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1.
Mundo saúde (Impr.) ; 48: e15762023, 2024.
Article in English, Portuguese | LILACS-Express | LILACS | ID: biblio-1532711

ABSTRACT

O objetivo desta pesquisa foi a identificação, por meio de espectroscopia no infravermelho com transformada de Fourier combinada com reflectância total atenuada (FTIR-ATR), de microplásticos extraídos do trato gastrointestinal de peixes coletados no Lago de Amatitlán, para determinar os principais polímeros e a possível origem da contaminação por esses materiais. Foram analisados 68 microplásticos, correspondendo a 10% do total de microplásticos extraídos. Estes originaram-se de 36 espécimes, sendo 35 da espécie Oreochromis niloticus e um de Parachromis managuensis, dos quais foram analisados de 1 a 5 microplásticos por espécime. Os polímeros identificados foram polipropileno (PP), nylon, polietileno de alta densidade (HDPE), tereftalato de polietileno (PET), látex, poliestireno (PE), polietileno de baixa densidade (LDPE) e poliuretano (PU). O polipropileno (32), o polietileno de alta densidade (13) e o nylon (10) foram os polímeros mais frequentes. Os possíveis itens plásticos que podem ter originado os microplásticos incluem brinquedos, equipamentos de laboratório, baldes, embalagens de alimentos, tubulações, isolamento para cabos, têxteis, cordas e móveis que são produzidos na indústria do plástico, localizada principalmente na vertente sul da cidade da Guatemala. Além disso, as espécies de peixes do presente estudo sustentam pescarias importantes, o que levanta problemas de saúde humana, uma vez que a ingestão de peixes que consomem plásticos tem o potencial de aumentar a carga corporal de substâncias químicas perigosas, pois estas aderem superficialmente aos plásticos no ambiente e são posteriormente bioacumuladas.


The objective of this research was the identification, through Fourier transform infrared spectroscopy combined with attenuated total reflectance (FTIR-ATR), of microplastics extracted from the gastrointestinal tract of fish collected in Lake Amatitlán, to determine the main polymers and the possible origin of contamination by these materials. 68 microplastics were analyzed, corresponding to 10% of the total microplastics extracted. These originated from 36 specimens, 35 of the species Oreochromis niloticus and one of Parachromis managuensis, of which 1 to 5 microplastics per specimen were analyzed. The polymers identified were polypropylene (PP), nylon, high-density polyethylene (HDPE), polyethylene terephthalate (PET), latex, polystyrene (PE), low-density polyethylene (LDPE) and polyurethane (PU). Polypropylene (32), high-density polyethylene (13) and nylon (10) were the most frequent polymers. Possible plastic items that may have caused microplastics include toys, laboratory equipment, buckets, food packaging, pipes, insulation for cables, textiles, ropes and furniture that are produced in the plastics industry, located mainly on the south side of Guatemala City. Furthermore, the fish species in the present study support important fisheries, which raises human health concerns, since the ingestion of fish that consume plastics has the potential to increase the body load of dangerous chemicals, as they adhere superficially to the plastics in the environment and are subsequently bioaccumulated.

