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1.
Huan Jing Ke Xue ; 43(1): 540-549, 2022 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-34989539

RESUMO

To study changes in phosphatase activity, we examined the diversity of phoC and phoD gene microbial communities in the rhizosphere and non-rhizosphere soil of plants under the treatment of chemical fertilizer and organic fertilizer combined with biochar. These results can provide a certain theoretical guidance for the conversion of insoluble phosphorus in the soil phosphorus pool to the inorganic phosphate ion that can be absorbed by plant roots and also provide a certain experimental basis for the improvement of the availability of phosphorus in the soil and the agricultural utilization of biochar. In this study, corn stalks and rice husk stalks were used as test materials, and the pot experimental method was adopted using the following treatments:set control (CK), traditional fertilization (F), chemical fertilizer+20 t·hm-2 rice husk biochar (FP), chemical fertilizer+10 t·hm-2rice husk biochar+10 t·hm-2 corn biochar (FPM), organic fertilizer+20 t·hm-2 rice husk biochar (PP), and fresh organic fertilizer+20 t·hm-2 rice husk biochar (NPP). We determined the rhizosphere and non-rhizosphere soil acid phosphatase (ACP) activity and alkaline phosphatase (ALP) activity and used T-RFLP technology to analyze the diversity of phoC and phoD genes in order to clarify the impact of biochar on the micro-ecosystem formed by the plants, soil, and microorganisms. The results showed that:① the ALP and ACP activities of each treatment in the non-rhizosphere soil were lower than that of CK. In the rhizosphere soil, the ALP activity was significantly increased after the combined application of chemical fertilizer and organic fertilizer with biochar, and the ACP activity in the rhizosphere soil was higher than that in the non-rhizosphere soil. ② The combined application of biochar with chemical fertilizers and organic fertilizers significantly increased the diversity of phoC and phoD genes communities in rhizosphere and non-rhizosphere soils (P<0.05); the diversity and richness of microbial communities in rhizosphere soil were higher than that in non-rhizosphere soils. ③ ACP activity was negatively correlated with phoC gene microbial community, and most ALP activity was positively correlated with phoD microbial community.


Assuntos
Fertilizantes , Microbiota , Carvão Vegetal , Fertilizantes/análise , Monoéster Fosfórico Hidrolases , Rizosfera , Solo , Microbiologia do Solo
2.
J Biol Chem ; : 101563, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998823

RESUMO

The cytidine deaminase APOBEC3B is an endogenous inducer of somatic mutations and causes chromosomal instability by converting cytosine to uracil in single-stranded DNA. Therefore, identification of factors and mechanisms that mediate APOBEC3B expression will be helpful for developing therapeutic approaches to decrease DNA mutagenesis. Arsenic is one well-known mutagen and carcinogen, but the mechanisms by which it induces mutations have not been fully elucidated. Herein we show that APOBEC3B is upregulated and required for arsenic-induced DNA damage and mutagenesis. We found that arsenic treatment causes a decrease of N6-methyladenosine (m6A) modification near the stop codon of APOBEC3B, consequently increasing the stability of APOBEC3B mRNA. We further reveal that the demethylase FTO is responsible for arsenic-reduced m6A modification of APOBEC3B, leading to increased APOBEC3B expression and DNA mutation rates in a manner dependent on the m6A reader YTHDF2. Our in vivo data also confirm that APOBEC3B is a downstream target of FTO in arsenic-exposed lung tissues. In addition, FTO protein is highly expressed and positively correlates with the protein levels of APOBEC3B in tumor samples from human non-small cell lung cancer (NSCLC) patients. These findings indicate a previously unrecognized role of APOBEC3B in arsenic-triggered somatic mutation, and might open new avenues to reduce DNA mutagenesis by targeting the FTO/m6A axis.

