RESUMO
α-DCs (α-dicarbonyls) have been proven to be closely related to aging and the onset and development of many chronic diseases. The wide presence of this kind of components in various foods and beverages has been unambiguously determined, but their occurrence in various phytomedicines remains in obscurity. In this study, we established and evaluated an HPLC-UV method and used it to measure the contents of four α-DCs including 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), and diacetyl (DA) in 35 Chinese herbs after they have been derivatized with 4-nitro-1,2-phenylenediamine. The results uncover that 3-DG is the major component among the α-DCs, being detectable in all the selected herbs in concentrations ranging from 22.80 µg/g in the seeds of Alpinia katsumadai to 7032.75 µg/g in the fruit of Siraitia grosuenorii. The contents of the other three compounds are much lower than those of 3-DG, with GO being up to 22.65 µg/g, MGO being up to 55.50 µg/g, and DA to 18.75 µg/g, respectively. The data show as well the contents of the total four α-DCs in the herbs are generally in a comparable level to those in various foods, implying that herb medicines may have potential risks on human heath in view of the α-DCs.
Assuntos
Desoxiglucose , Medicamentos de Ervas Chinesas , Glioxal , Aldeído Pirúvico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Aldeído Pirúvico/análise , Cromatografia Líquida de Alta Pressão , Desoxiglucose/análogos & derivados , Desoxiglucose/análise , Glioxal/análise , Diacetil/análise , Estrutura Molecular , Frutas/química , Plantas Medicinais/química , Sementes/químicaRESUMO
This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2â¶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.
Assuntos
Reserva Ovariana , Feminino , Masculino , Gravidez , Animais , Camundongos , Ácido Araquidônico , Proteômica , Ovário , Metabolismo dos LipídeosRESUMO
The phosphorus harvest along nitrogen removal in the partial nitritation/anammox (PNA) reactor is promising for saving space and simplifying the management of mainstream wastewater treatment facilities. In this study, the phosphorus recovery from the low-temperature mainstream wastewater was explored through iron phosphate crystallization in a pilot-scale PNA reactor. With the COD-alleviated municipal wastewater as the influent, the ammonium concentration of about 50 mg/L and the phosphorus concentration ranged from 5.4 to 7.1 mg/L, under the temperature of 15 °C and the addition of external ferrous iron of 14 mg/L, the achieved nitrogen removal efficiency and the phosphorus removal efficiency were 37.6 % and 62.7 %, respectively. The good settleability of sludge indicated that the formed iron phosphate was well combined with the biomass. The quantitative analysis confirmed that the main iron phosphate in dry sludge was graftonite, and qualitative analysis confirmed that the equivalent of P2O5 content in the sludge was 5.8 %, which was suitable as fertilizer on agricultural land to realize the direct recycle of discharged phosphorus. In all, this study proposed a pioneering scheme to realize the nitrogen removal and phosphorus cycle in human society and given a meaningful reference for further research and application.
Assuntos
Compostos de Amônio , Águas Residuárias , Humanos , Esgotos/química , Temperatura , Fósforo , Oxidação Anaeróbia da Amônia , Cristalização , Reatores Biológicos , Oxirredução , Compostos de Amônio/química , Nitrogênio , Fosfatos , Ferro , DesnitrificaçãoRESUMO
To overcome the shortcomings of conventional ecological floating bed (CEFB) in purifying landscape water, this study constructed a functional ecological floating bed (FEFB) through the suspension of calcium peroxide (CP) and sponge iron (SI) jointly below the CEFB. The purification effect of water quality and influence of sediment were compared in control check, CEFB, and FEFB systems, which were loaded the same sediment and reclaimed water in a field experiment. Results showed that the FEFB suspended with CP and SI had evident purification effect on the quality of landscape water supplied with reclaimed water and can maintain stably the nutrient status of the water body at mesotrophic levels and low turbidity. The FEFB promoted the degradation of humus, thus eliminating the chroma risk in water body caused by the decay of plants from the CEFB. Moreover, the FEFB can control the sediment mass produced, reduce the total nitrogen (TN) mass of sediment, and decrease the transformable TN (TTN) content in the sediment. The FEFB enhanced the stability of phosphorus (P) in the sediment, where the relative content of Ca-P and stable P reached 42.18% and 64.27%, respectively. To sum up, the FEFB suspended with SI and CP can not only effectively control the eutrophication and sensory index of landscape water but also change the TTN content and P forms in sediment, making the sediment more stable. Thus, the FEFB provides an innovative approach to reduce endogenous nutrient release for landscape water along with recharging with reclaimed water.
