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Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RTPCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting interEC adhesion proteins (zona occludens1, connexin 43 and Vascular endothelialCadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4, solute carrier family 7 member 11 and acylCoA synthase longchain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting interEC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. In vivo, inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.
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Permeabilidade Capilar , Ferroptose , Osteoartrite , Proteína rhoA de Ligação ao GTP , Proteína rhoA de Ligação ao GTP/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Animais , Humanos , Camundongos , Masculino , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Camundongos Endogâmicos C57BLRESUMO
This study aimed to characterize PANoptosis-related genes with immunoregulatory features in osteoarthritis (OA) and investigate their potential diagnostic and therapeutic implications. Gene expression data from OA patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis and functional enrichment analysis were conducted to identify PANoptosis-related genes (PRGs) associated with OA pathogenesis. A diagnostic model was developed using LASSO regression, and the diagnostic value of key PRGs was evaluated using Receiver Operating Characteristic Curve (ROC) analysis. The infiltration of immune cells and potential small molecule agents were also examined. A total of 39 differentially expressed PANoptosis-related genes (DE-PRGs) were identified, with functional enrichment analysis revealing their involvement in inflammatory response regulation and immune modulation pathways. Seven key PRGs, including CDKN1A, EZH2, MEG3, NR4A1, PIK3R2, S100A8, and SYVN1, were selected for diagnostic model construction, demonstrating high predictive performance in both training and validation datasets. The correlation between key PRGs and immune cell infiltration was explored. Additionally, molecular docking analysis identified APHA-compound-8 as a potential therapeutic agent targeting key PRGs. This study identified and analyzed PRGs in OA, uncovering their roles in immune regulation. Seven key PRGs were used to construct a diagnostic model with high predictive performance. The identified PRGs' correlation with immune cell infiltration was elucidated, and APHA-compound-8 was highlighted as a potential therapeutic agent. These findings offer novel diagnostic markers and therapeutic targets for OA, warranting further in vivo validation and exploration of clinical applications.
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OBJECTIVES: This study aimed to assess whether the national centralised volume-based procurement policy and the Shanghai government's supportive measures (coronary stent policies) implemented in Shanghai, China, on 20 January 2021 affected the cost-effectiveness of percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) in the year after surgery. DESIGN: A retrospective cohort study based on real-world data and propensity score (PS)-matched data was conducted to compare the cost-effectiveness of PCI before and after policy implementation. PATIENTS AND SETTING: Patients with ACS who had undergone first-time PCI over 1 year previously in hospitals in Shanghai and were discharged between 1 March 2019 and 30 April 2022 were included in the study. OUTCOME MEASURES: In the present study, cost was defined as total direct medical expenses, and effectiveness was defined as the prevention of major adverse cardiac events (MACEs). Incremental cost-effectiveness ratios (ICERs) were used to measure the cost-effectiveness of PCI in patients with ACS 1 year after surgery. RESULTS: The study included 31 760 patients. According to real-world and PS-matched data, the implementation of coronary stent policies in Shanghai reduced the total medical cost of patients with ACS 1 year after PCI by 24.39% (p<0.0001) and 22.26% (p<0.0001), respectively. The ICERs were ¥-1131.72 and ¥-842.00 thousand per MACE avoided, respectively. The ICERs were robust to parameter uncertainty, and there was a substantial chance for policy implementation to improve the cost-effectiveness of PCI among patients with ACS in the short term. CONCLUSIONS: The implementation of coronary stent policies has improved the cost-effectiveness of PCI for patients with ACS in the short term. The long-term impact of coronary stent policies on the cost-effectiveness of PCI in patients with ACS or other coronary heart diseases should be assessed in the future.
