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1.
Environ Int ; 134: 105293, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31731001

RESUMO

Early-life exposure to toxicants could affect health outcomes in adulthood. We determined the effects of early-life exposure to the organophosphorus flame-retardant tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in adult zebrafish. Embryos were exposed to TDCIPP from early embryogenesis (2 h post-fertilization) to 10 days post-fertilization (dpf), and larvae were transferred to clean water until adulthood (150 dpf). TDCIPP showed accumulation in larvae, but returned to control levels after 7 days of depuration. In adult zebrafish exposed to TDCIPP in early life, vulnerability to anxiety-like behavior was observed in females but not males, suggesting gender-dependent neurotoxicity. Decreased dopamine (DA) concentration and down-regulation of dopaminergic signaling related genes were observed in the brains of adult females. Upregulation of DNA methylation transferases (dnmt1, dnmt3a, and dnmt3b) genes were observed in larvae and brains of adult females. Further, the promoter regions of the selected key genes (bdnf, drd4b, zc4h2 and th) showed increased DNA methylation status, accompanied by down-regulation of gene transcription in larvae and brains of adult females. Our results indicate that early-life exposure to TDCIPP could cause delayed neurotoxicity in adult zebrafish.

2.
Cancer Immunol Res ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771985

RESUMO

CMTM6, a regulator of PD-L1 expression, also modulates tumor immunity. Little is known about the function of CMTM6 and its mechanism of action in head and neck squamous cell carcinoma (HNSCC). In this study, we found by immunohistochemistry (IHC) analysis that CMTM6 overexpression predicted a poor prognosis for HNSCC patients. We discovered that CMTM6 expression was correlated with increased activity through the Wnt/ß-catenin signaling pathway, which is essential for tumorigenesis, maintenance of the cancer stem cells (CSCs), and the epithelial-to-mesenchymal transition (EMT) characteristic of multiple cancers. We used short hairpin RNA (shRNA) to eliminate expression of CMTM6, which led, in HNSCC cells, to reduced expression of nuclear ß-catenin as well as inhibition of stem cell-like properties, TGF-ß-induced EMT and cell proliferation. Consistent with these results, we identified a significant positive correlation between expression of CMTM6 and EMT- and CSC-related genes in The Cancer Genome Atlas (TCGA). We found positive correlations for both RNA and protein between expression of CMTM6 and immune checkpoint components. CMTM6 silencing-induced PD-L1 downregulation delayed SCC7 tumor growth and increased CD8+ and CD4+ T-cell infiltration. The proportions of PD-1+, TIM-3+, VISTA+, LAG-3+, and B7-H3+ exhausted T cells were decreased significantly in the CMTM6-knockdown group. CMTM6 thus regulates stemness, EMT, and T-cell dysfunction and may be a promising therapeutic target in the treatment of HNSCC.

3.
Chemosphere ; 243: 125370, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31759216

RESUMO

In industrial wastewaters, rapid shifts of salinity leading to transient shocks caused damages on biological treatments. Aerobic granular sludge is a promising technology that showed its greater resistance to adverse conditions. However, the impact of short-term saline shocks on the performance of aerobic granular sludge process was not studied sufficiently. This study investigated salt-tolerance ability of aerobic granular sludge from aspects of chemical oxygen demand (COD) removal efficiency and sludge concentration under different saline shocks that shock concentration ranged from 0 to 60 gNaCl/L and shock duration was set at 6 h. The results showed that no obvious change of sludge concentration after all saline shocks. Moreover, COD removal efficiencies could revert to 90.7% and 87.5% that was near to the previous level (90.9%) in short-term recovery after 20 g/L and 40 g/L saline shocks. However, stable COD removal efficiency (73.8%) could not recover to the previous level (90.9%) after 60 g/L saline shock. These results suggest aerobic granular sludge has an excellent ability to withstand up to 40 g/L saline shock. The corresponding salt-tolerance reasons could be explained from three aspects. After 40 g/L saline shock, the specific oxygen uptake rate of aerobic granular sludge could recover to ensure biological activity. Aerobic granular sludge with the integrity coefficients of 87.6% maintained compact structure. In addition, aerobic granular sludge with relative small DNA leakage of 177.2% has advantages to diminish damage on cell structure. These results provide further insight into the application of aerobic granular sludge for saline-shock wastewater treatments.

