Resumo Fundamento: O antibiótico quimioterápico antraciclina doxorrubicina (DOX) pode induzir cardiotoxicidade cumulativa e levar à disfunção cardíaca. RNAs não codificantes longos (lncRNAs) podem funcionar como importantes reguladores na lesão miocárdica induzida por DOX. Objetivo: Este estudo tem como objetivo investigar o papel funcional e o mecanismo molecular do RNA antisense lncRNA OXCT1 1 (OXCT1-AS1) na lesão celular miocárdica induzida por DOX in vitro. Métodos: Cardiomiócitos humanos (AC16) foram estimulados com DOX para induzir um modelo de lesão celular miocárdica. A expressão de OXCT1-AS1, miR-874-3p e BDH1 em células AC16 foi determinada por RT-qPCR. A viabilidade das células AC16 foi medida pelo ensaio XTT. A citometria de fluxo foi empregada para avaliar a apoptose de células AC16. Western blotting foi utilizado para avaliar os níveis proteicos de marcadores relacionados à apoptose. O ensaio repórter de luciferase dupla foi conduzido para verificar a capacidade de ligação entre miR-874-3p e OXCT1-AS1 e entre miR-874-3p e BDH1. O valor de p<0,05 indicou significância estatística. Resultados: A expressão de OXCT1-AS1 foi diminuída em células AC16 tratadas com DOX. A superexpressão de OXCT1-AS1 reverteu a redução da viabilidade celular e a promoção da apoptose celular causada pela DOX. OXCT1-AS1 está ligado competitivamente ao miR-874-3p para regular positivamente o BDH1. A superexpressão de BDH1 restaurou a viabilidade das células AC16 e suprimiu a apoptose celular sob estimulação com DOX. A derrubada do BDH1 reverteu a atenuação da apoptose de células AC16 mediada por OXCT1-AS1 sob tratamento com DOX. Conclusão: LncRNA OXCT1-AS1 protege células miocárdicas humanas AC16 da apoptose induzida por DOX através do eixo miR-874-3p/BDH1. Fundamento (DOX cardíaca lncRNAs (lncRNAs Objetivo OXCT OXCT1AS1 OXCTAS AS1 AS (OXCT1-AS1 vitro Métodos AC (AC16 OXCT1AS1, AS1, miR8743p miRp miR 874 3p p BDH AC1 RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR XTT OXCT1-AS p005 0 05 p<0,0 estatística Resultados Conclusão miR8743p/BDH1. miR8743pBDH1 miRpBDH 3p/BDH1. miR-874-3p/BDH1 OXCT1AS (OXCT1-AS (AC1 87 p00 p<0, miR8743p/BDH1 pBDH miR8743pBDH 3pBDH1 3p/BDH1 miR-874-3p/BDH (AC 8 p0 p<0 miR8743p/BDH 3pBDH 3p/BDH p<