Assuntos
Ferro , Poluentes Químicos da Água , Fósforo , Eutrofização , Nitrogênio/análise , Poluentes Químicos da Água/análise , Sedimentos GeológicosRESUMO
OBJECTIVE: This study was to explore the risk factors for postoperative bladder neck contracture (BNC) after transurethral operation of prostate in patients with small-volume prostatic obstruction. METHODS: Clinicopathologic data at our center from February 2016 to January 2020 were retrospectively collected and analyzed. Clinicopathological characteristics between patients with and without BNC were compared. Multivariate logistic regression was used to determine the risk factors for postoperative BNC. RESULTS: There were a total of 39 patients (8.53%) with postoperative BNC. Multivariate logistic regression analysis demonstrated that preoperative bladder neck diameter (BND), intravesical prostatic protrusion (IPP), surgical methods (transurethral resection of prostate (TURP)/anatomical endoscopic enucleation of the prostate (AEEP)), and postoperative urinary tract infection (UTI) were independent risk factors for postoperative BNC in patients with small-volume prostatic obstruction (P < 0.05). The incidence of postoperative BNC in patients undergoing AEEP was significantly decreased compared with those undergoing TURP. The optimal cut-off value of preoperative IPP was 6.10 mm while the optimal cut-off value of preoperative BND was 2.52 cm. CONCLUSIONS: Larger preoperative bladder neck and higher preoperative IPP lead to decreased incidence of postoperative BNC in patients with small-volume prostatic obstruction. Active management of postoperative UTI could effectively prevent the occurrence of postoperative BNC. Compared with TURP, complete AEEP would contribute to reduce BNC in patients with small-volume prostatic obstruction.
Assuntos
Contratura , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Obstrução do Colo da Bexiga Urinária , Masculino , Humanos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/epidemiologia , Obstrução do Colo da Bexiga Urinária/etiologia , Obstrução do Colo da Bexiga Urinária/cirurgia , Estudos Retrospectivos , Contratura/epidemiologia , Contratura/etiologia , Contratura/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
OBJECTIVE: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.
Assuntos
Disfunção Erétil , Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Humanos , Masculino , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Disfunção Erétil/cirurgia , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the effect of combined application of Semen vaccariae seeds auricular acupressure and 5α-reductase inhibitor (finasteride tablets) on postoperative quality of life of patients after transurethral plasmakinetic enucleation of the prostate (PKEP). METHODS: 120 patients with benign prostatic hyperplasia (BPH) who were scheduled to undergo PKEP at the Department of Urology, Jintan People's Hospital Affiliated to Jiangsu University from January 2020 to December 2022, were randomly divided into 4 groups after voluntarily signing informed consent. Three days before the operation, 30 patients were given oryzanol tablets 5 mg orally once a night (placebo group), 31 patients were given Semen vaccariae seeds auricular acupressure (auricular acupressure group), 29 patients were given finasteride 5 mg orally once a night (finasteride group), and another 30 patients were given auricular acupressure combined with finasteride 5 mg orally once a night (combination therapy group). The above treatment was continued for 6 weeks after PKEP. The general data of the perioperative period and the 6-week postoperative follow-up results of the 4 groups were compared to observe the indicators such as the symptom score of nocturia, the self-rating depression scale, and the quality of life (QoL) after treatment among the groups. RESULTS: All patients who underwent PKEP completed the 6-week postoperative follow-up and no statistical difference in the relevant data of the 4 groups was found before the operation. After 2 and 4 weeks of follow-up, the nocturia symptom scores of the auricular acupressure group and the combination therapy group were better than those of the placebo group and the finasteride group. The depression symptom scores and QoL results showed that the auricular acupressure group, finasteride group, and combination therapy group were superior to the placebo group (P<0.05). After 6 weeks of follow-up, QoL in the combination therapy group was 1.65±0.55, which was significantly different from that in the other three groups (P<0.05). CONCLUSION: Combined application of auricular acupressure and 5α-reductase inhibitor can significantly alleviate symptoms such as nocturia and depression and improve the quality of life in BPH patients after PKEP.
