate. The nitrogen removal efficiency recovered to 99% after 10 days, and the enzyme activity also recovered to the original level. Membrane transport, transcription and cellular processes were promoted. Overall, the results of this work provide a feasible strategy to rapidly restore the metabolic activity of denitrifying granular sludge under Cu2+ stress.


Assuntos
Desnitrificação , Esgotos , Reatores Biológicos , Estudos de Viabilidade , Nitrogênio , Fosfatos
5.
Artigo em Inglês | MEDLINE | ID: mdl-34855147

RESUMO

Dapagliflozin (DAPA) exerts cardioprotective effects in non-diabetic patients. Nonetheless, the protective mechanism remains unknown. This study aims to evaluate the performance of DAPA on cardiac function and remodeling as well as its potential mechanism in mice with myocardial infarction (MI). Here, a MI mice model was established. One week after MI, mice were treated with saline or DAPA (1.5 mg/kg/day) for 4 weeks. At the end of this study, echocardiography was performed to assess cardiac structure and function. Myocardial apoptosis was analyzed by Western blot and immunofluorescence. Inflammatory cytokines and cardiac fibrosis were analyzed by real-time PCR and Masson's trichrome stain, respectively. Results showed that DAPA improved cardiac structure and function, attenuated cardiac fibrosis, and inhibited inflammatory cytokines and myocardial apoptosis. Moreover, the inhibition of PI3K/AKT/mTOR pathway might be related to the cardioprotective role of DAPA. These findings reveal that dapagliflozin is a potential therapeutic agent for MI patients without diabetes.

6.
Int J Cancer ; 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34888857

RESUMO

Elevated blood levels of C-reactive protein (CRP) have been linked to colorectal cancer (CRC) survival. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC-specific mortality. This study included 16,142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium. We identified 618 common single nucleotide polymorphisms (SNPs) associated with CRP levels from the NHGRI-EBI GWAS Catalog. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between SNPs and CRC-specific mortality adjusting for age, sex, genotyping platform/study, and principal components. We investigated their interactions with sex and lifestyle factors using likelihood ratio tests. Of 5,472 (33.9%) deaths accrued over up to 10 years of follow-up, 3,547 (64.8%) were due to CRC. No variants were associated with CRC-specific mortality after multiple comparison correction. We observed strong evidence of interaction between variant rs1933736 at FRK gene and sex in relation to CRC-specific mortality (corrected Pinteraction = 0.0004); women had higher CRC-specific mortality associated with the minor allele (HR = 1.11, 95% CI = 1.04 to 1.19) whereas an inverse association was observed for men (HR = 0.88, 95% CI = 0.82 to 0.94). There was no evidence of interactions between CRP-associated SNPs and alcohol, obesity or smoking. Our study observed a significant interaction between sex and a CRP-associated variant in relation to CRC-specific mortality. Future replication of this association and functional annotation of the variant are needed.

7.
Brain Behav ; : e2453, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878231

RESUMO

INTRODUCTION: Social rank has a profound influence on the behavior and health of humans and animals. METHODS: To explore the effect of a combination of living Bifidobacterium, Lactobacillus and Streptococcus (CLB) on anxiety- and depression-like behaviors and social rank, mice were subjected to a social dominance tube test (SDTT). The behaviors, rank, gut microbiota, and expression of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured. RESULTS: The results indicated that CLB improved the SDTT ranking score of the losers and alleviated anxiety-like behaviors of the winners. CLB decreased the level of Desulfovibrio and augmented the level of Mollicutes in the feces, increased BDNF content, and reduced the level of tumor necrosis factor-α in the hippocampus. CONCLUSION: These findings indicated that CLB may be used for the treatment of anxiety and improvement of the rank score via regulation of gut microbiota and anti-inflammatory effects.

