Publications by authors named "Yan Gao"

1,804 Publications

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Corrigendum: NPM1 Is a Prognostic Biomarker Involved in Immune Infiltration of Lung Adenocarcinoma and Associated With m6A Modification and Glycolysis.

Front Immunol 2021 31;12:751004. Epub 2021 Aug 31.

Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

[This corrects the article DOI: 10.3389/fimmu.2021.724741.].
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http://dx.doi.org/10.3389/fimmu.2021.751004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439576PMC
August 2021

Combined association of multiple chronic diseases and social isolation with the functional disability after stroke in elderly patients: a multicenter cross-sectional study in China.

BMC Geriatr 2021 Sep 16;21(1):495. Epub 2021 Sep 16.

Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 518035, Shenzhen, China.

Background: Multiple chronic diseases (MCDs) and social isolation are independent risk factors related to stroke and disability, but it is unknown whether the combination of these two conditions resulted from aging-related to functional disability in stroke patients. This study aimed to probe the relationship between the combination of MCDs, social isolation, and functional disability after stroke in elderly patients.

Methods: A multicenter and cross-sectional study was conducted in the Departments of Rehabilitation of 103 hospitals located in 23 cities across China. Stroke patients aged 60-90 years were selected for analysis. Demographic characteristics, lifestyles, and clinical information were investigated by questionnaires and medical records. MCDs (hypertension/ diabetes/ hyperlipidemia/heart disease/kidney disease) were categorized into three levels: 0, 1, and ≥ 2. Functional disability was assessed by the Barthel Index and categorized into four groups: no, mild, moderate, and severe disability. The multi-nominal logistic regression model was used to explore the independent and combined association of MCDs and social isolation with functional disability.

Results: A total of 4046 elderly stroke patients (55 % males) were included in the final analysis. The prevalence of social isolation, MCDs ≥ 2, and severe disability increased with aging. In the fully adjusted model, patients with social isolation or MCDs had a higher risk of functional disability significantly than those without. Patients with social isolation combined MCDs ≥ 2 were 35 times (95 % CI: 18.89-64.69) more likely to suffer severe disability after stroke, and 8 times (95 % CI: 18.89-64.69) for moderate disability than those without social isolation and MCDs.

Conclusions: MCDs, social isolation, and their combination were associated with a higher risk of functional disability after stroke in Chinese elderly patients. The elderly population should be encouraged to participate in more social activities, particularly in those with MCDs. Future secondary prevention and rehabilitation treatments to the functional ability of elderly stroke patients should underscore both social activity and the combined treatments of MCDs.

Trial Registration: NO: ChiCTR2000034067 .
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http://dx.doi.org/10.1186/s12877-021-02439-9DOI Listing
September 2021

Socket shield technique: A systemic review and meta-analysis.

J Prosthodont Res 2021 Sep 16. Epub 2021 Sep 16.

Affiliated Implantology center, Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Purpose: The aim of the present study was to evaluate the clinical feasibility of the socket shield technique (SST).

Study Selection: An electronic search of the PubMed, Cochrane Central Register of Controlled Trials, and Wiley Online Library databases, and a manual reference search for articles published up to September 2020 was conducted. Meta-analysis was performed to estimate marginal bone loss (MBL), changes in buccal bone width (cBBW), pink esthetic score (PES), implant stability quotient (ISQ), implant failure rate, and complication rate between SST and conventional immediate implant placement (IIP). All pooled analyses were based on random effects models.

Results: Sixteen relevant studies were ultimately selected by two independent reviewers: four randomized clinical trials (RCTs), four case-control studies, and eight retrospective studies. Meta-analysis revealed a trend toward lower MBL and cBBW and higher PES in the SST group. ISQ, implant failure rate, and complication rate were similar between the groups.

Conclusions: The included studies provided evidence that SST may be a feasible treatment option. However, this technique should not be used as a routine clinical protocol due to the lack of evidence-based consensus guidelines, large-scale RCTs, and long-term follow-up data. Therefore, there is an urgent need for well-conducted RCTs in this field.
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http://dx.doi.org/10.2186/jpr.JPR_D_20_00262DOI Listing
September 2021

Magnetic resonance imaging-based radiogenomics analysis for predicting prognosis and gene expression profile in advanced nasopharyngeal carcinoma.