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Síndrome Coronariana Aguda , Análise Custo-Benefício , Intervenção Coronária Percutânea , Pontuação de Propensão , Stents , Humanos , Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/cirurgia , China , Intervenção Coronária Percutânea/economia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Stents/economia , Idoso , Política de Saúde/economiaRESUMO
Multidrug-resistant tuberculosis (MDR-TB) is an essential cause of tuberculosis treatment failure and death of tuberculosis patients. The rapid and reliable profiling of Mycobacterium tuberculosis (MTB) drug resistance in the early stage is a critical research area for public health. Then, most traditional approaches for detecting MTB are time-consuming and costly, leading to the inappropriate therapeutic schedule resting on the ambiguous information of MTB drug resistance, increasing patient economic burden, morbidity, and mortality. Therefore, novel diagnosis methods are frequently required to meet the emerging challenges of MTB drug resistance distinguish. Considering the difficulty in treating MDR-TB, it is urgently required for the development of rapid and accurate methods in the identification of drug resistance profiles of MTB in clinical diagnosis. This review discussed recent advances in MTB drug resistance detection, focusing on developing emerging approaches and their applications in tangled clinical situations. In particular, a brief overview of antibiotic resistance to MTB was present, referred to as intrinsic bacterial resistance, consisting of cell wall barriers and efflux pumping action and acquired resistance caused by genetic mutations. Then, different drug susceptibility test (DST) methods were described, including phenotype DST, genotype DST and novel DST methods. The phenotype DST includes nitrate reductase assay, RocheTM solid ratio method, and liquid culture method and genotype DST includes fluorescent PCR, GeneXpert, PCR reverse dot hybridization, ddPCR, next-generation sequencing and gene chips. Then, novel DST methods were described, including metabolism testing, cell-free DNA probe, CRISPR assay, and spectral analysis technique. The limitations, challenges, and perspectives of different techniques for drug resistance are also discussed. These methods significantly improve the detection sensitivity and accuracy of multidrug-resistant tuberculosis (MRT) and can effectively curb the incidence of drug-resistant tuberculosis and accelerate the process of tuberculosis eradication.
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OBJECTIVE: This study aimed to analyze the effect of coronary stent policies implemented in Shanghai on the risk of percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) inpatients based on real-world data. METHODS: Two retrospective cohorts of inpatients with a first diagnosis of ACS who had undergone PCI for the first time in the previous year in Shanghai hospitals were examined (one for the postpolicy period and the other for the prepolicy period). χ2 tests were used to compare categorical variables between the two cohorts. Single- and multivariate Cox proportional hazards models were used to compare the risk of major adverse cardiovascular events (MACEs) between the two cohorts. RESULTS: A total of 31,760 ACS patients were included in this study. The proportion of ACS inpatients who had at least one bid-winning stent and 3 or more coronary stents implanted for first-time PCI in the postpolicy cohort was higher than that in the prepolicy cohort (86.52% vs. 55.67% and 6.27% vs. 4.39%, respectively; all p values < 0.0001). The single- and multivariate Cox proportional hazards models revealed that the unadjusted and adjusted hazard ratios for MACEs at 1 year after PCI for the postpolicy cohort relative to the prepolicy cohort were 0.869 (P<0.0001) and 0.814 (P = 0.0007), respectively. CONCLUSIONS: The implementation of coronary stent policies changed coronary stent utilization but had no significant adverse effects on the risk of PCI among ACS patients in Shanghai in the short term. However, the reasons for changes in the number of coronary stents implanted should be analyzed and addressed in the future.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/cirurgia , Síndrome Coronariana Aguda/diagnóstico , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , China/epidemiologia , Stents/efeitos adversos , Fatores de RiscoRESUMO
Organic semiconductor (OSC) gas sensors have garnered considerable attention due to their promising selectivity and inherent flexibility. Introducing a functional group or modification layer is an important route to modulate the doping/trapping state of the active layer and the gas absorption/desorption process. However, the majority of the functionalization lies in the surface/interface assembling process, which is difficult to control the functional group density. This in turn brings challenges for precise modulation of the charge transport and the doping/trapping density, which will affect the repeatability and reproducibility of sensing performance. Herein, we propose a facile bulk trapping strategy incorporating amino-terminated additive molecules via the vacuum deposition process, achieving ultrahigh sensitivity of â¼2000%/ppm at room temperature to NO2 gas and approaching â¼3000%/ppm at 50 °C. Additionally, the device exhibits commendable reproducibility, stability, and low concentration detection ability, reaching down to several ppb, indicating promising potential for future applications. Comprehensive analysis of electrical properties and density functional theory calculations reveals that these exceptional properties arise from the favorable electrical characteristics of the bulk trapping structure, the high mobility of C8-BTBT, and the elevated adsorption energy of NO2. This approach enables the construction of stable and reproducible sensitive sensors and helps to understand the sensing mechanism in OSC gas sensors.