8.
J Biomed Res ; 35(6): 425-435, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34857679

RESUMO

Acute myocardial infarction (AMI) is a severe cardiovascular disease. This study aimed to identify crucial microRNAs (miRNAs) and mRNAs in AMI by establishing a miRNA-mRNA network. The microarray datasets GSE31568, GSE148153, and GSE66360 were downloaded from the Gene Expression Omnibus (GEO) database. We identified differentially expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) in AMI samples compared with normal control samples. The consistently changing miRNAs in both GSE31568 and GSE148153 datasets were selected as candidate DE-miRNAs. The interactions between the candidate DE-miRNAs and DE-mRNAs were analyzed, and a miRNA-mRNA network and a protein-protein interaction network were constructed, along with functional enrichment and pathway analyses. A total of 209 DE-miRNAs in the GSE31568 dataset, 857 DE-miRNAs in the GSE148153 dataset, and 351 DE-mRNAs in the GSE66360 dataset were identified. Eighteen candidate DE-miRNAs were selected from both the GSE31568 and GSE148153 datasets. Furthermore, miR-646, miR-127-5p, miR-509-5p, miR-509-3-5p, and miR-767-5p were shown to have a higher degree in the miRNA-mRNA network. THBS-1 as well as FOS was a hub gene in the miRNA-mRNA network and the protein-protein interaction (PPI) network, respectively. CDKN1A was important in both miRNA-mRNA network and PPI network. We established a miRNA-mRNA network in AMI and identified five miRNAs and three genes, which might be used as biomarkers and potential therapeutic targets for patients with AMI.

9.
Environ Sci Technol ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34889591

RESUMO

Antibiotics are widely found in nitrogen-containing wastewater, which may affect the operation stability of anaerobic ammonium oxidation (anammox)-based biological treatment systems. Extracellular polymeric substances (EPSs) of anammox sludge play a pivotal role in combining with antibiotics; however, the exact role and how the structure of the leading component of EPSs (i.e., extracellular proteins) changes under antibiotic stress remain to be elucidated. Here, the interaction between sulfamethoxazole and the extracellular proteins of anammox sludge was investigated via multiple spectra and molecular simulation. Results showed that sulfamethoxazole statically quenched the fluorescent components of EPSs, and the quenching constant of the aromatic proteins was the largest, with a value of 1.73 × 104 M-1. The overall binding was an enthalpy-driven process, with ΔH = -75.15 kJ mol-1, ΔS = -0.175 kJ mol-1 K-1, and ΔG = -21.10 kJ mol-1 at 35 °C. The O-P-O and C═O groups responded first under the disturbance of sulfamethoxazole. Excessive sulfamethoxazole (20 mg L-1) would decrease the ratio of α-helix/(ß-sheet + random coil) of extracellular proteins, resulting in a loose structure. Molecular docking and dynamic simulation revealed that extracellular proteins would provide abundant sites to bind with sulfamethoxazole, through hydrogen bond and Pi-Akyl hydrophobic interaction forces. Once sulfamethoxazole penetrates into the cell surface and combines with the transmembrane ammonium transport domain, it may inhibit the NH4+ transport. Our findings enhance the understanding on the interaction of extracellular proteins and sulfamethoxazole, which may be valuable for deciphering the response property of anammox sludge under the antibiotic stress.

10.
Am J Clin Nutr ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34864844

RESUMO

BACKGROUND: Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) severity have been limited and inconsistent. OBJECTIVE: We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity. DESIGN: We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1,768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semi-quantitative, pre-pandemic food frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] levels were calculated based on a previously validated model including dietary and supplementary vitamin D intake, ultraviolet-B (UVB), and other behavioral predictors of vitamin D status. RESULTS: Higher predicted 25(OH)D levels, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D levels to the lowest, the multivariable-adjusted odds ratio was 0.76 (95% CI: 0.58, 0.99; P-trend = 0.04). Participants in the highest quartile of UVB (OR: 0.76; 95% CI: 0.66, 0.87; P-trend = 0.002) and UVA (OR: 0.76; 95% CI: 0.66, 0.88; P-trend<0.001) also had lower risk of SARS-CoV-2 infection compared to the lowest. High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P-trend = 0.04). CONCLUSIONS: Our study provides suggestive evidence on the association between higher predicted circulating 25(OH)D levels and a lower risk of SARS-CoV-2 infection. Greater intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data also support an association between exposure to UVB or UVA, independent of vitamin D, and SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted cautiously.

11.
Chem Sci ; 12(45): 15045-15053, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34909144

RESUMO

Hydrogen peroxide (H2O2) plays essential roles in various physiological and pathological processes. The electrochemical hydrogen peroxide reduction reaction (HPRR) has been recognized as an efficient approach to H2O2 sensing; however, the HPRR has always suffered from low tolerance against the oxygen reduction reaction (ORR), resulting in poor selectivity of the HPRR-based sensing platform. In this study, we find that the electrochemical HPRR occurs preferentially compared to the ORR when isolated Cu atoms anchored on carbon nitride (Cu1/C3N4) are used as a single-atom electrocatalyst, which is theoretically attributed to the lower energy barrier of the HPRR than that of the ORR on a Cu1/C3N4 single-atom catalyst (SAC). With the Cu1/C3N4 SAC as the electrocatalyst, we fabricated microsensors that have a good response to H2O2, but not to O2 or other electroactive neurochemicals. When implanted into a living rat brain, the microsensor shows excellent in vivo sensing performance, enabling its application in real-time quantitative investigation of the dynamics of H2O2 production induced by mercaptosuccinate and glutathione monoethyl ester in a living animal brain.

