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1.
Talanta ; 237: 122960, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736685

RESUMO

H2S has been reported to play essential roles in a variety of physiological and pathological procedures. In this work, a novel fluorescent probe, Rho-HS, for detecting H2S was developed by introducing the ortho-halogen to activate the least reactive recognition group 2,4-dinitrophenyl moiety. In combination of the structures from both Rhodamine B and fluorescein, Rho-HS could generate both the colorimetric and fluorescent responses. This feature was not frequently achieved and could lead to the quantitative and convenient for the end-user. In comparison with recent probes for H2S, the major advantages of Rho-HS included suiting wide pH range (6.0-10.0), relatively rapid response (within 15 min) and the high selectivity among the competing species including the biothiols. With low cytoxicity, Rho-HS was further applied in the biological imaging in living MCF-7 cells and Caenorhabditis elegans. We hope that the designing strategy in this work might provide useful information for more preferable implements in this field.


Assuntos
Sulfeto de Hidrogênio , Xantonas , Fluoresceína , Corantes Fluorescentes , Imagem Óptica
2.
Theranostics ; 11(20): 9967-9987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815798

RESUMO

Background: BRCA1 plays critical roles in mammary gland development and mammary tumorigenesis. And loss of BRCA1 induces mammary tumors in a stochastic manner. These tumors present great heterogeneity at both intertumor and intratumor levels. Methods: To comprehensively elucidate the heterogeneity of BRCA1 deficient mammary tumors and the underlying mechanisms for tumor initiation and progression, we conducted bulk and single cell RNA sequencing (scRNA-seq) on both mammary gland cells and mammary tumor cells isolated from Brca1 knockout mice. Results: We found the BRCA1 deficient tumors could be classified into four subtypes with distinct molecular features and different sensitivities to anti-cancer drugs at the intertumor level. Whereas within the tumors, heterogeneous subgroups were classified mainly due to the different activities of cell proliferation, DNA damage response/repair and epithelial-to-mesenchymal transition (EMT). Besides, we reconstructed the BRCA1 related mammary tumorigenesis to uncover the transcriptomes alterations during this process via pseudo-temporal analysis of the scRNA-seq data. Furthermore, from candidate markers for BRCA1 mutant tumors, we discovered and validated one oncogene Mrc2, whose loss could reduce mammary tumor growth in vitro and in vivo. Conclusion: Our study provides a useful resource for better understanding of mammary tumorigenesis induced by BRCA1 deficiency.

3.
Support Care Cancer ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34743239

RESUMO

PURPOSE: The objective of this current study was to describe the status of returning to work and work ability of colorectal cancer survivors and identify the key factors associated with returning to work and work ability of Chinese colorectal cancer patients. METHODS: A cross-sectional observational study was performed in 212 colorectal cancer survivors who have worked before their colorectal cancer diagnosis. We evaluated patient's return to work (Yes/No), work ability, and factors by questionnaires of the Work Ability Index (WAI), M. D. Anderson Symptom Inventory for Gastrointestinal (MDASI-GI), and the Self-Report Psychosocial Adjustment to Illness Scale (PAIS-SR). Logistic regression analysis and linear regression were used to find the potential predictors with returning to work and work ability. RESULTS: Participants mostly 145 have returned to work (68.4%). Work ability and psychosocial adjustment of colorectal cancer survivors were at a moderate level. After completing treatment, the patient still had many symptoms, and these symptoms were distress to live. In the two models, survivors with higher family monthly income per capita and lower psychosocial adjustment scores were more likely to have higher work ability and return to work. Survivors with lower symptom distress were more likely to have higher work ability (r = - 0.038, p = 0.010). Survivors with higher work ability were more likely to return to work (OR = 1.193, 95% CI = (1.116,1.274)). CONCLUSION: This study confirmed that symptom distress and psychosocial adjustment were significantly associated with colorectal cancer survivors' returning to work and work ability, which should be considered in future intervention research.

