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1.
Food Funct ; 12(19): 9360-9371, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606545

RESUMO

Anhydrosafflor yellow B (AHSYB) is a major active water-soluble pigment in Safflower, but it has not received enough attention yet. In this study, high-speed counter-current chromatography (HSCCC) was used to prepare AHSYB from safflower. The parameters of the separation process were optimized by response surface methodology for the first time. The entropy weight method (EWM) was applied to calculate the information entropy and the weight of five indexes, and then figure out a comprehensive index of the HSCCC separation effect. Under the optimized separation conditions, a HSCCC apparatus speed of 850 rpm, a flow rate of 2 mL min-1 for the mobile phase and a separation temperature of 40 °C for AHSYB were achieved with a purity of 98%. Furthermore, AHSYB was found to have cardio-protective effects by inhibiting apoptosis via the mitochondrial-mediated pathway in oxygen-glucose deprivation/reoxygenation-induced H9c2 cells. This research provides good method guides for the rapid and efficient separation of active compounds from food-grade Chinese herb medicines.

2.
Pak J Pharm Sci ; 34(3): 957-961, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602419

RESUMO

The present study was performed in order to investigate the safety and efficacy of different vasoactive drugs combined with enteral nutrition in terms of treating elderly patients with sepsis. A total of 75 elderly patients with sepsis treated with enteral nutrition in our hospital were randomly divided into three groups: group A (n = 25), group B (n = 25) and group C (n = 25). The three groups were treated with dopamine, dobutamine and norepinephrine respectively. One week after treatment, the therapeutic effects of the three groups were compared, the vascular elastic indexes, hemodynamic indexes and levels of inflammatory factors of the three groups were measured. After treatment, the clinical effective rate of group C was evidently higher than that of group A and group B. The vascular elasticity coefficient and stiffness coefficient in group C were significantly lower than those in group A and group B, and the arterial compliance in group C was significantly higher than that in group A and group B (P < 0.05). The levels of MAP and PVRI in group C were significantly higher than those in group A and B, and the levels of CI, CVP and HR in group C were significantly lower than those in group A and group B (P < 0.05). Norepinephrine elicited greater effects in terms of improving hemodynamic indexes, vascular elasticity and reducing the level of inflammatory factors compared with dopamine and dobutamine in elderly patients harboring sepsis.

3.
World J Gastroenterol ; 27(36): 6064-6078, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34629820

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related death worldwide. The 5-year survival rate of patients with early-stage CRC could reach 90%, but it is very low in patients with advanced-stage CRC. Recent studies have shown that circular RNAs play important roles in regulating the migration and invasion of CRC cells. AIM: To elucidate the role of circRNA_0084927 (circ_0084927) in the migration and invasion of CRC cells and its underlying mechanism. METHODS: Clinical tissue samples and cells were collected, and the expression of circ_0084927 was detected by quantitative polymerase chain reaction (qPCR). The diagnostic performance of circ_0084927 was assessed by receiver operating characteristic curve analysis. The role of circ_0084927 in CRC cell proliferation, migration, and invasion was determined using cell counting kit-8 assay, wound healing assay, and transwell assay, respectively. The regulatory relationship among circ_0084927, miRNA-20b-3p (miR-20b-3p), and glutathione S-transferase mu 5 (GSTM5) was identified using databases, luciferase reporter assay, qPCR, and Western blot analysis. AKT-mTOR signaling was also verified after circ_0084927 knockdown or miR-20b-3p mimic treatment. RESULTS: The expression of circ_0084927 was significantly increased in CRC tissues and cells, and it was higher in advanced-stage CRC compared with early-stage CRC. The area under the curve (AUC) of circ_0084927 was 0.806 [95% confidence interval (CI): 0.683-0.896]. In addition, the AUC was 0.874 (95%CI: 0.738-0.956) in patients with advanced-stage CRC and 0.713 (95%CI: 0.555-0.840) in those with early-stage CRC. Knockdown of circ_0084927 inhibited the migration and invasion of HCT116 cells. Moreover, circ_0084927 was found to act as a sponge of miR-20b-3p. MiR-20b-3p activation reduced the circ_0084927 level, whereas miR-20b-3p inhibition increased the circ_0084927 level. But the effect was not found after circ_0084927 mutation. In addition, miR-20b-3p expression in CRC patients was also reduced and negatively correlated with circ_0084927 expression. The function of circ_0084927 in HCT116 cells with circ_0084927 knockdown was rescued by miR-20b-3p. Moreover, GSTM5 expression was significantly decreased after overexpressing miR-20b-3p or inhibiting circ_0084927, but its expression was rescued when circ_0084927 and miR-20b-3p were both inhibited. Finally, AKT-mTOR signaling was markedly regulated by circ_0084927 and miR-20b-3p. CONCLUSION: The expression of circ_0084927 is significantly increased in CRC and higher in advanced-stage CRC than in early-stage CRC. Moreover, circ_0084927 potentially regulates CRC cell migration and invasion via the miR-20b-3p/GSTM5/ AKT/mTOR pathway.


