ABSTRACT
The AlGaN-based deep ultraviolet light-emitting diode (DUV LED) has advantages of environmentally friendly materials, tunable emission wavelength, and easy miniaturization. However, an increase in Al composition leads to a decline in the lattice quality, thereby reducing the internal quantum efficiency (IQE). In addition, the light extraction efficiency (LEE) is limited due to the strong transverse magnetization polarization emission from the multiple quantum wells. Here, we designed the topological corner structure in AlGaN-MQWs, and the high electric field intensity in a tiny space at the corner results in an extremely high local density of optical states (LDOS), which could shorten the luminescence decay time of the emitter and increase the radiative rate by 26 times. Meanwhile, because the excited topological corner state resonance mode is a transverse-electric mode, enhancing only the transverse-electric luminescence without any gain for transverse-magnetic luminescence, thereby significantly improving the light extraction efficiency. Finally, according to theoretical calculations, the IQE could reach 68.75% at room temperature.
ABSTRACT
BACKGROUND: Patients' medication adherence plays a critical role in the treatment and rehabilitation of disease. However, few tools are currently available that can be used to identify the reasons for their nonadherence with their medication regimens. It is possible to evaluate both the level of medication adherence of a patient as well as the reasons for it using the Adherence to Asthma Medication Questionnaire (AAMQ). The purpose of this study was to adapt the AAMQ for use in Chinese patients and a variety of asthma patients. METHODS: A total of 242 asthma patients were recruited from Jinzhou in China. The Adherence to Asthma Medication Questionnaire was translated and back-translated using the Brislin translation model. Test-retest reliability, internal consistency, and stability all play a large role in determining the reliability of a scale. Confirmatory factor analysis was used to examine the scale's construct validity, and expert consultation was used to verify the scale's content validity. Statistics were deemed significant at p < 0.05. RESULTS: The Cronbach's α value of the Chinese version of the AAMQ was 0.866, and the coefficient values for the three domains ranged between 0.702 and 0.798. The split-half reliability and stability values were 0.794 and 0.772, respectively. The content validity index of the scale (S-CVI) was 0.923, and the content validity index of the level of scale entry was 0.857-1.000. According to the confirmatory factor analysis, the chi-square degreed of freedom were 1.484, and the model fitting indices were all within normal limits. CONCLUSIONS: The AAMQ had good reliability and validity for asthmatic patients. The results of the scale's assessment can be used as a criterion for medication adherence among asthmatic patients and to understand the causes. This study provides a reference for solving the problem of medication adherence among asthma patients and implementing targeted nursing measures. PATIENT OR PUBLIC CONTRIBUTION: Gratitude is extended to all individuals collaborating in completing the survey and to the author.
Subject(s)
Asthma , Humans , Asthma/drug therapy , Psychometrics/methods , Reproducibility of Results , Surveys and Questionnaires , China , Medication AdherenceABSTRACT
OBJECTIVE: Constructing a demand-oriented Internet + community home care service indicator system, starting from the actual needs of the elderly, and quantifying the demand into specific service contents that can be provided, so as to realize the effective supply of services. It aims to provide a theoretical basis for the government to formulate relevant aging policies and provide a reference basis for promoting the innovation and development of the Internet + elderly care model. METHODS: Based on existence needs, relationship needs and growth needs abbreviated as "Existence, Relatedness, Growth (ERG)" demand theory, through the discussion in the group meeting, form the expert consultation questionnaire of the demand-oriented Internet + community home care service indicator system, select experts in related fields to conduct two rounds of Delphi expert consultation, summarize the experts' opinions to determine the indicator system items, and use the Analytic Hierarchy Process (AHP) method to construct the judgment matrix to derive the weighting coefficients of the indicators, and establish the ultimate demand-oriented Internet + community home care service indicator system. RESULTS: The effective recovery rates for the two rounds of expert consoulation questionnaires were 100%, with expert authority coefficients of 0.852 and 0.868, respectively. The Kendall coefficients for the second round of expert views varied from 0.226 to 0.431, with coefficients of variation for all indexes less than 0.25.The finalized demand-oriented Internet + community home care service indicator system includes 3 first-level indicators, 10 s-level indicators, and 46 third-level indicators. The consistency ratios of indicator judgment matrices at all levels are less than 0.10, suggesting that the hierarchical analysis findings are consistent, implying that the weight coefficient distribution is appropriate. CONCLUSION: The demand-oriented Internet + community home care service Indicator System, which was created through expert consultation and AHP method, has reasonable content and is more dependable as an evaluation tool for reliably assessing demand for elderly servic.