12.
Eur J Surg Oncol ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34955314

RESUMO

OBJECTIVE: To systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients. METHODS: PubMed, EMBASE and the Cochrane Library were searched up to March 1st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses. RESULTS: EHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01). CONCLUSION: EHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.

13.
Ann Transl Med ; 9(18): 1400, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733952

RESUMO

Background: Atrial fibrosis is involved in non-paroxysmal atrial fibrillation (NPAF) and is mainly mediated by the calcium-binding protein S100A4. This study aimed to verify the role of circulating S100A4 in the diagnosis of atrial fibrosis and the prognosis of NPAF. Methods: Consecutive NPAF patients undergoing catheter ablation were selected. Patients with low voltage amplitudes (<0.40 mV) in the left atrium (LA), defined as low voltage zones (LVZs), were grouped in the scar group by electroanatomic mapping (EAM). Circulating S100A4 was detected by a human enzyme-linked immunosorbent assay (ELISA). The role of S100A4 in atrial fibrosis was further evaluated by Masson's trichrome staining and immunochemistry (IHC) in NPAF (atrial pacing) and control dogs. The prognostic value of the circulating S100A4 was evaluated by Cox regression analyses, the Kaplan-Meier (KM) method, and receiver operating characteristic (ROC) curves. Results: We enrolled a total of 101 NPAF patients (age 60±8 years) who underwent EAM, including 53 patients with scars and 48 patients without scars at 1-year follow-up. The scar group showed a higher serum level of S100A4 (3.4±1.7 vs. 2.5±1.4 ng/mL, P<0.001) than the non-scar group. In the canine model, scar size matched the larger location of interstitial fibrosis in the NPAF group determined by Masson's trichrome staining. The expression of α-SMA and S100A4 was elevated in the NPAF group as determined by IHC compared to the control group (P<0.001). The clinical recurrence rate was markedly elevated in the scar group (27.1% vs. 8.9%, P<0.001), and the area under the ROC curve was high (0.865, 95% CI: 0.750-0.981) in predicting clinical recurrence of NPAF with the circulating S100A4 model. Conclusions: Circulating S100A4 plays a role in atrial fibrosis in NPAF patients following ablation. The level of serum S100A4 can predict the clinical recurrence of NPAF.

14.
Eur J Nutr ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799774

RESUMO

PURPOSE: L-Carnitine is abundant in animal source foods, particularly red meat, and circulating L-carnitine may be related to the incidence of coronary heart disease (CHD). We investigated whether long-term changes in plasma L-carnitine over 10 years were associated with the CHD incidence and also examined joint associations of carnitine-rich red meat consumption and L-carnitine changes on the subsequent risk of CHD. METHODS: This prospective nested case-control study included 772 healthy women at baseline (386 incident CHD cases and 386 healthy controls). Plasma L-carnitine levels were measured both at the first (1989-90) and second blood collections (2000-02). Incident cases of CHD were prospectively followed from the date of the second blood collection through 2016. RESULTS: Overall, a greater increase in L-carnitine from the first to the second time point was related to a higher risk of CHD, regardless of the initial L-carnitine levels (relative risk: 1.36 (95% CI 0.999, 1.84) per 1-SD increase). The 10-year changes in L-carnitine were positively associated with red meat consumption over time, and women with higher red meat intake (≥ 36 g/day) and with greater increases in L-carnitine had a 1.86 (95% CI 1.13, 3.09) times increased risk of CHD, as compared to those with lower red meat intake and lesser increases in L-carnitine. CONCLUSION: Long-term increases in L-carnitine levels were associated with the subsequent incidence of CHD, especially among women with higher intake of red meat. Our results suggest the importance of atherogenic L-carnitine changes and dietary intakes over time in the prevention of CHD.

