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1.
Small ; 17(46): e2103177, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34643037

RESUMO

Regulating the mutual stacking arrangements is of great interest for understanding the origin of chirality at different hierarchical levels in nature. Different from molecular level chirality, the control and manipulation of hierarchical chirality in polymer systems is limited to the use of external factors as the energetically demanding switching stimulus. Herein, the first self-assembly strategy of polymerization-induced helicity inversion (PIHI), in which the controlled packing and dynamic stereomutation of azobenzene (Azo) building blocks are realized by in situ polymerization without any external stimulus, is reported. A multiple helicity inversion and intriguing helix-helix transition of polymeric supramolecular nanofibers occurs during polymerization, which is collectively confirmed to be mediated by the transition between functionality-oriented π-π stacking, H-, and J-aggregation. The studies further reveal that helicity inversion proceeds through a delicate interplay of the thermodynamically and kinetically controlled, pathway-dependent interconversion process, which should provide new insight into the origin and handedness control of helical nanostructures with desired chirality.

2.
Fish Physiol Biochem ; 47(6): 1951-1967, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34633578

RESUMO

At present, due to the influence of global warming, seasonal change, diurnal variation, and eutrophication of the water body, hypoxia has become one of the major factors limiting the stable development of cobia (Rachycentron canadum) culture. In this study, the miRNAs involved in hypoxia stress were screened, and the target genes of miRNAs were annotated and analyzed. The results showed that a total of 184 conservative microRNA (miRNA) and 121 newly predicted miRNA were obtained by sequencing the liver of control (C) and hypoxic (dissolved oxygen, DO (2.64 ± 0.25) mg/L; 3 h) (S) groups. The pathways involved in energy metabolism included starch and sucrose metabolism (ko00500), glycosaminoglycan degradation (ko00531), and galactose metabolism (ko00052). The results indicate that the body maintains physiological activities by regulating some important pathways at the transcriptional level under hypoxia stress, such as the conversion of aerobic metabolism and anaerobic metabolism, the reduction of energy consumption, and the promotion of red blood cell proliferation to maintain the homeostasis of the body.

3.
J Environ Sci (China) ; 108: 188-200, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34465432

RESUMO

Environment-friendly nano-catalysts capable of activating peroxymonosulfate (PMS) have received increasing attention recently. Nevertheless, traditional nano-catalysts are generally well dispersed and difficult to be separated from reaction system, so it is particularly important to develop nano-catalysts with both good catalytic activity and excellent recycling efficiency. In this work, magnetically recoverable Fe3O4-modified ternary CoFeCu-layered double hydroxides (Fe3O4/CoFeCu-LDHs) was prepared by a simple co-precipitation method and initially applied to activate PMS for the degradation of Rhodamine B (RhB). X-ray diffraction (XRD), fourier transform infrared spectrometer (FT-IR), scanning electron microscope (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller method (BET), and vibrating sample magnetometer (VSM) were applied to characterize morphology, structure, specific surface area and magnetism. In addition, the effects of several key parameters were evaluated. The Fe3O4/CoFeCu-LDHs exhibited high catalytic activity, and RhB degradation efficiency could reach 100% within 20 min by adding 0.2 g/L of catalyst and 1 mmol/L of PMS into 50 mg/L of RhB solution under a wide pH condition (3.0-7.0). Notably, the Fe3O4/CoFeCu-LDHs showed good super-paramagnetism and excellent stability, which could be effectively and quickly recovered under magnetic condition, and the degradation efficiency after ten cycles could still maintain 98.95%. Both radicals quenching tests and electron spin resonance (ESR) identified both HO• and SO4•- were involved and SO4•- played a dominant role on the RhB degradation. Finally, the chemical states of the sample's surface elements were measured by X-ray photoelectron spectroscopy (XPS), and the possible activation mechanism in Fe3O4/CoFeCu-LDHs/PMS system was proposed according to comprehensive analysis.