3.
Int J Cardiol Heart Vasc ; 38: 100938, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34977329

RESUMO

Purpose: This study evaluated the diagnostic values of the extent of lung injury manifested in non-contrast enhanced CT (NCCT) images, the inflammatory and immunological biomarkers C-reactive protein (CRP) and lymphocyte for detecting acute cardiac injury (ACI) in patients with COVID-19. The correlations between the NCCT-derived parameters and arterial blood oxygen level were also investigated. Methods: NCCT lung images and blood tests were obtained in 143 patients with COVID-19 in approximately two weeks after symptom onset, and arterial blood gas measurement was also acquired in 113 (79%) patients. The diagnostic values of normal, moderately and severely abnormal lung parenchyma volume relative to the whole lungs (RVNP, RVMAP, RVSAP, respectively) measured from NCCT images for detecting the heart injury confirmed with high-sensitivity troponin I assay was determined. Results: RVNP, RVMAP and RVSAP exhibited similar accuracy for detecting ACI in COVID-19 patients. RVNP was significantly lower while both RVMAP and RVSAP were significantly higher in the patients with ACI. All of the NCCT-derived parameters exhibited poor linear and non-linear correlations with PaO2 and SaO2. The patients with ACI had a significantly higher CRP level but a lower lymphocyte level compared to the patients without ACI. Combining one of these two biomarkers with any of the three NCCT-derived parameter further improved the accuracy for predicting ACI in patients with COVID-19. Conclusion: The NCCT-delineated normal and abnormal lung parenchmyma tissues were statistically significant predictors of ACI in patients with COVID-19, but both exhibited poor correlations with the arterial blood oxygen level. The incremental diagnostic values of lymphocyte and CRP suggested viral infection and inflammation were closely related to the heart injury during the acute stage of COVID-19.

4.
Chemosphere ; 287(Pt 3): 132312, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34563785

RESUMO

Microplastics (MPs) and endocrine disrupting chemicals are ubiquitous pollutants in marine environments, but their combined ecological risk is unclear. This study exposed male marine medaka (Oryzias melastigma) to 10 ng/L 17α-ethynylestradiol (EE2) alone or EE2 plus 2, 20, and 200 µg/L polystyrene MPs for 28 days to investigate the impacts of MPs on the reproductive disruption of EE2. The results showed that 10 ng/L EE2 alone did not affect biometric parameters, while co-exposure to EE2 and 20, 200 µg/L MPs suppressed the growth and decreased gonadosomatic and hepatosomatic indices. Compared to EE2 alone, EE2 plus MPs exposure significantly increased plasma 17ß-estradiol (E2) levels in a dose-dependent manner, and co-exposure to EE2 and 20, 200 µg/L MPs significantly increased the ratios of E2/testosterone (T). Moreover, EE2 plus MPs exposure elevated the transcription levels of estrogen biomarker genes vitellogenin and choriogenin, and estrogen receptor (ERα and ERß). Morphological analysis also showed that co-exposure to EE2 and MPs induced more severe damage to the testes and livers, indicating that MPs increased the toxicity of EE2. The actual EE2 concentrations in the solution increased with the exposure concentrations of MPs, suggesting that MPs changed the fate and behavior of EE2 in the seawater. These findings demonstrate that MPs could increase the estrogenic effects of EE2 on marine fish, suggesting that the combined health risk of MPs and endocrine disrupting chemicals on marine organisms should be paid great attention.


Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Estrogênios/toxicidade , Etinilestradiol/toxicidade , Masculino , Microplásticos , Plásticos/toxicidade , Poliestirenos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
5.
Bioengineered ; 13(1): 190-205, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34964699

RESUMO

The phosphoprotein phosphatase catalytic subunit (PPPCs) family has been shown to play an important role in the development and progression of various malignancies, but its expression patterns and biological functions in breast cancer (BC) remain unclear. Therefore, we aimed to investigate the clinical significance and biological functions of the PPPCs family to understand its possible significance in the diagnosis, prognosis and treatment of breast cancer. We comprehensively investigated the expression levels, diagnostic accuracy, prognostic outcomes, biological functions and effects on immune cell infiltration of the PPPCs family in breast cancer using online databases. Except for PPP1CB, PPP1CC, PPP5C and PPEF1, the mRNA expression levels of the PPPCs family in breast cancer tissues were significantly different from those in paracancerous tissues. The differentially expressed genes (DEGs) were associated with the clinicopathological parameters and prognosis of breast cancer. The DEGs were mainly associated with the WNT signaling pathway, antigen presentation and DNA repair. In addition, the DEGs significantly affected the infiltration of immune cells in breast cancer tissues. Among the PPPCs family, PPP1CA and PPP4C played a prominent role in the progression of breast cancer, and inhibition of PPP1CA and PPP4C expression by siRNA can significantly inhibit breast cancer cells proliferation and migration. In conclusion, the PPPCs family, especially PPP1CA and PPP4C, could be used as new biomarkers to improve diagnostic accuracy, predict prognosis and novel targets for the treatment of breast cancer.

6.
Chemosphere ; 286(Pt 3): 131839, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34403901

RESUMO

Although (PS)2, the primary degradation product of emerging antifouling biocides metal pyrithiones (MePTs), can disrupt the reproductive behavior of fish at an environmentally relevant ng/L level, the underlying mechanism is still largely unknown. This study exposed sexually mature male guppy (Poecilia reticulata) to 20, 200, and 2000 ng/L (PS)2 to explore the compromised effect of (PS)2 on reproductive behavior through a realistic competing scenario. The results showed that (PS)2 suppressed male guppies' sexual interest to stimulus females, reduced their competitive behavior frequencies toward rival males, and decreased their mating time and frequency. (PS)2 exposure did not affect male guppies' secondary sexual characteristics or induce estrogenic activity. Whole-brain transcriptome sequencing identified 1070 differentially expressed genes (DEGs) with 872 up-regulated genes, which were functionally enriched into Gene Ontology terms pertaining to extracellular matrix (ECM) and extracellular region. KEGG enrichment for the DEGs uncovered that the activations of ECM-receptor interaction and focal adhesion pathways could be the underlying molecular mechanism implicated in the (PS)2 induced reproductive behavior impairment. This work would deliver a substantial contribution to the understanding of the ecological safety of MePTs biocides.


Assuntos
Desinfetantes , Poecilia , Animais , Feminino , Masculino , Poecilia/genética , Piridinas , Reprodução , Comportamento Sexual Animal
7.
Chemosphere ; 287(Pt 2): 132031, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34492408

RESUMO

Herein, bifunctional two-dimensional copper-aluminum modified filter paper composite (2D-Cu/Al-C) was successfully prepared by simple calcination and showed ultrahigh adsorption performance and degradation potential. The adsorption removal of TC on 2D-Cu/Al-C all exceeded 92.2% under solution conditions of 10-200 mg/L TC, 100 mg/L 2D-Cu/Al-C, pH 8 and 298 K. The pseudo-second-order kinetic and Langmuir models better fitted the kinetic and isotherm data via spontaneous and exothermic process, and the maximum capacity of the 2D-Cu/Al-C was 2391.78 mg/g. Additionally, 2D-Cu/Al-C showed desired specific adsorption for TC (TC: 98.7%, norfloxacin: 5.8%, sulfamethoxazole: 2.1%, and ciprofloxacin: 1.8%) and it could effectively adsorbed TC even in the binary system (various coexisting ions or natural organic matter). After TC adsorbed on adsorbent was mineralized into CO2 and H2O by adding peroxydisulfate to generate high electrode potential radical in another limited systems, the 2D-Cu/Al-C still had ∼89.12% on TC removal (initial concentration of 50 mg/L) after five experimental cycles. Zeta potential, FT-IR and XPS results indicated that the multi-adsorption mechanism, including electrostatic interactions, complexation, and H-bonds, played a vital role in the fast and efficient adsorption process. Thus, the way of combining adsorption and regeneration via degradation are green, non-polluting strategy which are expected to be applied for water purification in future environmental remediation.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Alumínio , Cobre , Concentração de Íons de Hidrogênio , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier , Tetraciclina
8.
Front Physiol ; 12: 750872, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887772