2.
Chinese Journal of Primary Medicine and Pharmacy ; (12): 1199-1204, 2023.
Article in Chinese | WPRIM | ID: wpr-991886

ABSTRACT

Objective:To investigate the effects of Zhibitai capsule combined with pitavastatin calcium tablets on blood lipids, blood glucose, and glycated hemoglobin in patients with coronary heart disease complicated by diabetes mellitus. Methods:A total of 100 patients with coronary heart disease and diabetes mellitus who received treatment in The Third Affiliated Hospital of Jinzhou Medical University from January 2017 to June 2020 were included in this study. They were divided into a control group ( n = 50) and an observation group ( n = 50) according to different treatment methods. Both groups were given conventional treatment such as pitavastatin calcium tablets. The control group was given pitavastatin calcium tablets based on conventional treatment. The observation group was given Zhibitai capsule combined with pitavastatin calcium tablets based on conventional treatment. After 6 months of treatment, serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and glycated hemoglobin were compared between the two groups. Results:After treatment, serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, glycated hemoglobin in the observation group were (4.26 ± 0.67) mmol/L, (1.85 ± 0.38) mmol/L, (3.16 ± 0.27) mmol/L, (8.29 ± 1.07) mmol/L, and (8.20 ± 0.77)%, respectively, and they were (4.50 ± 0.39) mmol/L, (1.99 ± 0.19) mmol/L, (3.28 ± 0.27) mmol/L, (8.80 ± 0.66) mmol/L, (8.54 ± 0.74)%, respectively in the control group. After treatment, these indices in each group were decreased compared with those before treatment (control group: t = 19.56, 14.60, 10.66, 8.60, 10.18; observation group: t = 15.04, 14.68, 11.36, 12.36, 12.89, all P < 0.05). After treatment, these indices in the observation group were significantly lower than those in the control group ( t = -2.12, -2.23, 2.26, -2.84, -2.44, all P < 0.05). After treatment, the level of high-density lipoprotein cholesterol in the observation and control groups was (1.16 ± 0.18) mmol/L and (1.09 ± 0.13) mmol/L, respectively. After treatment, the level of high-density lipoprotein cholesterol in each group was increased compared with that before treatment (control group: t = -11.10, observation group: t = -11.07, P < 0.05). After treatment, the level of high-density lipoprotein cholesterol in the observation group was significantly higher than that in the control group ( t = 2.11, P < 0.05). Conclusion:Zhibitai capsule combined with pitavastatin calcium tablets can greatly improve the level of blood lipids and blood glucose in patients with coronary heart disease complicated by diabetes mellitus.

3.
Journal of Pharmaceutical Analysis ; (6): 603-615, 2023.
Article in Chinese | WPRIM | ID: wpr-991168

ABSTRACT

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

4.
Journal of China Pharmaceutical University ; (6): 323-332, 2023.
Article in Chinese | WPRIM | ID: wpr-987649

ABSTRACT

@#Screening potential active compounds from molecular libraries is a common method for drug discovery.However, with the continuous exploration of chemical space, there are already compound libraries with more than billions of molecules, so molecular docking is no longer enough to quickly screen specific target inhibitors from the ultra-large compound libraries.This study proposes a method for screening potential active compounds, which involves filtering and selecting compounds from a candidate compound library containing over 5.5 billion molecules through a series of steps, including calculating physical and chemical property similarities, constructing machine learning prediction models, and molecular docking.In the end, 51 compounds with potential ataxia telangiectasia-mutated and rad3-related (ATR) inhibitory activity were obtained.This method is effective for rapidly screening novel potential active compounds from large compound libraries.

5.
Rev. mex. ing. bioméd ; 43(3): 1304, Sep.-Dec. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1450145

ABSTRACT

ABSTRACT COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. This virus's spread is mainly through droplets released from the nose or mouth of an infected person. Although vaccines have been developed that effectively reduce the effects that this viral infection causes, the most effective method to contain the virus's spread is numerous tests to detect and isolate possible carriers. However, the response time, combined with the cost of actual tests, makes this option impractical. Herein, we compare some machine learning methodologies to propose a reliable strategy to detect people positive to COVID-19, analyzing saliva spectra obtained by Fourier transform infrared (FTIR) spectroscopy. After analyzing 1275 spectra, with 7 strategies commonly used in machine learning, we concluded that a multivariate linear regression model (MLMR) turns out to be the best option to identify possible infected persons. According to our results, the displacement observed in the region of the amide I of the spectrum, is fundamental and reliable to establish a border from the change in slope that causes this displacement that allows us to characterize the carriers of the virus. Being more agile and cheaper than reverse transcriptase polymerase chain reaction (RT-PCR), it could be reliably applied as a preliminary strategy to RT-PCR.


RESUMEN La COVID-19 es una enfermedad infecciosa ocasionada por el virus SARS-CoV-2. La propagación de este virus se produce principalmente a través de gotitas liberadas por la nariz o la boca de una persona infectada. Aunque se han desarrollado vacunas que permiten reducir efectivamente los efectos que esta infección viral provoca, el método más eficaz para contener la propagación del virus son las numerosas pruebas para detectar y aislar los posibles portadores. Sin embargo, el tiempo de respuesta, combinado con el costo de las pruebas reales, hace que esta opción sea poco práctica. Aquí, comparamos algunas metodologías de machine learning para proponer una estrategia confiable para detectar personas positivas a COVID-19 analizando espectros de saliva obtenidos por espectroscopia infrarroja transformada de Fourier (FTIR). Tras analizar 1275 espectros, con 7 estrategias comúnmente empleadas en el área de machine learning, concluimos que un modelo de regresión lineal multivariante (MLMR) resulta ser la mejor opción para identificar posibles infectados. De acuerdo con nuestros resultados, el desplazamiento observado en la región de la amida I del espectro, resulta fundamental y confiable para establecer una frontera a partir del cambio de pendiente que este provoca. Al ser más ágil y económica que la reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR), podría aplicarse confiablemente como estrategia preliminar a RT-PCR.