Subject(s)
Delphi Technique , Home Care Services , Internet , Humans , Aged , Surveys and Questionnaires , Health Services Needs and Demand , Health Services for the Aged/standardsABSTRACT
Many processes, such as growth, aging, and adaptation to abiotic stress, are regulated in plants by NAC transcription factors. In woody plants, NAC transcription factors acts as a primary switch that regulates secondary xylem development by activating various downstream transcription factors and modulating expression levels of genes involved in the synthesis of the secondary cell wall. Our team had previously sequenced the whole genome of the camphor tree (Cinnamomum camphora). Here, we performed a detailed analysis of the NAC gene family of C. camphora and examined its evolutionary history. The genomic sequences of 121 NAC genes of C. camphora were identified and classified into 20 subfamilies in 2 major classes based on the phylogenetic analysis and structural features. Expansion of the CcNAC gene family occurred mainly by fragment replication and was influenced by the purifying selection. By analyzing predicted interactions of the homologous AtNAC proteins, we identified five CcNACs that potentially regulate xylem development in C. camphora. RNA sequencing revealed distinct expression profiles of CcNACs in seven different plant tissues. Subcellular localization prediction revealed that 120, 3, and 2 CcNACs have biological functions in the nucleus, cytoplasm, and chloroplast, respectively. Furthermore, we verified expression patterns of five CcNACs (CcNAC012, CcNAC028, CcNAC055, CcNAC080, and CcNAC119) in various tissue types using qRT-PCR. Our results will facilitate further in-depth studies of the molecular mechanisms by which CcNAC transcription factors regulate wood formation and other processes in C. camphora.
Subject(s)
Cinnamomum camphora , Wood , Wood/metabolism , Genes, Plant , Cinnamomum camphora/chemistry , Cinnamomum camphora/genetics , Cinnamomum camphora/metabolism , Phylogeny , Transcription Factors/metabolism , Plant Proteins/geneticsABSTRACT
The hydrolysis of extracellular polymeric substances (EPS) represents a critical bottleneck in the anaerobic fermentation of waste activated sludge (WAS), while tryptophan is identified as an underestimated constituent of EPS. Herein, we harnessed a tryptophan-degrading microbial consortium (TDC) to enhance the hydrolysis efficiency of WAS. At TDC dosages of 5%, 10%, and 20%, a notable increase in SCOD was observed by factors of 1.13, 1.39, and 1.88, respectively. The introduction of TDC improved both the yield and quality of short chain fatty acids (SCFAs), the maximum SCFA yield increased from 590.6 to 1820.2, 1957.9 and 2194.9 mg COD/L, whilst the acetate ratio within SCFAs was raised from 34.1% to 61.2-70.9%. Furthermore, as TDC dosage increased, the relative activity of protease exhibited significant increments, reaching 116.3%, 168.0%, and 266.1%, respectively. This enhancement facilitated WAS solubilization and the release of organic substances from bound EPS into soluble EPS. Microbial analysis identified Tetrasphaera and Soehngenia as key participants in WAS solubilization and the breakdown of protein fraction. Metabolic analysis revealed that TDC triggered the secretion of enzymes associated with amino acid metabolism and fatty acid biosynthesis, thereby fostering the decomposition of proteins and production of SCFAs.
