Latest Issue
Issue 9 ， 2020
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Roles of miRNA and lncRNA in triple-negative breast cancer
Abstract：Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies, which makes its pathogenesis an important target for research. A growing number of studies have shown that non-coding RNA (ncRNA), including microRNA (miRNA) and long non-coding RNA (lncRNA), plays a significant role in tumorigenesis. This review summarizes the roles of miRNA and lncRNA in the progression, diagnosis, and neoadjuvant chemotherapy of TNBC. Aberrantly expressed miRNA and lncRNA are listed according to their roles. Further, it describes the multiple mechanisms that lncRNA shows for regulating gene expression in the nucleus and cytoplasm, and more importantly, describes lncRNA-regulated TNBC progression through complete combining with miRNA at the post-transcriptional level. Focusing on miRNA and lncRNA associated with TNBC can provide new insights for early diagnosis and treatment—they can be targeted in the future as a novel anticancer target of TNBC.Keywords：Biomarker;Long non-coding RNA (lncRNA);MicroRNA;Regulation mechanism;Triple-negative breast cancer (TNBC)- 39
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MicroRNAs involved in drug resistance of breast cancer by regulating autophagy
Abstract：Autophagy is a conserved catabolic process characterized by degradation and recycling of cytosolic components or organelles through a lysosome-dependent pathway. It has a complex and close relationship to drug resistance in breast cancer. MicroRNAs (miRNAs) are small noncoding molecules that can influence numerous cellular processes including autophagy, through the posttranscriptional regulation of gene expression. Autophagy is regulated by many proteins and pathways, some of which in turn have been found to be regulated by miRNAs. These miRNAs may affect the drug resistance of breast cancer. Drug resistance is the main cause of distant recurrence, metastasis and death in breast cancer patients. In this review, we summarize the causative relationship between autophagy and drug resistance of breast cancer. The roles of autophagy-related proteins and pathways and their associated miRNAs in drug resistance of breast cancer are also discussed.Keywords：Autophagy;MicroRNA;Breast cancer;Drug resistance- 136
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Published：2022-01-05
Review
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RGFP966 inactivation of the YAP pathway attenuates cardiac dysfunction induced by prolonged hypothermic preservation
Abstract：Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4–6 h. The aim of this study was to investigate whether the histone deacetylase 3 (HDAC3) inhibitor RGFP966 could protect against cardiac injury induced by prolonged hypothermic preservation. Rat hearts were hypothermically preserved in Celsior solution with or without RGFP966 for 12 h followed by 60 min of reperfusion. Hemodynamic parameters during reperfusion were evaluated. The expression and phosphorylation levels of mammalian STE20-like kinase-1 (Mst1) and Yes-associated protein (YAP) were determined by western blotting. Cell apoptosis was measured by the terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Addition of RGFP966 in Celsior solution significantly inhibited cardiac dysfunction induced by hypothermic preservation. RGFP966 inhibited the hypothermic preservation-induced increase of the phosphorylated (p)-Mst1/Mst1 and p-YAP/YAP ratios, prevented a reduction in total YAP protein expression, and increased the nuclear YAP protein level. Verteporfin (VP), a small molecular inhibitor of YAP–transcriptional enhanced associate domain (TEAD) interaction, partially abolished the protective effect of RGFP966 on cardiac function, and reduced lactate dehydrogenase activity and malondialdehyde content. RGFP966 increased superoxide dismutase, catalase, and glutathione peroxidase gene and protein expression, which was abolished by VP. RGFP966 inhibited hypothermic preservation-induced overexpression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cleaved caspase-3, increased Bcl-2 mRNA and protein expression, and reduced cardiomyocyte apoptosis. The antioxidant and anti-apoptotic effects of RGFP966 were cancelled by VP. The results suggest that supplementation of Celsior solution with RGFP966 attenuated prolonged hypothermic preservation-induced cardiac dysfunction. The mechanism may involve inhibition of oxidative stress and apoptosis via inactivation of the YAP pathway.Keywords：Hypothermic preservation;RGFP966;Yes-associated protein (YAP);Oxidative stress;Apoptosis- 141
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Genome-wide identification of the Sec-dependent secretory protease genes in
