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[This corrects the article on p. 1968 in vol. 14, PMID: 36310707.].
ABSTRACT
BACKGROUND: Non-small cell lung cancer (NSCLC) is heterogeneous. Molecular subtyping based on the gene expression profiles is an effective technique for diagnosing and determining the prognosis of NSCLC patients. METHODS: Here, we downloaded the NSCLC expression profiles from The Cancer Genome Atlas and the Gene Expression Omnibus databases. ConsensusClusterPlus was used to derive the molecular subtypes based on long-chain noncoding RNA (lncRNA) associated with the PD-1-related pathway. The LIMMA package and least absolute shrinkage and selection operator (LASSO)-Cox analysis were used to construct the prognostic risk model. The nomogram was constructed to predict the clinical outcomes, followed by decision curve analysis (DCA) to validate the reliability of this nomogram. RESULTS: We discovered that PD-1 was strongly and positively linked to the T-cell receptor signaling pathway. Furthermore, we identified two NSCLC molecular subtypes yielding a significantly distinctive prognosis. Subsequently, we developed and validated the 13-lncRNA-based prognostic risk model in the four datasets with high AUC values. Patients with low-risk showed a better survival rate and were more sensitive to PD-1 treatment. Nomogram construction combined with DCA revealed that the risk score model could accurately predict the prognosis of NSCLC patients. CONCLUSIONS: This study demonstrated that lncRNAs engaged in the T-cell receptor signaling pathway played a significant role in the onset and development of NSCLC, and that they could influence the sensitivity to PD-1 treatment. In addition, the 13 lncRNA model was effective in assisting clinical treatment decision-making and prognosis evaluation.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , RNA, Long Noncoding/genetics , Programmed Cell Death 1 Receptor/genetics , Reproducibility of Results , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Receptors, Antigen, T-CellABSTRACT
Exopolysaccharides (EPS) from lactic acid bacteria (LAB) as edible and safe bioproducts with health benefits have become an interesting topic. In this study, aqueous two-phase system (ATPS) was established using ethanol and (NH4)2SO4 as phase-forming substances to separate and purify LAB EPS from Lactobacillus plantarum 1.0665. The operating conditions were optimized by a single factor and response surface method (RSM). The results indicated that an effectively selective separation of LAB EPS was achieved by the ATPS consisted of 28 % (w/w) ethanol and 18 % (w/w) (NH4)2SO4 at pH 4.0. Under optimized conditions, the partition coefficient (K) and recovery rate (Y) were well matched with the predicted value of 3.83 ± 0.019 and 74.66 ± 1.05 %. The physicochemical properties of purified LAB EPS were characterized by various technologies. According to the results, LAB EPS was a complex polysaccharide with a triple helix structure mainly composed of mannose, glucose and galactose in the molar ratio of 1.00: 0.32: 0.14, and it proved that the ethanol/(NH4)2SO4 system had good selectivity for LAB EPS. In addition, LAB EPS displayed excellent antioxidant activity, antihypertension activity, anti-gout capacity and hypoglycemic activity in vitro analysis. The results suggested that LAB EPS could be a dietary supplement applied in functional foods.
Subject(s)
Lactobacillales , Lactobacillus plantarum , Ethanol/chemistry , Polysaccharides, Bacterial/pharmacology , Polysaccharides, Bacterial/chemistry , Lactobacillus plantarum/chemistry , Antioxidants/chemistry , Water/chemistryABSTRACT
The development of intelligent indicator film that can detect changes in food quality is a new trend in the food packaging field. The WPNFs-PU-ACN/Gly film was prepared based on whey protein isolate nanofibers (WPNFs). Anthocyanin (ACN) and glycerol (Gly) were used as the color indicator and the plasticizer, respectively, while pullulan (PU) was added to enhance mechanical properties of WPNFs-PU-ACN/Gly edible film. In the study, the addition of ACN improved the hydrophobicity and oxidation resistance of the indicator film; with an increase in pH, the color of the indicator film shifted from dark pink to grey, and its surface was uniform and smooth. Therefore, the WPNFs-PU-ACN/Gly edible film would be suitable for sensing the pH of salmon, which changes with deterioration, as the color change of ACN was completely consistent with fish pH. Furthermore, the color change after being exposed to grey was evaluated in conjunction with hardness, chewiness, and resilience of salmon as an indication. This shows that intelligent indicator film made of WPNFs, PU, ACN, and Gly could contribute to the development of safe food.