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Background: Anaplastic Thyroid Carcinoma (ATC) is a rare and deadly malignant tumor in humans. It is prone to developing resistance to radiotherapy and chemotherapy. Molecular targeted therapy offers a novel way to treat ATC. The BRAF mutation is closely associated with many cancers, including thyroid carcinoma. Vemurafenib, a small-molecule inhibitor, is specifically designed to target the mutant serine/threonine kinase BRAF. The objective of this study is to elucidate the regulatory mechanisms underlying the effects of vemurafenib on human anaplastic thyroid carcinoma cell line FRO and to assess its potential therapeutic role. Methods: The effects of vemurafenib on the proliferation of FRO cells were assessed by the CCK-8 method and Colony-forming assay. Transwell chambers and scratch tests were employed to examine the impact of vemurafenib on the invasion and migration of FRO cells. Apoptosis and cycle distribution of FRO cells were analyzed by tunel assay and flow cytometry. The effects of vemurafenib on the expression of BRAF-activated non-protein coding RNA (BANCR), Bax, Bcl2, and E-cadherin were evaluated by qRT-PCR. Furthermore, the effects of vemurafenib on the expression of phosphoinositol-3-kinase (PI3K)/phosphoinositol-3-kinase (AKT) pathway-related proteins, BRAF, CyclinD1, Bcl-2, Bax, and E-cadherin proteins in FRO cells were investigated through the western-blot method. All experiments were conducted in three replicates. Results: Vemurafenib was observed to inhibit proliferation and induce apoptosis in a dose- and time-dependent manner (P < 0.05). The formation of FRO cell colonies, as well as migration and invasion, all showed a dose-dependent reduction (P < 0.05). Flow cytometric analysis indicated G0/G1 cell cycle arrest (P < 0.05). QRT-PCR revealed that vemurafenib could suppress the expression of BANCR and Bcl2 while increasing the expression of Bax and E-cadherin in a dose-dependent manner (P < 0.05). The protein expression levels of Bax and E-cadherin were up-regulated significantly, and the expression levels of BRAF, CyclinD1, Bcl-2, p-PI3K, p-AKT, and p-mTOR were markedly down-regulated with increasing concentrations of vemurafenib (P < 0.05). Conclusions: The proliferation and metastasis of FRO cells can be suppressed by vemurafenib through the silencing of BRAF and BANCR expression, inhibition of PI3K/AKT signaling pathway activation, induction of apoptosis, and cell cycle arrest.
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Buried interface modification can effectively improve the compatibility between interfaces. Given the distinct interface selections in perovskite solar cells (PSCs), the applicability of a singular modification material remains limited. Consequently, in response to this challenge, we devised a tailored molecular strategy based on the electronic effects of specific functional groups. Therefore, we prepared three distinct silane coupling agents, and due to the varying inductive effects of these functional groups, the electronic distribution and molecular dipole moments of the coupling agents are correspondingly altered. Among them, trimethoxy (3,3,3-trifluoropropyl)-silane (F3 -TMOS), which possesses electron-withdrawing groups, generates a molecular dipole moment directed toward the hole transport layer (HTL). This approach changes the work function of the HTL, optimizes the energy level alignment, reduces the open-circuit voltage loss, and facilitates carrier transport. Furthermore, through the buffering effect of the coupling agent, the interface strain and lattice distortion caused by annealing the perovskite are reduced, enhancing the stability of the tin-based perovskite. Encouragingly, tin PSCs treated with F3 -TMOS achieved a champion efficiency of 14.67 %. This strategy provides an expedient avenue for the design of buried interface modification materials, enabling precise molecular adjustments in accordance with distinct interfacial contexts to ameliorate mismatched energetics and enhance carrier dynamics.