Assuntos
Acupressão , Noctúria , Hiperplasia Prostática , Masculino , Humanos , Finasterida/uso terapêutico , Próstata , Qualidade de Vida , OxirredutasesRESUMO
To explore the risk factors for in-stent restenosis (ISR) after stent implantation in patients with coronary heart disease (CHD) using logistic regression analysis. From February 2020 to February 2022, 350 patients with CHD after percutaneous coronary intervention (PCI) were divided into a stent stenosis group and a stent nonstenosis group based on coronary angiography results performed 2 years after PCI. Univariate and multivariate logistic regressions were used to analyze the factors related to ISR after coronary stent implantation in patients with CHD. This study was approved by the Ethics Committee of Shandong University of Traditional Chinese Medicine. Patient signed informed consent. Of the 350 patients with CHD, 138 (39.43%) had stent restenosis while 212 did not. Univariate analysis showed that a family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, discontinuation of aspirin, use of conventional dose statins, calcified lesions,â ≥â 3 implanted stents, stent lengthâ ≥â 30 mm, stent diameterâ <â 3 mm, and tandem stent increased the risk of restenosis. The incidence of restenosis was higher in the stent group than that in the nonstent group (Pâ <â .05). There were no significant differences in the blood lipid level, left ventricular ejection fraction, clopidogrel/ticagrelor or beta-blocker withdrawal, location of culprit vessels, and thrombotic lesions between the 2 groups (Pâ >â .05). Multivariate logistic regression analysis showed that family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, aspirin withdrawal, use of conventional doses of statins, calcified lesions,â ≥â 3 implanted stents, stent lengthâ ≥â 30 mm, stent diameterâ <â 3 mm, and tandem stenting were risk factors for ISR within 2 years after PCI. A family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, discontinuation of aspirin, use of conventional dose statins, calcified lesions,â ≥â 3 stent implantations, stent lengthâ ≥â 30 mm, stent diameterâ <â 3 mm, and tandem stenting are risk factors for ISR within 2 years after PCI in patients with CHD.
Assuntos
Doença da Artéria Coronariana , Reestenose Coronária , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/cirurgia , Constrição Patológica , Intervenção Coronária Percutânea/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Volume Sistólico , Reestenose Coronária/epidemiologia , Reestenose Coronária/etiologia , Função Ventricular Esquerda , Stents/efeitos adversos , Fatores de Risco , Aspirina/uso terapêuticoRESUMO
Objective: Coronary heart disease (CHD) is the leading cause of death from cardiovascular disease and has become an important public health problem worldwide. Guizhi Gancao Decoction (GGD) has been shown to be used in the treatment of CHD with good efficacy, but its specific therapeutic mechanism and active ingredients have not been fully clarified. This study aims to identify the active compounds and key targets of GGD in the treatment of CHD, explore the therapeutic mechanism of GGD, and provide candidate compounds for anti-CHD drug development. Methods: The main compounds of GGD were determined by UPLC-MS/MS analysis and screened by SwissADME. The corresponding targets of GGD compounds were obtained from SwissTargetPrediction, and the targets of CHD were obtained from the HERB and GeneCards databases. The STRING 11.5 database was used to analyze the PPI (Protein-Protein Interactions) network of potential therapeutic targets of GGD compounds. Cytoscape 3.7.2 was used to construct target-related networks and find core targets. The GEO database was used to validate the differential expression of core targets. The PANTHER Classification System was used to functionally classify potential therapeutic targets for GGD. The GO biological process analysis and KEGG pathway analysis of targets were completed by DAVID 6.8 database. AutoDockTools 1.5.6 and PyMol 2.5.2 were used to perform molecular docking of core targets with the active GGD compounds. Results: 7 active GGD compounds were obtained based on UPLC-MS/MS and pharmacological parameter evaluation, which corresponded to 131 CHD-related targets. Among them, EGFR, MAPK3, RELA, CCND1, ESR1, PTGS2, NR3C1, CYP3A4, MMP9, and PTPN11 were considered core targets. According to the targets related to CHD, glycyrrhetinic acid, liquiritigenin, and schisandrin are considered key active ingredients. GO biological process and KEGG analysis indicated that the potential targets of GGD in the treatment of CHD involve a variety of biological processes and therapeutic mechanisms. Molecular docking results showed that both the core targets and the corresponding compounds had the good binding ability. Conclusions: This study contributes to a more comprehensive understanding of the therapeutic mechanism and active ingredients of GGD for CHD and provides candidate compounds for drug development of CHD.