6.
Acta Pharmaceutica Sinica B ; (6): 1339-1350, 2022.
Article in English | WPRIM | ID: wpr-929373

ABSTRACT

DNA damage response (DDR) is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs. Hence, small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy. Through a recent chemical library screen, we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins. Mechanistically, shikonin inhibited the activation of ataxia telangiectasia mutated (ATM), and to a lesser degree ATM and RAD3-related (ATR), two master upstream regulators of the DDR signal, through inducing degradation of ATM and ATR-interacting protein (ATRIP), an obligate associating protein of ATR, respectively. As a result of DDR inhibition, shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models. While degradation of ATRIP is proteasome dependent, that of ATM depends on caspase- and lysosome-, but not proteasome. Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs. These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin. Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.

7.
Acta Pharmaceutica Sinica ; (12): 593-604, 2022.
Article in Chinese | WPRIM | ID: wpr-922902

ABSTRACT

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

8.
Journal of Leukemia & Lymphoma ; (12): 701-704, 2022.
Article in Chinese | WPRIM | ID: wpr-954022

ABSTRACT

Almost 50% myelodysplastic syndromes (MDS) patients have different splicing factor mutations, including SF3B1, SRSF2, U2AF1. Different splicing factor mutations cause the various mechanisms of slicing abnormality and eventually lead to the similar MDS phenotypes, indicating that splicing factor mutations might generate the common pathopoiesia pathway different from slicing abnormality. Recent studies have shown that SF3B1, U2AF1 and SRSF2 mutations could contribute to the accumulation of R-loop, cause DNA damage and repair abnormality, activate ATR-Chk1 pathway and finally promote apoptosis and tumorigenesis. This paper reviews the role of R-loop in the pathogenesis of MDS and the progress of related targeted drugs.

9.
Acta Pharmaceutica Sinica B ; (6): 1813-1834, 2021.
Article in English | WPRIM | ID: wpr-888836

ABSTRACT

Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol (PPD)-, protopanaxatriol (PPT)-, ocotillol (OCT)- and oleanane (OA)-type saponins known as active compounds of

10.
Acta Pharmaceutica Sinica B ; (6): 309-321, 2021.
Article in English | WPRIM | ID: wpr-881138

ABSTRACT

Cullin-RING ligases (CRLs) recognize and interact with substrates for ubiquitination and degradation, and can be targeted for disease treatment when the abnormal expression of substrates involves pathologic processes. Phosphorylation, either of substrates or receptors of CRLs, can alter their interaction. Phosphorylation-dependent ubiquitination and proteasome degradation influence various cellular processes and can contribute to the occurrence of various diseases, most often tumorigenesis. These processes have the potential to be used for tumor intervention through the regulation of the activities of related kinases, along with the regulation of the stability of specific oncoproteins and tumor suppressors. This review describes the mechanisms and biological functions of crosstalk between phosphorylation and ubiquitination, and most importantly its influence on tumorigenesis, to provide new directions and strategies for tumor therapy.

11.
Acta Pharmaceutica Sinica B ; (6): 2983-2994, 2021.
Article in English | WPRIM | ID: wpr-922779

ABSTRACT

Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.

12.
China Journal of Chinese Materia Medica ; (24): 5284-5290, 2021.
Article in Chinese | WPRIM | ID: wpr-921674

ABSTRACT

This study aimed to investigate the enhancing effect of muscone on the transdermal penetration of traditional Chinese medicine ingredients and explore its possible mechanism of action. The Franz diffusion cells were employed to investigate the effect of muscone on the transdermal permeation of a series of model drugs with a wide range of log P values. The solubilities at saturation and the stratum corneum(SC)/vehicle partition coefficients of model drugs were measured to evaluate the effect of muscone on drug thermodynamic activities and partition of drugs into SC. Attenuated total reflectance-Fourier transform infrared spectroscopy(ATR-FTIR) was employed to explore the effect of muscone on the molecular structure of SC. The results showed that muscone significantly promoted the transdermal penetration of hydrophilic and lipophilic drugs, and the enhancement ratio(ER) increased with the decrease in the log P. Muscone could interact with the SC lipids to increase the disorder and fluidity of lipid bilayer packing, which improved skin permeability and promoted transdermal absorption of drugs. This study provides a scientific basis for the application of muscone in traditional Chinese medicine topical preparations.