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Obesity associated with diet and intestinal dysbiosis is a worldwide public health crisis, and exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) have prebiotic potential to ameliorate obesity. Therefore, the present study obtained LAB with the ability to produce high EPS, examined the structure of EPS, and explained its mechanism of alleviating obesity by in vivo and in vitro models. The results showed that Weissella cibaria PFY06 with a high EPS yield was isolated from strawberry juice, and pure polysaccharide (PFY06-EPS) was purified by Sephadex G-100. The structural characteristics of PFY06-EPS showed that the molecular weight was 8.08 × 106 Da and composed of α-(1,6)-D glucosyl residues. An in vitro simulated human colon fermentation test demonstrated that PFY06-EPS increased the abundance of Prevotella and Bacteroides. Cell tests confirmed that PFY06-EPS after fecal fermentation inhibited fat accumulation by promoting the secretion of endogenous gastrointestinal hormones and insulin and inhibiting the secretion of inflammatory factors. Notably, PFY06-EPS reduced weight gain, fat accumulation, inflammatory reactions and insulin resistance in a high-fat diet-induced obesity mouse model and improved glucolipid metabolism. PFY06-EPS intervention reversed obesity-induced microflora disorders, such as reducing the Firmicutes/Bacteroides ratio and increasing butyrate-producing bacteria (Roseburia and Oscillibacter), and reduced endotoxemia to maintain intestinal barrier integrity. Therefore, in vivo and in vitro models showed that PFY06-EPS had potential as a prebiotic that may play an anti-obesity role by improving the function of the gut microbiota.
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Dieta Hiperlipídica , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Fermentação , Obesidade/tratamento farmacológico , Bacteroides , Modelos Animais de DoençasRESUMO
Klebsiella pneumoniae is listed by the WHO as a priority pathogen of extreme importance that can cause serious consequences in clinical settings. Due to its increasing multidrug resistance all over the world, K. pneumoniae has the potential to cause extremely difficult-to-treat infections. Therefore, rapid and accurate identification of multidrug-resistant K. pneumoniae in clinical diagnosis is important for its prevention and infection control. However, the limitations of conventional and molecular methods significantly hindered the timely diagnosis of the pathogen. As a label-free, noninvasive, and low-cost method, surface-enhanced Raman scattering (SERS) spectroscopy has been extensively studied for its application potentials in the diagnosis of microbial pathogens. In this study, we isolated and cultured 121 K. pneumoniae strains from clinical samples with different drug resistance profiles, which included polymyxin-resistant K. pneumoniae (PRKP; n = 21), carbapenem-resistant K. pneumoniae, (CRKP; n = 50), and carbapenem-sensitive K. pneumoniae (CSKP; n = 50). For each strain, a total of 64 SERS spectra were generated for the enhancement of data reproducibility, which were then computationally analyzed via the convolutional neural network (CNN). According to the results, the deep learning model CNN plus attention mechanism could achieve a prediction accuracy as high as 99.46%, with robustness score of 5-fold cross-validation at 98.87%. Taken together, our results confirmed the accuracy and robustness of SERS spectroscopy in the prediction of drug resistance of K. pneumoniae strains with the assistance of deep learning algorithms, which successfully discriminated and predicted PRKP, CRKP, and CSKP strains. IMPORTANCE This study focuses on the simultaneous discrimination and prediction of Klebsiella pneumoniae strains with carbapenem-sensitive, carbapenem-resistant, and polymyxin-resistant phenotypes. The implementation of CNN plus an attention mechanism makes the highest prediction accuracy at 99.46%, which confirms the diagnostic potential of the combination of SERS spectroscopy with the deep learning algorithm for antibacterial susceptibility testing in clinical settings.
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Long noncoding RNAs (lncRNAs) play important regulatory roles in stem cell self-renewal, pluripotency maintenance, and differentiation. Till now, there is very limited knowledge about how lncRNAs regulate intestinal stem cells (ISCs), and lncRNAs mediating ISC regeneration in Drosophila have yet been characterized. Here, we identify a lncRNA, CR46040, that is essential for the injury-induced ISC regeneration in Drosophila. Loss of CR46040 greatly impairs ISC proliferation in response to tissue damage caused by dextran sulfate sodium (DSS) treatment. We demonstrate that CR46040 is a genuine lncRNA that has two isoforms transcribed from the same transcription start site and works in trans to regulate intestinal stem cells. Mechanistically, CR46040 knock-out flies failed to fully activate JNK, JAK/STAT, and HIPPO signaling pathways after tissue damage, which are required for ISC proliferation after intestinal injury. Moreover, CR46040 knock-out flies are highly susceptible to DSS treatment and enteropathogenic bacteria Erwinia carotovora ssp. carotovora 15 (Ecc15) infection. Our findings characterize, for the first time, a lncRNA that mediates damage-induced ISC proliferation in Drosophila and provide new insights into the functional links among the long noncoding RNAs, ISC proliferation, and tissue homeostasis.