Subject(s)
Sewage , Tryptophan , Humans , Fermentation , Sewage/chemistry , Anaerobiosis , Tryptophan/metabolism , Fatty Acids, Volatile/metabolism , Hydrogen-Ion ConcentrationABSTRACT
Cinnamomum camphora is one of the most commonly used tree species in landscaping. Improving its ornamental traits, particularly bark and leaf colors, is one of the key breeding goals. The basic helix-loop-helix (bHLH) transcription factors (TFs) are crucial in controlling anthocyanin biosynthesis in many plants. However, their role in C. camphora remains largely unknown. In this study, we identified 150 bHLH TFs (CcbHLHs) using natural mutant C. camphora 'Gantong 1', which has unusual bark and leaf colors. Phylogenetic analysis revealed that 150 CcbHLHs were divided into 26 subfamilies which shared similar gene structures and conserved motifs. According to the protein homology analysis, we identified four candidate CcbHLHs that were highly conserved compared to the TT8 protein in A. thaliana. These TFs are potentially involved in anthocyanin biosynthesis in C. camphora. RNA-seq analysis revealed specific expression patterns of CcbHLHs in different tissue types. Furthermore, we verified expression patterns of seven CcbHLHs (CcbHLH001, CcbHLH015, CcbHLH017, CcbHLH022, CcbHLH101, CcbHLH118, and CcbHLH134) in various tissue types at different growth stages using qRT-PCR. This study opens a new avenue for subsequent research on anthocyanin biosynthesis regulated by CcbHLH TFs in C. camphora.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Cinnamomum camphora , Basic Helix-Loop-Helix Transcription Factors/metabolism , Anthocyanins , Cinnamomum camphora/metabolism , Phylogeny , Plant Breeding , Gene Expression Regulation, Plant , Plant Proteins/geneticsABSTRACT
Lysine acetylation is one of the most basic molecular mechanisms to mediate protein functions in living organisms, and its abnormal regulation has been linked to many diseases. The drug development associated to this process is of great significance but severely hindered by the complex interplay of lysine acetylation and deacetylation in thousands of proteins, and we reasoned that targeting a specific protein acetylation or deacetylation event instead of the related enzymes should be a feasible solution to this issue. Toward this goal, we devised an orthogonal lysine acylation and deacylation (OKAD) system, which potentially could precisely dissect the biological consequence of an individual acetylation or deacetylation event in living cells. The system includes a genetically encoded acylated lysine (PhOAcK) that is not a substrate of endogenous deacetylases, and an evolved sirtuin (CobB2/CobB3) that displays PhOAcK deacylase activities as well as reduced deacetylase activities. We believe the strategy introduced here holds potential for future in-depth biological applications.
Subject(s)
Histone Deacetylases/metabolism , Lysine/metabolism , Acylation , Lysine/chemistry , Molecular StructureABSTRACT
Highly sensitive ultraviolet (UV) photodetectors are highly desired for industrial and scientific applications. However, the responsivity of silicon photodiodes in the UV wavelength band is relatively low due to high-density Si/SiO2 interface states. In this paper, a coplanar avalanche photodiode (APD) was developed with a virtual guard ring design. When working in Geiger mode, it exhibited a strong UV response. The responsivity of 4 × 103 A/W (corresponding to a gain of 8 × 106) at 261 nm is measured under the incident power of 0.6 µW with an excess bias of 1.5 V. To the best of our knowledge, the maximum 3-dB bandwidth of 1.4 GHz is the first report ever for a Si APD when working in the Geiger mode in spite of the absence of an integrated CMOS read-out circuit.
ABSTRACT
BaTiO3 dielectric capacitors, one of the important energy storage devices, play critical roles in storing electricity from renewable energies of water, wind, solar, etc. The synthesis of BaTiO3 ceramics with weak temperature dependence and a high dielectric constant at room temperature (εRT') is an urgent problem to meet the miniaturization and large capacity of dielectric capacitors. Doping rare earth elements into BaTiO3 can solve this problem, but it is still challenging. In this work, we adopt a synergistic strategy of increasing εRT' and improving the temperature stability by codoping Gd3+ and Ho3+, respectively, to address this challenge. By carefully adjusting the synthesis conditions in the solid-state reaction, codoping 7% Gd3+ and 7% Ho3+ in BaTiO3 (BGTH7) ceramics were synthesized. The temperature-dependent dielectric constant reveals that the obtained optimal BGTH7 ceramic satisfies the X7U specification and displays a stable ε' in the temperature range of -55~125 °C. The optimal BGTH7 ceramic after sintering at 1400 °C for 6 h exhibits a high dielectric constant of 5475 and low dielectric loss (tan δ) of 0.0176, hitherto exhibiting the best performance in X7U ceramics. The findings in this work are conducive to the miniaturization and stabilization of dielectric energy storage devices.