RESUMO

Background: Several studies have demonstrated that using a higher dose of statin can easily induce liver injury and myopathy. Low-density lipoprotein cholesterol (LDL-C) is a well-established modifiable risk factor for cardiovascular disease; however, the large majority of Chinese patients cannot meet the target level of LDL-C recommended by the Chinese expert consensus. Evolocumab has been demonstrated to reduce LDL-C by approximately 60% in many studies. Nevertheless, whether combined evolocumab and moderate-intensity statin is as effective in lowering LDL-C and decreasing incidence of MACE in Chinese patients presenting with the acute phase of acute coronary syndrome (ACS) remains unknown. Therefore, the "Evolocumab added to Moderate-Intensity Statin therapy on LDL-C lowering and cardiovascular adverse events in patients with Acute Coronary Syndrome" (EMSIACS) is conducted. Methods: The EMSIACS is a prospective, randomized, open-label, parallel-group, multicenter study involving analyzing the feasibility and efficacy of evolocumab added to moderate-intensity statin therapy on lowering LDL-C levels in adult Chinese patients hospitalized for acute phase ACS. The sample size calculation is based on the primary outcome, and 500 patients will be planned to recruit. Patients are randomized in evolocumab arm (evolocumab 140mg every 2weeks plus rosuvastatin 10mg/day or atorvastatin 20mg/day) and statin-only arm (rosuvastatin 10mg/day or atorvastatin 20mg/day). The primary outcome is the percentage change in LDL-C in weeks 4 and week 12 after treatment. The secondary outcome is the occurrence of MACE after 12weeks and 1year of treatment. Discussion: If the EMSIACS trial endpoints prove statistically significant, the evolocumab added to moderate-intensity statin therapy will have the potential to effectively lower subjects' LDL-C levels, especially for the Chinese patients with acute phase ACS. However, if the risk of MACE is not significantly different between the two groups, we may extend follow-up time for secondary outcome when the clinical trial is over. Clinical trial registration: The study is registered to ClinicalTrials.gov (NCT04100434), which retrospectively registered on November 24, 2020.

9.
Front Hum Neurosci ; 15: 777762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867247

RESUMO

Strabismus occurs in about 2% of children and may result in amblyopia or lazy eyes and loss of depth perception. However, whether/how long-term strabismus shapes the brain structure and functions in children with concomitant strabismus (CS) is still unclear. In this study, a total of 26 patients with CS and 28 age-, sex-, and education-matched healthy controls (HCs) underwent structural and resting-state functional magnetic resonance imaging examination. The cortical thickness and amplitude of low-frequency fluctuation (ALFF) were calculated to assess the structural and functional plasticity in children with CS. Compared with HCs group, patients with CS showed increased cortical thickness in the precentral gyrus and angular gyrus while decreased cortical thickness in the left intraparietal sulcus, parieto-occipital sulcus, superior and middle temporal gyrus, right ventral premotor cortex, anterior insula, orbitofrontal cortex, and paracentral lobule. Meanwhile, CS patients exhibited increased ALFF in the prefrontal cortex and superior temporal gyrus, and decreased ALFF in the caudate and hippocampus. These results show that children with CS have abnormal structure and function in brain regions subserving eye movement, controls, and high-order cognitive functions. Our findings revealed the structural and functional abnormalities induced by CS and may provide new insight into the underlying neural mechanisms for CS.