Assuntos
Neoplasias Colorretais , MicroRNAs , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Glutationa Transferase , Humanos , MicroRNAs/genética , RNA Circular
4.
Opt Lett ; 46(18): 4498-4501, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525031

RESUMO

We present multi-exposure interferometric diffusing wave spectroscopy (MiDWS), which measures brain blood flow index (BFI) continuously and non-invasively. MiDWS employs interferometry to detect low light levels, probing the optical field autocorrelation indirectly by varying the sensor exposure time. Here MiDWS is compared with conventional interferometric diffusing wave spectroscopy and speckle contrast optical spectroscopy in phantoms. Notably, the MiDWS approach enables the use of low frame rate, two-dimensional complementary metal-oxide semiconductor cameras in a short exposure time regime, where detector noise greatly exceeds the sample photon count. Finally, we show that MiDWS can monitor the BFI simultaneously at two source-collector separations (1 and 3 cm) on the adult human head on a single camera, enabling the use of superficial signal regression techniques to improve brain specificity.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34554361

RESUMO

OBJECTIVES: To examine the association between modifiable lifestyle factors and the main semen parameter values, the number of qualified sperm donors, and to provide some sensible guidance for sperm donors. METHODS: Healthy men screened as potential sperm donors were recruited in the Hunan Province Human Sperm Bank of China from March 2019 to December 2019. Participants were invited to complete interviewer-assisted questionnaires on eleven items of information. Univariate and multivariate analyses were conducted to analyze which lifestyle factors collected by the questionnaire had an impact on the eligibility and main semen parameters of sperm donors. RESULTS: The eligibility of men as sperm donors was strongly influenced by the duration of abstinence (P = 0.002). The rate of eligibility sperm donors increased significantly with the number of days of abstinence. In addition, semen volume increased with abstinence time (P = 0.000). Exercise frequency (P = 0.025) and abstinence time (P = 0.000) were positively correlated with sperm concentration, and masturbation frequency was negatively correlated with sperm concentration (P = 0.013). Progressive sperm motility was significantly affected by abstinence time (P = 0.000) and bedtime (P = 0.047). CONCLUSIONS: Abstinence time was highly associated with semen parameters and donor qualification. Increase the abstinence time before donation may be meaningful in improving the proportion of eligible sperm donors.

6.
Glob Chang Biol ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525229

RESUMO

Subtropical forests are important ecosystems globally due to their extensive role in carbon sequestration. Extreme climate events are known to introduce disturbances in the ecosystem that cause long-term changes in carbon balance and radiation reflectance. However, how these ecosystem function changes contribute to global warming in terms of radiative forcing (RF), especially in the years following a disturbance, still needs to be investigated. We studied an extreme snow event that occurred in a subtropical evergreen broadleaved forest in south-western China in 2015 and used 9 years (2011-2019) of net ecosystem CO2 exchange (NEE) and surface albedo (α) data to investigate the effect of the event on the ecosystem RF changes. In the year of the disturbance, leaf area index (LAI) declined by 40% and α by 32%. The annual NEE was -718 ±â€…128 g C m-2 as a sink in the pre-disturbance years (2011-2014), but after the event, the sink strength dropped significantly by 76% (2015). Both the vegetation, indicated by LAI, and α recovered to pre-disturbance levels in the fourth post-disturbance year (2018). However, the NEE recovery lagged and occurred a year later in 2019, suggesting a more severe and lasting impact on the ecosystem carbon balance. Overall, the extreme event caused a positive (warming effect) net RF which was predominantly caused by changes in α (90%-93%) rather than those in NEE. This result suggests that, compared to the climate effect caused by forest carbon sequestration changes, the climate effect of α alterations can be more sensitive to vegetation damage induced by natural disturbances. Moreover, this study demonstrates the important role of vegetation recovery in driving canopy reflectance and ecosystem carbon balance during the post-disturbance period, which determines the ecosystem feedbacks to the climate change.