Subject(s)
Edible Films , Food Packaging , Animals , Seafood , Fishes , Anthocyanins/chemistry , Hydrogen-Ion ConcentrationABSTRACT
BACKGROUND: Police officers are a high-stress group with special job characteristics, and the Chinese police management system places particularly high demands on police officers. Whether the influence of job demands on officers' job burnout can be deduced to general stress response needs to be verified. Based on the JD-R model, the study aims to explore the impact of job demands on police stress response, whether job autonomy as a job resource has a moderating effect, and whether basic psychological needs mediate this effect. METHODS: A total of 251 police officers in a district-level public security bureau of China, were surveyed using Chinese-language versions of the Job Demands Scale, the Stress Response Scale, the Job Autonomy Scale, and the Basic Psychological Needs Scale. The mediating effect of basic psychological needs and the moderating effect of job autonomy were tested by regression analysis and bootstrap test. RESULTS: Job demands increase police officers' stress response, and job autonomy does not play a buffer role but enhances this impact, and job demands can partially reduce the police stress response through the satisfaction of basic psychological needs, that is, there is a masking effect of basic psychological needs. CONCLUSIONS: Adjusting and optimizing the ratio of job demands and autonomy in police work to provide high guidance under high demands is of great value to reduce the negative stress responses among police officers.
Subject(s)
Burnout, Professional , Police , Humans , Police/psychology , Stress, Psychological/epidemiology , Stress, Psychological/psychology , Burnout, Professional/epidemiology , Personal Satisfaction , Surveys and Questionnaires , Job SatisfactionABSTRACT
The abnormal activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the pathogenesis of psoriasis. Accordingly, the inhibition of NLRP3 inflammasome may be an effective strategy for psoriasis treatment. However, the NLRP3 inflammasome inhibitors are not available in the clinic. Repurposing FDA-approved drugs is a highly attractive way for identifying new drugs. Here, proteasome inhibitor bortezomib, a marketed drug for treating multiple myeloma, was found to specifically inhibit NLRP3 inflammasome activation at nanomolar concentrations. Mechanistically, bortezomib did not inhibit reactive oxygen species generation, ion efflux, NLRP3 oligomerization, and NLRP3-ASC interactions. Bortezomib reduced ASC oligomerization and ASC speck formation. In addition, bortezomib inhibited the activity of the core subunit ß5i in the immunoproteasome and reduced ß5i binding to NLRP3. Bortezomib reduced the production of interleukin-1ß and attenuated the severity of skin lesions in the imiquimod-induced psoriatic mouse model. Thus, bortezomib is a potential therapeutic drug for psoriasis. Our study also revealed that ß5i may be an indirect target for regulating NLRP3 inflammasome activation and treating psoriasis and other NLRP3 inflammasome-related diseases.
Subject(s)
Inflammasomes , Psoriasis , Animals , Mice , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NF-kappa B/metabolism , Bortezomib/pharmacology , Interleukin-1beta/metabolism , Inflammation/metabolism , Carrier Proteins/metabolism , Psoriasis/drug therapy , Caspase 1/metabolismABSTRACT
BACKGROUND: Interleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated. AIM: To investigate whether and how IL-34 affects the proliferation of GC cells and EMT. METHODS: Using immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting. RESULTS: Expression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice. CONCLUSION: IL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC.
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There is considerable heterogeneity in the genomic drivers of lung adenocarcinoma, which has a dismal prognosis. Bioinformatics analysis was performed on lung adenocarcinoma (LUAD) datasets to establish a multi-autophagy gene model to predict patient prognosis. LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database as a training set to construct a LUAD prognostic model. According to the risk score, a Kaplan-Meier cumulative curve was plotted to evaluate the prognostic value. Furthermore, a nomogram was established to predict the three-year and five-year survival of patients with LUAD based on their prognostic characteristics. Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001). The Kaplan-Meier cumulative curve showed that low-risk patients had significantly better overall (P<0.0001). The validation dataset GSE68465 further confirmed the nomogram's robust ability to assess the prognosis of LUAD patients. A prognosis model of autophagy-related genes based on a LUAD dataset was constructed and exhibited diagnostic value in the prognosis of LUAD patients. Moreover, real-time qPCR confirmed the expression patterns of EIF2AK3 and ITGB1 in LUAD cell lines. Two key autophagy-related genes have been suggested as prognostic markers for lung adenocarcinoma.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Adenocarcinoma of Lung/pathology , Autophagy/genetics , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , Prognosis , Proportional Hazards ModelsABSTRACT
To investigate the effects of different binding modes on the structure, function, and digestive properties of the phosvitin (Pv) and gallic acid (GA) complex, Pv was covalently and noncovalently combined with different concentrations of GA (0.5, 1.5, and 2.5 mM). The structural characterization of the two Pv-GA complexes was performed by Fourier transform infrared, circular dichroism, and LC-MS/MS to investigate the covalent and noncovalent binding of Pv and GA. In addition, the microstructure of the two Pv-GA complexes was investigated by super-resolution microscopy and transmission electron microscopy. The particle size and zeta potential results showed that the addition of GA increased the particle size and the absolute potential of Pv. The determination of protein digestibility, polyphenol content, SH and S-S group levels, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and antioxidant capacity of the digests indicated that noncovalent complexes had greater antioxidant and protective effects on polyphenols. Molecular docking revealed that GA was conjugated with Pv through hydrogen bond interactions.