4.
Biomed Res Int ; 2019: 4506876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737663

RESUMO

Inflammation plays a central role in knee osteoarthritis (OA) pathogenesis (C. R. Scanzello, 2017). The synovial membrane inflammation is associated with disease progression and represents a primary source of agony in knee OA (L. A. Stoppiello et al., 2014). Many inflammatory mediators may have biomarker utility. To identify synovium related to knee OA pain biomarkers, we used canonical correlation analysis to analyze the miRNA-mRNA dual expression profiling data and extracted the miRNAs and mRNAs. After identifying miRNAs and mRNAs, we built an interaction network by integrating miRWalk2.0. Then, we extended the network by increasing miRNA-mRNA pairs and identified five miRNAs and four genes (TGFBR2, DST, TBXAS1, and FHLI) through the Spearman rank correlation test. For miRNAs involved in the network, we further performed the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses, whereafter only those mRNAs overlapped with the Online Mendelian Inheritance in Man (OMIM) genetic database were analyzed. Receiver operating characteristic (ROC) curve and support vector machine (SVM) classification were taken into the analysis. The results demonstrated that all the recognized miRNAs and their gene targets in the network might be potential biomarkers for synovial-associated pain in knee OA. This study predicts the underlying risk biomarkers of synovium pain in knee OA.

5.
Nat Plants ; 5(11): 1104, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31712751
6.
Trials ; 20(1): 619, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675982

RESUMO

BACKGROUND: Postoperative pulmonary complications (PPCs) are the most common perioperative complications following surgical site infection (SSI). They prolong the hospital stay and increase health care costs. A lung-protective ventilation strategy is considered better practice in abdominal surgery to prevent PPCs. However, the role of the inspiratory oxygen fraction (FiO2) in the strategy remains disputed. Previous trials have focused on reducing SSI by increasing the inhaled oxygen concentration but higher FiO2 (80%) was found to be associated with a greater incidence of atelectasis and mortality in recent research. The trial aims at evaluating the effect of different FiO2 added to the lung-protective ventilation strategy on the incidence of PPCs during general anesthesia for abdominal surgery. METHODS AND DESIGN: PROtective Ventilation with a low versus high Inspiratory Oxygen fraction trial (PROVIO) is a single-center, prospective, randomized controlled trial planning to recruit 252 patients undergoing abdominal surgery lasting for at least 2 h. The patients will be randomly assigned to (1) a low-FiO2 (30% FiO2) group and (2) a high-FiO2 (80% FiO2) group in the lung-protective ventilation strategy. The primary outcome of the study is the occurrence of PPCs within the postoperative 7 days. Secondary outcomes include the severity grade of PPCs, the occurrence of postoperative extrapulmonary complications and all-cause mortality within the postoperative 7 and 30 days. DISCUSSION: The PROVIO trial assesses the effect of low versus high FiO2 added to a lung-protective ventilation strategy on PPCs for abdominal surgery patients and the results should provide practical approaches to intraoperative oxygen management. TRIAL REGISTRATION: www.ChiCTR.org.cn , identifier: ChiCTR18 00014901 . Registered on 13 February 2018.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31702532

RESUMO

One aerobic, Gram-stain-negative, rod-shaped bacterium, designated strain RB1R5T, was isolated from Renlongba glacier in Tibet Autonomous Region, China. Growth was observed at 4-25 °C and pH 7.0-8.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain RB1R5T belongs to the genus Flavobacterium, and its closest relatives are Flavobacterium luteum IMCC26026T and Flavobacterium psychroterrae CCM 8827T with 97.75 and 97.42% gene sequence similarities, respectively. The average nucleotide identity and DNA-DNA hybridization values between strain RB1R5T and its closest relative Flavobacterium luteum IMCC26026T were 78.02 and 21.8 %, respectively. The major cellular fatty acids were anteiso-C15 : 0 and summed feature 3 (comprising C16:1ω7c/C16:1ω6c). The sole menaquinone was MK-6. The major phospholipid was phosphatidylethanolamine. On the basis of phenotypic, phylogenetic and chemotaxonomic characterizations, strain RB1R5T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium psychrotolerans sp. nov. is proposed. The type strain is RB1R5T (=CGMCC 1.23024T=NBRC 113060T).