Head Neck 2021 Sep 13. Epub 2021 Sep 13.

Department of Otolaryngology - Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.

Background: To establish a radiomics nomogram for survival prediction and determine if genomic data were related to radiomics signature in advanced nasopharyngeal carcinoma (NPC).

Methods: Radiomics features were extracted from contrast-enhanced T1-weighted images (CE-T1WI) in 316 patients. A progression-free survival (PFS) nomogram was developed and validated by the combination of the radiomics signature and clinicopathologic factors. Whole transcriptomics sequencing was performed in pretreatment tumor samples; correlation of gene expression and radiomics signature was further investigated.

Results: A 24-feature-combined radiomics signature was highly correlated with PFS; its integration with clinical predictors showed good prediction performance in the training and the validation cohort (C-index: 0.80 and 0.73). A significant correlation was observed between certain gene expression and Rad-score, especially the mRNA expression of CDKL2, PLIN5, and SPAG1.

Conclusion: As a noninvasive method, the MRI-based radiomics signature might enable the pretreatment prediction of prognosis and gene expressions profile in advanced NPC.
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http://dx.doi.org/10.1002/hed.26867DOI Listing
September 2021

Single-Cell RNA-Sequencing Portraying Functional Diversity and Clinical Implications of IFI6 in Ovarian Cancer.

Front Cell Dev Biol 2021 25;9:677697. Epub 2021 Aug 25.

Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Ovarian cancer (OC) is one of the most lethal gynecologic malignancies. Most patients die of metastasis due to a lack of other treatments aimed at improving the prognosis of OC patients. In the present study, we use multiple methods to identify prognostic S1 as the dominant subtype in OC, possessing the most ligand-receptor pairs with other cell types. Based on markers of S1, the consensus clustering algorithm is used to explore the clinical treatment subtype in OC. As a result, we identify two clusters associated with distinct survival and drug response. Notably, IFI6 contributes to the cluster classification and seems to be a vital gene in OC carcinogenesis. Functional enrichment analysis demonstrates that its functions involve G2M and cisplatin resistance, and downregulation of IFI6 suppresses proliferation capabilities and significantly potentiates cisplatin-induced apoptosis of OC cells . To explore possible mechanisms of IFI6 influencing OC proliferation and cisplatin resistance, GSEA is conducted and shows that IFI6 is positively correlated with the NF-κB pathway, which is validated by RT-qPCR. Significantly, we develop a prognostic model including IFI6, RiskScore, which is an independent prognostic factor and presents encouraging prognostic values. Our findings provide novel insights into elucidating the biology of OC based on single-cell RNA-sequencing. Moreover, this approach is potentially helpful for personalized anti-cancer strategies and predicting outcomes in the setting of OC.
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http://dx.doi.org/10.3389/fcell.2021.677697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425592PMC
August 2021

A multicenter retrospective study on survival rate and complications of very preterm infants.

Zhongguo Dang Dai Er Ke Za Zhi 2021 Aug;23(8):814-820

Department of Neonatology, Yangzhou Maternal and Child Care Service Centre, Yangzhou, Jiangsu 225001, China.

Objectives: To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications.

Methods: The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants.

Results: A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25 weeks, 2626 weeks, 27-27 weeks, 2828 weeks, 2929 weeks, 3030 weeks, and 31-31 weeks had a survival rate of 32.5%, 60.6%, 68.0%, 82.9%, 90.1%, 92.3%, and 94.8% respectively. The survival rate tended to increase with the gestational age (<0.05) and the survival rate without serious complications in each gestational age group was 7.5%, 18.1%, 34.5%, 52.2%, 66.7%, 75.7%, and 81.8% respectively, suggesting that the survival rate without serious complications increased with the gestational age (<0.05). The multivariate logistic regression analysis showed that high gestational age, high birth weight, and prenatal use of glucocorticoids were protective factors against death in very preterm infants (<0.05), and 1-minute Apgar score ≤3 was a risk factor for death in very preterm infants (<0.05); high gestational age and high birth weight were protective factors against serious complications in very preterm infants who survived (<0.05), while 5-minute Apgar score ≤3 and maternal chorioamnionitis were risk factors for serious complications in very preterm infants who survived (<0.05).