ABSTRACT
Endometriosis is an inflammation-dependent disease that shares similarities with malignant tumors including attachment and infiltration. Tripartite motif-containing 24 (TRIM24) has been illustrated in inflammatory responses and gynecological tumors, and Nod-like receptor protein 3 (NLRP3) inflammasome has been implicated in endometriosis. However, the involvement of TRIM24 and the role of NLRP3/caspase-1/interleukin-1ß (IL-1ß)-mediated pyroptosis in endometriosis remain obscure. In this study, we originally detected the decreased expression of TRIM24 in the ectopic endometrium of endometriosis compared with the normal endometrium. Then we measured the promoted protein expression of pyroptotic biomarkers (NLRP3, procaspase-1, caspase-1, pro-IL-1ß, and IL-1ß) using Western blot analysis and the stimulated secretion of IL-1ß and IL-18 by enzyme-linked immunosorbent assay in ectopic human endometrial stromal cells (hESC) compared with normal hESC. TRIM24-small-interfering RNA (siTRIM24) was used to silence TRIM24, whereas TRIM24-pcDNA3.1 was used for overexpressing TRIM24. The migration of hESC was determined by a Transwell migration assay. Coimmunoprecipitation and ubiquitination analyses were conducted to explore the interaction between TRIM24 and NLRP3. Subsequently, we found that TRIM24 negatively regulated NLRP3/caspase-1/IL-1ß-mediated pyroptosis and cell migration of hESC, and CY-09, the specific inhibitor of NLRP3, could reverse the promoted pyroptosis and cell migration induced by siTRIM24. Furthermore, TRIM24 interacted with NLRP3 and the upregulation of TRIM24 facilitated the ubiquitination of NLRP3 in ectopic hESC. Our findings suggest that TRIM24 may participate in the progression of endometriosis through the NLRP3/caspase-1/IL-1ß-mediated pyroptotic pathway via ubiquitination of NLRP3, which reveals the significant molecular mechanism underlying endometriosis.
Subject(s)
Carrier Proteins/physiology , Endometriosis/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Adult , Caspase 1/metabolism , Cells, Cultured , Female , Humans , Interleukin-1beta/metabolism , Pyroptosis , Young AdultABSTRACT
BACKGROUND: Diagnosing chronic periprosthetic joint infection (PJI) is challenging. No single biomarker can accurately recognize PJI preoperatively in a timely manner. Therefore, the aim of the present study was to investigate the usefulness of the serum neutrophil-to-lymphocyte ratio (NLR) in aiding the diagnosis of chronic PJI. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 158 patients who had undergone revision arthroplasty (104 with aseptic mechanic failure and 54 with chronic PJI) from July 2011 to July 2020. Univariate analysis followed by multivariate logistic regression was applied to compare NLR, C-reactive protein (CRP), and erythrocyte sedimentation ratio (ESR) between the two groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of NLR alone and in combination with CRP and ESR. RESULTS: NLR, CRP, and ESR were significantly higher in patients with chronic PJI than in the aseptic revision group (p < 0.05). ROC curve analysis revealed that NLR had a sensitivity of 57.41% and a specificity of 77.88% with an optimal threshold of 2.56. The optimal threshold for CRP and ESR was 7.00 mg/L (sensitivity 62.50% and specificity 83.12%) and 43 mm/h (sensitivity 59.38% and specificity 80.52%), respectively. The combined diagnostic value of NLR with CRP and ESR was shown to have no additional diagnostic value in predicting chronic PJI. CONCLUSION: Compared with traditional inflammatory biomarkers (ESR and CRP), the value of serum NLR alone or combined with CRP and ESR for diagnosing chronic PJI is limited. LEVEL OF EVIDENCE: Level 3.