8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 660-665, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762234

RESUMO

OBJECTIVE: To investigate the ability of osteogenic differentiation and the expression of histone demethylases KDM6B in bone marrow mesenchymal stem cells (BMSCs) in diabetic environment. METHODS: Diabetic model rats was successfully established, and BMSCs from diabetic model rats and normal rats were isolated and cultured for further study. When cultured cells, we added high concentration of glucose and advanced glycosylation products (AGE) in the medium to imitating the diabetic environment. BMSCs were divided into 6 groups: diabetes group (derived from diabets SD rats), normal group (derived from normal SD rats), high glucose group (30 mmol/L D-glucose), normal glucose group (5.5 mmol/L D-glucose), AGE group (AGE 300 µg/mL) and BSA group (BSA 300 µg/mL). BMSCs in diabetes group were derived from diabetes SD rats, while others were derived from normal SD rats. After 7 d of osteogenic induction, the cells were examined the ability of osteogenic differentiation by alkaline phosphatase (ALP) staining, the transcription levels of Runt-related transcription factor 2 (Runx2) and KDM6B were determined by RT-PCR, and the expression levels of H3K27Me3 protein were examined by Western bolt. RESULTS: Compared with the control groups, the numbers of ALP stained cells and the mRNA levels of Runx2 and KDM6B in diabetes group, high glucose group and AGE group were all decreased (P < 0.05), while H3K27Me3 protein expression levels were all increased (P < 0.05). CONCLUSION: The ability of osteogenic differentiation of BMSCs in diabetic environment was weakened, and the expression of Runx2 mRNA was inhibited, which may be related to the increased expression of H3K27Me3 after the inhibition of KDM6B expression.

9.
J Exp Bot ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677347

RESUMO

Neighbor detection and allelochemical response are important mediators in plant-plant interactions. Despite increasing knowledge of plant allelochemicals in response to the presence of competitors involved in the neighbor-derived signaling chemicals, less is known about which signaling chemicals are responsible for the neighbor-induced allelochemical response. Here, we experimentally demonstrated (-)-loliolide, a carotenoid metabolite, as a signaling chemical in barnyardgrass-rice allelopathic interactions. The production of rice allelochemicals momilactone B and tricin was increased in the presence of five biotypes of barnyardgrass. (-)-Loliolide was found in all biotypes of barnyardgrass and their root exudates and rhizosphere soils. There were significant positive relationships between rice allelechemicals and (-)-loliolide concentrations across biotypes of barnyardgrass. Furthermore, (-)-loliolide elicited the production of momilactone B and tricin. Comparative transcriptome analysis showed regulation of (-)-loliolide on diterpenoid and flavonoid biosynthesis pathway. The expression of key genes involved in the biosynthesis of momilactone B (CPS4, KSL4 and MAS) and tricin (CYP75B3 and CYP75B4) was up-regulated by (-)-loliolide. These findings suggest that (-)-loliolide as a signaling chemical participates in barnyardgrass-rice allelopathic interactions. Through the signaling chemical, allelopathic rice plants can detect competing barnyardgrass and respond by increasing allelochemical levels to provide an advantage for their own growth.

10.
Cancer Med ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692291

RESUMO

The response to icotinib in advanced non-small cell lung cancers (NSCLC) with EGFR uncommon mutation (EGFRum) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFRum NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFRum in a multi-center study in China. Circulating tumor DNA (ctDNA) was detected and analyzed using next-generation sequencing (NGS) after progression from icotinib. The efficacy, safety and the potential resistance mechanism of icotinib were explored. After a median follow-up of 6.2 months, 69 patients (70.41%) developed disease progression, the objective rate (ORR) and disease control rate (DCR) were 13.27% and 29.59% respectively, and the median progression-free survival (PFS) was 5.5 months (95% CI: 1.2-13.0 months). Both complex-pattern with EGFR classical mutations (EGFRcm) and single-pattern have better PFS than complex-pattern without EGFRcm (median PFS was 7.2 (95% CI: 4.65-9.75), 5.2 (95% CI: 3.24-7.16) and 3.2 (95% CI: 2.97-3.44) months, respectively, P < .05); patients harboring S768I mutation had the worst PFS than others (2.0 months, P < .05). Diarrhea was the most frequent side effect (42.9%). Forty-eight (69.6%) patients developed drug resistance after 3.0 months and 81.2% of them acquired T790M mutation. Better response was observed in complex-pattern with the EGFRcm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib-resistant EGFRum NSCLC patients.