Conclusions: The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.
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http://dx.doi.org/10.7499/j.issn.1008-8830.2102037DOI Listing
August 2021

Long non-coding RNA AC012668 suppresses non-alcoholic fatty liver disease by competing for microRNA miR-380-5p with lipoprotein-related protein LRP2.

Bioengineered 2021 Dec;12(1):6738-6747

Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, China.

Nonalcoholic fatty liver disease (NAFLD) is characterized by high morbidity. Although long noncoding RNAs (lncRNAs) are known to have a role in NAFLD pathogenesis, the identified lncRNA types are limited. In this study, NAFLD models were established in vitro and in vivo using free fatty acid-treated LO2 cells and high-fat diet-fed mice, respectively. Microarray data were downloaded from the Gene Expression Omnibus database, and was selected for further analysis. Cell viability and apoptosis were measured using Cell Counting Kit 8 and flow cytometry assays. RNA expression was detected using reverse transcription-quantitative polymerase chain reaction. Triglyceride (TG) content and lipid deposition were detected using enzyme-linked immunosorbent assay and Oil-Red O staining. Western blotting was used to visualize protein expression. Starbase and TargetScan were used to predict the target miRNA and gene, and the predictions were verified through RNA pull-down and luciferase reporter assays. expression levels were significantly suppressed in NAFLD models, whereas overexpression inhibited lipogenesis-related gene () expression and TG/lipid accumulation in vitro. Subsequently, was predicted and verified to target , and its expression was notably increased in the NAFLD cell model. Moreover, transfection of antagonized the effects of on lipid formation and accumulation. was confirmed to be the target gene of and was downregulated in the NAFLD cell model. Silencing reversed the effects of the inhibitor on lipid formation and accumulation. inhibited NAFLD progression via the / axis. These findings may provide a novel strategy against NAFLD.
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http://dx.doi.org/10.1080/21655979.2021.1960463DOI Listing
December 2021

Tetrahydroxy stilbene glycoside regulates TGF-β/fractalkine/CX3CR1 based on network pharmacology in APP/PS1 mouse model.

Neuropeptides 2021 Sep 4;90:102197. Epub 2021 Sep 4.

Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China. Electronic address:

Alzheimer's disease (AD) is a serious, progressive neurodegenerative disease that involves irreversible neuronal death. Tetrahydroxy stilbene glycoside (TSG) is an active compound extracted from P. multiflorum, a traditional Chinese herbal medicine, but its role in neuroprotection is unclear. Herein, we aimed to validate the effects of TSG on APP/PS1 model mice and the underlying mechanism. RNA-seq was performed to identify differentially expressed genes in APP/PS1 mouse, with PCR and immunohistochemistry used for validation. Experiments were performed after bioinformatic analysis for verification. Neuronal damage was observed by H&E staining. Key proteins involved in the pathway such as CX3CR1, Iba1 and TGF-β were examined by immunohistochemical analysis. The KEGG analysis suggested that these genes might act by multiple pathways to build the pharmacological network of TSG in AD progression. These data provide the credible evidence that TSG improved neuronal damage and regulated neuroprotective mechanisms. Together, our work has detailed the whole and major genes in APP/PS1 model mouse regulated by TSG, and highlighted the anti-inflammatory function of TSG in mediating CX3CR1 and TGF-β as the TGF-β/fractalkine/CX3XR1 signaling pathway, especially in microglia. Moreover, TSG has potential value in synaptic transmission and neurotrophic action on neurodegenerative diseases. In summary, TSG is a promising candidate for preventing and treating the progression of AD.
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http://dx.doi.org/10.1016/j.npep.2021.102197DOI Listing
September 2021

Nonmonotonic response of type 2 diabetes by low concentration organochlorine pesticide mixture: Findings from multi-omics in zebrafish.

J Hazard Mater 2021 08 27;416:125956. Epub 2021 Apr 27.