Abstract Background: The anthracycline chemotherapeutic antibiotic doxorubicin (DOX) can induce cumulative cardiotoxicity and lead to cardiac dysfunction. Long non-coding RNAs (lncRNAs) can function as important regulators in DOX-induced myocardial injury. Objective: This study aims to investigate the functional role and molecular mechanism of lncRNA OXCT1 antisense RNA 1 (OXCT1-AS1) in DOX-induced myocardial cell injury in vitro. Methods: Human cardiomyocytes (AC16) were stimulated with DOX to induce a myocardial cell injury model. OXCT1-AS1, miR-874-3p, and BDH1 expression in AC16 cells were determined by RT-qPCR. AC16 cell viability was measured by XTT assay. Flow cytometry was employed to assess the apoptosis of AC16 cells. Western blotting was used to evaluate protein levels of apoptosis-related markers. Dual-luciferase reporter assay was conducted to verify the binding ability between miR-874-3p and OXCT1-AS1 and between miR-874-3p and BDH1. The value of p<0.05 indicated statistical significance. Results: OXCT1-AS1 expression was decreased in DOX-treated AC16 cells. Overexpression of OXCT1-AS1 reversed the reduction of cell viability and promotion of cell apoptosis caused by DOX. OXCT1-AS1 is competitively bound to miR-874-3p to upregulate BDH1. BDH1 overexpression restored AC16 cell viability and suppressed cell apoptosis under DOX stimulation. Knocking down BDH1 reversed OXCT1-AS1-mediated attenuation of AC16 cell apoptosis under DOX treatment. Conclusion: LncRNA OXCT1-AS1 protects human myocardial cells AC16 from DOX-induced apoptosis via the miR-874-3p/BDH1 axis. Background (DOX dysfunction noncoding non coding lncRNAs (lncRNAs DOXinduced induced Objective OXCT OXCT1AS1 OXCTAS AS1 AS (OXCT1-AS1 vitro Methods AC (AC16 model OXCT1AS1, AS1, miR8743p, miR8743p miRp miR 874 3p, 3p p BDH AC1 RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR apoptosisrelated related markers Dualluciferase Dual luciferase OXCT1-AS p005 0 05 p<0.0 significance Results DOXtreated treated stimulation OXCT1AS1mediated OXCTASmediated mediated treatment Conclusion miR8743p/BDH1 miR8743pBDH1 miRpBDH 3p/BDH1 miR-874-3p/BDH axis OXCT1AS (OXCT1-AS (AC1 87 p00 p<0. miR8743p/BDH pBDH miR8743pBDH 3pBDH1 3p/BDH (AC 8 p0 p<0 3pBDH p<

Transarterial chemoembolization (TACE) is an established therapeutic strategy for intermediate stage Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC). However, patients who are early refractory to TACE may not benefit from repeated TACE treatment. Our primary objective was to assess the diagnostic value of inflammatory markers in identifying early TACE refractory for patients with early (BCLC 0 and A) or intermediate (BCLC B) stage HCC. We retrospectively reviewed the HCC patients who underwent TACE as the initial treatment in two hospitals. Patients with early TACE refractoriness had significantly poorer median overall survival (OS) (16 vs 40 months, P<0.001) and progression-free survival (PFS) (7 vs 23 months, P<0.001) compared to TACE non-refractory patients. In the multivariate regression analysis, tumor size (P<0.001), bilobular invasion (P=0.007), high aspartate aminotransferase-to-platelet ratio index (APRI) (P=0.007), and high alpha fetoprotein (AFP) level (P=0.035) were independent risk factors for early TACE refractoriness. The predictive model showcasing these factors exhibited high ability proficiency, with an area under curve (AUC) of 0.833 (95%CI=0.774-0.892) in the training cohort, 0.750 (95%CI: 0.640-0.861) in the internal-validation cohort, and 0.733 (95%CI: 0.594-0.872) in the external-validation cohort. Calibration curve analysis revealed good agreement between the actual and predicted probabilities of early TACE refractoriness. Our preliminary study estimated the potential value of inflammatory markers in predicting early TACE refractoriness and provides a predictive model to assist in identifying patients who may not benefit from repeat TACE treatment. (TACE BCLC . (HCC) However A B hospitals OS (OS 16 (1 4 months P<0.001 P0001 P 001 progressionfree progression free PFS (PFS 7 ( 2 nonrefractory non P<0.001, , (P<0.001) P=0.007, P0007 P=0.007 007 (P=0.007) aminotransferasetoplatelet aminotransferase platelet APRI (APRI AFP (AFP P=0.035 P0035 035 (P=0.035 proficiency AUC (AUC 0833 833 0.83 95%CI=0.7740.892 95CI07740892 CI 95%CI=0.774 0.892 95 774 892 (95%CI=0.774-0.892 cohort 0750 750 0.75 95%CI 95CI (95%CI 0.6400.861 06400861 0.640 0.861 640 861 0.640-0.861 internalvalidation internal validation 0733 733 0.73 0.5940.872 05940872 0.594 0.872 594 872 0.594-0.872 externalvalidation external (HCC 1 P<0.00 P000 00 (P<0.001 P=0.00 (P=0.007 P=0.03 P003 03 (P=0.03 083 83 0.8 7740 95%CI=0.7740.89 95CI0774089 95CI0774 95%CI=0.77 0892 0.89 9 77 89 (95%CI=0.774-0.89 075 75 0.7 6400 0.6400.86 0640086 0640 0.64 0861 0.86 64 86 0.640-0.86 073 73 5940 0.5940.87 0594087 0594 0.59 0872 0.87 59 87 0.594-0.87 P<0.0 P00 (P<0.00 P=0.0 (P=0.00 (P=0.0 08 8 0. 95%CI=0.7740.8 95CI077408 95CI077 95%CI=0.7 089 (95%CI=0.774-0.8 07 0.6400.8 064008 064 0.6 086 6 0.640-0.8 0.5940.8 059408 059 0.5 087 5 0.594-0.8 P<0. P0 (P<0.0 P=0. (P=0. 95%CI=0.7740. 95CI07740 95CI07 95%CI=0. (95%CI=0.774-0. 0.6400. 06400 06 0.640-0. 0.5940. 05940 05 0.594-0. P<0 (P<0. P=0 (P=0 95%CI=0.7740 95CI0 95%CI=0 (95%CI=0.774-0 0.6400 0.640-0 0.5940 0.594-0 P< (P<0 P= (P= 95%CI= (95%CI=0.774- 0.640- 0.594- (P< (P (95%CI=0.774 (95%CI=0.77 (95%CI=0.7 (95%CI=0. (95%CI=0 (95%CI=