Subject(s)
Arthroplasty, Replacement, Hip , Prosthesis-Related Infections , Biomarkers , Humans , Lymphocytes , Neutrophils , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/surgery , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Evidence indicates that inflammatory response is significant during the physiological process of human parturition; however, the specific signaling pathway that triggers inflammation is undefined. Toll-like receptors (TLRs) are key upstream gatekeepers that control inflammatory activation before preterm delivery. Our previous study showed that TLR4 expression was significantly increased in human pregnancy tissue during preterm and term labor. Therefore, we explore whether TLR4 plays a role in term labor by initiating inflammatory responses, therefore promoting uterine activation. The results showed that expression of TLR4, interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), CC chemokine ligand 2 (CCL-2), and uterine contraction-associated proteins (CAPs) was upregulated in the human and mice term labor (TL) group compared with the not-in-labor (TNL) group, and the TLR4 level positively correlated with CAP expression. In pregnant TLR4-knockout (TLR4-/- ) mice, gestation length was extended by 8 hr compared with the wild-type group, and the expression of IL-1ß, IL-6, TNF-α, CCL-2, and CAPs was decreased in TLR4-/- mice. Furthermore, nuclear factor-κB (NF-κB) and P38MAPK activation is involved in the initiation of labor but was inhibited in TLR4-/- mice. In uterine smooth muscle cells, the expression of inflammatory cytokines and CAPs decreased when the NF-κB and P38MAPK pathway was inhibited. Our data suggest that TLR4 is a key factor in regulating the inflammatory response that drives uterine activation and delivery initiation via activating the NF-κB/P38MAPK pathway.
Subject(s)
MAP Kinase Signaling System/genetics , Parturition/physiology , Toll-Like Receptor 4/metabolism , Uterus/physiology , Animals , Cells, Cultured , Chemokine CCL2/metabolism , Female , Humans , Inflammation/immunology , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/metabolism , Parturition/immunology , Pregnancy , Toll-Like Receptor 4/genetics , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
OBJECTIVES: To evaluate the changes of corneal sub-basal nerve (SBN) and dendritic cell (DC) in contact lens (CL) wearers with mild dry eye and their potential relationship. METHODS: Twenty mild dry eye volunteers who had never worn CLs were recruited for long-term CL wearing. Each subject underwent ocular surface evaluations at baseline and at 1, 4, 12, and 24 weeks, including Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time (TBUT), and Schirmer I test. In vivo confocal microscopy was used to examine the density, area, number of dendrites, total dendritic length of DC, and SBN densities in central and peripheral corneas. Only right eyes were included. RESULTS: The DCs were activated and peaked at week 4 after wearing CLs. The peripheral DC density increased beginning the first week, whereas the central ones increased by week 4. After 4 weeks, both began to decrease, but still higher than baseline at week 24. The central and peripheral SBN densities decreased. However, the peripheral SBN tended to increase beginning at week 12. In early period, SBN was negatively correlated with DC parameters. After 4 weeks, the correlation changed to be positive. The OSDI increased, whereas the Schirmer I test and TBUT showed no significant change. CONCLUSIONS: After wearing CLs, corneal DC were activated and increased, indicating ocular surface inflammation and decreased after week 4. In the early period, increases in DC may lead to decreases in SBN. Upon decrease of DC, the SBN may regenerate.