Department of Environmental Energy Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea; Department of Environmental Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea. Electronic address:

Exposure to a single organochlorine pesticide (OCP) at high concentration and over a short period of exposure constrain our understanding of the contribution of chemical exposure to type 2 diabetes (T2D). A total of 450 male and female zebrafish was exposed to mixtures of five OCPs at 0, 0.05, 0.25, 2.5, and 25 μg/L for 12 weeks. T2D-related hematological parameters (i.e., glucose, insulin, free fatty acid, and triglycerides) and mitochondrial complex I to IV activities were assessed. Metabolomics, proteomics, and transcriptomics were analyzed in female livers, and their data-driven integration was performed. High fasting glucose and low insulin levels were observed only at 0.05 μg/L of the OCP mixture in females, indicating a nonlinear and sexually dependent response. We found that exposure to the OCP mixture inhibited the activities of mitochondrial complexes, especially III and IV. Combining individual and integrated omics analysis, T2D-linked metabolic pathways that regulate mitochondrial function, insulin signaling, and energy homeostasis were altered by the OCP mixture, which explains the observed phenotypic hematological effects. We demonstrated the cause-and-effect relationship between exposures to OCP mixture and T2D using zebrafish model. This study gives an insight into mechanistic research of metabolic diseases caused by chemical exposure using zebrafish.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125956DOI Listing
August 2021

Mitochondria-Targeted Nanomedicine for Enhanced Efficacy of Cancer Therapy.

Front Bioeng Biotechnol 2021 19;9:720508. Epub 2021 Aug 19.

College of Science, Key Laboratory of Forest Genetics and Biotechnology (Ministry of Education of China), Nanjing Forestry University, Nanjing, China.

Nanomedicines have been designed and developed to deliver anticancer drugs or exert anticancer therapy more selectively to tumor sites. Recent investigations have gone beyond delivering drugs to tumor tissues or cells, but to intracellular compartments for amplifying therapy efficacy. Mitochondria are attractive targets for cancer treatment due to their important functions for cells and close relationships to tumor occurrence and metastasis. Accordingly, multifunctional nanoplatforms have been constructed for cancer therapy with the modification of a variety of mitochondriotropic ligands, to trigger the mitochondria-mediated apoptosis of tumor cells. On this basis, various cancer therapeutic modalities based on mitochondria-targeted nanomedicines are developed by strategies of damaging mitochondria DNA (mtDNA), increasing reactive oxygen species (ROS), disturbing respiratory chain and redox balance. Herein, in this review, we highlight mitochondria-targeted cancer therapies enabled by nanoplatforms including chemotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), radiodynamic therapy (RDT) and combined immunotherapy, and discussed the ongoing challenges.
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http://dx.doi.org/10.3389/fbioe.2021.720508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418302PMC
August 2021

Psi-Caller: A Lightweight Short Read-Based Variant Caller With High Speed and Accuracy.

Front Cell Dev Biol 2021 13;9:731424. Epub 2021 Aug 13.

Center for Bioinformatics, Faculty of Computing, Harbin Institute of Technology, Harbin, China.

With the rapid development of short-read sequencing technologies, many population-scale resequencing studies have been carried out to study the associations between human genome variants and various phenotypes in recent years. Variant calling is one of the core bioinformatics tasks in such studies to comprehensively discover genomic variants in sequenced samples. Many efforts have been made to develop short read-based variant calling approaches; however, state-of-the-art tools are still computationally expensive. Meanwhile, cutting-edge genomics studies also have higher requirements on the yields of variant calling. Herein, we propose Partial-Order Alignment-based single nucleotide polymorphism (SNV) and Indel caller (Psi-caller), a lightweight variant calling algorithm that simultaneously achieves high performance and yield. Mainly, Psi-caller recognizes and divides the candidate variant site into three categories according to the complexity and location of the signatures and employs various methods including binomial model, partial-order alignment, and de Bruijn graph-based local assembly to handle various categories of candidate variant sites to call and genotype SNVs/Indels, respectively. Benchmarks on simulated and real short-read sequencing data sets demonstrate that Psi-caller is times faster than state-of-the-art tools with higher or equal sensitivity and accuracy. It has the potential to well handle large-scale data sets in cutting-edge genomics studies.
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http://dx.doi.org/10.3389/fcell.2021.731424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414796PMC
August 2021

Early Warning Value of ASL-MRI to Estimate Premorbid Variations in Patients With Early Postoperative Cognitive Dysfunctions.

Front Aging Neurosci 2021 17;13:670332. Epub 2021 Aug 17.