11.
Adv Mater ; : e1905711, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31693256

RESUMO

The commercial ceramic nanoparticle coated microporous polyolefin separators used in lithium batteries are still vulnerable under external impact, which may cause short circuits and consequently severe safety threats, because the protective ceramic nanoparticle coating layers on the separators are intrinsically brittle. Here, a nacre-inspired coating on the separator to improve the impact tolerance of lithium batteries is reported. Instead of a random structured ceramic nanoparticle layer, ion-conductive porous multilayers consisting of highly oriented aragonite platelets are coated on the separator. The nacre-inspired coating can sustain external impact by turning the violent localized stress into lower and more uniform stress due to the platelet sliding. A lithium-metal pouch cell using the aragonite platelet coated separator exhibits good cycling stability under external shock, which is in sharp contrast to the fast short circuit of a lithium-metal pouch cell using a commercial ceramic nanoparticle coated separator.

12.
Nat Plants ; 5(10): 1028, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31595061
13.
Artigo em Inglês | MEDLINE | ID: mdl-31585755

RESUMO

OBJECTIVES: Predicting perioperative morbidity and mortality in cardiac surgery for adult congenital heart disease is challenging because it encompasses a wide spectrum of disease. There is a paucity of published outcome data, and there are no perioperative risk score calculators for this population group. We set out to identify robust determinants of morbidity and mortality in this patient population under going cardiac surgery. METHODS: We collected data on 20 socioeconomic and pathophysiologic variables in 784 consecutive adults with congenital heart disease who underwent cardiac surgery between 2004 and 2015 at a single center. Using logistic regression, we sought to identify which of these factors were associated with the primary composite adverse outcome of in-hospital mortality, prolonged ventilation exceeding 7 days, and severe acute renal failure requiring dialysis. Secondary outcome analysis identified variables that were significant predictors for 1-year mortality. RESULTS: Composite adverse outcome occurred in 54 of 784 patients (6.9%). Significant predictors of the composite adverse outcome by multivariate regression include Mayo End-Stage Liver Disease modified score, cognitive impairment, number of chest wall incisions from previous cardiac surgery, body mass index, and cardiac anatomic category. Two survivors of the composite adverse outcome died within a few weeks postdischarge. Only 657 of 784 patients had 1-year follow-up data; 40 of 657 patients died at 1 year. One-year mortality was predicted by anticoagulation, Mayo End-Stage Liver Disease modified score, and anatomic category. CONCLUSIONS: Recognition and quantification of noncardiac comorbidities preoperatively predict the risk of adverse events and mortality in addition to cardiac anatomic factors.

14.
J Hazard Mater ; 384: 121365, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593863

RESUMO

Selenium (Se) is an essential nutrient for human beings at trace concentrations, but also a hazardous contaminant at high concentrations. As an important geological adsorbent, the transformation of 2-line ferrihydrite (Fh) strongly influences the geochemical behavior of selenium. However, little is known about the effect of the recrystallization of Fh on the fate of adsorbed Se(IV) in the reducing environments. We investigated the redistribution and transformation of Se(IV) during the recrystallization of Se(IV)-adsorbed Fh accelerated by Fe(II) under anaerobic conditions. Synchrotron based X-ray absorption near edge structure (XANES) spectroscopy was utilized to characterize oxidation state of Se. Results revealed that the adsorbed Se(IV) inhibited the Fe(II)-catalyzed recrystallization of ferrihydrite to goethite. Transmission electron microscopy (TEM) images showed that pH and the presence of Se(IV) had significant impacts on the morphology of the produced goethite. Approximately 30-75% adsorbed Se(IV) transformed to phosphate-unextractable form, indicating that the adsorbed Se transformed to more stable phase during the recrystallization of Fh. The XANES results indicated that a small fraction of Se(IV) was reduced to elemental Se. Our study demonstrated that the stability of adsorbed Se(IV) on ferrihydrite could be enhanced during Fe(II)-catalytic transformation of Fh under anoxic environments.