Subject(s)
Gallic Acid , Phosvitin , Antioxidants/chemistry , Chromatography, Liquid , Digestion , Gallic Acid/chemistry , Molecular Docking Simulation , Phosvitin/chemistry , Polyphenols , Sodium Dodecyl Sulfate , Tandem Mass SpectrometryABSTRACT
Monoclonal antibody (mAb) interchain disulfide bond reduction has been observed in a recent large-scale clinical manufacturing operation. A massive reduction/precipitation at post-clarification steps has occurred. This note presents the development of a novel analytical approach to identify the "potential reduction"-a unique approach to predict the propensity of a monomeric-profiled mAb to be reduced in the post-harvest stage, such as harvest clarification and/or purification steps. The core of this new approach includes comparing the non-reducing capillary electrophoresis profiles of pre- and post-vacuum treated mAb in harvest cell culture fluid (HCCF). Using this approach, the potential reductions of two in-house mAbs in the unclarified and clarified cell culture harvest were assessed.
Subject(s)
Antibodies, Monoclonal , Disulfides , Animals , Antibodies, Monoclonal/chemistry , CHO Cells , Cell Culture Techniques , Cricetinae , Cricetulus , Disulfides/chemistryABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune-related adverse events (irAEs) remain poorly understood, especially in a real-world setting. METHODS: A multicenter observational study was conducted. Medical records of lung cancer patients treated with ICIs at 26 hospitals from January 1, 2015, to February 28, 2021, were retrieved. Types of ICIs included antiprogrammed cell death 1 or antiprogrammed cell death ligand 1 (PD-L1) monotherapy, anticytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy. RESULTS: In total, 1905 patients with advanced lung cancer were evaluated. The median age was 63 (range 28-87) years, and the male/female ratio was 3.1:1 (1442/463). The primary histological subtype was adenocarcinoma (915). A total of 26.9% (512/1905) of the patients developed 671 irAEs, and 5.8% (110/1905) developed 120 grade 3-5 irAEs. Median duration from ICI initiation to irAEs onset was 56 (range 0-1160) days. The most common irAEs were thyroid dysfunction (7.2%, 138/1905), pneumonitis (6.5%, 124/1905), and dermatological toxicities (6.0%, 115/1905). A total of 162 irAEs were treated with steroids and 11 irAEs led to death. Patients with positive PD-L1 expression (≥1%) and who received first-line ICI treatment developed more irAEs. Patients who developed irAEs had a better disease control rate (DCR, 71.3% [365/512] vs. 56.0% [780/1145]; p < 0.001). CONCLUSIONS: The incidence rate of irAEs was 26.9% in a real-world setting. IrAEs might be related to a better DCR, but clinicians should be more aware of irAE recognition and management in clinical practice.