4.
Sci Total Environ ; 806(Pt 2): 150279, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600205

RESUMO

The growing contamination of arsenic and plastics has severely effects on the soil fauna health, including shifts of gut microbiota community. A few studies have focused on effects of microplastics and metal(loid) in soil and fauna gut microbiome. However, the environmental effect of nanoplastics and arsenic on the earthworm gut microbiota, especially on arsenic biotransformation in the gut, remain largely unknown. Here, a microcosm study was performed to explore the effects of nanoplastics and arsenic on the microbiota characteristics in earthworm Metaphire vulgaris gut using Illumina high throughput sequencing, and to investigate changes in the gut microbiota-mediated arsenic biotransformation genes (ABGs) by using high-throughput quantitative PCR. Our results demonstrated that the concentration of arsenic in the earthworm body tissues after exposure to arsenic and nanoplastics was significantly lower from that with arsenic alone exposure. Moreover, the clearly different bacterial community was observed in the soil compared with the earthworm gut, which was dominated by Proteobacteria, Actinobacteria, and Firmicutes at phylum level. Arsenic exposure significantly disturbed bacterial community structure in the earthworm gut, but exposure to nanoplastics did not induce gut microbiota changes. More interestingly, nanoplastics can relieve adverse effect of arsenic on the gut microbiota possibly by adsorbing arsenic. In addition, a total of 16 ABGs were detected, and predominant genes involved in arsenic reduction and transport process were observed in the earthworm guts. In short, this study provides a new picture of the effects of nanoplastics and arsenic on the gut microbiota and arsenic biotransformation in soil fauna gut.

5.
Front Plant Sci ; 12: 704618, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646282

RESUMO

Phototropins, namely, phototropin 1 (phot1) and phototropin 2 (phot2), mediate chloroplast movement to maximize photosynthetic efficiency and prevent photodamage in plants. Phot1 primarily functions in chloroplast accumulation process, whereas phot2 mediates both chloroplast avoidance and accumulation responses. The avoidance response of phot2-mediated chloroplasts under high-intensity blue light (HBL) limited the understanding of the function of phot1 in the chloroplast accumulation process at the HBL condition. In this study, we showed that the phot2 mutant exhibits a chloroplast accumulation response under HBL, which is defective when the root phototropism 2 (RPT2) gene is mutated in the phot2 background, mimicking the phenotype of the phot1 phot2 double mutant. A further analysis revealed that the expression of RPT2 was induced by HBL and the overexpression of RPT2 could partially enhance the chloroplast accumulation response under HBL. These results confirmed that RPT2 also participates in regulating the phot1-mediated chloroplast accumulation response under HBL. In contrast, RPT2 functions redundantly with neural retina leucine zipper (NRL) protein for chloroplast movement 1 (NCH1) under low-light irradiation. In addition, no chloroplast accumulation response was detected in the phot2 jac1 double mutant under HBL, which has been previously observed in phot2 rpt2 and phot1 phot2 double mutants. Taken together, our results indicated that phot1 mediates the HBL-induced chloroplast accumulation response in an RPT2-dependent manner and is also regulated by j-domain protein required for chloroplast accumulation response 1 (JAC1).