RESUMO
Objective: To explore the reasons of failure in a case of pulmonary tuberculosis (PTB) after 9 years systematic treatment. Methods: We extracted the patients' treatment history, drug susceptibility testing (DST), Computed tomography (CT) images, and sequenced the isolated strains by whole gene sequencing (WGS). Results: Although most results of the phenotypical DSTs were consistent with the genotype DST, the occurrence of gene resistance to amikacin (AMK), capreomycin (CAP), moxifloxacin (MFX) was earlier than the phenotypical DST. Based on the continuously reversed results of phenotypical DSTs, CT images in different stages and WGS, it can be confirmed that the patient was infected with two different strains of Mycobacterium tuberculosis (M.TB). Moreover, severe cavities may be another factor leading to treatment failure. Conclusion: Given the suggestive effect of genotype DST is earlier than the phenotypical DST, so genotype DST can play a better guiding role in patients with MDR-TB. Additionally, for patients who have not been cured for a long time, medication should be more cautious and the role of WGS in drug resistance surveillance should be fully utilized.
Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Amicacina/farmacologia , Amicacina/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Capreomicina/farmacologia , Capreomicina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Testes de Sensibilidade Microbiana , Moxifloxacina/farmacologia , Moxifloxacina/uso terapêutico , Mycobacterium tuberculosis/genética , Falha de Tratamento , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
At present, although the early treatment of sepsis is advocated, the treatment effect of sepsis is unsatisfactory, and the mortality rate remains high. Shenfu injection (SFI) has been used to treat sepsis with good clinical efficacy. Based on network pharmacology, this study adopted a new research strategy to identify the potential therapeutic targets and key active ingredients of SFI for sepsis from the perspective of the pathophysiology of sepsis. This analysis identified 28 active ingredients of SFI based on UHPLC-QQQ MS, including 18 ginsenosides and 10 aconite alkaloids. 59 targets were associated with the glycocalyx and sepsis pathways. Based on the number of targets related to the pathophysiological process of sepsis, we identified songorine, ginsenoside Rf, ginsenoside Re, and karacoline as the key active ingredients of SFI for the treatment of sepsis. According to the cluster analysis of MCODE and the validation on the GEO dataset, LGALS3, BCHE, AKT1, and IL2 were identified as the core targets. This study further explored the therapeutic mechanism and the key active ingredients of SFI in sepsis and provided candidate compounds for drug development.
RESUMO
BACKGROUND: Heart failure (HF) is the end stage of the development of heart disease, whose prognosis is poor. The previous research of our team indicated that the formulae containing Aconiti Lateralis Radix Praeparata and Lepidii Semen Descurainiae Semen (ALRP-LSDS) could inhibit myocardial hypertrophy, inhibit cardiomyocyte apoptosis, delay myocardial remodeling (REM), and improve the prognosis of patients with HF effectively. In order to explore the mechanism of ALRP-LSDS for the treatment of HF, a combined approach of network pharmacology and molecular docking was conducted. METHODS: Public database TCMSP was used to screen the active compounds of ALRP-LSDS. The targets of screened active compounds were obtained from the TCMSP database and predicted using the online analysis tool PharmMapper. The targets of HF were obtained from 6 databases including GeneCards, OMIM, DrugBank, TTD, PharmGKB, and DisGeNET. Protein-protein interaction and enrichment analysis were performed, respectively, by STRING and Metascape online tools after merging the targets of active compounds and HF. Cytoscape software was used to conduct networks. Finally, molecular docking was performed by Vina to verify the correlation between key targets and active compounds. RESULTS: Final results indicated that the active compounds including ß-sitosterol, isorhamnetin, quercetin, kaempferol, and (R)-norcoclaurine, the targets including AKT1, CASP3, and MAPK1 might be the main active compounds and key targets of ALRP-LSDS for the treatment of HF separately. The binding ability of AKT1 to the main active compounds was better compared with the other 2 key targets, which means it might be more critical. The pathways including AGE-RAGE signaling pathway in diabetic complications, Pathways in cancer, and Fluid shear stress and atherosclerosis might play important roles in the treatment of HF with ALRP-LSDS. In general, ALRP-LSDS could inhibit cardiomyocyte apoptosis, delay REM, and improve cardiac function through multicompound, multitarget, and multipathway, which contributes to the treatment of HF. CONCLUSIONS: Based on the combined approach of network pharmacology and molecular docking, this study screened out the main active compounds, key targets, and main pathways of ALRP-LSDS for the treatment of HF, and revealed its potential mechanisms, providing a theoretical basis for further research.
Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Aconitum/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , SementesRESUMO
Shixiao powder comes from the Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and consists of two herbs, Puhuang (PH) and Wulingzhi (WLZ). PH-WLZ is a commonly used drug pair for the treatment of coronary heart disease (CHD), and its clinical effect is remarkable. However, our understanding of the mechanism of treatment of CHD is still unclear. In this study, the method of network pharmacology was used to explore the mechanism of PH-WLZ in the treatment of CHD. A total of 56 active ingredients were identified from PH-WLZ, of which 93 targets of 41 active ingredients overlapped with those of CHD. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we obtained the main pathways associated with CHD and those associated with the mechanism of PH-WLZ in the treatment of CHD. By constructing the protein-protein interaction (PPI) network of common targets, 10 hub genes were identified. Based on the number of hub genes contained in the enrichment analysis, we obtained the key pathways of PH-WLZ in the treatment of CHD. The key KEGG pathway in the treatment of CHD by PH-WLZ is mainly enriched in atherosclerosis, inflammation, immunity, oxidative stress, and infection-related pathways. Moreover, the results of molecular docking showed that the active ingredients of PH-WLZ had a good affinity with the hub genes. The results indicate that the mechanism of PH-WLZ in the treatment of CHD may be related to regulation of lipid metabolism, regulation of immune and inflammatory responses, regulation of downstream genes of fluid shear stress, antiaging and oxidative stress, and virus inhibition.
RESUMO
Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.
Assuntos
Pneumopatias , Physalis , Animais , Flavonoides , Flavonóis , Inflamação , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Physalis/química , Physalis/metabolismoRESUMO
BACKGROUND: This study retrospectively analyzed and evaluated the potential correlations of serum calcium, serum phosphorus, and calcium-phosphorus product (Ca-P product) with the incidence of osteoporotic vertebral compression fractures (OVCFs), with the aim of exploring whether the Ca-P product can be used as a serological indicator to predict the risk of OVCFs. METHODS: This study randomly enrolled 400 elderly patients in our hospital with OVCFs and 400 patients with hip and knee arthroplasty due to femoral head necrosis or osteoarthritis from August 2013 to April 2021. Age, sex, past medical history, and admission biochemical indicators, including albumin, blood urea nitrogen, serum creatinine, serum calcium and serum phosphorus, were collected for statistical analysis. RESULTS: Albumin, serum calcium, serum phosphorus, Ca-P product, corrected serum calcium and corrected Ca-P product were lower in the OVCF group than in the non-OVCF group (P < 0.05). Multivariate logistic regression analysis showed that low values of serum calcium, serum phosphorus, Ca-P product, corrected blood calcium, and corrected Ca-P product can all be risk factors for OVCF. The ROC curve showed that the Ca-P product and corrected Ca-P product were effective in predicting the risk of OVCFs. The predictive value of the Ca-P product was the best; the cutoff point was 29.88, the sensitivity was 0.72 and the specificity was 0.62. The cutoff point of the corrected Ca-P product was 30.50, the sensitivity was 0.74, and the specificity was 0.62. CONCLUSION: The Ca-P product and corrected Ca-P product can be used as serological indicators to predict the risk of OVCFs in elderly individuals. Early clinical interventions targeting this risk factor can further reduce the risk of OVCFs. Also, timely and regular testing of the serum calcium and phosphorus level is recommended and encouraged for this group of people.
