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951.
Jia Li Chenghui Yan Yilong Wang Can Chen Haibo Yu Dan Liu Kai Huang Yaling Han 《Cell death & disease》2022,13(4)
Pathological cardiac hypertrophy is a process of abnormal remodeling of cardiomyocytes in response to pressure overload or other stress stimuli, resulting in myocardial injury, which is a major risk factor for heart failure, leading to increased morbidity and mortality. General control nonrepressed protein 5 (GCN5)/lysine acetyltransferase 2 A, a member of the histone acetyltransferase and lysine acetyltransferase families, regulates a variety of physiological and pathological events. However, the function of GCN5 in pathological cardiac hypertrophy remains unclear. This study aimed to explore the role of GCN5 in the development of pathological cardiac hypertrophy. GCN5 expression was increased in isolated neonatal rat cardiomyocytes (NRCMs) and mouse hearts of a hypertrophic mouse model. GCN5 overexpression aggravated the cardiac hypertrophy triggered by transverse aortic constriction surgery. In contrast, inhibition of GCN5 impairs the development of pathological cardiac hypertrophy. Similar results were obtained upon stimulation of NRCMs (having GCN5 overexpressed or knocked down) with phenylephrine. Mechanistically, our results indicate that GCN5 exacerbates cardiac hypertrophy via excessive activation of the transforming growth factor β-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK)/p38 signaling pathway. Using a TAK1-specific inhibitor in rescue experiments confirmed that the activation of TAK1 is essential for GCN5-mediated cardiac hypertrophy. In summary, the current study elucidated the role of GCN5 in promotion of cardiac hypertrophy, thereby implying it to be a potential target for treatment.Subject terms: Heart failure, Cell signalling 相似文献
952.
Liang Ji Zhi-hong Wang Yu-hua Zhang Yi Zhou De-sheng Tang Chang-sheng Yan Jia-min Ma Kun Fang Lei Gao Nian-sheng Ren Long Cheng Xiao-yu Guo Bei Sun Gang Wang 《Cell death & disease》2022,13(3)
The present study was performed to explore whether and how impaired autophagy could modulate calcium/calmodulin-dependent protein kinase II (CAMKII)-regulated necrosis in the pathogenesis of acute pancreatitis (AP). Wistar rats and AR42J cells were used for AP modeling. When indicated, genetic regulation of CAMKII or ATG7 was performed prior to AP induction. AP-related necrotic injury was positively regulated by the incubation level of CAMKII. ATG7 positively modulated the level of CAMKII and necrosis following AP induction, indicating that there might be a connection between impaired autophagy and CAMKII-regulated necrosis in the pathogenesis of AP. microRNA (miR)-30b-5p was predicted and then verified as the upstream regulator of CAMKII mRNA in our setting of AP. Given that the level of miR-30b-5p was negatively correlated with the incubation levels of ATG7 after AP induction, a rescue experiment was performed and indicated that the miR-30b-5p mimic compromised ATG7 overexpression-induced upregulation of CAMKII-regulated necrosis after AP induction. In conclusion, our results indicate that ATG7-enhanced impaired autophagy exacerbates AP by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway.Subject terms: Cytokines, Acute inflammation 相似文献
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955.
Vladimír Hojka Petr astný James J. Tufano Dan Omcirk Martin T. Janikov Martin Komarc Radim Jebavý 《Biology of sport / Institute of Sport》2022,39(2):341
Manufacturers recommend that linear position transducers (LPTs) should be placed on the side of a barbell (or wooden dowel) to measure countermovement jump (CMJ) height, but the validity and reliability of this placement have not been compared to other attachment sites. Since this recommended attachment site is far from the centre of mass, a belt attachment where the LPT is placed between the feet may increase the validity and reliability of CMJ data. Thirty-six physical education students participated in the study (24.6 ± 4.3 years; 177.0 ± 7.7 cm; 77.2 ± 9.0 kg). Parameters from the two LPT attachments (barbell and belt) were simultaneously validated to force plate data, where the nature of bias was analysed (systematic vs random). The within-session and between-session reliability of both attachment sites were compared to force plate data using a test-retest protocol of two sets of 5 CMJs separated by 7 days. The LPT provided highly reliable and valid measures of peak force, mean force, mean power, and jump height, where the bias was mostly systematic (r2 > 0.7; ICC > 0.9). Peak velocity, mean velocity, and peak power were in very good agreement with the force plate and were highly reliable (r2 > 0.5; ICC > 0.7). Therefore, both attachment sites produced similar results with a systematic bias compared to force plate data. Thus, both attachment sites seem to be valid for assessing CMJs when the measuring tool and site remain consistent across measurements. However, if LPT data are to be compared to force plate data, recalculation equations should be used. 相似文献
956.