Assuntos
Hidróxidos , Peróxidos , Rodaminas , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Thorac Cancer ; 12(22): 3005-3010, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34581508

RESUMO

BACKGROUND: Brain metastases (BM) from esophageal carcinoma (EC) is clinically rare and has not yet been reported in elderly patients. This study aimed to investigate the clinicopathological characteristics, outcomes and prognostic factors of BM in elderly patients with EC, in order to provide guidance for clinical practice. METHODS: A total of 20 EC patients older than 65 years who were diagnosed with BM were identified from the fourth Hospital of Hebei Medical University between January 1, 2009 and December 31, 2018. Survival was evaluated by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The median time from diagnosis of EC to BM was 11.8 months (0-249.2 months). The median overall survival (OS) was 4.8 months (1.13-23.3 months), with 20% of patients achieving the 1-year survival rate. Patients with KPS score of ≥70 had a significantly better OS than those with KPS score<70 (8.4 vs. 3.9 months, p = 0.033). Compared to patients without brain radiotherapy, patients with brain radiotherapy showed better outcomes in both median OS (8.4 vs. 2.9 months) and 1-year survival rate (23.1% vs. 14.3%, p = 0.043). The median OS of patients with radiotherapy combined with chemotherapy and/or targeted therapy and radiotherapy alone was 9.7 months (3.4-23.3 months) and 7.2 months (1.7-18.4 months), respectively, with no significant difference between the two groups (p = 0.215). CONCLUSIONS: Brain radiotherapy provided clinically meaningful survival benefit for elderly patients with BM from EC. Thus, active treatments for those patients might be required.

5.
Technol Cancer Res Treat ; 20: 15330338211036528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34378452

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths and pulmonary carcinoids (PCs) account for almost 2% of all pulmonary malignancies. However, few published articles have reported prognosis and related factors of pulmonary carcinoid patients. MATERIAL AND METHOD: The Surveillance, Epidemiology, and End Results (SEER) database was used to collect data of patients diagnosed with metastatic PCs from 2010 to 2016. The prognosis and survival of these patients were compared by employing Cox proportional hazards and the Kaplan-Meier survival analysis. RESULTS: A total of 1763 patients were analyzed. The liver (668, 25.6%) was shown to be the most common metastatic site in the isolated organ metastasis cohort, followed by the lung (636, 24.4%), bone (562, 21.6%), and brain (460, 17.6%). Among the patients, the tumor metastasized to a single distant site included the liver, bone, lung, and brain. Cancer-specific survival (CSS) in metastatic PCs is determined by the site of metastasis and the total number of such sites. Pulmonary carcinoid patients with isolated liver metastasis manifested more favorable survival rates in comparison to patients having isolated metastasis in the lung, brain, or bone. The median CSS was 45, 7, 6, 5 months (P = 0.011). The number of distant metastatic sites and the location of distant metastasis were found to be independent risk factors for CSS. For patients with distant isolated metastasis, liver metastasis (P < 0.0001) had better CSS in comparison to those with bone metastasis. When compared to patients whose carcinoids had metastasized to the bones, patients with a brain (P = 0.273) or lung (P = 0.483) metastasis had the same CSS. CONCLUSION: Cancer-specific survival in metastatic PCs depends on the site of metastasis and the total number of such locations. PC patients with isolated liver metastasis manifested more favorable survival in comparison to patients with isolated metastasis in the lung, brain, or bone.