6.
Chemosphere ; : 132568, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34656626

RESUMO

Biomass burning has been recognized as an important primary source of atmospheric phosphorus (P), but the measurements of P from biomass burning particles are lacking. In this work, emission factors of different P forms, including total P (TP), total dissolved P (TDP), dissolved inorganic P (DIP) and dissolved organic P (DOP), in emission particles from four types of crop residues burning were measured in a number of chamber experiments. Based on the measured emission factors and the amount of crop residue burned, a high-resolution (0.25° × 0.25°) emission inventory of P for China during 2011-2015 was firstly developed. The emission factors of TP, DIP and DOP were 0.23, 0.06 and 0.13 g/kg, 0.57, 0.17 and 0.27 g/kg, 0.52, 0.15 and 0.27 g/kg, 0.43, 0.13 and 0.25 g/kg for wheat, corn, soybean and rice straw burning, respectively. The total emissions of TP, TDP, DIP, and DOP from the four types of crop straw open burning were 72.0 × 103 ± 6.7 × 103 Tons, 56.3 × 103 ± 5.5 × 103, 20.9 × 103 ± 2.0 × 103 and 35.4 × 104 ± 3.4 × 103 Tons, respectively. TDP dominated the TP fraction, indicating that biomass burning was the important source of bioavailable P. The high P emission areas were mainly distributed in the Northeast and North China Plain, where were the main grain production areas in China, while P emission in economically developed areas such as Beijing and Shanghai and western areas such as Tibet and Qinghai was lower. Affected by the harvesting periods of crops, high P emissions peaked in March, April, June and October. The results herein can provide a dataset for modeling research in calculating the contribution of biomass burning sources to atmospheric P; therefore reduce uncertainties in estimating atmospheric P deposition.

7.
Int J Nurs Sci ; 8(4): 388-393, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34631988

RESUMO

Objectives: Patients after cardiac surgery with cardiopulmonary bypass (CPB) require a stay in the ICU postoperatively. This study aimed to investigate the incidence of prolonged length of stay (LOS) in the ICU after cardiac surgery with CPB and identify associated risk factors. Methods: The current investigation was an observational, retrospective study that included 395 ICU patients who underwent cardiac surgery with CPB at a tertiary hospital in Guangzhou from June 2015 to June 2017. Data were obtained from the hospital database. Binary logistic regression modeling was used to analyze risk factors for prolonged ICU LOS. Results: Of 395 patients, 137 (34.7%) had a prolonged ICU LOS (>72.0 h), and the median ICU LOS was 50.9 h. Several variables were found associated with prolonged ICU LOS: duration of CPB, prolonged mechanical ventilation and non-invasive assisted ventilation use, PaO2/FiO2 ratios within 6 h after surgery, type of surgery, red blood cell infusion during surgery, postoperative atrial arrhythmia, postoperative ventricular arrhythmia (all P < 0.05). Conclusions: These findings are clinically relevant for identifying patients with an estimated prolonged ICU LOS, enabling clinicians to facilitate earlier intervention to reduce the risk and prevent resulting delayed recovery.

8.
J Integr Med ; 19(6): 545-554, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34686466

RESUMO

OBJECTIVE: To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms. METHODS: A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation. RESULTS: FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation. CONCLUSION: BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis.


Assuntos
Berberina , Hepatopatia Gordurosa não Alcoólica , Berberina/farmacologia , Colesterol , Proteína Forkhead Box O1/genética , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Sirtuína 1/genética , Proteínas de Ligação a Elemento Regulador de Esterol
9.
Adv Sci (Weinh) ; 8(22): e2101176, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34605222

RESUMO

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco-phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient-specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.

10.
Nat Commun ; 12(1): 6011, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650057

RESUMO

Defective pericyte-endothelial cell interaction in tumors leads to a chaotic, poorly organized and dysfunctional vasculature. However, the underlying mechanism behind this is poorly studied. Herein, we develop a method that combines magnetic beads and flow cytometry cell sorting to isolate pericytes from tumors and normal adjacent tissues from patients with non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC). Pericytes from tumors show defective blood vessel supporting functions when comparing to those obtained from normal tissues. Mechanistically, combined proteomics and metabolic flux analysis reveals elevated hexokinase 2(HK2)-driven glycolysis in tumor pericytes, which up-regulates their ROCK2-MLC2 mediated contractility leading to impaired blood vessel supporting function. Clinically, high percentage of HK2 positive pericytes in blood vessels correlates with poor patient overall survival in NSCLC and HCC. Administration of a HK2 inhibitor induces pericyte-MLC2 driven tumor vasculature remodeling leading to enhanced drug delivery and efficacy against tumor growth. Overall, these data suggest that glycolysis in tumor pericytes regulates their blood vessel supporting role.