Subject(s)
Animals , Rats , Administration, Cutaneous , Cycloparaffins , Medicine, Chinese Traditional , Permeability , Rats, Sprague-Dawley , Skin/metabolism , Skin Absorption
14.
Malaysian Journal of Medicine and Health Sciences ; : 162-169, 2020.
Article in English | WPRIM | ID: wpr-975185

ABSTRACT

@#Introduction: Non-destructive analysis of biological evidence has been paramount importance in the forensic investigation since it is an effective tool in establishing a standard that could be employed to differentiate ensuing destructive tests of bio-fluids upon sample division between the plaintiff and defendant. Species identification of bloodstain found at the crime scene is very crucial in routine forensic work as this can assist the initial investigation by incorporating or excluding stain that is not human and to identify its origin if animal blood is involved. Methods: In this research, identification and discrimination of various blood species collected from seven domestic animals namely chicken, cow, deer, duck, fish, goat, and pig were investigated using non-destructive analytical techniques; ATRFTIR and visible spectroscopy coupled with principal component analysis and linear discriminant analysis (PCALDA) for classification purposes. Results: ATR-FTIR FTIR spectroscopic study demonstrated a higher rate of successful classification (≥ 90%) as compared to visible spectroscopic technique. Conclusion: ATR-FTIR spectroscopy has been an ideal, robust, and suitable tool for determining the blood species of domestic animals. The predictive model from PCA-LDA analysis can be utilised to produce higher classification rate for species determination from blood traces.

15.
Journal of Medical Postgraduates ; (12): 32-37, 2020.
Article in Chinese | WPRIM | ID: wpr-818370

ABSTRACT

Objective At present, the main studies of ginsenoside Rg1 are almost on the field of solid tumors and acute leukemias, and few on chronic leukemias. We aims to figure out the role of ATR-Chk1 pathway on cell aging in ginsenoside Rg1-treated leukemia K562 cells. Methods K562 cells were treated with ginsenoside Rg1 at different concentrations and divided into a control group (with 50 μL PBS culture solution) and 5 μmol/L ginsenoside group, 10 μmol/L ginsenoside group, 20 μmol/L ginsenoside group, 40 μmol/L ginsenoside group, 80 μmol/L ginsenoside group. CCK-8 assay,colony formation assay and flow cytometry for cell cycle detection were used to determine the effect of ginsenoside Rg1 on the aging of K562 cells. SA-β-Gal staining and Wright’s staining were used to observe the morphological changes of K562 cells’ aging. Real-time quantitative PCR and Western blot were used to detect the changes of ATR and Chk1 expression. Results The colony formation rate of K562 cells in the 20 μmol/L ginsenoside group was significantly lower than that in the other groups (P<0.05). CCK-8 test results showed that K562 cell proliferation of ginsenoside Rg1 induced groups was higher than that of the control group at 24, 48, and 72 hours (P<0.05). K562 cell proliferation inhibition rate was the highest in 20 μmol/L ginsenoside group for 48 hours treatment (P<0.05). The rate of SA-β-Gal positive cells [(95.833 ± 1.528) %] in 20 μmol/L ginsenoside-treated K562 cells for 48 h was significantly higher than that of the control group [(3.083 ± 0.764) %]. Cells blocked in G0/G1 phase and entered S and G2/M phases were significantly higher and lower than those in the control group, respectively (P<0.05).The ATR and Chk1 mRNA expression levels [(0.0117 ± 0.0038) %, (0.0120 ± 0.0021) %] were significantly higher than that of the control group ([0.0027 ± 0.0006) %, (0.0058 ± 0.0019) %) (P<0.05). ATR and Chk1 relative protein expression levels [(19.370 ± 0.994) %, (43.520 ± 1.236) %] were significantly increased compared with that of the control group [(17.080 ± 1.274) %, (39.100 ± 0.969) %) (P<0.05). Conclusion Ginsenoside Rg1 can induce the aging of K562 cells by regulating the ATR-Chk1 pathway, providing a new target for clinical leukemia treatment.