转座子是基因组中可移动和扩展的元件,能够插入新的位点,影响基因组和基因的结构和功能,是基因组进化的内在驱动。为探讨转座子的时空表达特性,首先通过生物信息学方法鉴定出斑马鱼9个疑似活性转座子,包括DNA转座子Tc1家族(Tc-a、Tc-b、Tc-c、Tc-d、Tc-e)、反转录转座子ERV家族(ERV-1、ERV-2)和LINE家族(L1-323、L1-21),然后采用实时荧光定量PCR法检测上述转座子在斑马鱼早期胚胎发育7个阶段及成鱼各主要脏器的表达活性。结果表明:Tc1家族在0.75、2.00、3.00 h各阶段无转录活性,在6.00、15.00、24.00、48.00 h各阶段各转座子均有较高转录活性;反转录转座子转录活性最早出现于3 h,最晚出现于15 h,且随着发育时间的延长,转录活性显著增强。9种转座子在成鱼心脏、大脑、肌肉、肝脏、睾丸和卵巢均有表达,且大脑和心脏中的表达水平显著高于其他组织,睾丸表达水平最低。分析表明转座子的表达具有时间和组织的特异性,可能参与斑马鱼胚胎和组织器官发育调控,尤其是大脑和心脏发育。这些结果为进一步研究转座子是否具有基因表达调控功能提供重要参考。 相似文献
957.
Xin Hu Bili Zhang Xi Zheng Haoyan Ji Kun Feng Xiaosong Hu Isma Gul Muhammad Nadeem Abbas Hongjuan Cui Yong Zhu 《Current issues in molecular biology》2022,44(2):777
Eicosanoids are crucial downstream signals in the insect immune responses. Phospholipase A2 (PLA2) catalyzes phospholipids, the initial step in eicosanoid biosynthesis. In mammals, the biological roles of Ca2+-independent Phospholipase A2 (iPLA2) have been extensively studied; however, only a few studies have attempted to explore iPLA2 functions in insects. In this study, we identified two iPLA2 genes (designated as BmiPLA2A and BmiPLA2B) in the silkworm, Bombyx mori. BmiPLA2A had a 2427 base pair (bp) open reading frame (ORF) that coded for a protein with 808 amino acids. In contrast, BmiPLA2B had a 1731 bp ORF that coded for a protein with 576 amino acids. Domain analysis revealed that BmiPLA2A had six ankyrin repeat domains, but BmiPLA2B lacks these domains. BmiPLA2A and BmiPLA2B were transcribed widely in various tissues and developmental stages with different expression patterns. The administration of 20-hydroxyecdysone increased their expression levels in the epidermis and hemocytes. Furthermore, challenged with virus, fungus, Gram-negative bacteria, and Gram-positive bacteria induced the expression of BmiPLA2A and BmiPLA2B with variable degrees along with different time points. Our findings imply that BmiPLA2A and BmiPLA2B may have important biological roles in the development and innate immunity of B. mori. 相似文献
958.
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960.
Anjiang Zhao Dan Li Xiongmin Mao Mengliu Yang Wuquan Deng Wenjing Hu Chen Chen Gangyi Yang Ling Li 《Cell death & disease》2022,13(3)
G-protein gamma subunit 2 (GNG2) is involved in several cell signaling pathways, and is essential for cell proliferation and angiogenesis. However, the role of GNG2 in tumorigenesis and development remains unclear. In this study, 1321 differentially expressed genes (DEGs) in breast cancer (BC) tissues were screened using the GEO and TCGA databases. KEGG enrichment analysis showed that most of the enriched genes were part of the PI3K-Akt signaling pathway. We identified GNG2 from the first five DEGs, its expression was markedly reduced in all BC subtype tissues. Cox regression analysis showed that GNG2 was independently associated with overall survival in patients with luminal A and triple-negative breast cancers (TNBC). GNG2 over-expression could significantly block the cell cycle, inhibit proliferation, and promote apoptosis in BC cells in vitro. In animal studies, GNG2 over-expression inhibited the growth of BC cells. Further, we found that GNG2 significantly inhibited the activity of ERK and Akt in an MRAS-dependent manner. Importantly, GNG2 and muscle RAS oncogene homolog (MRAS) were co-localized in the cell membrane, and the fluorescence resonance energy transfer (FRET) experiment revealed that they had direct interaction. In conclusion, the interaction between GNG2 and MRAS likely inhibits Akt and ERK activity, promoting apoptosis and suppressing proliferation in BC cells. Increasing GNG2 expression or disrupting the GNG2–MRAS interaction in vivo could therefore be a potential therapeutic strategy to treat BC.Subject terms: Breast cancer, Breast cancer 相似文献