Subject(s)
Contact Lenses, Hydrophilic , Cornea/innervation , Cornea/metabolism , Dendritic Cells/metabolism , Dry Eye Syndromes/metabolism , Ophthalmic Nerve/metabolism , Female , Humans , Male , Microscopy, Confocal , Surveys and Questionnaires , Tears/metabolism , Young AdultABSTRACT
The aim of this study was to evaluate whether a patented single-channel applicator, which was modified from the traditional tandem applicator and wrapped with an oval-shield alloy around the source channel, has the same clinical efficacy and safety as the standard Fletcher-type applicator in high dose rate (HDR) brachytherapy for carcinoma of the cervix. Between December 2011 and February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (2009) stage Ib2-IVa cervical cancer were recruited to the trial and finished the allocated intervention. Of the first 151 patients, 71 were allocated to the Fletcher group and 80 to the single-channel group, satisfying the criteria for a preliminary analysis. All but 3 patients were treated with concurrent cisplatin chemotherapy and external beam radiotherapy followed by HDR brachytherapy. The 2-year overall survival, progression-free survival, and locoregional failure-free survival was 80.3%, 77.5%, and 78.9%, respectively, for the Fletcher group, and 86.3%, 82.5%, and 83.8%, respectively, for the single-channel group. The seriousness of acute treatment-related toxicities was similar in the 2 groups. The cumulative rate of late rectal complications of grade 3-4 in the Fletcher group and the single-channel group was 2.8% and 2.5%, respectively. The cumulative rate of grade 3 bladder complications was 2.8% for the Fletcher group and 1.3% for the single-channel group. The preliminary results of our study show that the patented single-channel intracavitary applicator might be able to provide protection for the rectum and bladder and seems to have the same clinical efficacy as the standard Fletcher-type 3-channel applicator in HDR brachytherapy for carcinoma of the cervix. This trial was registered with the Chinese Clinical Trial Registry (registration no. ChiCTR-TRC-12002321).
Subject(s)
Brachytherapy/instrumentation , Chemoradiotherapy/methods , Cisplatin/administration & dosage , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Cisplatin/therapeutic use , Female , Humans , Middle Aged , Neoplasm Staging , Prospective Studies , Radiotherapy Dosage , Survival Analysis , Treatment Outcome , Uterine Cervical Neoplasms/pathology , Young AdultABSTRACT
In this work, we explore the possibility of using hybrid graphene/GaN phototransistors to get high responsivity, high speed, and large photosensitive area. The responsivity of our hybrid graphene/GaN phototransistors with a relatively large 15.2 mm2 active area reaches 361 mA/W at 10 V and the response time is ~5 ms, much better performance than traditional GaN photodetectors. This is because graphene acts as the carrier transport channel with a high mobility and greatly increases the charge collection efficiency. Our results should shed more light on the role of graphene in hybrid phototransistors and open a feasible pathway to develop large area ultraviolet photodetectors with high responsivity and high speed.
ABSTRACT
Whole-cell catalysis with co-expression of two or more enzymes in a single host as a simple low-cost biosynthesis method has been widely studied and applied but hardly with regulation of multi-enzyme expression. Here we developed an efficient whole-cell catalyst for biosynthesis of L-phenylglycine (L-Phg) from benzoylformic acid through co-expression of leucine dehydrogenase from Bacillus cereus (BcLeuDH) and NAD+-dependent mutant formate dehydrogenase from Candida boidinii (CbFDHA10C) in Escherichia coli with tunable multi-enzyme-coordinate expression system. By co-expressing one to four copies of CbFDHA10C and optimization of the RBS sequence of BcLeuDH in the expression system, the ratio of BcLeuDH to CbFDH in E. coli BL21/pETDuet-rbs 4 leudh-3fdh A10C was finally regulated to 2:1, which was the optimal one determined by enzyme-catalyzed synthesis. The catalyst activity of E. coli BL21/pETDuet-rbs 4 leudh-3fdh A10C was 28.4 mg L-1 min-1 g-1 dry cell weight for L-Phg production using whole-cell transformation, it's was 3.7 times higher than that of engineered E. coli without enzyme expression regulation. Under optimum conditions (pH 8.0 and 35 °C), 60 g L-1 benzoylformic acid was completely converted to pure chiral L-Phg in 4.5 h with 10 g L-1 dry cells and 50.4 g L-1 ammonium formate, and with enantiomeric excess > 99.9%. This multi-enzyme-coordinate expression system strategy significantly improved L-Phg productivity and demonstrated a novel low-cost method for enantiopure L-Phg production.