7.
Org Biomol Chem ; 19(38): 8301-8306, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34545902

RESUMO

An efficient method for direct trifluoromethylation and perfluoroalkylation at C3 of imidazopyridines through visible light-promoted C-H bond functionalization was developed. Under the irradiation of a blue LED, a series of C3-perfluoroalkyl-substituted imidazopyridines were synthesized from the corresponding imidazopyridines and perfluoroalkyl iodides in moderate to good yields at room temperature. It should be mentioned that this reaction proceeded in the absence of any transition-metal catalyst, oxidant and photocatalyst.

8.
J Am Coll Health ; : 1-9, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468281

RESUMO

OBJECTIVE: This study aims to: (1) examine gender differences for weight conscious drinking among college students accounting for the broader phenomenon (e.g. including the Alcohol Effects dimension); and (2) longitudinally examine the effect of weight conscious drinking behaviors on body mass index (BMI). Participants: United States freshmen students from eight participating universities (N= 1,149). Methods: Structural equation modeling was used to model the effect of gender on weight conscious drinking dimensions at 7-month follow-up. Results: Findings suggest a significant effect of gender on Alcohol Effects (ß = -.15, SE = .05, p = .005) at 7-month follow-up among college freshmen. Weight conscious drinking dimensions predicted no significant change in BMI at 7-month follow-up among college freshmen. Conclusion: Findings contribute to weight conscious drinking theory and provide campus weight conscious drinking prevention initiatives with evidence to tailor their programming to address female tendencies to engage in compensatory strategies to enhance the psychoactive effects of alcohol.

9.
ACS Appl Mater Interfaces ; 13(33): 39806-39818, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34387459

RESUMO

Silver nanomaterials have attracted a great deal of interest due to their broad-spectrum antimicrobial activity. However, it is still challenging to balance the high antibacterial efficiency with low damage to biological cells of silver nanostructures, especially when the diameter decreases to less than 10 nm. Here, we developed a new type of Ag nanohybrid material via a unimolecular micelle template method, which presents amazing antibacterial activities and almost noncytotoxicity. First, water-soluble multiarm star-shaped brushlike copolymer α-CD-g-[(PEO40-g-PAA50)-b-PEO5]18 was precisely synthesized and its micelle behavior in different solvents was revealed. Then, nanocrystal clusters assembled by Ag grains (Ag@Template NCs) were prepared through an in situ redox route using the unimolecular micelle of α-CD-g-[(PEO40-g-PAA50)-b-PEO5]18 as the soft template, AgNO3 as a precursor, and tetrabutylammonium borohydride (TBAB) as the reducing agent. The overall size of the achieved Ag@Template NCs is controlled by the template structure at around 40 nm (Dh in DMF), and the size of the Ag grain can be easily regulated from ∼1 to ∼5 nm by adjusting the feeding ratio of AgNO3/acrylic acid (AA) units in the template from 1:10 to 1:1. Benefitting from the structural design of the template, all Ag@Template NCs prepared here exhibit excellent dispersibility and chemical stability in different aqueous environments (neutral, pH = 5.5, and 0.9% NaCl physiological saline solution), which play a crucial role in the long-term storage and potential application in a complex physiological environment. The antibacterial and cytotoxicity tests indicate that Ag@Template NCs display much better performance than Ag nanoparticles (Ag NPs), which have a comparable overall size of ∼25 nm. The inhibitory capability of Ag@Template NCs to bacteria strongly depends on the grain size. Specifically, the Ag@Template-1 NC assembled by the smallest grains (1.6 ± 0.3 nm) presents the best antibacterial activity. For E. coli (-), the MIC value is as low as 5 µg/mL (0.36 µg/mL of Ag), while for S. aureus (+), the value is around 10 µg/mL (0.72 µg/mL of Ag). The survival rate of L02 cells and lactate dehydrogenase assay together illustrate the low cytotoxicity possessed by the prepared Ag@Template NCs. Therefore, the proposed Ag@Template NC structure successfully resolves the high reactivity, instability, and fast oxidation issues of the ultrasmall Ag nanoparticles, and integrates high antibacterial efficiency and nontoxicity to biological cells into one platform, which implies its broad potential application in biomedicine.


Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/química , Nanopartículas Metálicas/química , Prata/química , Antibacterianos/metabolismo , Boroidretos/química , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Polímeros/química , Compostos de Amônio Quaternário/química , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Nanomedicina Teranóstica
10.
Zhongguo Zhen Jiu ; 41(7): 789-91, 2021 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-34259413

RESUMO

Professor ZHENG Liang believes that the main pathogenesis of postoperative facial paralysis is related to the retarded circulation of qi and blood and malnutrition of tendons and vessels in local area because of local retention of "stasis" after surgical trauma. In treatment of postoperative facial paralysis with acupotomy, the abnormal facial structure after operation should be considered specially. The region where acupotomy is exerted is determined by taking surgical scar as the center so that the local adhesion can be released and separated. In treatment, the knife needle should be as fine as possible and the attention be paid to the direction of needle insertion and the release amplitude. The frequency of acupotomy should be once per week.


Assuntos
Terapia por Acupuntura , Paralisia Facial , Paralisia Facial/etiologia , Paralisia Facial/terapia , Humanos , Terapias Mente-Corpo , Período Pós-Operatório , Tendões
12.
Front Immunol ; 12: 679090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054869

RESUMO

Immune checkpoint inhibitors (ICIs) have become a promising area of research for cancer treatment. In addition to the well-known ICIs targeting PD-1/PD-L1, HLA-G/ILT-2/-4 is relatively new immune checkpoint that has been evaluated in early clinical trials in patients with advanced solid tumors. In this study, the expression of HLA-G (n=157), ILT-2/4 (n=82), and PD-L1 (n=70) in epithelial cell adhesion molecule (EpCAM)-positive colorectal cancer (CRC) cells was analyzed by multicolor flow cytometry, and the prognostic significance of these molecules was evaluated. In EpCAM+ CRC cells, the median percentages of HLA-G, ILT-2, ILT-4, and PD-L1 were 14.90%, 67.70%, 8.55% and 80.30%, respectively. In addition, a positive correlation was observed between them (all p<0.001). Higher levels of these immune checkpoint proteins are associated with lymph node metastasis. In addition to the AJCC stage (p=0.001), Kaplan-Meier survival analysis showed that higher levels of HLA-G (p=0.041), ILT-2 (p=0.060), ILT-4 (p<0.001), PD-L1 (p=0.012), HLA-GILT4 (p<0.001) and ILT-2ILT-4 (p<0.001) were significantly associated with shorter survival of CRC patients. When CRC patients were stratified by early and advanced AJCC stages, HLA-G levels were only related to the survival among CRC patients with early disease stage (p=0.024), while ILT-4 levels were significant for both CRC patients with early (p=0.001) and advanced (p=0.020) disease stages. Multivariate cox regression analysis revealed that advanced AJCC stage (HR=2.435; p=0.005) and higher ILT-4 levels (HR=2.198; p=0.063) were independent risk factors for poor outcomes in patients with CRC. In summary, among the immune checkpoints, HLA-G/ILT-2/4 and PD-L1, ILT-4 is the most significant prognostic indicator of CRC. This finding indicated that a combination of immunotherapy strategies, such as ILT-4 blockade, could improve the clinical outcomes in patients with cancer. Moreover, multicolor flow cytometry can be employed as a reliable and efficient, alternative to immunohistochemistry, for evaluating the immune checkpoint proteins expressed in tumor lesions.

13.
Subst Use Misuse ; 56(9): 1266-1274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34011246

RESUMO

BACKGROUND: There is a positive cross-sectional relationship between alcohol-related proactive dietary restriction to feel the effects of alcohol faster (APDR) and binge drinking, a health and safety issue impacting college students. Objective: To examine: 1) the longitudinal predictive ability of varying levels of APDR on binge drinking frequency; and 1a) the strength of the relationship between varying levels of APDR and binge drinking frequency during freshman year of college (n = 1,149). METHODS: Ordinal logistic regression was used to model the relationship between APDR and binge drinking frequency. RESULTS: Main findings suggest APDR of students who reported eating less than usual (low APDR) prior to drinking to feel the effects of alcohol faster was a significant predictor of binge drinking frequency (1.27 (95% CI, 0.06 to 0.42), Wald χ2 (1) = 8.46, p=.009) at baseline, but not at 7-month follow-up (1.02 (95% CI, -0.18 to 0.23), Wald χ2 (1) = .51, p=.83). APDR for students who reported skipping one or more meals (high APDR) to feel the effects of alcohol faster was not a significant predictor of binge drinking frequency at baseline nor at 7-month follow-up. CONCLUSION: Low APDR is a significant predictor of binge drinking frequency that is established early in the first semester of college with no significant change occurring in binge drinking frequency over the course of students' freshman year at 7-month follow-up. Campus health professionals are urged to emphasize the detrimental health effects of low APDR early in the first semester of college.