Department of Anesthesiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

: Postoperative cognitive dysfunction (POCD) is a general complication following cardiac and major non-cardiac surgery amongst the elderly, yet its causes and mechanisms are still unknown. The present study aimed to detect whether regional cerebral blood flow (CBF) is altered in the brain before surgery in POCD patients compared with non-POCD (NPOCD) patients, thus, CBF variation may potentially predict the occurrence of early POCD. : Fifty patients scheduled for spinal stenosis surgery were enrolled in the study. All study participants completed a battery of neuropsychological tests (NPTs) by a well-trained neuropsychologist before the surgery and 1 week after the surgery. POCD was defined when the preoperative to postoperative difference of at least two of the NPTs' |Z|-scores with reference to a control group exceeded 1.96. Pulsed arterial spin-labeling (ASL) MRI was scanned at least 1 day before surgery. The ASLtbx toolkit and SPM12 were applied to preprocess and correct the images, which were then normalized to the MNI brain template space to obtain standardized cerebral perfusion images. : POCD was identified in 11 out of 50 patients (22%). The CBF of the right superior temporal lobe, right and left middle cingulate gyrus, and the right hippocampus, and parahippocampal gyrus in POCD group was lower than that in NPOCD group ( < 0.001). The CBF of the pars triangularis of inferior frontal gyrus in POCD group was higher than that in NPOCD group ( < 0.001). : These preliminary findings suggest that CBF premorbid alterations may happen in cognitively intact elderly patients that develop early POCD. Alterations of preoperative CBF might be a bio-marker for early POCD that can be detected by noninvasive MRI scans.
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http://dx.doi.org/10.3389/fnagi.2021.670332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416237PMC
August 2021

CREBBP cooperates with the cell cycle machinery to attenuate chidamide sensitivity in relapsed/refractory diffuse large B-cell lymphoma.

Cancer Lett 2021 Sep 2;521:268-280. Epub 2021 Sep 2.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China; Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China. Electronic address:

Diffuse large B-cell lymphoma (DLBCL) exhibits frequent inactivating mutations of the histone acetyltransferase CREBBP, highlighting the attractiveness of targeting CREBBP deficiency as a therapeutic strategy. In this study, we demonstrate that chidamide, a novel histone deacetylase (HDAC) inhibitor, is effective in treating a subgroup of relapsed/refractory DLBCL patients, achieving an overall response rate (ORR) of 25.0% and a complete response (CR) rate of 15.0%. However, the clinical response to chidamide remains poor, as most patients exhibit resistance, hampering the clinical utility of the drug. Functional in vitro and in vivo studies have shown that CREBBP loss of function is correlated with chidamide sensitivity, which is associated with modulation of the cell cycle machinery. A combinatorial drug screening of 130 kinase inhibitors targeting cell cycle regulators identified AURKA inhibitors, which inhibit the G2/M transition during the cell cycle, as top candidates that synergistically enhanced the antitumor effects of chidamide in CREBBP-proficient DLBCL cells. Our study demonstrates that CREBBP inactivation can serve as a potential biomarker to predict chidamide sensitivity, while combination of an AURKA inhibitor and chidamide is a novel therapeutic strategy for the treatment of relapsed/refractory DLBCL.
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http://dx.doi.org/10.1016/j.canlet.2021.09.002DOI Listing
September 2021

Schisanhenol improves early porcine embryo development by regulating the phosphorylation level of MAPK.

Theriogenology 2021 Aug 17;175:34-43. Epub 2021 Aug 17.

Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun, 130062, Jilin, China. Electronic address:

Schisanhenol (SAL), a biphenyl cyclooctene-type lignin compound which can be extracted and isolated from many plants of the Schisandra family, exhibits a variety of biological activities including anti chronic cough, night sweating, thirst, diabetes, and obesity. However, its effects on the female reproductive system are unclear. Previous studies showed that SAL had potential antioxidant activity in heart, liver, and brain. Therefore, we hypothesized that SAL could improve porcine early development by reducing oxidative stress. The purpose of this study was to investigate the effects of SAL on preimplantation porcine embryos and the potential mechanisms. In this study, we analyzed the effects of SAL on embryo quality, reactive oxygen species (ROS) accumulation, mitochondrial function, cell proliferation and apoptosis, and the activation of MAPK pathway. The results showed that 10 μM SAL significantly increased the blastocyst formation rate, proliferation ability, and mitochondrial activity while reducing ROS accumulation and apoptosis level. During this process, the phosphorylation levels of ERK1/2, JNK1/2/3, and p38 were decreased. In summary, 10 μM SAL improves porcine preimplantation embryo development by reducing ROS accumulation.
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http://dx.doi.org/10.1016/j.theriogenology.2021.08.019DOI Listing
August 2021

An integrated transcriptomics and proteomics analysis implicates lncRNA MALAT1 in the regulation of lipid metabolism.