Subject(s)
Escherichia coli/genetics , Escherichia coli/metabolism , Glycine/analogs & derivatives , Metabolic Engineering , Bacillus cereus/enzymology , Bacillus cereus/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Candida glabrata/enzymology , Candida glabrata/genetics , Formate Dehydrogenases/genetics , Formate Dehydrogenases/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Glycine/biosynthesis , Leucine Dehydrogenase/genetics , Leucine Dehydrogenase/metabolismABSTRACT
Preclinical Research Osteoarthritis (OA) is a widely prevalent degenerative joint disease that severely impairs the health of the elderly population resulting in a heavy economic burden worldwide. Coenzyme Q10 (CoQ10) has shown anti-inflammatory effects in some diseases. The present study aimed to investigate if CoQ10 would suppress catabolic responses of interleukin (IL)-1ß-induced chondrocytes. Rat chondrocytes were cultured and pretreated with CoQ10, and then stimulated with or without IL-1ß (10 ng/ml). The expression and production of matrix metalloproteinase (MMP)-3, MMP-9, and MMP13 were determined using real-time PCR and Western blotting. CoQ10 suppressed MMP-3, MMP-9, and MMP13 production induced by IL-1ß, and markedly inhibited IL-1ß-induced MAPK pathways in rat chondrocytes. The present study provides insight into potential mechanisms by which CoQ10 protects against degeneration of cartilage in patients with OA, which may lead to new approaches for the treatment of OA.Drug Dev Res 78 : 403-410, 2017. © 2017 Wiley Periodicals, Inc.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Chondrocytes/cytology , Interleukin-1beta/adverse effects , MAP Kinase Signaling System/drug effects , Ubiquinone/analogs & derivatives , Vitamins/pharmacology , Animals , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Chondrocytes/drug effects , Down-Regulation , Gene Expression Regulation/drug effects , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 3/metabolism , Matrix Metalloproteinases, Secreted/genetics , Matrix Metalloproteinases, Secreted/metabolism , Models, Biological , Rats , Rats, Sprague-Dawley , Ubiquinone/pharmacologyABSTRACT
Endotoxin lipopolysaccharide (LPS) plays an important role in the acceleration of inflammatory reaction of hepatitis as the second attack. Compounds that can prevent inflammation by targeting LPS have potential therapeutic clinical application. Epigallocatechin-3-gallate (EGCG) has potent hepatocyte-protective effect and mild anti-hepatitis virus function. Here, we investigated whether EGCG attenuated the severity of inflammatory response in LPS-stimulated L02 hepatocytes. L02 hepatocytes were pretreated with EGCG for 2 h, then stimulated by LPS at 250 ng/ml. The expression levels of chemokine regulated upon activation normal T-cell expressed and secreted (Rantes) and monocyte chemotactic protein-1 (MCP-1), pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ, adhesion molecule intercellular adhesion molecule-1 (ICAM-1), oxidant stress molecules nitric oxide (NO), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) were tested by enzyme-linked immunosorbent assay. The expression of total extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-ERK1/2 (p-ERK1/2), p-AKT, total p38, phospho-p38 (p-p38), total p65 and phospho-p65 (p-p65), IκBα, phospho-IκBα (p-IκBα) and TNF receptor associated factor 2 were tested by western blot analysis. Our results showed that pre-treatment with EGCG could significantly reduce the production of TNF-α, Rantes, MCP-1, ICAM-1, NO, VEGF, and MMP-2 in LPS-stimulated L02 hepatocytes in a dose-dependent manner. The effect of EGCG may be related to the inhibition of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by down-regulation of p-IκBα, p65, p-p65, p-p38, p-ERK1/2, and p-AKT. These results indicate that EGCG suppresses LPS-induced inflammatory response and oxidant stress and exerts its hepatocyte-protective activity partially by inhibiting NF-κB and MAPK pathways.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Catechin/analogs & derivatives , Cytokines/antagonists & inhibitors , Hepatocytes/drug effects , Hepatocytes/metabolism , Lipopolysaccharides/pharmacology , Catechin/pharmacology , Cell Line , Cell Survival/drug effects , Cytokines/biosynthesis , Humans , Intercellular Adhesion Molecule-1/biosynthesis , Matrix Metalloproteinase 2/biosynthesis , Mitogen-Activated Protein Kinases/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