Abstract Background Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. Methods Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. Results In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. Conclusions Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis. Highlights Microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs) exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes. Microvesicles from propofol post-treated HUVECs ((HR + P)-EMVs) induced diminished oxidative stress and apoptosis in IR-injured cardiomyocytes compared with microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs). lncCCT4-2 was significantly highly expressed in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs, and reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. lncCCT4-2 inhibited HR-EMVs induced oxidative stress and apoptosis in HR-injured AC16 cells by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in AC16 cells.

Abstract A series of Trolox amide derivatives were synthesized by modifying the carboxyl groups of Trolox. Thirty target compounds were obtained and characterized through nuclear magnetic resonance and mass spectrometry. Trolox derivatives were employed to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) and hydroxyl radical assays. DPPH scavenging activity test results illustrated that compounds exhibited scavenging activities similar to L-ascorbic acid and Trolox, with compounds 14a, 18a, 24a and 26a in particular exhibiting higher scavenging activities than L-ascorbic acid. The results demonstrated that compounds displayed ABTS scavenging activities similar to L-ascorbic acid and Trolox, with compounds 26a and 29a in particular having potency twofold higher. FRAP assay results indicated that compounds 11a, 19a, 25a, 29a and 30a had activity similar to Trolox. The results revealed that compounds 6a and 19a had similarly high hydroxyl radical-scavenging activities as Trolox. The results of α-glucosidase experiments uncovered that compounds 10a, 25a, 28a and 29a had excellent inhibitory activity, which was similar to that of acarbose and different from Trolox. The results of acetylcholinesterase and butyrylcholinesterase experiments demonstrated that some compounds had weak anticholinesterase activities. 26a and 29a are important Trolox derivatives with better biological activity profiles and deserve further study. spectrometry structureantioxidant structure relationships 1,1diphenyl2picrylhydrazyl 11diphenyl2picrylhydrazyl diphenylpicrylhydrazyl 1,1 diphenyl 2 picrylhydrazyl 1 DPPH, , (DPPH) 2,2′azinobis3ethylbenzothiazoline6sulfonic 22azinobis3ethylbenzothiazoline6sulfonic azinobisethylbenzothiazolinesulfonic 2,2′ azino bis 3 ethylbenzothiazoline 6 sulfonic ABTS, (ABTS) (FRAP assays Lascorbic L ascorbic 14a a 18a 11a 25a radicalscavenging αglucosidase α glucosidase 10a study 1diphenyl2picrylhydrazyl 11 1, (DPPH azinobis3ethylbenzothiazoline6sulfonic azinobis 22 2,2 (ABTS 2,