Mol Cell Proteomics 2021 Aug 31:100141. Epub 2021 Aug 31.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in various cancers, and its overexpression is associated with tumor growth and metastasis. MALAT1 has been recognized as a key player in the regulation of RNA splicing and transcription, however, the landscape of gene expression regulated by MALAT1 remains unclear. In this study, we employed an integrated transcriptomics and proteomics strategy to characterize the alterations in gene expression induced by MALAT1 knockdown in hepatocellular carcinoma (HCC) cells, and identified 2662 differentially expressed transcripts and 1149 differentially expressed proteins. Interestingly, downregulation of MALAT1 reduced the abundances of multiple genes in the AMP-activated protein kinase (AMPK) signaling and biosynthesis of unsaturated fatty acids pathways. Further investigation showed that MALAT1 knockdown inhibited glucose uptake and lipogenesis by reducing the expression levels of these lipid metabolism related genes, which contributes to the oncogenic role of MALAT1 in tumor cell proliferation and invasion. This study uncovers the function of MALAT1 in the modulation of cancer lipid metabolism, reveals the underlying molecular mechanism, and further supports the potential therapeutic opportunities for targeting MALAT1 in HCC treatment.
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http://dx.doi.org/10.1016/j.mcpro.2021.100141DOI Listing
August 2021

F-FDG PET/CT metabolic parameters correlate with EIF2S2 expression status in colorectal cancer.

J Cancer 2021 3;12(19):5838-5847. Epub 2021 Aug 3.

Postgraduate Training Basement of Jinzhou Medical University, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.

We sought to investigate whether the expression of the gene EIF2S2 is related to F-FDG PET/CT metabolic parameters in patients with colorectal cancer (CRC). The expression of EIF2S2 in CRC and its relationship with clinicopathological features were obtained through the ONCOMINE, UALCAN and GEPIA databases. EIF2S2 and GLUT1 expression were examined by immunohistochemistry in 42 CRC patients undergoing preoperative PET-CT examination. Spearman correlation analysis was used to assess the relationship between EIF2S2 and GLUT1 levels and clinical parameters. Correlation analysis between EIF2S2 and Reactome-Glycolysis signatures was performed using GEPIA2. We describe the effect of EIF2S2 knockdown on lactate production and the mRNA levels of glycolysis-related genes in human colon cancer SW480 cells. Immunohistochemistry revealed an upregulation of EIF2S2 protein expression in tumor tissues of colorectal cancer patients, which is consistent with the significant upregulation of EIF2S2 transcript levels in the database. These colorectal cancer patients included 24 cases of colon cancer and 18 cases of rectal cancer, ranging in age from 31 to 78 years. The transcription was significantly related to histological subtypes and TP53 mutations (P <0.05). The value of SUVmax in CRC significantly correlated with the expression of EIF2S2 (rho = 0.462, P <0.01). Although SUVmax and SUVmean was not correlate with the expression of GLUT1 (P <0.05), a significant correlation was observed between the expression of GLUT1 and the volumetric PET parameters, such as MTV and TLG ( < 0.01). GLUT1 expression in CRC was positively correlated with EIF2S2 status (rho = 0.470, P <0.01). In SW480 cells, RNAi-mediated depletion of EIF2S2 inhibited lactic acid production (P <0.05) and SLC2A1, SLC2A3, SLC2A10, HK2, PKM2, LDHA mRNA level (P <0.01). Primary CRC FDG uptake is strongly associated with the overexpression of EIF2S2, and EIF2S2 may promote glycolysis in CRC by mediating GLUT1.
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http://dx.doi.org/10.7150/jca.57926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408126PMC
August 2021

KDM6B epigenetically regulated-interleukin-6 expression in the dorsal root ganglia and spinal dorsal horn contributes to the development and maintenance of neuropathic pain following peripheral nerve injury in male rats.