10.
Am J Cancer Res ; 11(11): 5402-5414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34873468

RESUMO

m6A methylation has been demonstrated to be one of the most important epigenetic regulation mechanisms in cell differentiation and cancer development especially m6A derived diagnostic and prognostic biomarkers have been identified in the past several years. However, systemic investigation to the interaction between germline single-nucleotide polymorphisms (SNPs) and m6A has not been conducted yet. In this study, we collected previous identified significant thyroid cancer associated SNPs from UKB cohort (358 cases and 407,399 controls) and ICR cohort (3,001 patients and 287,550 controls) and thyroid eQTL (sample size = 574 from GTEx project) and m6A-SNP (N = 1,678,126) were applied to prioritize the candidate SNPs. Finally, five candidate genes (PLEKHA8, SMUG1, CDC123, RMI2, ACSM5) were identified to be thyroid cancer associated m6A-related genetic susceptibility. Loss and gain function studies of m6A writer proteins confirm that ACSM5 is regulated by m6A methylation of mRNA. Moreover, ACSM5 is downregulated in thyroid cancer and inversely correlated with PTC malignancy and patient survival. Together, our study highlight mRNA-seq and m6A-seq double analysis provided a novel approach to identify cancer biomarkers and understanding the heterogeneity of human cancers.

11.
Endocr Relat Cancer ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34874277

RESUMO

Increasing body of recent studies determining the expression of tumor-specific major histocompatibility complex (MHC) class II protein support its potential role in several malignancies but little is known in human medullary thyroid cancer (MTC). Here we report the expression of MHC-II and its clinicopathologic and prognostic relevance in MTC patients. Immunohistochemistry staining revealed a significant reduction in tumor cell specific MHC-II expression in a higher AJCC stage and its poor prognostic correlation with human MTC development. Further statistical analysis identified the low MHC-II expression as a significant and independent risk factor for MTC recurrence and patient survival. Moreover, in vitro studies showed that the MHC-II expression was remarkably increased by RET inhibitors, which were prescribed to treat advanced MTC. Similarly, inhibitors blocking the MAPK/ERK and AKT/mTOR pathways also augmented MHC-II expression, suggesting their implications in RET-MHC-II signaling axis. Importantly, in vitro assays manifested enhanced peripheral blood leukocytes-mediated cytotoxicity in MTC cells treated with RET inhibitors, which were partially alleviated by HLA knock-down. Together, our study demonstrates that low MHC-II expression levels may serve as a prognostic biomarker for aggressive diseases in MTC patients and indicates that RET activation may promote MTC immune escape through down-regulating MHC-II expression.

12.
Nat Commun ; 12(1): 7213, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893641

RESUMO

Nonalcoholic steatohepatitis (NASH) is a key step in the progression of nonalcoholic fatty liver (NAFL) to cirrhosis. However, the molecular mechanisms of the NAFL-to-NASH transition are largely unknown. Here, we identify methyltransferase like 3 (METTL3) as a key negative regulator of NASH pathogenesis. Hepatocyte-specific deletion of Mettl3 drives NAFL-to-NASH progression by increasing CD36-mediated hepatic free fatty acid uptake and CCL2-induced inflammation, which is due to increased chromatin accessibility in the promoter region of Cd36 and Ccl2. Antibody blockade of CD36 and CCL2 ameliorates NASH progression in hepatic Mettl3 knockout mice. Hepatic overexpression of Mettl3 protects against NASH progression by inhibiting the expression of CD36 and CCL2. Mechanistically, METTL3 directly binds to the promoters of the Cd36 and Ccl2 genes and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27 in  their promoters, thus suppressing Cd36 and Ccl2 transcription. Furthermore, METTL3 is translocated from the nucleus to the cytosol in NASH, which is associated with CDK9-mediated phosphorylation of METTL3. Our data reveal a mechanism by which METTL3 negatively regulates hepatic Cd36 and Ccl2 gene transcription via a histone modification pathway for protection against NASH progression.