Assuntos
Cálcio/sangue , Fósforo/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas por Compressão/sangue , Humanos , Incidência , Masculino , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/sangue , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Resultado do TratamentoRESUMO
Calycosin (CAL) is the main active component present in Astragalus and reportedly possesses diverse pharmacological properties. However, the cardioprotective effect and underlying mechanism of CAL against doxorubicin- (DOX-) induced cardiotoxicity need to be comprehensively examined. Herein, we aimed to investigate whether the cardioprotective effects of CAL are related to its antipyroptotic effect. A cardiatoxicity model was established by stimulating H9c2 cells and C57BL/6J mice using DOX. In vitro, CAL increased H9c2 cell viability and decreased DOX-induced pyroptosis via NLRP3, caspase-1, and gasdermin D signaling pathways in a dose-dependent manner. In vivo, CAL-DOX cotreatment effectively suppressed DOX-induced cytotoxicity as well as inflammatory and cardiomyocyte pyroptosis via the same molecular mechanism. Next, we used nigericin (Nig) and NLRP3 forced overexpression to determine whether CAL imparts antipyroptotic effects by inhibiting the NLRP3 inflammasome in vitro. Furthermore, CAL suppressed DOX-induced mitochondrial oxidative stress injury in H9c2 cells by decreasing the generation of reactive oxygen species and increasing mitochondrial membrane potential and adenosine triphosphate. Likewise, CAL attenuated the DOX-induced increase in malondialdehyde content and decreased superoxide dismutase and glutathione peroxidase activities in H9c2 cells. In vivo, CAL afforded a protective effect against DOX-induced cardiac injury by improving myocardial function, inhibiting brain natriuretic peptide, and improving the changes of the histological morphology of DOX-treated mice. Collectively, our findings confirmed that CAL alleviates DOX-induced cardiotoxicity and pyroptosis by inhibiting NLRP3 inflammasome activation in vivo and in vitro.
Assuntos
Cardiotoxicidade/tratamento farmacológico , Doxorrubicina/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamassomos/efeitos dos fármacos , Isoflavonas/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Isoflavonas/farmacologia , Masculino , Camundongos , PiroptoseRESUMO
The formation of anammox-hydroxyapatite (HAP) coupled granules has been shown to be an approach to efficient nitrogen removal and phosphorus recovery in the anammox EGSB reactor. However, the granulation cycle mechanism of anammox-HAP coupled granules for sustainable regeneration and growth is still not well understood. In this study, the microstructure, chemical composition and microbial structure of a total of six different-sized granules, from 0.25 mm to 2.8 mm, was determined. An SEM-EDS analysis indicated that the small granules (<0.5 mm) were composed of poly-pellet clusters with anammox biofilms attached to the HAP cores, and the large granules (>0.5 mm) consisted of a three-layer structure: a surface anammox biofilm layer, a middle connection layer, and a HAP mineral inner core. The analysis of elemental composition and microbial structure suggested homogenous granular characteristics regardless of granule size. The dominant microorganisms were anammox bacteria of Candidatus Kuenenia stuttgartiensis and heterotrophic denitrifying bacteria. Based on these results, a granulation cycle mechanism for anammox-HAP coupled granules was proposed for the first time. The growth of the small granules with the simultaneous enlargement of anammox biofilms and HAP cores results in the formation of large granules. Large granules regenerate new small granules in a two-step procedure. The first step is the separation of embryo HAP crystals from the mother core via heterogeneous growth, and the second step is the separation of the biofilms due to biodegradation and shear stress.