Erwinia amylovora and analysis of their expression during infection of immature pear fruitAbstract：The general secretory (Sec) pathway represents a common mechanism by which bacteria secrete proteins, including virulence factors, into the extracytoplasmic milieu. However, there is little information about this system, as well as its associated secretory proteins, in relation to the fire blight pathogen Erwinia amylovora. In this study, data mining revealed that E. amylovora harbors all of the essential components of the Sec system. Based on this information, we identified putative Sec-dependent secretory proteases in E. amylovora on a genome-wide scale. Using the programs SignalP, LipoP, and Phobius, a total of 15 putative proteases were predicted to contain the N-terminal signal peptides (SPs) that might link them to the Sec-dependent pathway. The activities of the predicted SPs were further validated using an Escherichia coli-based alkaline phosphatase (PhoA) gene fusion system that confirmed their extracytoplasmic property. Transcriptional analyses showed that the expression of 11 of the 15 extracytoplasmic protease genes increased significantly when E. amylovora was used to inoculate immature pears, suggesting their potential roles in plant infection. The results of this study support the suggestion that E. amylovora might employ the Sec system to secrete a suite of proteases to enable successful infection of plants, and shed new light on the interaction of E. amylovora with host plants.Keywords：Erwinia amylovora;Sec-dependent pathway;Protease;Gene expression;Plant infection- 97
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Early use of dexamethasone increases
Nr4a1 in Kupffer cells ameliorating acute liver failure in mice in a glucocorticoid receptor-dependent mannerAbstract：Background and objective:Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice.Methods:Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively. Results:A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition. Conclusions:In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.Keywords：Glucocorticoid;Dexamethasone;Kupffer cells;Acute liver failure;Nuclear receptor subfamily 4 group A member 1 (Nr4a1)- 71
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Published：2022-01-05
Article
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Characteristics of chemotherapy-induced diabetes mellitus in acute lymphoblastic leukemia patients#
Abstract：Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%–37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and β cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).Keywords：Acute lymphoblastic leukemia;Diabetes mellitus;Clinical characteristics- 12
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Published：2022-01-05 -
Anti-migratory effects of
Piper betle leaf aqueous extract on cancer cells and its microtubule targeting properties#Abstract：Piper betle (PB), also known as “betel” in Malay language, is a tropical Asian vine. PB leaves are commonly chewed by Asians along with betel quid. It contains phenols such as eugenol and hydroxychavicol along with chlorophyll, β-carotene, and vitamin C (Salehi et al., 2019). Extracts from PB leaves have various medicinal properties including anticancer, antioxidant, anti-inflammatory, and antibacterial effects (Salehi et al., 2019). Previous research has shown that PB induces cell cycle arrest at late S or G2/M phase and causes apoptosis at higher doses (Wu et al., 2014; Guha Majumdar and Subramanian, 2019). A combination of PB leaf extract has also been shown to enhance the cytotoxicity of the anticancer drug, 5-fluorouracil (5-FU), in cancer cells (Ng et al., 2014).Keywords：Piper betle;Cell migration;Microtubules;Tubulin network- 127
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Published：2022-01-05 -
Gastrointestinal involvement of COVID-19 and potential faecal transmission of SARS-CoV-2
Abstract：Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was found initially in Wuhan, China in early December 2019. The pandemic has spread to 216 countries and regions, infecting more than 23310 000 people and causing over 800 000 deaths globally by Aug. 24, 2020, according to World Health Organization (https://www.who.int/emergencies/diseases/ novel-coronavirus-2019). Fever, cough, and dyspnea are the three common symptoms of the condition, whereas the conventional transmission route for SARS-CoV-2 is through droplets entering the respiratory tract. To date, infection control measures for COVID-19 have been focusing on the involvement of the respiratory system. However, ignoring potential faecal transmission and the gastrointestinal involvement of SARS-CoV-2 may result in mistakes in attempts to control the pandemic.Keywords：COVID-19;SARS-CoV-2;Gastrointestinal involvement;Faecal transmission- 122
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Published：2022-01-05 -
Understanding and reducing the fear of COVID-19
Abstract：The world is now plagued by a pandemic of unprecedented nature caused by a novel, emerging, and still poorly understood infectious disease, coronavirus disease 2019 (COVID-19) (Wu and McGoogan, 2020). In addition to the rapidly growing body of scientific and medical literature that is being published, extensive public reports and stories in both the traditional media and social media have served to generate fear, panic, stigmatization, and instances of xenophobia (Zarocostas, 2020).Keywords：Pandemic;COVID-19;Fear;Infodemic;Rumour- 16
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Published：2022-01-05
Correspondence
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