Subject(s)
Lung Neoplasms , Pneumonia , Adult , Aged , Aged, 80 and over , China/epidemiology , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Incidence , Lung Neoplasms/drug therapy , Male , Middle Aged , Pneumonia/drug therapy , Retrospective StudiesABSTRACT
BACKGROUND: Aquaporin 9 (AQP9) is recognized as a key regulator in several cancers, whereas little is known about its clinical implication in non-small cell lung cancer (NSCLC). Thus, we aimed to explore AQP9 expression and its relationship with clinical features, prognosis in NSCLC patients. METHODS: One hundred ninety-eight NSCLC patients who received resection were retrospectively enrolled. This study contained two cohorts: in cohort A, AQP9 protein expression (from formalin fixed paraffin embedded tumor and paired adjacent tissue specimens) in 198 patients was detected by immunohistochemistry (IHC). In cohort B, AQP9 mRNA expression (from fresh-frozen tumor and paired adjacent tissues) in 108 patients (out of 198 patients) was detected by RT-qPCR. RESULTS: In cohort A, increased AQP9 IHC score and greater proportion of AQP9 protein high expression cases were shown in tumor tissue than adjacent tissue (both P < 0.001). Tumor AQP9 protein high expression correlated with lymph node (LYN) metastasis (P = 0.002) and raised TNM stage (P = 0.012). Interestingly, tumor AQP9 protein high expression related to worse disease-free survival (DFS) (P = 0.002) and overall survival (OS) (P = 0.026). In cohort B, AQP9 mRNA expression in tumor tissue was increased than adjacent tissue (P < 0.001), and tumor AQP9 mRNA high expression linked to LYN metastasis (P = 0.024) and increased TNM stage (P = 0.032) as well; tumor AQP9 mRNA high expression was related to shorter DFS (P = 0.009), and it presented with a trend to be correlated with worse OS (P = 0.054), but without statistical significance. CONCLUSION: AQP9 serves as a potential indicator for monitoring disease progression and prognostication in NSCLC patients.
Subject(s)
Aquaporins/metabolism , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aquaporins/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/pathology , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: Lymph node metastasis (LNM) has a significant impact on the prognosis of patients with early gastric cancer (EGC). Our aim was to identify the independent risk factors for LNM and construct nomograms for male and female EGC patients, respectively. METHODS: Clinicopathological data of 1,742 EGC patients who underwent radical gastrectomy and lymphadenectomy in the First Affiliated Hospital, Second Affiliated Hospital, and Fourth Affiliated Hospital of Anhui Medical University between November 2011 and April 2021 were collected and analyzed retrospectively. Male and female patients from the First Affiliated Hospital of Anhui Medical University were assigned to training sets and then from the Second and Fourth Affiliated Hospitals of Anhui Medical University were enrolled in validation sets. Based on independent risk factors for LNM in male and female EGC patients from the training sets, the nomograms were established respectively, which was also verified by internal validation from the training sets and external validation from the validation sets. RESULTS: Tumor size (odd ratio (OR): 1.386, p = 0.030), depth of invasion (OR: 0.306, p = 0.001), Lauren type (OR: 2.816, p = 0.000), lymphovascular invasion (LVI) (OR: 0.160, p = 0.000), and menopause (OR: 0.296, p = 0.009) were independent risk factors for female EGC patients. For male EGC patients, tumor size (OR: 1.298, p = 0.007), depth of invasion (OR: 0.257, p = 0.000), tumor location (OR: 0.659, p = 0.002), WHO type (OR: 1.419, p = 0.001), Lauren type (OR: 3.099, p = 0.000), and LVI (OR: 0.131, p = 0.000) were independent risk factors. Moreover, nomograms were established to predict the risk of LNM for female and male EGC patients, respectively. The area under the ROC curve of nomograms for female and male training sets were 87.7% (95% confidence interval (CI): 0.8397-0.914) and 94.8% (95% CI: 0.9273-0.9695), respectively. For the validation set, they were 92.4% (95% CI: 0.7979-1) and 93.4% (95% CI: 0.8928-0.9755), respectively. Additionally, the calibration curves showed good agreements between the bias-corrected prediction and the ideal reference line for both training sets and validation sets in female and male EGC patients. CONCLUSIONS: Nomograms based on risk factors for LNM in male and female EGC patients may provide new insights into the selection of appropriate treatment methods.
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ABSTRACT: Gastric cancer (GC) is a common cancerous tumor, and is the third leading cause of cancer mortality worldwide. Although comprehensive therapies of GC have been widely used in clinical set ups, advanced gastric cancer carries is characterized by poor prognosis, probably due to lack of effective prognostic biomarkers. Mammalian histone deacetylase family, histone deacetylases (HDACs), play significant roles in initiation and progression of tumors. Aberrant expression of HDACs is reported in many cancer types including gastric cancer, and may serve as candidate biomarkers or therapeutic targets for GC patients.Gene Expression Profiling Interactive Analysis was used to explore mRNA levels of HDACs in GC. Kaplan-Meier plotter was used to determine the prognostic value of HDACs mRNA expression in GC. Genomic profiles including mutations of HDACs were retrieved from cBioPortal webserver. A protein-protein interaction network was constructed using STRING database. GeneMANIA was used to retrieve additional genes or proteins related to HDACs. R software was used for functional enrichment analyses.Analysis of mRNA levels of HDAC1/2/4/8/9 showed that they were upregulated in GC tissues, whereas HDAC6/10 was downregulated in GC tissues. Aberrant expression of HDAC1/3/4/5/6/7/8/10/11 was all correlated with prognosis in GC. In addition, expression levels of HDACs were correlated with different Lauren classifications, and clinical stages, lymph node status, treatment, and human epidermal growth factor receptor 2 status in GC.The findings of this study showed that HDAC members are potential biomarkers for diagnosis or prognosis of gastric cancer. However, further studies should be conducted to validate these findings.