INTRODUCTION: Mucosa-associated lymphoid tissue 1 (MALT1) modulates T helper cell differentiation, pro-inflammatory cytokine production, and epidermal hyperplasia to participate in the pathology of psoriasis. This study aimed to explore the correlation of blood MALT1 with treatment outcomes in psoriasis patients. METHODS: MALT1 was detected in peripheral blood mononuclear cells by reverse transcription-quantitative polymerase chain reaction in 210 psoriasis patients before starting or converting to a new therapy, 50 disease controls, and 50 healthy controls. The psoriasis area severity index (PASI) score was evaluated at month (M)1, M3, and M6 in psoriasis patients. RESULTS: MALT1 was increased in psoriasis patients versus disease controls and healthy controls (both p < .001); and positively related to body mass index (p = .019) and PASI score (p < .001) in psoriasis patients. PASI75 rate at M1, M3, and M6 was 22.9%, 46.2%, and 71.0%, respectively; while PASI90 rate at M1, M3, and M6 was 3.8%, 29.0%, and 50.5%, respectively, in psoriasis patients. PASI75/90 rates at M1, M3, and M6 were increased in psoriasis patients receiving biologics versus those without (all p < .05). Pretreatment MALT1 was higher in psoriasis patients who achieved PASI75 (p = .001) and PASI90 (p < .001) at M6 compared to those who did not achieve that. Subgroup analyses discovered that pretreatment MALT1 had a stronger ability to predict PASI75 and 90 realizations in psoriasis patients receiving biologics (area under the curve [AUC]: 0.723 and 0.808) versus those without (AUC: 0.594 and 0.675). CONCLUSION: Blood MALT1 measurement may assist in predicting outcomes in psoriasis patients, especially in those receiving biologics.
Subject(s)
Biological Products , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein , Psoriasis , Humans , Biological Products/therapeutic use , Leukocytes, Mononuclear/metabolism , Prospective Studies , Psoriasis/diagnosis , Psoriasis/drug therapy , Treatment OutcomeABSTRACT
OBJECTIVE: To compare the effects of three types of ultrasound-guided nerve blocks on post-operative recovery quality in patients undergoing modified radical mastectomy for unilateral breast cancer. METHODS: In this randomized double-blinded trial (chictr.org.cn, ChiCTR2200059428), 150 female patients were equally assigned to S group (serratus anterior plane block, SAPB) group, P group (paravertebral block, PVB) or ST group (serratus anterior combined with transverse thoracic muscle plane blocks, SA-TTMPB). The primary outcome was QoR-15 at five time points after surgery. Secondary outcomes were pain scores, time of first rescue analgesic and chronic pain incidence at 3 months. RESULTS: The QoR-15 total score of S group at 24 h, 48 h, 72 h and 7 days post-surgery was significantly lower in groups P and ST, while there was no significant difference between groups P and ST (S vs. P vs. ST, 100.29 ± 6.20 vs. 108.51 ± 7.46 vs. 106.46 ± 6.95; 105.59 ± 6.18 vs. 113.06 ± 7.44 vs. 111.22 ± 6.56; 112.51 ± 6.32 vs. 119.88 ± 6.44 vs. 117.62 ± 6.09; 123.00 ± 5.78 vs. 128.86 ± 5.96 vs. 126.92 ± 5.72, p < 0.05). The dynamic and rest NRS scores at 6 and 12 h post-surgery were significantly higher in group S than in groups P and ST. CONCLUSION: Serratus anterior plane block combined with transverse thoracic muscle plane block and paravertebral block both have better effects than serratus anterior plane block alone in improving patients' early post-operative recovery quality, and also have an advantage in improving early post-operative pain. CLINICAL TRIAL REGISTRATION: chictr.org.cn (ChiCTR2200059428). DATE OF REGISTRATION: 29 April 2022. SIGNIFICANCE: Serratus anterior combined with transverse thoracic muscle plane block may be a safer, easier, and equally effective nerve block strategy than paravertebral block in patients undergoing modified radical mastectomy for unilateral breast cancer.