15.
Cancers (Basel) ; 13(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34771505

RESUMO

Tumor-immune cell compositions and immune checkpoints comprehensively affect TNBC outcomes. With the significantly improved survival rate of TNBC patients treated with ICI therapies, a biomarker integrating multiple aspects of TIME may have prognostic value for improving the efficacy of ICI therapy. Immune-related hub genes were identified with weighted gene co-expression network analysis and differential gene expression assay using The Cancer Genome Atlas TNBC data set (n = 115). IRGPI was constructed with Cox regression analysis. Immune cell compositions and TIL status were analyzed with CIBERSORT and TIDE. The discovery was validated with the Molecular Taxonomy of Breast Cancer International Consortium data set (n = 196) and a patient cohort from our hospital. Tumor expression or serum concentrations of CCL5, CCL25, or PD-L1 were determined with immunohistochemistry or ELISA. The constructed IRGPI was composed of CCL5 and CCL25 genes and was negatively associated with the patient's survival. IRGPI also predicts the compositions of M0 and M2 macrophages, memory B cells, CD8+ T cells, activated memory CD4 T cells, and the exclusion and dysfunction of TILs, as well as PD-1 and PD-L1 expression of TNBC. IRGPI is a promising biomarker for predicting the prognosis and multiple immune characteristics of TNBC.

16.
Mol Cell Biochem ; 2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34657240

RESUMO

DAL-1/4.1B is frequently absent in lung cancer tissues, which is significantly related to the occurrence and development of lung cancer. In this research, we found that DAL-1/4.1B affected the uptake of exosomes by lung cancer cells. When the expression of DAL-1/4.1B increased and decreased, the ability of exosome uptake enhanced and attenuated correspondingly. And we found that when cells were treated with different vesicles uptake inhibitors (chlorpromazine, methyl-ß-cyclodextrin (MßCD), cytochalasin D, chloroquine and heparin) and heparinase (HSPE), only heparin and HSPE counteracted the uptake enhancement effect caused by DAL-1/4.1B. Therefore, we speculated that DAL-1/4.1B might promote the uptake of exosomes through the heparan sulfate proteoglycans (HSPGs) pathway. After screening the expression of HSPGs and HSPE in H292 cells, the expression of heparan sulfate proteoglycan 2 (HSPG2) increased with overexpression of DAL-1/4.1B and decreased with knockdown of DAL-1/4.1B. Meanwhile, exosome uptake decreased with HSPG2 knockdown in H292 and DAL-1/4.1B-overexpressing H292 cells. Moreover, knockdown of DAL-1/4.1B and HSPG2 in lung cancer A549 cells resulted in a similar decrease in exosome uptake, and the expression of HSPG2 was also decreased with DAL-1/4.1B knockdown. These results indicated that HSPG2 directly affected the uptake of exosomes, while DAL-1/4.1B positively affected the expression of HSPG2. Therefore, DAL-1/4.1B may promote cellular adhesion and inhibit migration in cancer cells.

17.
Chem Sci ; 12(36): 12118-12129, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34667577

RESUMO

Exploitation of stimuli-responsive nanoplatforms is of great value for precise and efficient cancer theranostics. Herein, an in situ activable "nanocluster-bomb" detonated by endogenous overexpressing legumain is fabricated for contrast-enhanced tumor imaging and controlled gene/drug release. By utilizing the functional peptides as bioligands, TAMRA-encircled gold nanoclusters (AuNCs) endowed with targeting, positively charged and legumain-specific domains are prepared as quenched building blocks due to the AuNCs' nanosurface energy transfer (NSET) effect on TAMRA. Importantly, the AuNCs can shelter therapeutic cargos of DNAzyme and Dox (Dzs-Dox) to aggregate larger nanoparticles as a "nanocluster-bomb" (AuNCs/Dzs-Dox), which could be selectively internalized into cancer cells by integrin-mediated endocytosis and in turn locally hydrolyzed in the lysosome with the aid of legumain. A "bomb-like" behavior including "spark-like" appearance (fluorescence on) derived from the diminished NSET effect of AuNCs and cargo release (disaggregation) of Dzs-Dox is subsequently monitored. The results showed that the AuNC-based disaggregation manner of the "nanobomb" triggered by legumain significantly improved the imaging contrast due to the activable mechanism and the enhanced cellular uptake of AuNCs. Meanwhile, the in vitro cytotoxicity tests revealed that the detonation strategy based on AuNCs/Dzs-Dox readily achieved efficient gene/chemo combination therapy. Moreover, the super efficacy of combinational therapy was further demonstrated by treating a xenografted MDA-MB-231 tumor model in vivo. We envision that our multipronged design of theranostic "nanocluster-bomb" with endogenous stimuli-responsiveness provides a novel strategy and great promise in the application of high contrast imaging and on-demand drug delivery for precise cancer theranostics.