16.
Malaysian Journal of Medicine and Health Sciences ; : 112-117, 2020.
Article in English | WPRIM | ID: wpr-829459

ABSTRACT

@#Introduction: Accelerants and fabrics are commonly used to spread fire attributable to their highly flammable properties. Hence, having the ability to discriminate the different types of accelerants on various types of fabrics after fire and/or arson using the non-destructive Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy coupled with chemometric techniques appears forensically relevant. Methods: Six types of fabrics viz. cotton, wool, silk, rayon, satin, and polyester, were burnt completely with RON95 and RON97 gasoline as well as diesel. Subsequently, the samples were analyzed by ATR-FTIR spectroscopy followed by Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) for discriminating the different types of accelerants on such burned fabrics. Results: RON95 showed the fastest rate of burning on all fabric types. Results also revealed that while wool had the slowest burning rate for all the three different accelerants, polyester, cotton, and satin demonstrated the highest rate of burning in RON95, RON97, and diesel, respectively. FTIR spectra revealed the presence of alkane, alcohol, alkene, alkyne, aromatic, and amine compounds for all fabrics. The two dimensional PCA (PC1 versus PC2) demonstrated 71% of variance and it was improved by cross-validation through the three dimensional LDA technique with correct classification of 77.8%. Conclusion: ATR-FTIR spectroscopy coupled with chemometric techniques had enabled identification of the functional groups, as well as statistically supported discrimination of the different accelerants, a matter of relevance in forensic fire and arson investigations.

17.
Article | IMSEAR | ID: sea-201323

ABSTRACT

Background: The development of research capacity at undergraduate level is essential to produce good quality researchers in the long run. The core curriculum must ensure that relevant and appropriate research expertise is attained by all graduates who are then provided with a suitable foundation from which they can develop such specialized research skills as may be required in their careers.Methods: A cross sectional study was conducted in Terna Medical College, Nerul, Navi Mumbai from May 2016- September 2016. All students of second and third year who willingly participated were included in the study. Preformed pretested and validated proforma was used. For checking attitudes a standard attitudes towards research scale was been used which contained 32 questions.Results: 74.9% said that research methodology should be the part of curriculum. 37.7% said that they would like to opt a carrier as a researcher. 70.6% students either identified no opportunities, gave no response or didn’t know about opportunities. Biggest barriers identified were lack of knowledge (36.5%), lack of time (34.7%), lack of infrastructure (25.1%). Correlation coefficients between ATR sub-scales were also calculated.Conclusions: Students’ want to conduct research at undergraduate level and want incorporation of research methodology in curriculum. Lack of knowledge, time and resources are common barriers while opportunities, majority are not aware about it. Though students find research difficult and are anxious about it, they have positive attitude towards conducting research.

18.
Cancer Research and Treatment ; : 1167-1179, 2019.
Article in English | WPRIM | ID: wpr-763163

ABSTRACT

PURPOSE: The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor. MATERIALS AND METHODS: A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings. RESULTS: Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug. CONCLUSION: In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.


Subject(s)
Animals , Humans , Mice , Apoptosis , Ataxia Telangiectasia , Biliary Tract Neoplasms , Biliary Tract , Cell Cycle , Cell Cycle Checkpoints , Cell Line , Cisplatin , Comet Assay , DNA Damage , DNA Repair , DNA , ATP Binding Cassette Transporter, Subfamily B, Member 1
19.
Braz. dent. sci ; 22(1): 111-117, 2019. tab, ilus
Article in English | LILACS, BBO | ID: biblio-986946