Assuntos
Vasos Sanguíneos/anormalidades , Glicólise , Hexoquinase/metabolismo , Neoplasias de Tecido Vascular/metabolismo , Pericitos/metabolismo , Células A549 , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Miosinas Cardíacas/genética , Miosinas Cardíacas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Hexoquinase/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Cadeias Leves de Miosina/genética , Cadeias Leves de Miosina/metabolismo , Neoplasias/metabolismo , Neoplasias de Tecido Vascular/tratamento farmacológico , Neoplasias de Tecido Vascular/genética , Neoplasias de Tecido Vascular/patologia , Microambiente Tumoral/fisiologia , Regulação para Cima , Quinases Associadas a rho
11.
Geriatr Nurs ; 42(6): 1303-1308, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34560524

RESUMO

INTRODUCTION: While traditional "non-medical" prevention and control measures have achieved remarkable results during the COVID-19 pandemic, they have generated difficult situations for older adult patients with chronic disease. The purpose of this study was to understand and identify the COVID-19 risk perception process and trajectory among older adults with chronic disease living in the community. MATERIAL AND METHODS: This was a qualitative research study that used in-depth semi-structured interviews to explore the experiences of 21 older adult patients with chronic disease. Data were analyzed using conventional content analysis methods. RESULTS: Three themes emerged: restricted travel, psychological shock and panic, and unintended consequences. CONCLUSIONS: The perceptions of epidemic risk among older adult patients with chronic disease living in the community had varying characteristics at different stages. Correct identification of risk perception processes and trajectories will assist in formulating more scientific emergency measures in the event of future public health emergencies.

12.
IUBMB Life ; 73(12): 1406-1422, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34590407

RESUMO

Deficiency of G protein-coupled receptor kinase 2 (GRK2) was found to protect mice from dextran sulfate sodium (DSS)-induced colitis. Paeoniflorin-6'-O-benzene sulfonate (CP-25) has been shown to exert anti-inflammatory immune regulatory effects in animal models of inflammatory autoimmune disease. This study aimed to investigate the of GRK2 in the pathogenesis of ulcerative colitis (UC) and its effects on macrophage polarization, macrophage subtype regulation of intestinal barrier function, and therapeutic effects of CP-25 in mice with DSS-induced colitis. We found imbalanced macrophage polarization, intestinal barrier dysfunction, and abnormal activation of GRK2 and TLR4-NF-κB-NLRP3 inflammasome signaling pathway in the colonic mucosa of patients with UC. CP-25, restored the damaged intestinal barrier function by inhibiting the transmembrane region of GRK2 in macrophages stimulated by lipopolysaccharides. CP-25 exerted therapeutic effects by ameliorating clinical manifestation, regulating macrophage polarization, and restoring abnormally activated TLR4-NF-κB-NLRP3 inflammasome signaling pathway by inhibiting GRK2. These data suggest the pathogenesis of UC may be related to the imbalance of macrophage polarization, which leads to abnormal activation of TLR4-NF-κB-NLRP3 inflammasome signaling pathway mediated by GRK2 and destruction of the intestinal mucosal barrier. CP-25 confers therapeutic effects on colitis by inhibiting GRK2 translocation to induce the downregulation of TLR4-NF-κB-NLRP3 inflammasome signaling in macrophages.