6.
Mol Biol Rep ; 48(10): 6897-6909, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34453674

RESUMO

BACKGROUND: Environmental hypoxia affects the survival and development of organisms. It is also an important environmental factor that leads to oxidative damage. Hypoxia is a condition in which tissues are deprived of oxygen; reoxygenation is the phenomenon in which hypoxic tissues are exposed to oxygen. Hypoxia-reoxygenation is vital in pathogenesis, where the production of reactive oxygen species and antioxidant disparity significantly contribute to disease progression, and it is one of the most common physiological stressors in the aquaculture industry. METHODS AND RESULTS: In this study, the full length of complementary DNA (cDNA) of the manganese superoxide dismutase (Mn-SOD) gene of healthy cobia Rachycentron canadum was analysed using rapid amplification of cDNA ends. The real-time quantitative Polymerase Chain Reaction was used to measure the expression levels of Mn-SOD mRNAs in various tissues (heart, muscle, brain, liver, kidney, gill, intestine, and spleen). The 2-ΔΔCT method was used to performed the expression analysis. The experimental data were analysed using SPSS ver. 19.0 ( https://spss.software.informer.com/19.0/ ). P < 0.05 and P < 0.01 were set as significant differences. The values were articulated as mean ± standard deviation. The Mn-SOD gene cDNA sequence was 1209 bp long, including a 684 bp open reading frame, 42 bp 5'UTR and 483 bp 3'UTR, encoding 227 amino acids. Under hypoxia-reoxygen stress, the expression of Mn-SOD in brain tissue was significantly lower than in the control group after 8 h of reoxygenation and higher than the control group after 24 h. Hypoxia and subsequent reoxygenation triggered a disturbance in antioxidant homeostasis, displayed in the modification of GPx expression/activity in the liver: GPx was improved. CONCLUSIONS: These results provide valuable information on the role of Mn-SOD regulation in oxidative stress caused by hypoxia.

7.
J Vet Med Sci ; 83(10): 1593-1596, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34456197

RESUMO

Clostridium perfringens is an important zoonotic pathogen. This study was designed to explore the prevalence and toxin types of C. perfringens in retail beef collected from Beijing, China. Among 221 beef samples collected, 53 samples were positive for C. perfringens, resulting in the average prevalence as 23.98%. By toxin gene-based typing, the most C. perfringens strains belong to type A (96.23%, 51/53), only 2 strains were identified as type D. By a multi-locus sequence typing (MLST)-based analysis, a total of 36 sequence types (STs) were detected, and the most STs (n=30) represented just a single strain. These finding suggested that the prevalence of C. perfringens in retail beef in Beijing was considerably high and these bacteria displayed extreme diversity in genetics.


Assuntos
Doenças dos Bovinos , Infecções por Clostridium , Animais , Pequim , Bovinos , China/epidemiologia , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/veterinária , Clostridium perfringens/genética , Tipagem de Sequências Multilocus/veterinária
8.
Clin Transplant ; 35(11): e14469, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34448256

RESUMO

Kidney transplantation is the best therapy for end-stage renal disease. Demand for kidney transplantation rises year-on-year, and the gap between kidney supply and demand remains large. To meet this clinical need, a gradual expansion in the supply of donors is required. However, clinics lack appropriate tools capable of quickly and accurately predicting post-transplant renal allograft function, and thus assess donor-kidney quality before transplantation. Mitochondrial DNA (mtDNA) is a key component of damage-associated molecular patterns (DAMPs) and plays an important part in ischemia-reperfusion injury (IRI), accelerating the progression of IRI by inducing inflammation and type I interferon responses. mtDNA is known to be closely involved in delayed graft function (DGF) and acute kidney injury (AKI) after transplantation. Thus, mtDNA is a potential biomarker able to predict post-transplant renal allograft function. This review summarizes mtDNA biology, the role mtDNA plays in renal transplantation, outlines advances in detecting mtDNA, and details mtDNA's able to predict post-transplant renal allograft function. We aim to elucidate the potential value of mtDNA as a biomarker in the prediction of IRI, and eventually provide help for predicting donor-kidney quality.

9.
Front Oncol ; 11: 614531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277395

RESUMO

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, with high morbidity and mortality, yet its molecular mechanisms of tumorigenesis are still unclear. In this study, gene expression profile of GSE62232 was downloaded from the Gene Expression Omnibus (GEO). The RNA-seq expression data and relative clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. The datasets were analyzed by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) to obtain the overlapping genes. Then, we performed a functional enrichment analysis to understand the potential biological functions of these co-expression genes. Finally, we constructed the protein-protein interaction (PPI) analysis combined with survival analysis. MARCO, CLEC4M, FCGR2B, LYVE1, TIMD4, STAB2, CFP, CLEC4G, CLEC1B, FCN2, FCN3 and FOXO1 were identified as the candidate hub genes using the CytoHubba plugin of Cytoscape. Based on survival analysis, the lower expression of FCN3 and FOXO1 were associated with worse overall survival (OS) in HCC patients. Furthermore, the expression levels of FCN3 and FOXO1 were validated by the Human Protein Atlas (HPA) database and the qRT-PCR. In summary, our findings contribute new ideas for the precise early diagnosis, clinical treatment and prognosis of HCC in the future.