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Proteínas de Drosophila , RNA Longo não Codificante , Animais , Proliferação de Células , Drosophila/genética , Proteínas de Drosophila/metabolismo , Intestinos , Regeneração/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Células-Tronco/metabolismoRESUMO
It has been reported that a highly varying proportion (1% â¼ 93%) of genes in various prokaryotes have antisense RNA (asRNA) transcription. However, the extent of the pervasiveness of asRNA transcription in the well-studied E. coli K12 strain has thus far been an issue of debate. Furthermore, very little is known about the expression patterns and functions of asRNAs under various conditions. To fill these gaps, we determined the transcriptomes and proteomes of E. coli K12 at multiple time points in five culture conditions using strand-specific RNA-seq, differential RNA-seq, and quantitative mass spectrometry methods. To reduce artifacts of possible transcriptional noise, we identified asRNA using stringent criteria with biological replicate verification and transcription start sites (TSSs) information included. We identified a total of 660 asRNAs, which were generally short and largely condition-dependently transcribed. We found that the proportions of the genes which had asRNA transcription highly depended on the culture conditions and time points. We classified the transcriptional activities of the genes in six transcriptional modes according to their relative levels of asRNA to mRNA. Many genes changed their transcriptional modes at different time points of the culture conditions, and such transitions can be described in a well-defined manner. Intriguingly, the protein levels and mRNA levels of genes in the sense-only/sense-dominant mode were moderately correlated, but the same was not true for genes in the balanced/antisense-dominant mode, in which asRNAs were at a comparable or higher level to mRNAs. These observations were further validated by western blot on candidate genes, where an increase in asRNA transcription diminished gene expression in one case and enhanced it in another. These results suggest that asRNAs may directly or indirectly regulate translation by forming duplexes with cognate mRNAs. Thus, asRNAs may play an important role in the bacterium's responses to environmental changes during growth and adaption to different environments. IMPORTANCE: The cis -antisense RNA (asRNA) is a type of understudied RNA molecules in prokaryotes, which is believed to be important in regulating gene expression. Our current understanding of asRNA is constrained by inconsistent reports about its identification and properties. These discrepancies are partially caused by a lack of sufficient samples, biological replicates, and culture conditions. This study aimed to overcome these disadvantages and identified 660 putative asRNAs using integrated information from strand-specific RNA-seq, differential RNA-seq, and mass spectrometry methods. In addition, we explored the relative expression between asRNAs and sense RNAs and investigated asRNA regulated transcriptional activity changes over different culture conditions and time points. Our work strongly suggests that asRNAs may play a crucial role in bacterium's responses to environmental changes during growth and adaption to different environments.
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At present, there are relatively few studies on the production of exopolysaccharide (EPS) by yeasts. Therefore, exploring the properties of EPS produced by yeast can not only enrich the source of EPS, but also play an important role in its future application in the food field. The aim of this study was to explore the biological activities of EPS (named SPZ) from Sporidiobolus pararoseus PFY-Z1, as well as the dynamic changes in physical and chemical properties that occur during simulated gastrointestinal digestion, and the effects of SPZ on microbial metabolites during fecal fermentation in vitro. The results revealed that SPZ had good water solubility index, water-holding capacity, emulsifying ability, coagulated skim milk, antioxidant properties, hypoglycemic activities, and bile acid-binding abilities. Furthermore, the content of reducing sugars increased from 1.20 ± 0.03 to 3.34 ± 0.11 mg/mL after gastrointestinal digestion, and had little effect on antioxidant activities. Moreover, SPZ could promote the production of short-chain fatty acids during fermentation for 48 h, in particular, propionic acid and n-butyric acid increased to 1.89 ± 0.08 and 0.82 ± 0.04 mmol/L, respectively. Besides this, SPZ could inhibit LPS production. In general, this study can help us to better understand the potential bioactivities, and the changes in bio-activities of compounds after digestion of SPZ.