Assuntos
Reatores Biológicos , Durapatita , Oxidação Anaeróbia da Amônia , Nitrogênio , FósforoRESUMO
In order to realize the active and synchronous control of nitrogen (N) and organic matter (OM) release from sediments, this study compared the spatiotemporal changes in the physical, chemical, and biological indicators in the water system under different CaO2 dosing modes. Results from 90-day incubation experiment showed that CaO2 formed a dense barrier layer near its dosing position, improved the anoxic condition of water system, increased the physical adsorption of pollutants by sediments, and reduced the nutrients in overlying water, interstitial water, and sediments. Comprehensive comparison, the improvement effect of shallow injection group (I1) was the most obvious. Meanwhile, the activities of ammonia oxidizing bacteria and nitrite oxidizing bacteria near dosing position and those of denitrifiers and anammox bacteria adjacent to dosing site were significantly increased in all test groups (p < 0.01), thereby realizing the biological removal of N and OM in sediments. In addition, DO and ORP were steadily higher than 5 mg L-1 and 100 mV in I1, where the NH4+-N concentration in overlying water was stable below 1 mg L-1, and the easily released N content in the upper (0-3 cm) and middle (4-6 cm) sediments decreased by 41.64% and 43.56%, respectively. Compared with the large pollutant flux in control (14.31 TN mg m-2 d-1 and 194.05 mg TCOD m-2 d-1), I1 completely inhibited the pollutant release and reduced the original nutrients in overlying water. In general, CaO2 efficiently and synchronously controlled the endogenous release of N and OM under the combined actions of physical interception, physical adsorption, chemical oxidation, and biological transformation. Therefore, this study may provide valuable reference and guidance for the active and synchronous removal of N and OM in sediments and inhibition of endogenous pollutant release under anoxic condition.
Assuntos
Nitrogênio , Poluentes Químicos da Água , Sedimentos Geológicos , Nitrogênio/análise , Peróxidos , Fósforo , Poluentes Químicos da Água/análiseRESUMO
Trichosanthes kirilowii Maxim. and Bulbus allii Macrostemi are the components of Gualou Xiebai decoction (GLXB), a commonly used herbal combination for the treatment of coronary heart disease (CHD) in traditional Chinese medicine. Although GLXB is associated with a good clinical effect, its active compounds and mechanism of action remain unclear, which limits its clinical application and the development of novel drugs. In this study, we explored key compounds, targets, and mechanisms of action for GLXB in the treatment of CHD using the network pharmacology approach. We identified 18 compounds and 21 action targets via database screening. Enrichment analysis indicated that the effects of GLXB in patients with CHD are primarily associated with the regulation of signalling pathways for tumour necrosis factor, nuclear factor-kappa B, hypoxia-inducible factor-1, arachidonic acid metabolism, and insulin resistance. GLXB thus exerts anti-inflammatory, antihypoxic, and antiagglutinating effects; regulates lipid metabolism; and combats insulin resistance in CHD via these pathways, respectively. After reverse targeting, we observed that the main active compounds of GLXB in the treatment of CHD were quercetin, naringenin, ß-sitosterol, ethyl linolenate, ethyl linoleate, and prostaglandin B1. To explore the potential of these compounds in the treatment of CHD, we verified the affinity of the compounds and targets via molecular docking analysis. Our study provides a bridge for the transformation of natural herbs and molecular compounds into novel drug therapies for CHD.
RESUMO
Radix Astragali and Semen Lepidii (HQ-TLZ) is a commonly used herbal medicine combination for treatment of heart failure, which has a good clinical effect. However, its active components and mechanism of action are not clear, which limits its clinical application and development. In this study, we explored the mechanism of action of HQ-TLZ in the treatment of heart failure based on network pharmacology. We obtained 11 active ingredients and 109 targets from the TCMSP database and SwissTargetPrediction database. Next, we constructed the action network and carried out enrichment analysis. The results showed that HQ-TLZ treatment of heart failure is primarily achieved by regulating the insulin resistance, erbB signaling pathway, PI3K-Akt signaling pathway, and VEGF signaling pathway. After inverse targeting, molecular docking, and literature search, we determined that the equivalent molecular groups of HQ-TLZ in the treatment of heart failure were quercetin and kaempferol. Based on network pharmacology, we reveal the mechanism of action of HQ-TLZ in the treatment of heart failure to a certain extent. At the same time, we determined the composition of the equivalent molecular group. This provides a bridge for the consistency evaluation of natural herbs and molecular compounds, which is beneficial to the development of novel drugs and further research.