10.
Transl Lung Cancer Res ; 10(6): 2614-2624, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34295666

RESUMO

Background: Immune checkpoint inhibitors (ICIs) and bevacizumab-based therapy are a promising treatment approach to significantly improving overall survival (OS) of non-small cell lung cancer (NSCLC) patients. However, the incidence of adverse events induced by a combination treatment with programmed cell death-1 or programmed death ligand 1 [PD-(L)1] inhibitor and bevacizumab remains unknown. The current evidence from prospective studies is limited. Thus, efforts using real-world data to further improve our understanding of the potential adverse events will be necessary. Methods: The present study included 15,872 participants with NSCLC in the FDA Adverse Event Reporting System (FAERS) database from April 2013 to September 2019. The definition of adverse events (AEs) relied on the Medical Dictionary for Regulatory Activities (MedDRA). Statistical analysis was performed, and odds ratio (ORs) with 95% confidence intervals (CIs) were calculated. Results: Of the 15,872 participants with NSCLC, 15,463 cases were treated with the PD-(L)1 inhibitor monotherapy, while 409 cases were treated with both PD-(L)1 inhibitor and bevacizumab. Compared with monotherapy, combination therapy had lower risks of pneumonitis, respiratory failure, edema, disease progression, and death; however, combination therapy was also associated with significantly higher risks of pyrexia, general physical health deterioration, stomatitis, dehydration, thrombocytopenia, peripheral neuropathy, nephritis, bone marrow failure, immune thrombocytopenic purpura, neutropenia, and serious AEs. The results of the multivariate analysis suggested that combination therapy was the independent risk factor for pyrexia, neutropenia, nephritis, ITP, and the independent protective factor for respiratory failure. Conclusions: We observed that the spectrum and risk of irAEs differed widely between therapeutic regimens, and irAEs involved multiple organ systems both in monotherapy or combination therapy. Deepening our understanding of irAEs has a great clinical value for improving individualized clinical patient management and the safety of medication use.

11.
Technol Cancer Res Treat ; 20: 15330338211027923, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34159861

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal malignant cancer, whose survival rate and quality of life of patients are still not satisfactory. Nevertheless, the TNM staging system currently used in clinical cannot make accurate survival predictions and precise treatment decisions for ccRCC patients. Therefore, there is an urgent need for more reliable biomarkers to identify high-risk subgroups of ccRCC patients to guide timely intervention and treatment. Recently, MiRNAs have been shown to be closely related to the procession of a variety of tumors, and they have high stability in various tissues, which makes them suggested to have the potential as a prognostic biomarker of ccRCC. In this study, by analyzing and processing the miRNAs expression profile of ccRCC patients from the TCGA database, we finally constructed an excellent miRNAs signature and verified it through a variety of methods. In order to build a more accurate and reliable clinical predictive model, we integrated the miRNAs signature with other prognostic-related clinical parameters to construct a nomogram. Functional enrichment analysis showed that miRNAs in the signature may regulate the genes involved in the Hippo signaling pathway, Tight junction, and Wnt signaling pathway to cause different prognoses of ccRCC patients, which may provide a reference for subsequent basic research and targeted therapy. To conclude, our study constructed a useful miRNAs signature, which allows the prognosis stratification for ccRCC patients and thereby guides the timely and effective interventions on high-risk patients. At the same time, this study also found the potential biological pathways involved in the procession of ccRCC.