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Antioxidantes , Aditivos Alimentares , Antioxidantes/farmacologia , Fermentação , Leveduras , Água , Glicolipídeos/farmacologiaRESUMO
The flavonoids in Panax notoginseng were qualitatively analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), and the content of three main flavonoids in P. notoginseng of different specifications and grades collected from different habitats was determined by HPLC-DAD. Flavonoids and anthocyanins were analyzed by UPLC-Q-TOF-MS/MS in the positive and negative ion modes, respectively. Twelve flavonoid glycosides and one anthocyanin glycoside in P. notoginseng were identified, but no flavonoid aglycones were detected. Among them, 12 compounds were identified in the underground part of P. notoginseng for the first time and eight compounds were first reported in this plant. Moreover, six and four compounds were identified in the Panax genus and the Araliaceae family for the first time, respectively. A method for simultaneous determination of three flavonoids in P. notoginseng was established by HPLC-DAD. The content of flavonoids in 721 P. notoginseng samples of 124 specifications and grades collected from 20 different habitats was simultaneously determined. Among three flavonoids determined, the content of quercetin-3-O-(2″-β-D-xylosyl)-β-D-galactoside was the highest with the average content in the tested samples of 161.0 μg·g~(-1). The content of compounds quercetin-3-O-hexosyl-hexoside and kaempferol-3-O-pentosyl-hexoside was relatively low, with the average content of 18.5 μg·g~(-1)(calculated as quercetin-3-O-sophoroside) and 49.4 μg·g~(-1)(calculated as kaempferol-3-O-sangbu diglycoside). There were significant differences in flavonoids content of samples from different production area. The content of flavonoids in spring P. notoginseng was significantly lower than that in winter P. notoginseng when the other influencing factors such as production areas, germplasm resources, and cultivation conditions were fixed. As for P. notoginseng of different specifications, the flavonoid content in the part connecting the taproot and the aboveground stem was significantly higher than that in other parts. The results of large-scale data showed that the flavonoid content gradually increased with the increase in the number of heads. There were significant differences between the flavonoid content in most specifications and grades, especially the 20-head P. notoginseng and countless head P. notoginseng, whose content was significantly lower and significantly higher than that of other specifications and grades, respectively. This study provides a scientific basis for the study of the effective components and quality control of P. notoginseng from the perspective of flavonoids.
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Flavonoides/análise , Antocianinas/análise , Quercetina , Cromatografia Líquida de Alta Pressão/métodos , Quempferóis , Espectrometria de Massas em Tandem/métodos , GlicosídeosRESUMO
OBJECTIVE@#To investigate the effect of Bushen Chushi decoction combined with platelet-rich plasma(PRP) to treat knee osteoarthritis(KOA) in early and middle stage and its regulation on TGF-β1 and Smad-1 expression in serum.@*METHODS@#Total of 45 patients with KOA in early and middle stage from May 2020 to April 2022 were treated and divided into control group and observation group. In control group, there were 30 patients including 12 males and 18 females, aged from 43 to 69 years old with an average of(57.3±6.5) years old and disease duration ranged from 1.5 to 5.0 years with an average of(3.8±1.7) years, and there were 8 cases in gradeⅠ, 13 cases in gradeⅡ, and 9 cases in grade Ⅲ according to Kellgren-Lawrence Grade, PRP 5 ml was injected into knee joint on the first day of No1, 3 week together for 2 times. In the observation group, there were 15 cases including 7 males and 8 females, aged from 45 to 70 years old with an average of (56.7±6.2) years old and disease duration ranged from 1.8 to 5.7 years with an average of (4.0±1.8) years, there were 4 cases in gradeⅠ, 9 cases in gradeⅡand 4 cases in grade Ⅲ according to the Kellgren-Lawrence Grade, PRP 5 ml were injected into knee joints that the time and frequency were the same as those in the control group, and at the same time Bushen Chushi decoction orally were taken 1 dose per day with a total of 28 doses. All patients were treated for four weeks. Visual analogue scale(VAS) and Lequesne MG score before and after treatment were used to evaluate improvement of knee pain and joint function. The TGF-β1 and Smad-1 levels in serum were measured before and after treatment in two groups. The incidence of complications in two groups was observed.@*RESULTS@#All patients were followed up for 26 to 30 days with an average of (28.0±0.6) days. There was no significant difference in VAS and knee Lequesne MG scores between two groups before treatment(P>0.05). The scores of VAS and knee Lequesne MG on the first day after treatment in both groups were lower than those before treatment(P<0.05). The VAS and knee Lequesne MG scores in observation group were lower than those in control group(P<0.05) on the first day after treatment. The TGF-β1 level in serum after treatment were higher significantly than that before treatment in two groups(P<0.05). After treatment, TGF-β1 level in serum in observation group were lower than those in control group with statistically significant differences(P<0.05). The Smad-1 levels in serum after treatment in observation group were higher significantly than that in control group(P<0.05). The levels of Smad-1 were not statistically significant between before and after treatment(P>0.05). There was no significant difference in postopertaive complications between two groups (P>0.05).@*CONCLUSION@#The efficacy of Bushen Chushi decoction combined with PRP in treatment of early and middle KOA is better than that of PRP injection alone. The combined treatment could reduce TGF-β1 level and increase Smad-1 level in serum, which may be a mechanism to inhibit inflammation and alleviate cartilage degeneration to some extent.