13.
Front Neurosci ; 15: 797378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899177

RESUMO

Electroencephalogram (EEG) is often used in clinical epilepsy treatment to monitor electrical signal changes in the brain of patients with epilepsy. With the development of signal processing and artificial intelligence technology, artificial intelligence classification method plays an important role in the automatic recognition of epilepsy EEG signals. However, traditional classifiers are easily affected by impurities and noise in epileptic EEG signals. To solve this problem, this paper develops a noise robustness low-rank learning (NRLRL) algorithm for EEG signal classification. NRLRL establishes a low-rank subspace to connect the original data space and label space. Making full use of supervision information, it considers the local information preservation of samples to ensure the low-rank representation of within-class compactness and between-classes dispersion. The asymmetric least squares support vector machine (aLS-SVM) is embedded into the objective function of NRLRL. The aLS-SVM finds the maximum quantile distance between the two classes of samples based on the pinball loss function, which further improves the noise robustness of the model. Several classification experiments with different noise intensity are designed on the Bonn data set, and the experiment results verify the effectiveness of the NRLRL algorithm.

14.
World J Clin Cases ; 9(33): 10151-10160, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34904085

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) was introduced in China in 2007. Over time, the scope of ERAS has expanded from abdominal surgery to orthopedics, urology and other fields. Continuous development and research has contributed to progress of ERAS in China. In 2019, to promote the application of ERAS in bone tumor surgery, we formed the "Consensus of Experts on Perioperative Management of Accelerated Rehabilitation in Major Surgery of Bone Tumors in China". AIM: To evaluate the effect of enhanced recovery after bone tumor surgery in perioperative management in China. METHODS: One hundred and seven patients who underwent bone tumor surgery at the Second Affiliated Hospital of Xi'an Jiaotong University between May 2019 and April 2021 were randomized into a study group (53 cases) and a control group (54 cases). The study group adopted the ERAS protocol and the control group adopted conventional care. Main outcome measures included postoperative length of stay (LOS), postoperative complications, mortality, and 30-d readmission rates. Secondary outcomes included postoperative visual analog scale (VAS) score of pain, number of blood transfusions, drainage volume in 24 h after operation, patient satisfaction 30 d after discharge, VAS score at 30 d after discharge, and daily standing walking time. RESULTS: There were no significant differences in the baseline data, clinical features and surgical site between the two groups. The LOS in the study group with the ERAS protocol was 7.72 ± 3.34 d compared with 10.28 ± 4.27 d in the control group who followed conventional care. The incidence of postoperative nausea and vomiting (PONV) in the study group was 19% and 37% in the control group. The VAS scores of pain on postoperative day 1 (POD1) and POD3 in the study group were 4.79 ± 2.34 and 2.79 ± 1.53 compared with 5.28 ± 3.27 and 3.98 ± 2.27 in the control group. The drainage volume in 24 h after the operation was 124.36 ± 23.43 mL in the study group and 167.43 ± 30.87 mL in the control group. The number of blood transfusions in the study group was also lower. The patient satisfaction rate was higher in the study group than in the control group. CONCLUSION: The ERAS protocol in the perioperative period of bone tumor surgery can decrease LOS, PONV, and postoperative pain, blood transfusion and 24-h drainage, improve patient satisfaction and accelerate recovery.