12.
Biochem Biophys Res Commun ; 567: 154-160, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34157442

RESUMO

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase and mutations in EGFR is a major driver force of lung cancer. EGFR tyrosine kinase inhibitors (TKIs) are group of promising agents to treat cancer patients with EGFR mutations. However, the application of TKIs is often hampered by the development of drug-resistance. In the present study, we studied the role of Glutathione peroxidase 4 (GPX4) and mammalian target of rapamycin (mTOR) in regulation of lung cancer cells response to Lapatinib (Lap). Lap resistant NSCLC cells A549/Lap and H1944/Lap were created and GPX4 was knockdown by lentivirus shGPX4. Change of cell viabilities and cell death were measured by MTT and flow cytometry, respectively. ROS, MDA, GSH and Fe2+ were detected by commercial kits. Xenograft mice was used to assay the in vivo effects of GPX4 on the sensitivity of Lap. We found that GPX4 and mTORC1 signalling was upregulated in Lap resistant NSCLC cells when compared to Lap sensitive NSCLC cells. Mechanistically, upregulation of GPX4 was due to enhanced activation of mTORC1 in Lap resistant NSCLC cells. Inhibition of mTORC1 led to the downregulation of GPX4 which promoted Lap induced ferroptosis as evidenced by increase of ROS, MDA, Fe 2+ and decrease of GSH. Rescue experiments confirmed the role of GPX4 in regulation of Lap induced ferroptosis. In vivo experiments also indicated that silencing of GPX4 enhanced the anticancer effect of Lap via promoting ferroptosis. Overall, targeting GPX4 might be a potential strategy to enhance antitumor effects of Lap.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Lapatinib/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Ferroptose/efeitos dos fármacos , Inativação Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Serina-Treonina Quinases TOR/genética
13.
Aging (Albany NY) ; 13(9): 13023-13038, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962398

RESUMO

Bladder cancer (BC) is a commonly occurring malignant tumor affecting the urinary tract. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and are therefore attractive biomarker candidates for BC prognosis. In this study, we profiled the expression of ZNFs in The Cancer Genome Atlas (TCGA) BC cohort and developed a novel prognostic signature based on 7 ZNF-coding genes. After external validation of the model in the GSE48276 dataset, we integrated the 7-ZNF-gene signature with patient clinicopathological data to construct a nomogram that forecasted 1-, 2-, and 3-year OS with good predictive accuracy. We then accessed The Genomics of Drug Sensitivity in Cancer database to predict the therapeutic drug responses of signature-defined high- and low-risk BC patients in the TCGA cohort. Greater sensitivity to chemotherapy was revealed in the low-risk group. Finally, we conducted gene set enrichment analysis of the signature genes and established, by applying the ESTIMATE algorithm, distinct correlations between the two risk groups and the presence of stromal and immune cell types in the tumor microenvironment. By allowing effective risk stratification of BC patients, our novel ZNF gene signature may enable tailoring more intensive treatment for high-risk patients.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias da Bexiga Urinária/genética , Dedos de Zinco/genética , Biomarcadores Tumorais/metabolismo , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Humanos , Prognóstico , Fatores de Risco , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Microambiente Tumoral/genética , Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia
14.
Sci Rep ; 11(1): 9491, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947884

RESUMO

Obesity increases the risk of developing cardiovascular disease and other metabolic diseases. We intended to compare three different anthropometric indicators of obesity, in predicting the incidence of cardiovascular events in Chinese type 2 diabetes. Beijing Community Diabetes Study was a prospective multi-center study conducted in Beijing community health centers. Type 2 diabetes patients from fourteen community health centers were enrolled at baseline. The primary endpoint was cardiovascular events. The upper quartile of neck circumference (NC) was set as greater NC. A total of 3299 diabetes patients were enrolled. In which, 941 (28.52%) had cardiovascular disease at baseline. Logistic analysis showed that central obesity (waist circumference (WC) above 90 cm in men and 85 cm in women) and greater NC were all related to baseline cardiovascular disease (adjusted OR = 1.49, and 1.55). After 10-year follow-up, 340 (10.31%) had cardiovascular events. Compared with patients without cardiovascular events, those having cardiovascular events had higher BMI, larger WC and NC. Cox regression analysis showed that greater WC and NC were all associated with the occurrence of cardiovascular events (adjusted HR = 1.41, and 1.38). A higher NC and WC might increase the risk of cardiovascular events by about 40% in type 2 diabetes patients in Beijing communities.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Pescoço/fisiologia , Circunferência da Cintura/fisiologia , Idoso , Antropometria/métodos , Pequim , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Obesidade Abdominal/fisiopatologia , Estudos Prospectivos , Fatores de Risco
15.
Water Sci Technol ; 83(9): 2160-2168, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33989183