13.
Acta Pharmacol Sin ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34363008

RESUMO

Acute pancreatitis (AP), an inflammatory disorder of the pancreas, is a complicated disease without specific drug therapy. (R)-4,6-dimethoxy-3-(4-methoxy phenyl)-2,3-dihydro-1H-indanone [(R)-TML104] is a synthesized analog of the natural product resveratrol sesquiterpenes (±) -isopaucifloral F. This study aimed to investigate the effect and underlying mechanism of (R)-TML104 on AP. The experimental AP model was induced by caerulein hyperstimulation in BALB/c mice. (R)-TML104 markedly attenuated caerulein-induced AP, as evidenced by decreased pancreatic edema, serum amylase levels, serum lipase levels, and pancreatic myeloperoxidase activity. In addition, (R)-TML104 significantly inhibited the expression of pancreatic chemokines C-C motif chemokine ligand 2 and macrophage inflammatory protein-2 and the infiltration of neutrophils and macrophages. Mechanistically, (R)-TML104 activated AMP-activated protein kinase and induced sirtuin 1 (SIRT1) expression. (R)-TML104 treatment markedly induced the SIRT1-signal transducer and activator of transcription 3 (STAT3) interaction and reduced acetylation of STAT3, thus inhibiting the inflammatory response mediated by the interleukin 6-STAT3 pathway. The effect of (R)-TML104 on SIRT1-STAT3 interaction was reversed by treatment with a SIRT1 inhibitor selisistat (EX527). Together, our findings indicate that (R)-TML104 alleviates experimental pancreatitis by reducing the infiltration of inflammatory cells through modulating SIRT1.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1129-1135, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362492

RESUMO

OBJECTIVE: To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells. METHODS: The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA. RESULTS: The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle. CONCLUSION: Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.


Assuntos
Proteínas de Ciclo Celular , Leucemia , Proteína Quinase CDC2 , Proteínas de Ciclo Celular/genética , Proliferação de Células , Humanos , Mitose , Fosforilação , Proteínas Proto-Oncogênicas/genética
15.
Psychiatry Investig ; 18(7): 636-644, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34340274

RESUMO

OBJECTIVE: The current study aims to explore precipitating and social risk factors for internet addiction (IA) in university undergraduate students, and to provide evidence for interventions and the early prevention of IA in different genders. METHODS: Four thousand eight hundred and fifty-eight college sophomores completed an online survey on their internet use-related behaviours and social risk factors. RESULTS: We found that more male (8.3%) than female students (5.4%) had moderate and severe IA. The main online activity in the moderate and severe IA groups was online gaming in males and online streaming in females. Roommates engaging in similar internetbased entertainment was a risk factor of IA only for males, while not being in a romantic relationship was a risk factor of IA for females only. Infatuation with the internet before college and adjustment problems for college life were shared risk factors for both genders in the mild and moderate IA groups. CONCLUSION: IA was a common phenomenon in college students with shared and unique precipitating and social risk factors in males and females. The gender-sensitive risk factors for IA warranted earlier and individualized intervention and prevention strategies for IA in this population.

16.
Zool Res ; 42(5): 562-573, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34355875

RESUMO

Inositol requiring mutant 80 (INO80) is a chromatin remodeler that regulates pluripotency maintenance of embryonic stem cells and reprogramming of somatic cells into pluripotent stem cells. However, the roles and mechanisms of INO80 in porcine pre-implantation embryonic development remain largely unknown. Here, we show that INO80 modulates trophectoderm epithelium permeability to promote porcine blastocyst development. The INO80 protein is highly expressed in the nuclei during morula-to-blastocyst transition. Functional studies revealed that RNA interference (RNAi)-mediated knockdown of INO80 severely blocks blastocyst formation and disrupts lineage allocation between the inner cell mass and trophectoderm. Mechanistically, single-embryo RNA sequencing revealed that INO80 regulates multiple genes, which are important for lineage specification, tight junction assembly, and fluid accumulation. Consistent with the altered expression of key genes required for tight junction assembly, a permeability assay showed that paracellular sealing is defective in the trophectoderm epithelium of INO80 knockdown blastocysts. Importantly, aggregation of 8-cell embryos from the control and INO80 knockdown groups restores blastocyst development and lineage allocation via direct complementation of the defective trophectoderm epithelium. Taken together, these results demonstrate that INO80 promotes blastocyst development by regulating the expression of key genes required for lineage specification, tight junction assembly, and fluid accumulation.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Blastocisto/fisiologia , Cromatina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Mórula/fisiologia , Suínos , ATPases Associadas a Diversas Atividades Celulares/genética , Animais , Proteínas de Ligação a DNA/genética , Técnicas de Cultura Embrionária/veterinária , Fertilização In Vitro , Regulação da Expressão Gênica/fisiologia , Oócitos/fisiologia , Permeabilidade
17.
Chem Biol Drug Des ; 98(5): 835-849, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34416096

RESUMO

As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.