15.
Blood Press Monit ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31658108

RESUMO

OBJECTIVE: The aim of this study was to evaluate the accuracy of the automated oscillometric upper arm blood pressure monitor HL868ED for clinical use and self-measurement according to the International Protocol of the European Society of Hypertension revision 2010. METHOD: Systolic and diastolic blood pressure were measured sequentially in 43 adult Chinese (21 women, mean age 51.7 years) using a mercury sphygmomanometer (two observers) and the HL868ED device (one supervisor). A total of 99 pairs of comparisons were obtained from 43 participants for judgements in two parts with three grading phases. RESULTS: The HL868ED device achieved the targets in part 1 of the validation study. The number of absolute differences between device and observers within 5, 10 and 15 mmHg was 68/99, 91/99 and 97/99, respectively, for systolic blood pressure and 85/99, 95/99 and 99/99, respectively, for diastolic blood pressure. The device also fulfilled the criteria in part 2 of the validation study. Twenty-four and 30 participants for systolic and diastolic blood pressure, respectively, had at least two of the three device-observer differences within 5 mmHg (required ≥24). Three participants for systolic and one participant for diastolic blood pressure had all the three device-observer comparisons greater than 5 mmHg. CONCLUSION: The Health & Life blood pressure monitor HL868ED has passed the requirements of the International Protocol revision 2010 and hence can be recommended for blood pressure measurements in adults.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31606425

RESUMO

OBJECTIVE: This study aimed to explore the relationship between the expression of the coxsackie-adenovirus receptor (CAR) in oral squamous cell carcinoma (OSCC) and the clinicopathologic parameters associated with the disease. The diagnostic and prognostic potential of CAR in OSCC was also investigated. STUDY DESIGN: Immunohistochemistry was performed on human tissue microarrays, containing 42 oral mucosa, 69 dysplasia, and 176 OSCC tissue sections, to reveal the expression pattern of CAR. Statistical analysis was used to determine the correlation between CAR expression and the patient survival rate as a measure of the prognostic value of CAR. RESULTS: CAR was overexpressed in human OSCC tissues (P = .002), and higher expression of CAR was associated with a lower survival rate, which was not statistically significant (P = .123). In addition, patients with OSCC in the human papillomavirus (HPV)-positive group showed significantly higher CAR expression compared with the HPV- negative group (P = .0491). CONCLUSIONS: This study indicated that CAR expression was upregulated in human OSCC and that patients with OSCC with higher expression of CAR had a lower survival rate. Moreover, CAR expression may be associated with HPV infection.

17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(4): 414-417, 2019 Sep 26.
Artigo em Chinês | MEDLINE | ID: mdl-31612678

RESUMO

OBJECTIVE: To explore the spatial-temporal distribution of malaria in Jiangxi Province from 1950 to 2017, so as to provide scientific evidence for developing the malaria elimination strategy. METHODS: The epidemic situation of malaria, demographic data, historical species of malaria parasites and transmission vectors were collected from each county of Jiangxi Province from 1950 to 2017 to create a geographic information system database of malaria in Jiangxi Province. The software ArcGIS 10.3 was used to analyze the incidence of malaria and display the spatial-temporal distribution of malaria in Jiangxi Province, so as to explore the spatial-temporal patterns of malaria in the province. RESULTS: From 1950 to 2017, the prevalence of malaria was classified into 3 stages in Jiangxi Province, including the peak period (from 1950 to 1975), the continuous decline period (from 1976 to 1997), and the low-level fluctuation period (from 1998 to 2017). During the period from 1950 through 2017, the incidence of malaria declined, the epidemic area of malaria shrank, and the intensity of malaria transmission gradually reduced to no local infections in Jiangxi Province. The spatial distribution of epidemic areas of malaria shifted from southern mountainous areas to northern plain areas, and finally aggregated, retained and disappeared in plain areas. The species of malaria parasites shifted from a co-endemic area for Plasmodium vivax, P. falciparum and P. malariae to a single endemic area for P. vivax, and finally a co-endemic area for imported P. vivax, P. falciparum, P. malariae and P. ovale. The transmission vectors shifted from multiple vectors of Anopheles sinensis, An. minimus, An. anthropophagus and others to a single vector of An. sinensis. CONCLUSIONS: There are no local malaria cases for successive 6 years since 2012, and the transmission of malaria has been interrupted in Jiangxi Province, in which the criteria for malaria elimination have been achieved. However, the risk of malaria transmission secondary to imported malaria will emerge in Jiangxi Province for a long period of time.