RESUMO

Alicyclic amines are widely used in several types of industries, and considerable attention has been devoted to possible environmental pollution by alicyclic amines in hypersaline industrial wastewater. In this study, a new hypersaline tolerant bacterial TYUT067 capable of growing in liquid basal salt medium with cyclohexylamine (CHAM) as the sole carbon source and energy source, was isolated from soil, and discovered with highly efficient CHAM degrading ability. The strain TYUT067 was identified as Paenarthrobacter sp. based on 16S rDNA gene sequence, and its degradation characteristic was examined. The results revealed that the isolated TYUT067 could grow well under pH range of 6.5-10.0, temperature from 20 °C to 30 °C. For degradation of 60 mM of cyclohexylamine, 100% degradation could be finished within 120 h. The TYUT067 could degrade 10 mM CHAM under hypersaline conditions (3-5% NaCl, w/v), revealed the hypersaline tolerance of TYUT067. Different type of amines was also tested with TYUT067, the degradations of >90% were achieved toward several alicyclic amines. The current results suggested that TYUT067 was a potential species could be efficiently used for the degradation of alicyclic amines and might be applicable to a hypersaline wastewater treatment system for the removal of alicyclic amines.


Assuntos
Aminas , Purificação da Água , Bactérias , Biodegradação Ambiental , RNA Ribossômico 16S/genética , Águas Residuárias
16.
Front Oncol ; 11: 619385, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055598

RESUMO

Background: Immune-related adverse events (irAEs) may complicate the immune checkpoint inhibition (ICI) therapy. The effect of age on these irAEs is not elucidated. The aim of the study was to compare the occurrence of irAEs in different age groups. Methods: Patients with lung cancer receiving anti-programmed death- (ligand)1 (PD-(L)1) were selected from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Immune cell infiltration data set was obtained from TIMER 2.0 web server. The patients were stratified for age as follows: <65 year-old (young patients, YP), 65 to 75 year-old (middle aged patients, MP), ≥75 year-old (old patients, OP). The severity of irAEs was compared using logistic binary regression model. The distribution differences of immune cell infiltration were estimated using non-parametric tests. Results: Of all the 17,006 patients treated by anti-PD-(L)1, 7,355 were <65 (YP), 6,706 were 65-75 (MP), and 2,945 were ≥75 (OP). In general, we analyzed a total of 16 irAEs in this article and found that pulmonary toxicity was more frequent in OP (OP vs. YP: OR = 1.45, 95% CI: 1.28-1.64) and MP (MP vs. YP: OR = 1.38, 95% CI: 1.24-1.52), but hepatitis was less frequent in OP (OP vs. YP: OR = 0.56, 95% CI: 0.32-0.97) and MP (MP vs. YP: OR = 0.57, 95%CI: 0.38-0.85). Further analysis demonstrated that older patients showed less B cell, CD8+ T cell and myeloid dendritic cell infiltration than younger patients. Conclusions: Elderly patients exhibited higher incidences of pulmonary toxicity, while hepatitis was found at low incidence. Therefore, clinicians should carefully monitor comorbidities in elderly patients.

17.
Cancer Manag Res ; 13: 4067-4076, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34040445

RESUMO

Background: This study aimed to evaluate the properties and functions of polysaccharide-based porous microsphere (PPM) for drug delivery, as well as its inhibitory effect on malignant tumors. Materials and Methods: PPM was prepared using the inverse emulsion polymerization method. FT-IR measurements were conducted to measure the wavenumber of PPM. Particle size distribution was tested with a particle analyzer, and surface morphologies of PPM were observed using a scanning electron microscope (SEM). Dialysis method, Cell Counting Kit-8 (CCK-8), and cell apoptosis analysis were adopted to evaluate the drug release, cytotoxicity and biocompatibility of mitomycin-C (MMC), respectively. Finally, an in vivo study was performed in C57BL/6 mice to confirm the function of MMC-loaded PPM on tumor growth. Results: FT-IR spectra proved the successful preparation of MMC-loaded PPM. PPM had an average size of 25.90 ± 0.34 µm and then increased to 30.10 ± 0.20 µm after drug loading. Under SEM, the surface morphology was lotus seedpod surface-like, with macropits on the surface and micropores in macropits. Compared with the free MMC group, MMC-loaded PPM exhibited a delayed drug release rate in a pH-dependent manner and higher cell viability. Flow cytometry results showed that the cell apoptosis in the PPM/MMC group was lower than that in the free MMC group. In vivo experiment revealed the inhibitory efficacy of MMC-loaded PPM on malignant tumors. Conclusion: In summary, MMC-loaded PPM exhibited favorable surface morphology, sustained drug release ability, nontoxicity and excellent biocompatibility, suggesting that PPM might be a potential drug carrier for tumor treatment.