ABSTRACT

Objective: To evaluate the fracture resistance (RF) of Class II Glass-ionomer Cement (GIC) ART restorations with and without proximal retentions. Material and Methods: 20 freshly extracted human molars were used. Forty (40) standard Mesial-Occlusal (MO) and DistalOcclusal (DO) preparations (20 for each material) were performed with a 245 bur. The unprepared surfaces of the teeth were protected with nail polish and the specimens submerged in 0.5Mol EDTA solution, pH 7.4 for 8h under stirring. The preparations were finished with dentine spoons and 50% received proximal retention with # 3 excavators. 20 cavities were restored with Chemfil Rock (10 with retention and 10 without retention) and 20 cavities were restored with Equia Fil (10 with retention and 10 with no retention) and were stored in an oven at 37ºC and 100% relative humidity for 24h and submitted to axial compression loading in Test Machine - EMIC at a rate of 0.5 mm / minute, until restoration fracture occurred. The values were analyzed by two-way ANOVA (p<0.05). Results: ChemFil Rock presented 300.84 (69.20) (without retention) and 361.70 (81.08) (with retention) and Equia Fil showed 314.60 (69.97) (without retention) and 366.67 (103.38) (with retention). Data obtained with retention were statistically superior to those obtained with non-retained ART restorations (p=0.014). No statistical differences were detected between materials (p=0.761). Conclusion: Retentive grooves improved fracture resistance of Class II GIC ART restorations. (AU)


Objetivo: avaliar a resistência à fratura (FR) de restaurações de ART de Classe II de Cimento de ionômero de vidro (CIV) com e sem retenções proximais. Material e Métodos: Foram utilizados 20 molares humanos recém-extraídos. 40 cavidades padronizadas no sentido Mesial-Oclusal (MO) e Oclusal-Distal (OD) (20 para cada material) foram realizadas com uma broca 245. Os preparos cavitários foram submersos em solução 0,5 mol Mol EDTA, pH 7,4 por 8h sob agitação e foram finalizados com colheres de dentina, nos quais 50% receberam retenções proximais com escavadores #3. 20 cavidades foram restauradas com Chemfil Rock (10 com e 10 sem retenção) e 20 cavidades foram restauradas com Equia Fil (10 com e 10 sem retenção) e armazenadas em estufa a 37ºC e 100% de umidade relativa por 24h e submetidos a carga axial de compressão na máquina de ensaios EMIC a uma taxa de 0,5mm/min, até que a fratura de restauração ocorresse. Os valores foram analisados por ANOVA twoway (p<0,05). Resultados: ChemFil Rock apresentou 300.84 (69.20) (sem retenção) e 361.70 (81.08) (com retenção) e o Equia Fil apresentou 314.60 (69.97) (sem retenção) e 366.67 (103.38) (com retenção). Os dados obtidos com retenção foram estatisticamente superiores àqueles sem retenção (p=0.014). Não houve diferença estatística entre os materiais (p=0.761). Conclusão: Os sulcos retentivos melhoraram a resistência à fratura de restaurações de ART de Classe II de Cimento de ionômero de vidro (CIV).(AU)


Subject(s)
Weight-Bearing , Dental Materials , Glass Ionomer Cements
20.
Chinese Pharmacological Bulletin ; (12): 859-863, 2019.
Article in Chinese | WPRIM | ID: wpr-857240

ABSTRACT

Aim: To investigate the effects of gender differences and estrogen levels on ACE, -Ang II -ATR axis in the aorta tissue of renovascular hypertension (RVH) rats. Methods: Forty-five rats were made two-kidney one-clip (2K1C) model of renovascular hypertension and divided into three groups: female two kidney one clip group (2K1C-F), male two kidney one clip group (2K1C-M), and ovariectomized group (2K1C-0VX). After 32 weeks of routine feeding, the blood pressure was measured, blood was taken and-serum and plasma were prepared. Serum estrogen and plasma Ang II were measured and mRNA and protein expression levels of ACE, AT, R, AT2R in aorta tissue were detected. Results: Systolic blood pressure of 2K1C-F group was significantly higher than that of 2K1C-M group and 2K1C-0VX group (P < 0.05). The content of Ang II in 2K1C-F group was significantly lower than that in 2K1C-M and 2K1C-0VX group(P <0. 01). Compared with 2K1C-F group, the mRNA and protein expressions of ACE!, AT, R, AT2R in 2K1C-M group were up-regulated significantly (P < 0. 05), while the mRNA expression of ATlb R, ACE, was up-regulated, and the mRNA expression of AT2R was down-regulated in 2K1C-OVX group (P < 0. 05); compared with 2K1C-M group, the mRNA expression of ACE, ATlb R, AT2R and protein expression of ACE, AT2R were down-regulated significantly in 2K1C-OVX group(P < 0. 05). Conclusions: The mRNA and protein expressions of ACE, Ang II, AT1aR and AT1bR in aorta tissue show gender and estrogen differences, and estrogen can reduce the activity of ACE, -Ang II -AT, R axis.

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