18.
Anal Chem ; 93(43): 14552-14559, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34677940

RESUMO

Herein, we subtly engineered a pH and membrane receptor dual-activatable aptamer therapeutic for bispecific tumor cell imaging and in situ drug release by utilizing a hairpin-contained i-motif as the acid-responsive element to be complementary with a tumor-targeted aptamer, named as an aptamer "molecule-doctor" (pH-Apt-MD). Specifically, the pH-Apt-MD consisted of two DNA strands, where the Apt-sgc8c was labeled with AF488 and Cy3 at its 5'- and 3'-end, respectively. The I-strand, a hairpin-contained i-motif, was complementary to the Apt-sgc8c strand partially, labeled with a BHQ2 in the middle, thus generating Cy3 with quenched fluorescence and only AF488-emitted fluorescence. The double-helix region of pH-Apt-MD was designed rich in GC bases, providing sites for doxorubicin (Dox) intercalation. Once target cells were encountered, the pH-Apt-MD disassembled due to the specific recognition of the aptamer and conformation change of the i-motif, with activated fluorescence resonance energy transfer (FRET) signals between AF488 and Cy3, accompanied by Dox release in situ. Benefiting from the design of the hairpin-contained i-motif, the pH-Apt-MD presented a narrow pH response range (pH 6.0-6.8) with a transition midpoint (pHT) of 6.50 ± 0.04. Furthermore, living cell studies revealed that the stimuli-responsive FRET signal activation of pH-Apt-MD was successfully achieved on the HCT116 cell surface with ultralow background and enhanced imaging contrast. Then, the cytotoxicity experiments proved that accurate drug release and cell killing were realized to target cells in an acidic microenvironment. As a facile double stimuli-responsive strategy, the pH-Apt-MD may hold great promise for application in precise diagnosis and therapy of cancer cells.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Transferência Ressonante de Energia de Fluorescência , Homicídio , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral
19.
Surg Oncol ; 39: 101663, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34583091

RESUMO

BACKGROUND: Sorafenib is the standard treatment for patients with advanced HCC with improvement in survival and radiologic progression of the disease. Recently, few studies have advocated the Sorafenib + HAIC combination therapy results in better overall survival and progression-free survival than Sorafenib monotherapy in patients with advanced HCC. Herein, we aim to identify the best possible treatment option among the above two lines of therapy for patients with advanced HCC. METHODS: The fixed effects and a random-effects model were used to perform a meta-analysis for overall response rate overall survival, and adverse events. Subgroup analysis of the data of univariate analysis in each included trial was performed to identify the specific patient population who could be benefitted from the combination therapy. RESULTS: Four RCTs containing 609 patients were included in the final analysis. The overall response rate (OR: 3.81; 95% CI 1.01 to 14.42; P = 0.05) and overall survival (HR: 0.70; 95% CI 0.40 to 1.24; P > 0.05) were comparable. Subgroup analysis of OS showed that patients with Child-Pugh score B (HR: 0.30; 95% CI 0.13 to 0.72; P < 0.05) and AFP <400 ng/ml (HR: 0.72; 95% CI 0.52 to 0.99; P < 0.05) were associated with significantly improved survival in the Sorafenib + HAIC group. Bone marrow suppression (OR: 3.76; 95% CI 2.58 to 5.48; P < 0.001) was significantly higher in the Sorafenib + HAIC group, but hepatic function impairment, constitutional symptoms, gastrointestinal events, and dermatological events were comparable (p > 0.05). CONCLUSIONS: Patients with Child-Pugh score B and AFP <400 ng/ml may be benefited most from Sorafenib + HAIC combination therapy.

20.
J BUON ; 26(4): 1693, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34565049

RESUMO

Retraction of "HHIP gene overexpression inhibits the growth, migration and invasion of human liver cancer cells", by Xiaobin Wang, Wenjie Ma, Jun Yin, Meizhu Chen, Hong Jin. JBUON 2020;25(5):2424-2429; PMID: 33277865 Following the publication of the above article, readers drew to our attention that part of the data was unreliable: Figures of this article appeared in other articles (by totally different authors). The authors were requested to provide the raw data and were also asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. Given above, we decided to retract this article. Authors were informed of the retraction. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

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