Abstract Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous neurosensory disorder, usually characterized by congenital or prelingual hearing loss. We report a Han Chinese male, born to consanguineous parents, presenting with nonsyndromic sensorineural hearing loss, whose clinical phenotype was also consistent with auditory neuropathy spectrum disorder (ANSD). After exome sequencing, a gap junction protein beta 2 gene (GJB2) c.235delC variant in the homozygous state was detected in the patient. Both parents were heterozygous for this variant, as documented by Sanger sequencing. The known pathogenic GJB2 c.235delC variant was not detected in 200 healthy controls. It is predicted to be a disease-causing alteration by generating a truncated protein p.(L79Cfs*3), disturbing the appropriate folding and/or oligomerization of connexins and leading to defective gap junction channels. This study shows that the association of homozygosity of the GJB2 c.235delC variant with ARNSHL and ANSD in a patient.

The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-β/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.

Safeners are an important tool used to ensure the safe using of herbicide. The objective of this paper was to investigate the protective effect of four 3-dichloroacetyl oxazolidine safeners (3-dichloroacetyl-2,2-dimethyl-1,3-oxazolidine [R-28725], racemate of 3-dichloroacetyl-2,2-dimethyl-4- ethyl-1,3-oxazolidine, and its two chiral stereoisomers) in reducing the injury caused by imazethapyr. Physiological and biochemical tests were conducted under laboratory condition, by using seed treatment with safeners and soil treatment with imazethapyr, respectively. The interaction of two safeners (R-28725 and R-stereoisomer) and imazethapyr reduced the injury of maize significantly, and also increased glutathione content, activity of glutathione S-transferases, and activity of acetolactate synthase in maize. When induced by R-stereoisomer, the GSH content in root and in shoot increased 100.7% and 73.6%, respectively. When induced by R-28725, the GST activity in vivo increased threefold and the GST activity in vitro more than doubled. The kinetic parameter Vmax of GST in the maize treated with R-28725 and R-stereoisomer increased by 102.2% and 81.9%, respectively, compared with the control. The results also showed that R-28725 and R-stereoisomer induced glutathione S-transferases affinity for the substrate of conjugation reaction significantly.

In this study we focused on the development of Cabernet Sauvignon grapes and investigated changes in the activity of alcohol dehydrogenase (ADH) and hydroperoxide lyase (HPL) in different tissues. We sampled grape skin at four, six, seven, eight, nine, 10, 12, 14 and 16 weeks after anthesis; developing flowers when blooming at 0%, 5%, 50%, and 90%; and leaves at two and four weeks before anthesis and at two, four, six, eight, nine, and 10 weeks after anthesis. We also examined the type and fluctuation of volatile contents. ADH activity increased with the development of flowers and grape skins, which led to the increasing of types and concentration of alcohols. Low levels of 9-HPL led to low concentrations of C9 compounds. According to this paper, C6 compounds became abundant with the development of grape berries, while the activity of 13-HPL kept at a low level in the flowers and grape skins. There might have been a high level of 13-HPL activity from the end of flowering until fruit setting that we did not detect. Furthermore, similar C6 and C5 compounds were detected across all tissues, including hexanal, (E)-2-hexenal, (Z)-3-hexenal, (Z)-2-penten-1-ol, (Z)-3-hexen-1-ol, 1-hexanol and 3-hexen-1-ol. Generally speaking, the concentrations of C6 and C5 compounds could be used as the criterion of maturation of the three grape tissues.