15.
Eur J Surg Oncol ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34952748

RESUMO

BACKGROUND: A survival benefit from esophagectomy was observed in elderly patients. But it's unclear how to identify specific patients who can benefit. Thus, we aimed to establish a predictive model to identify optimal candidates for esophagectomy. METHODS: Patients (age ≥75 years) with esophageal cancer in Surveillance, Epidemiology and End Results (SEER) database were used to establish the predictive model. Propensity-score matching (PSM) was applied to eliminate the imbalance between esophagectomy group and non-esophagectomy group. We hypothesized that elderly patients could benefit from esophagectomy with longer cancer specific survival (CSS) time than those who did not receive esophagectomy. Patients received surgery were divided into beneficial group and non-beneficial group according to the median CSS time of non-esophagectomy group. Prognostic factors affecting patients' long-term survival were identified. Among esophagectomy group, a logistic regression model based on these factors was established to build a nomogram. RESULTS: A total of 7,025 eligible patients were extracted from the SEER database, with 831 patients received esophagectomy. Surgery was independently associated with better long-term survival (median CSS time in the matched population: 35 vs. 8 months, p < 0.001). As a result, 361 (68.6%) patients were divided into beneficial group (CSS >8 months). Factors including age, tumor site, histology, differentiation grade, TNM stage, and tumor size were used to formulate the nomogram, which was named as esophagectomy candidates screening score (ECSS). The validation from two aspects showed the model a useful and stable one. CONCLUSION: A predictive model was established to distinguish optimal candidates for esophagectomy among elderly patients with EC.

16.
Zhongguo Zhong Yao Za Zhi ; 46(21): 5683-5692, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951222

RESUMO

The present study explored the potential mechanism of Jingfang Granules in relieving alcohol and protecting liver by network pharmacology and molecular docking and verified the effects and related pathways by animal experiments. The active components of Jingfang Granules were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Targets of drugs and diseases were obtained from PubChem, Swiss Target Prediction and CTD. The common targets were uploaded to STRING to plot the protein-protein interaction(PPI) network. The core targets were screened out and the target organs were identified by Bio GPS and Metascape, followed by Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of common targets. The acute drunk mouse model was established and the effects of Jingfang Granules on serum ethanol level and the expression of proteins related to the phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(Akt) signaling pathway in the liver tissue of mice were observed. A total of 187 active components of Jingfang Granules were obtained, including 47 common targets with alcoholic liver injury. GO enrichment analysis and KEGG pathway analysis showed that Jingfang Granules might play the role of relieving alcohol and protecting liver through the PI3 K-Akt signaling pathway. The drug-component-target and component-target-pathway networks revealed that the important active components of Jingfang Granules in relieving alcohol and protecting liver included quercetin, 5-O-methylvisamminol, glyasperin M, glyasperin B and hederagenin. Molecular docking showed that the active components had a good affinity with AKT1, EGFR, ESR1 and PTGS2. Experimental results showed that Jingfang Granules(15 and 10. 5 g·kg-1) could significantly reduce the content of serum ethanol in mice and up-regulate the protein expression ratios of p-PI3 K/PI3 K and p-Akt/Akt in the liver tissue. Jingfang Granules could relieve alcohol and protect liver through multi-component and multitarget, and the mechanism may be related to the activation of the PI3 K-Akt signaling pathway.


Assuntos
Medicamentos de Ervas Chinesas , Animais , Biologia Computacional , Medicamentos de Ervas Chinesas/farmacologia , Etanol , Fígado , Medicina Tradicional Chinesa , Camundongos , Simulação de Acoplamento Molecular , Tecnologia
17.
Environ Res ; : 112453, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34843726

RESUMO

To explore green technology for wheat straw pretreatment, this study combined the microwave or hydrothermal with ionic liquid ([Bmim][OAc]) on wheat straw followed by rumen fermentation. The optimal conditions of microwave assisted ionic liquids pretreatment (M-I) and hydrothermal assisted ionic liquids pretreatment (H-I) treatment were 360 W and 200 °C, and the corresponding lignin removal rates reached 35.3% and 25.4%, respectively. Rumen fermentation showed that the highest volatile fatty acid (VFA) yield was found in M-I group, followed by H-I group at 234 and 180 mg/g, respectively. As for enzymatic hydrolysis, the saccharification rates at 3 days of M-I (360 W) and H-I (200 °C) were determined to be 393 and 320 mg/g. The optimal ionic liquid dosage was determined to be 30% in consideration of cost and VFA conversion rate. M-I pretreatment plus the rumen fermentation enjoyed the benefit of no enzyme addition and high product recovery, which was worth further investigating.