Assuntos
Consumo de Álcool na Faculdade , Consumo Excessivo de Bebidas Alcoólicas , Consumo de Bebidas Alcoólicas , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Humanos , Estudantes , Universidades
14.
Sci Adv ; 7(20)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33980479

RESUMO

Cerebral blood flow (CBF) is essential for brain function, and CBF-related signals can inform us about brain activity. Yet currently, high-end medical instrumentation is needed to perform a CBF measurement in adult humans. Here, we describe functional interferometric diffusing wave spectroscopy (fiDWS), which introduces and collects near-infrared light via the scalp, using inexpensive detector arrays to rapidly monitor coherent light fluctuations that encode brain blood flow index (BFI), a surrogate for CBF. Compared to other functional optical approaches, fiDWS measures BFI faster and deeper while also providing continuous wave absorption signals. Achieving clear pulsatile BFI waveforms at source-collector separations of 3.5 cm, we confirm that optical BFI, not absorption, shows a graded hypercapnic response consistent with human cerebrovascular physiology, and that BFI has a better contrast-to-noise ratio than absorption during brain activation. By providing high-throughput measurements of optical BFI at low cost, fiDWS will expand access to CBF.

15.
Biomed Pharmacother ; 139: 111587, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33865013

RESUMO

Salvia-Nelumbinis naturalis (SNN) formula is a traditional Chinese medicine prescription, and has been confirmed to be effective in treating non-alcoholic steatohepatitis (NASH), but the underlying mechanisms are still unknown. Here we showed that 4-week SNN administration alleviated methionine-choline-deficiency (MCD) diet-induced hepatic steatosis and inflammation as well as serum levels of alanine transaminase (ALT) increase in C57BL/6 mice. Fecal 16S rDNA sequencing indicated that SNN altered the structure of gut microbiota and partially reversed the gut dysbiosis. Simultaneously, we analyzed the fecal BA profile using liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS) -based metabolomics, and found that SNN modulated fecal BA profile, predominantly increased the microbiomes related BA species (e.g. nordeoxycholic acid) which in turn, activated farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway in the colon but not the ileum. The activation of intestinal FXR-FGF15 signaling was accompanied by increase of liver protein kinase B (PKB/Akt) phosphorylation, and decrease of p-65 subunit of NF-κB phosphorylation, resulting in less liver CD68 positive macrophages, and inflammatory cytokine IL-1ß and TNF-α expression. Our results established the link between SNN treatment, gut microbiota, BA profile and NASH, which might shed light into the mechanisms behind the beneficial effects of SNN on NASH, thus provide evidence for the clinical application of SNN.


Assuntos
Deficiência de Colina/complicações , Medicamentos de Ervas Chinesas/uso terapêutico , Metionina/deficiência , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Animais , Deficiência de Colina/genética , Deficiência de Colina/metabolismo , Deficiência de Colina/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Dieta , Medicamentos de Ervas Chinesas/farmacologia , Disbiose/tratamento farmacológico , Disbiose/genética , Disbiose/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Substâncias Protetoras/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Artigo em Inglês | MEDLINE | ID: mdl-33793030

RESUMO

Reductive carboxylation of organo (pseudo)halides with CO2 is a powerful method to provide carboxylic acids quickly. Notably, the catalytic reductive carbo-carboxylation of unsaturated hydrocarbons via CO2 fixation is a highly challenging but desirable approach for structurally diverse carboxylic acids. There are only a few reports and no examples of alkenes via transition metal catalysis. We report the first asymmetric reductive carbo-carboxylation of alkenes with CO2 via nickel catalysis. A variety of aryl (pseudo)halides, such as aryl bromides, aryl triflates and inert aryl chlorides of particular note, undergo the reaction smoothly to give important oxindole-3-acetic acid derivatives bearing a C3-quaternary stereocenter. This transformation features mild reaction conditions, wide substrate scope, facile scalability, good to excellent chemo-, regio- and enantioselectivities. The method highlights the formal synthesis of (-)-Esermethole, (-)-Physostigmine and (-)-Physovenine, and the total synthesis of (-)-Debromoflustramide B, (-)-Debromoflustramine B and (+)-Coixspirolactam A; thereby, opening an avenue for the total synthesis of chiral natural products with CO2 .

17.
Molecules ; 26(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921192

RESUMO

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-ß1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-ß1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.