Subject(s)
Computational Biology/methods , DNA, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Histone Deacetylases/genetics , Stomach Neoplasms/genetics , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , DNA, Neoplasm/metabolism , Histone Deacetylases/biosynthesis , Humans , Prognosis , Stomach Neoplasms/metabolismABSTRACT
Respiratory syncytial virus (RSV) is a highly contagious virus causing severe infection in infants and the elderly. Various approaches are being used to develop an effective RSV vaccine. The RSV fusion (F) subunit, particularly the cleaved trimeric pre-fusion F, is one of the most promising vaccine candidates under development. The pre-fusion conformation elicits the majority of neutralizing antibodies during natural infection. However, this pre-fusion conformation is metastable and prone to conversion to a post-fusion conformation, thus hindering the potential of this construct as a vaccine antigen. The Vaccine Research Center (VRC) at the National Institutes of Health (NIH) designed a structurally stabilized pre-fusion F glycoprotein, DS-Cav1, that showed high immunogenicity and induced a neutralizing response in animal studies. To advance this candidate to clinical manufacturing, a production process that maintained product quality (i.e. a cleaved trimer with pre-fusion conformation) and delivered high protein expression levels was required. This report describes the development of the vaccine candidate including vector design and cell culture process development to meet these challenges. Co-transfection of individual plasmids to express DS-Cav1 and furin (for DS-Cav1 cleavage and activation) demonstrated a superior protein product expression and pre-fusion conformation compared to co-expression with a double gene vector. A top clone was selected based on these measurements. Protein expression levels were further increased by seeding density optimization and a biphasic hypothermia temperature downshift. The combined efforts led to a high-yield fed-batch production of approximately 1,500 mg/L (or up to 15,000 doses per liter) at harvest. The process was scaled up and demonstrated to be reproducible at 50 L-scale for toxicity and Phase I clinical trial use. Preliminary phase I data indicate the pre-fusion antigen has a promising efficacy (Crank et al., 2019).
Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Respiratory Syncytial Virus, Human , Aged , Animals , Antibodies, Viral , Humans , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Vaccines/genetics , Respiratory Syncytial Virus, Human/genetics , Vaccines, Subunit , Viral Fusion Proteins/geneticsABSTRACT
Osteoarthritis (OA) is the most common arthropathy, characterized by progressive degeneration of the articular cartilage. Currently, there are no disease-modifying approaches for OA treatment. Adeno-associated virus (AAV)-mediated gene therapy has recently become a potential treatment for OA due to its exceptional characteristics; however, the tropism and transduction efficiency of different AAV serotypes to articular joints and the safety profile of AAV applications are still unknown. The present study aims to screen an ideal AAV serotype to efficiently transfer genes to arthritic cartilage. AAV vectors of different serotypes expressing eGFP protein were injected into the knee joint cavities of mice, with all joint tissues collected 30 days after AAV injection. The transduction efficiency of AAVs was quantified by assessing the fluorescent intensities of eGFP in the cartilage of knee joints. Structural and morphological changes were analyzed by toluidine blue staining. Changes to ECM metabolism and pyroptosis of chondrocytes were determined by immunohistochemical staining. Fluorescence analysis of eGFP showed that eGFP was expressed in the cartilage of knee joints injected with each AAV vector. Quantification of eGFP intensity indicated that AAV2, 7 and 8 had the highest transduction efficiencies. Both toluidine blue staining and Mankin score showed that AAV6 aggravated cartilage degeneration. The analysis of key molecules in ECM metabolism suggested that AAV5 and 7 significantly reduced collagen type II, while AAV9 increased ADAMTS-4 but decreased MMP-19. In addition, transduction with AAV2, 5, 7 and 8 had no obvious effect on pyroptosis of chondrocytes. Comprehensive score analysis also showed that AAV2 had the highest score in intra-articular gene transfer. Collectively, our findings point to AAV2 as the best AAV serotype candidate for gene transfer on arthritic cartilage, resulting in minimal impact to ECM metabolism and pyroptosis of chondrocytes.