18.
J Nanobiotechnology ; 19(1): 395, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34838028

RESUMO

Stimulus-responsive therapy that allows precise imaging-guided therapy is limited for osteoarthritis (OA) therapy due to the selection of proper physiological markers as stimulus. Based on that the over-production of Reactive Oxygen Species (ROS) is associated with the progression in OA, we selected ROS as markers and designed a cartilage targeting and ROS-responsive theranostic nanoprobe that can be used for effective bioimaging and therapy of OA. This nanoprobe was fabricated by using PEG micelles modified with ROS-sensitive thioketal linkers (TK) and cartilage-targeting peptide, termed TKCP, which was then encapsulated with Dexamethasone (DEX) to form TKCP@DEX nanoparticles. Results showed that the nanoprobe can smartly "turn on" in response to excessive ROS and "turn off" in the normal joint. By applying different doses of ROS inducer and ROS inhibitor, this nanoprobe can emit ROS-dependent fluorescence according to the degree of OA severity, helpful to precise disease classification in clinic. Specifically targeting cartilage, TKCP@DEX could effectively respond to ROS and sustained release DEX to remarkably reduce cartilage damage in the OA joints. This smart, sensitive and endogenously activated ROS-responsive nanoprobe is promising for OA theranostics.

19.
Oxid Med Cell Longev ; 2021: 1699990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840665

RESUMO

In the past two decades, testicular tissue grafting and xenografting have been well established, with the production of fertilization-competent sperm in some studies. However, few studies have been carried out to observe the development of grafted prepubertal testicular tissue of rats and compare the biological differences between in situ testis and grafted testis. In this study, we established the prepubertal testicular tissue xenografting model using a 22-day-old rat and evaluated certain parameters, including testicular histology, testosterone production, and ultrastructure of the grafted testes. We also assessed gene expression of cell proliferation markers, testicular cell markers, and antioxidative defense system. Our results showed that 47 days after transplantation, intratesticular testosterone concentration was not significantly altered; however, cell proliferation, spermatogenesis, and Sertoli cell markers in the transplanted testes were significantly disrupted compared with the control group, accompanied by aggravated apoptosis and oxidative damage. Moreover, the transplanted testes showed smaller tubular diameter and disrupted spermatogenic epithelium with apparent vacuoles, distorted and degenerated germ cells with obscure nuclear margin, and no spermatids in the center of the tubules. Although testis xenografting has been extensively tested and attained great achievement in other species, the prepubertal rat testicular tissue xenografting to immunodeficient mice exhibited obvious spermatogenesis arrest and oxidative damage. The protocol still needs further optimization, and there are still some unknown factors in prepubertal rat testes transplantation.

20.
Nat Commun ; 12(1): 6653, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789768

RESUMO

BRCA1-BARD1 heterodimers act in multiple steps during homologous recombination (HR) to ensure the prompt repair of DNA double strand breaks. Dysfunction of the BRCA1 pathway enhances the therapeutic efficiency of poly-(ADP-ribose) polymerase inhibitors (PARPi) in cancers, but the molecular mechanisms underlying this sensitization to PARPi are not fully understood. Here, we show that cancer cell sensitivity to PARPi is promoted by the ring between ring fingers (RBR) protein RNF19A. We demonstrate that RNF19A suppresses HR by ubiquitinating BARD1, which leads to dissociation of BRCA1-BARD1 complex and exposure of a nuclear export sequence in BARD1 that is otherwise masked by BRCA1, resulting in the export of BARD1 to the cytoplasm. We provide evidence that high RNF19A expression in breast cancer compromises HR and increases sensitivity to PARPi. We propose that RNF19A modulates the cancer cell response to PARPi by negatively regulating the BRCA1-BARD1 complex and inhibiting HR-mediated DNA repair.

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