Assuntos
Anopheles , Malária , Animais , China/epidemiologia , Erradicação de Doenças , Malária/epidemiologia , Malária/parasitologia , Malária/transmissão , Mosquitos Vetores/parasitologia , Plasmodium/fisiologia , Prevalência , Fatores de Risco
18.
Sci Rep ; 9(1): 15500, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664106

RESUMO

The gene optrA is the first gene that confers resistance to the oxazolidinone tedizolid, a last resort antimicrobial agent in human medicine. In this study we investigated the presence of optrA and the multi-resistance genes poxtA and cfr in enterococci and staphylococci from (i) pet animals known to be fed raw meat and vegetables and (ii) the respective food items. We examined 341 bacterial isolates from cats and dogs, 195 bacterial isolates from supermarket food items and only one E. faecium collected from industrial food in Beijing during 2016. Thirty-five (6.5%) of the 537 isolates, including 31/376 (8.2%) enterococci and 4/161 (2.5%) staphylococci, were positive for optrA, while all isolates were negative for poxtA and cfr. S1-nuclease pulsed-field gel electrophoresis (PFGE) and Southern blotting confirmed that optrA was located in the chromosomal DNA of 19 isolates and on a plasmid in the remaining 16 isolates. Whole genome sequencing revealed several different genetic environments of optrA in plasmid- or chromosome-borne optrA genes. PFGE, multilocus sequence typing (MLST) and/or SNP analysis demonstrated that the optrA-carrying Staphylococcus and Enterococcus isolates were genetically heterogeneous. However, in single cases, groups of related isolates were identified which might suggest a transfer of closely related optrA-positive E. faecalis isolates between food items and dogs.

19.
Sci Rep ; 9(1): 15442, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659222

RESUMO

The conventional method for effective or toxic chemical substance identification of multicomponent herbal medicine is based on single component separation, which is time-consuming, labor intensive, inefficient, and neglects the interaction and integrity among the components; therefore, it is necessary to find an alternative routine to evaluate the components more efficiently and scientifically. In this study, sodium aescinate injection (SAI), obtained from different manufacturers and prepared as "components knockout" samples, was chosen as the case study. The chemical fingerprints of SAI were obtained by high-performance liquid chromatography to provide the chemical information. The effectiveness and irritation of each sample were evaluated using anti-inflammatory and irritation tests, and then "Gray correlation" analysis (GCA) was applied to rank the effectiveness and irritability of each component to provide a preliminary judgment for product optimization. The prediction model of the proportions of the expected components was constructed using the artificial neural network. The results of the GCA showed that the irritation sorting of each SAI component was in the order of B > A > G > J > I > H > D > F > E > C and the effectiveness sorting of SAI components was in the order of D > C > B > A > F > E > H > I > G > J; the predictive proportion of SAI was optimized by the BP neural network as A: B: C: D: E: F = 0.7526: 0.5005: 5.4565: 1.4149: 0.8113: 1.0642. This study provided a scientific, accurate, reliable, and efficient approach for the proportion optimization of multicomponent drugs, which has a good prospect of popularization and application in product upgrading and development of herbal medicine.

20.
Int J Biol Sci ; 15(11): 2408-2418, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595158

RESUMO

Meiotic maturation of oocyte is an important process for successful fertilization, in which cytoskeletal integrality takes a significant role. The p-21 activated kinases (PAKs) belong to serine/threonine kinases that affect wide range of processes that are crucial for cell motility, survival, cell cycle, and proliferation. In this study, we used a highly selective inhibitor of PAK4, PF-3758309, to investigate the functions of PAK4 during meiotic maturation of mouse oocytes. We found that PAK4 inhibition resulted in meiotic arrest by inducing abnormal microfilament and microtubule dynamics. PAK4 inhibition impaired the microtubule stability and led to the defective kinetochore-microtubule (K-M) attachment which inevitably resulted in aneuploidy. Also, PAK4 inhibition induced abnormal acentriolar centrosome assembly during meiotic maturation. In conclusion, all these combined results suggest that PAK4 is necessary for the oocyte meiosis maturation as a regulator of cytoskeleton.

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