Subject(s)
Arthritis, Experimental , Cartilage, Articular/metabolism , Chondrocytes/metabolism , Genetic Therapy , Genetic Vectors , Knee Joint/metabolism , Parvovirinae , ADAMTS4 Protein/biosynthesis , ADAMTS4 Protein/genetics , Animals , Arthritis, Experimental/genetics , Arthritis, Experimental/metabolism , Arthritis, Experimental/pathology , Arthritis, Experimental/therapy , Cartilage, Articular/pathology , Chondrocytes/pathology , Collagen Type II/biosynthesis , Collagen Type II/genetics , Dependovirus , Knee Joint/pathology , Male , Matrix Metalloproteinases, Secreted/biosynthesis , Matrix Metalloproteinases, Secreted/genetics , Mice , Transduction, GeneticABSTRACT
BACKGROUND: To systematically evaluate the efficacy and safety of combined aclidinium bromide and formoterol fumarate for chronic obstructive pulmonary disease (COPD). METHODS: Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) database were searched for studies on the use of combined aclidinium bromide and formoterol fumarate in the treatment of COPD. Two independent researchers performed literature screening, data extraction, and assessment of quality of studies. The strength of the association of the efficacy and safety of combined aclidinium bromide and formoterol fumarate in the treatment of COPD was evaluated according to the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). Statistical analysis was carried out via using RevMan 5.3 software. RESULTS: The results of the present study will be published in a peer-reviewed journal. CONCLUSION: The conclusion of the present study will provide evidence to judge whether combined aclidinium bromide and formoterol fumarate is an effective and safety intervention in the treatment of COPD. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202070063.
Subject(s)
Bronchodilator Agents/therapeutic use , Formoterol Fumarate/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Research Design , Tropanes/therapeutic use , Drug Combinations , Humans , Meta-Analysis as Topic , Systematic Reviews as TopicABSTRACT
We propose a new method to generate optical needles by focusing vector beams comprised of radially polarized component and azimuthally polarized vortex components. The radial part can generate longitudinal polarization, while the azimuthal parts can generate left- and right-handed polarization. Hence, an arbitrary 3D polarization can be obtained. To our knowledge, it may be the first time that arbitrarily polarized optical needles whose transverse sizes are under 0.5λ have been achieved. The polarized homogeneity of the needles is beyond 0.97.
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BACKGROUND: Early growth response proteins (EGRs), as a transcriptional regulatory family, are involved in the process of cell growth, differentiation, apoptosis, and even carcinogenesis. However, the role of EGRs in tumors, their expression levels, and their prognostic value remain unclear. METHODS: Using the Oncomine database, Kaplan-Meier Plotter, bcGenExMiner v4.2, cBioPortal, and other tools, the association between the survival data of breast carcinoma (BC) patients and transcriptional levels of four EGRs was investigated. RESULTS: According to the Oncomine database, in comparison to normal tissues, the expression level of EGR2/3 mRNA in BC tissues was decreased, but there was no difference in the expression level of EGR4 mRNA. On the basis of the Scarff-Bloom-Richardson (SBR) grading system, the downregulated expression level of EGR1/2/3 and upregulated expression level of EGR4 were correlated with an increased histological differentiation level, with significant differences (p < 0.05). Kaplan-Meier curves suggest that a reduction in EGR2/3 mRNA expression is related to recurrence-free survival (RFS) in BC patients. In addition, the mRNA expression level of EGR1/2/3 was related to metastatic relapse-free survival (MRFS) in BC patients with metastatic recurrence (p < 0.05). CONCLUSION: EGR1/2/3 can be utilized as an important factor for evaluating prognosis and may be relevant to diagnosis. EGR4 may play a role in the occurrence and development of BC. The specific function and mechanism of EGRs in BC deserve further study.
ABSTRACT
Symmetry of electric spin angular momentum (SAM) density in the tight focusing of linearly polarized vortex beams is investigated in this paper. By calculating analytic expressions of SAM density, reflection symmetry and rotation symmetry of SAM density are found in the focal region. The vortex phase can break some symmetry, leading to non-zero longitudinal SAM. When the vortex phase vanishes, more symmetry will occur. It is proved that longitudinal SAM is zero when the topological charge is zero, and that transverse SAM is always zero. This paper is expected to advance our understanding of distribution of SAM density and optical spin-orbit coupling.