Assuntos
Movimento Celular/efeitos dos fármacos , Cisplatino/farmacologia , Resveratrol/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Cryobiology ; 100: 58-62, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33831370

RESUMO

Techniques for the cryopreservation of epididymal sperm was are widely used in clinical practice. However, given the unique characteristics of sperm from patients with obstructive azoospermia, epididymal sperm cryopreservation is more difficult because of low count and weak motility; therefore, conventional methods of sperm cryopreservation may not result in the best outcomes. We used the micro-straw method to store small quantities of sperm obtained from patients with severe oligozoospermia or azoospermia and achieved successful deliveries in the previous study. This retrospective study of ICSI cycles included the first ICSI cycles of fresh or frozen/thawed epididymal sperm that were performed in patients suffering from obstructive azoospermia who were admitted to the CITIC-Xiangya Hospital of Reproduction and Genetics of China from June 1, 2015 to June 31, 2019. A total of 2441 patients with obstructive azoospermia were divided according to the use of fresh (n = 2342) or frozen/thawed (n = 99) epididymal sperm. The results showed that the fertilisation rate was higher with fresh epididymal sperm than that with frozen/thawed epididymal sperm (85.14% vs. 79.26%, respectively; p = 0.000). However, the rates of embryo cleavage, high-quality embryos, clinical pregnancy, miscarriage, singletons and birth defect were similar between fresh and frozen/thawed epididymal sperm (98.28% vs. 99.13%, 60.34% vs. 57.29%, 67.90% vs. 70.51%, 8.12% vs. 10.91%, 57.76% vs. 49.09%, 1.59% vs. 1.45%respectively; p = 0.088, 0.109, 0.628, 0.462,0.203 and 0.686). In addition, the short-term cryostorage of small quantities of epididymal sperm did not affect clinical outcomes. The results indicated that in cases of obstructive azoospermia, cryostorage of small quantities epididymal sperm is a reliable option.


Assuntos
Azoospermia , Oligospermia , China , Criopreservação/métodos , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Espermatozoides , Testículo
19.
Adv Sci (Weinh) ; 8(7): 2002715, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33854880

RESUMO

The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disease Registry priority list of hazardous substances. Here, we assess cross-generational effects of iAs in an exclusive male-lineage transmission paradigm. The exposure of male mice to 250 ppb iAs causes glucose intolerance and hepatic insulin resistance in F1 females, but not males, without affecting body weight. Hepatic expression of glucose metabolic genes, glucose output, and insulin signaling are disrupted in F1 females. Inhibition of the glucose 6-phosphatase complex masks the intergenerational effect of iAs, demonstrating a causative role of hepatic glucose production. F2 offspring from grandpaternal iAs exposure show temporary growth retardation at an early age, which diminishes in adults. However, reduced adiposity persists into middle age and is associated with altered gut microbiome and increased brown adipose thermogenesis. In contrast, F3 offspring of the male-lineage iAs exposure show increased adiposity, especially on a high-calorie diet. These findings have unveiled sex- and generation-specific heritable effects of iAs on metabolic physiology, which has broad implications in understanding gene-environment interactions.

20.
J Cell Physiol ; 236(10): 6948-6962, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33682931

RESUMO

ACSS1/2 converts acetate into acetyl-coenzyme A, which contributes to histone acetylation in the mitochondria and cytoplasm. Zygotic genome activation (ZGA) is critical for embryo development involving drastic histone modification. An efficient crRNAs-Cas13a targeting strategy was employed to investigate the ACSS1/2 function during ZGA. The results showed that nuclear accumulation of ACSS1 and ACSS2 occurs during ZGA. Knockdown of ACSS1/2 did not affect blastocyst formation when using a normal medium. On culturing embryos in a medium with acetate and no pyruvate (-P + Ace), knockdown of ACSS1 did not affect histone acetylation levels but significantly reduced ATP levels, whereas knockdown of ACSS2 significantly reduced histone acetylation levels in porcine embryos. Inhibition of fatty acid beta-oxidation by etomoxir significantly reduced ATP levels, which could be restored by acetate. The histone acetylation levels in the ACSS1 and ACSS2 knockdown groups both decreased considerably after etomoxir treatment. Moreover, acetate showed dose-dependent effects on SIRT1 and SIRT3 levels when under metabolic stress. The C-terminus of ACSS1 regulated the nuclear translocation. In conclusion, ACSS1/2 helps to maintain ATP and histone acetylation levels in porcine early embryos under metabolic stress during ZGA.

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