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Wheat bran-based food is rich in bioactive compounds, and steam explosion enhances the nutritional properties of wheat bran. This study examined the potential utilization of steam-exploded wheat bran (SWB) in cookie formulation. The influence of steam explosion on the chemical compounds in wheat bran and the effects of SWB on the physical properties, antioxidant capacity, and starch digestibility of cookies were investigated. The results showed that steam explosion facilitated the release of reducing sugar, flavonoids, phenolic substances, and amino acid nitrogen in wheat bran, thereby improving its nutritional properties. The reduction of sugar, total flavonoids, total phenolics, and amino acid nitrogen contents of wheat bran after steam explosion increased by 34.22, 183.02, 284.09, and 93.39%, respectively, compared with those of native wheat bran. Substitution of SWB for wheat flour mainly induced higher water, sodium carbonate, and sucrose solvent retention capacities, which were positively related to the spread ratio and hardness of cookies. The cookies with more SWB substitution (30-50%) expressed a higher spread ratio and harder texture than the others. The substitution of SWB caused changes in the antioxidant properties of cookies, which were related to the phenolic content. The cookies with SWB showed a higher DPPH radical scavenging activity (16.30-30.93%) than that of the control (14.74%). SWB might form a matrix barrier to hinder starch digestion, thus reducing the digestibility of cookies. The cookies enriched with 30-50% of the SWB exhibited greater physical properties and antioxidant capacity but lower starch digestibility than those of other cookies. The results will contribute to expanding the application range and improving the quality of bran-rich flour products.
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Tuberculosis (TB) is a chronic and fatal zoonotic infectious disease caused by Mycobacterium tuberculosis (M. tb) infection. The THP-1 cell line is a cell model for studying the function, mechanism and signaling pathways of macrophages; macrophages are the primary host cells of M. tb. Macrophages are important for the progression of tuberculosis, as they affect the release of various inflammatory cytokines, including IL-1ß, IL-6 and TNF-α. Vitamin C is a trace element for the human body. Its biological efficacy depends on its redox abilities and its role as a cofactor in several enzymatic reactions. However, whether vitamin C can protect THP-1 cells from M. tb infection has not yet been reported. The present study aimed to further investigate the effects of vitamin C on M. tb infection-induced THP-1 cell injury and its mechanism. In the present study, MTT assay, reverse transcription-quantitative PCR, EdU cell proliferation assay, western blotting, immunohistochemistry, flow cytometry and TUNEL staining assays were used to assess the cell viability, inflammation and apoptotic levels of THP-1 cells induced by M. tb following vitamin C treatment. The effect of vitamin C on M. tb infection was also assessed using Balb/c mice; pulmonary injury was assessed by H&E staining of the lung tissue. The results demonstrated that vitamin C markedly attenuated cellular damage caused by M. tb infection. The results demonstrated that vitamin C reduced the expression of M. tb-induced apoptosis-related proteins (Cleaved-caspase-9, Cleaved-caspase-3, Bcl-2, Cyt-c) and inflammatory factors (IL-1ß, IL-6, NLRP3, TNF-α, IL-8, NF-κB) in THP-1 cells and reduced apoptosis. Overall, these results suggested that vitamin C may reduce lung damage caused by M. tb infection.