18.
Huan Jing Ke Xue ; 42(7): 3348-3357, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212660

RESUMO

Protein-like dissolved organic matter (pDOM), which is ubiquitous in natural waters, is a critical precursor of nitrogenous disinfection byproducts. Recently, the control and elimination of pDOM have been a growing concern during drinking water treatment processes. In this study, a high-performance size exclusion chromatography system coupled with photo-diode array, fluorescence detector, and online organic carbon detector (HPSEC-PDA/FLD/OCD) was used to determine the removal behaviors of different-sized pDOM from two full-scale drinking water treatment plants (DWTPs). Coagulation and activated carbon adsorption were selected for bench-scale experiments to further assess the removal behavior of pDOM during conventional water treatment processes. The results showed that different-sized pDOM fractions exhibited different removal characteristics. Pre-oxidation can effectively remove some tyrosine-like and tryptophan-like components with high MW, and as the oxidization effect was enhanced, more high MW fractions decomposed into low MW ones. Conversely, some aliphatic pDOM fractions in high MW (e.g., aliphatic proteins) were not subject to pre-oxidation removal. The coagulation-sedimentation unit was efficient in removing high MW fractions, specifically tryptophan-like fractions. Additionally, some pDOM components may be released during coagulation. pDOM with low MW and high hydrophobicity were easily removed during activated carbon filtration. However, long-term operation of the activated carbon filter may breed microorganisms, resulting in the partial release of pDOM fractions. Moreover, UV disinfection processes promoted the degradation of low MW pDOM components. Due to the complex water quality and uncontrollable microbial activities, the aforementioned water treatment units did not exhibit a synergistic effect on pDOM removal. In comparison with humic-like substances, pDOM was susceptible to water quality changes, and its removal was limited in the surveyed DWTPs. Therefore, DWTPs must strengthen pDOM monitoring in influent and effluent and adjust the operating parameters of different treatment units in a timely manner. Moreover, the combination of advanced water treatment processes, such as ozone-biological activated carbon process and nanofiltration, should also be considered to strictly control pDOM component removal.


Assuntos
Água Potável , Poluentes Químicos da Água , Purificação da Água , Carvão Vegetal , Filtração , Compostos Orgânicos/análise , Poluentes Químicos da Água/análise
19.
Cancer Nurs ; 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34310390

RESUMO

BACKGROUND: First-degree relatives of patients with colorectal cancer have an elevated risk of colorectal cancer. However, the behavior and factors potential influencing first-degree relatives regarding colorectal cancer screening in China remain unknown. OBJECTIVE: The aim of this study was to explore the screening behavior and related factors of first-degree relatives of colorectal cancer patients. METHODS: A cross-sectional design was applied, and 201 first-degree relatives participated from August 2018 to July 2019. Data were collected about demographic information, the "Colorectal Cancer Perceptions Scale," and screening behavior of first-degree relatives. Factors associated with screening behavior were identified using logistic regression analysis. RESULTS: Only 18.9% of first-degree relatives had participated in colonoscopy screening. Two Health Belief Model factors were the influencing factors of their participation in colorectal cancer screening. Higher possibility of colorectal cancer screening of first-degree relatives was associated with higher perceived susceptibility (odds ratio, 1.224; 95% confidence interval, 1.075-1.395) and lower perception of barriers (odds ratio, 0.880; 95% confidence interval, 0.820-0.944) of first-degree relatives. CONCLUSIONS: Participation in colorectal cancer screening by first-degree relatives requires improvement; perceived susceptibility and perception of barriers were the most important predictors. IMPLICATIONS FOR PRACTICE: Health professionals can enhance awareness of colorectal cancer susceptibility and address barriers to colorectal cancer screening among first-degree relatives at both individual and social levels.

20.
Neurosci Bull ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34235622

RESUMO

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

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