19.
Transl Lung Cancer Res ; 10(3): 1424-1443, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33889520

RESUMO

Background: Neutrophils can play a pro-tumor or anti-tumor role depending on the tumor microenvironment. The effects of concurrent treatment with granulocyte colony-stimulating factor (G-CSF) and radiotherapy (RT) on neutrophils have not yet to be described. Methods: Hypofractionated radiation of 8 Gy ×3 fractions was administered with or without recombinant G-CSF to Lewis lung carcinoma tumor-bearing C57BL/6 model mice. The activation status of cytotoxic T cells in the mice was measured, along with the levels of tumor-associated neutrophils, cytotoxic T cells, and Treg cells. Tumor growth, survival, cytokine expression, and signaling pathways underlying anti-tumor effects of tumor-associated neutrophils after treatment were also studied. To ascertain the effects of concurrent RT and G-CSF on tumor-associated neutrophils, neutrophil depletion was performed. Results: RT affected early neutrophil infiltration, which is the first-line immune response. Subsequently, enhanced accumulation of lymphocytes, particularly CD8 cytotoxic T cells, was observed. Notably, lymphocytic infiltration was inhibited by neutrophil depletion but enhanced by G-CSF treatment. RT generated persistent DNA damage, as evidenced by an accumulation of phosphorylation of histone H2AX (γH2AX), and subsequently triggered inflammatory chemokine secretion. The chemokines CXCL1, CXCL2, and CCL5 were upregulated in both radiation-treated cells and the corresponding supernatants. Neutrophils that were newly recruited after RT improved radiosensitivity by inhibiting epithelial-mesenchymal transition via the reactive oxygen species-mediated PI3K/Akt/Snail signaling pathway, and G-CSF treatment enhanced this effect. Conclusions: The results of this study suggest that RT activates neutrophil recruitment and polarizes newly recruited neutrophils toward an antitumor phenotype, which is enhanced by the concurrent administration of G-CSF. Mesenchymal-epithelial transition induced by reactive oxygen species accumulation plays a major role in this process. Thus, the polarization of tumor-associated neutrophils might play a role in future cancer immunotherapies.

20.
Front Genet ; 12: 599952, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33659024

RESUMO

The incidences of renal cell carcinoma (RCC) increase in number each year and account for about 2-3% of all malignant tumors. Many patients have metastasis by the time of diagnosis, and their prognosis is poor. Therefore, it is essential that new diagnostic and prognostic markers for kidney cancer are identified. In this study, we assessed the potential of IFI16 as a diagnostic and prognostic marker for RCC. We analyzed the TCGA and UALCAN databases and found IFI16 to be highly expressed in ccRCC. In addition, high IFI16 levels positively correlated with lymphatic metastasis, tumor stage, and histopathological grade. Kaplan-Meier curve analysis showed that IFI16 expression was related to the prognosis of patients, and high IFI16 expression indicated a worse overall survival (p = 5.1E-0.7). Receiver operating characteristic curve analysis showed that a combination of IFI16 expression and histopathological grade improved predictive accuracy (AUC = 0.697; 95%CI: 0.628-0.765, P < 0.001). Finally, the relative levels of IFI16 in ACHN and Caki-1 cells were higher than that of HK-2 cells by western blotting analysis and RT-PCR. Functional tests showed that knocking down IFI16 expression inhibited migration and invasion in vitro. Therefore, IFI16 is a potential biomarker for the diagnosis and prognosis of RCC patients.

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