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Tuberculosis is a serious zoonotic disease caused by Mycobacterium tuberculosis (M.tb) and the M.tb complex. Mycolic acid is an extracellular carbohydrate polymer produced, secreted, and accumulated outside the cells of various Mycobacterium tuberculosis strains. Mycolic acid produced by Mycobacterium plays an important role in infection. However, there have been few reports on drugs that inhibit mycolic acid-induced cytotoxicity. The purpose of this study was to investigate the role of the panned peptide in Mycobacterium-derived mycolic acid (M.tb-MA)-induced cell injury. The heptapeptide (APTX4870) was isolated from various phage libraries using phage display (Ph.D-7, Ph.D-12, and Ph.D-C7C). The efficacy of APTX4870 against mycolic acid was demonstrated by evaluating clinical samples and conducting in vitro and Vivo. APTX4870 inhibited apoptosis, increased autophagy to decrease inflammation, and reduced M.tb-MA-induced lung damage. These findings suggest that this heptapeptide, which selectively targets M.tb-MA, might be exploited as a potential novel M.tb therapeutic treatment.
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At present, the study on exopolysaccharid is mainly focused on lactic acid bacteria, and the research on exopolysaccharide produced by yeast, especially Sporidiobolus pararoseus, is relatively few. Therefore, the aim of this study was to explore the characterization and antioxidant activities of a novel neutral exopolysaccharide SPZ, which was isolated and purified from S. pararoseus PFY-Z1. The results showed that SPZ was mainly composed of mannose, followed by glucose, with a molecular weight was 24.98 kDa, had O-glycosidic bonds, no crystalline, and no triple helix structure. Based on fourier transform-infrared, high-performance liquid chromatography and nuclear magnetic resonance analyses, SPZ was identified to be a exopolysaccharide with some side chains, presence of α-, ß-pyranose ring and nine sugar residues. Furthermore, the morphology features of SPZ have performed a relatively rough and uneven surface, covered with small pores and fissures. Moreover, SPZ had higher antioxidant activities and the maximum scavenging abilities of â OH, NO2- and reducing power were 28.05 ± 0.73%, 92.76 ± 1.86% and 0.345 ± 0.024, respectively. Hence, SPZ could be used as a potential antioxidant application in the food and pharmaceutical industries.
Assuntos
Antioxidantes , Basidiomycota , Antioxidantes/farmacologia , Leveduras , Peso MolecularRESUMO
Over the past decades, conventional methods and molecular assays have been developed for the detection of tuberculosis (TB). However, these techniques suffer limitations in the identification of Mycobacterium tuberculosis (Mtb), such as long turnaround time and low detection sensitivity, etc., not even mentioning the difficulty in discriminating antibiotics-resistant Mtb strains that cause great challenges in TB treatment and prevention. Thus, techniques with easy implementation for rapid diagnosis of Mtb infection are in high demand for routine TB diagnosis. Due to the label-free, low-cost and non-invasive features, surface enhanced Raman spectroscopy (SERS) has been extensively investigated for its potential in bacterial pathogen identification. However, at current stage, few studies have recruited handheld Raman spectrometer to discriminate sputum samples with or without Mtb, separate pulmonary Mtb strains from extra-pulmonary Mtb strains, or profile Mtb strains with different antibiotic resistance characteristics. In this study, we recruited a set of supervised machine learning algorithms to dissect different SERS spectra generated via a handheld Raman spectrometer with a focus on deep learning algorithms, through which sputum samples with or without Mtb strains were successfully differentiated (5-fold cross-validation accuracy = 94.32%). Meanwhile, Mtb strains isolated from pulmonary and extra-pulmonary samples were effectively separated (5-fold cross-validation accuracy = 99.86%). Moreover, Mtb strains with different drug-resistant profiles were also competently distinguished (5-fold cross-validation accuracy = 99.59%). Taken together, we concluded that, with the assistance of deep learning algorithms, handheld Raman spectrometer has a high application potential for rapid point-of-care diagnosis of Mtb infections in future.