Brain Behav Immun 2021 Aug 28;98:265-282. Epub 2021 Aug 28.

Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China; Neuroscience Research Institute, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China. Electronic address:

The lysine specific demethylase 6B (KDM6B) has been implicated as a coregulator in the expression of proinflammatory mediators, and in the pathogenesis of inflammatory and arthritic pain. However, the role of KDM6B in neuropathic pain has yet to be studied. In the current study, the neuropathic pain was determined by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) following lumbar 5 spinal nerve ligation (SNL) in male rats. Immunohistochemistry, Western blotting, qRT-PCR, and chromatin immunoprecipitation (ChIP)-PCR assays were performed to investigate the underlying mechanisms. Our results showed that SNL led to a significant increase in KDM6B mRNA and protein in the ipsilateral L4/5 dorsal root ganglia (DRG) and spinal dorsal horn; and this increase correlated a markedly reduction in the level of H3K27me3 methylation in the same tissue. Double immunofluorescence staining revealed that the KDM6B expressed in myelinated A- and unmyelinated C-fibers in the DRG; and located in neuronal cells, astrocytes, and microglia in the dorsal horn. Behavioral data showed that SNL-induced mechanical allodynia and thermal hyperalgesia were impaired by the treatment of prior to i.t. injection of GSK-J4, a specific inhibitor of KDM6B, or KDM6B siRNA. Both microinjection of AAV2-EGFP-KDM6B shRNA in the lumbar 5 dorsal horn and sciatic nerve, separately, alleviated the neuropathic pain following SNL. The established neuropathic pain was also partially attenuated by repeat i.t. injections of GSK-J4 or KDM6B siRNA, started on day 7 after SNL. SNL also resulted in a remarkable increased expression of interleukin-6 (IL-6) in the DRG and dorsal horn. But this increase was dramatically inhibited by i.t. injection of GSK-J4 and KDM6B siRNA; and suppressed by prior to microinjection of AAV2-EGFP-KDM6B shRNA in the dorsal horn and sciatic nerve. Results of ChIP-PCR assay showed that SNL-induced enhanced binding of STAT3 with IL-6 promoter was inhibited by prior to i.t. injection of GSK-J4. Meanwhile, the level of H3K27me3 methylation was also decreased by the treatment. Together, our results indicate that SNL-induced upregulation of KDM6B via demethylating H3K27me3 facilitates the binding of STAT3 with IL-6 promoter, and subsequently mediated-increase in the expression of IL-6 in the DRG and dorsal horn contributes to the development and maintenance of neuropathic pain. Targeting KDM6B might a promising therapeutic strategy to treatment of chronic pain.
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http://dx.doi.org/10.1016/j.bbi.2021.08.231DOI Listing
August 2021

Identification of distinct clinical phenotypes of acute respiratory distress syndrome with differential responses to treatment.

Crit Care 2021 08 30;25(1):320. Epub 2021 Aug 30.

Department of Critical Care Medicine, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China.

Background: Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome, and the identification of homogeneous subgroups and phenotypes is the first step toward precision critical care. We aimed to explore whether ARDS phenotypes can be identified using clinical data, are reproducible and are associated with clinical outcomes and treatment response.

Methods: This study is based on a retrospective analysis of data from the telehealth intensive care unit (eICU) collaborative research database and three ARDS randomized controlled trials (RCTs) (ALVEOLI, FACTT and SAILS trials). We derived phenotypes in the eICU by cluster analysis based on clinical data and compared the clinical characteristics and outcomes of each phenotype. The reproducibility of the derived phenotypes was tested using the data from three RCTs, and treatment effects were evaluated.

Results: Three clinical phenotypes were identified in the training cohort of 3875 ARDS patients. Of the three phenotypes identified, phenotype I (n = 1565; 40%) was associated with fewer laboratory abnormalities, less organ dysfunction and the lowest in-hospital mortality rate (8%). Phenotype II (n = 1232; 32%) was correlated with more inflammation and shock and had a higher mortality rate (18%). Phenotype III (n = 1078; 28%) was strongly correlated with renal dysfunction and acidosis and had the highest mortality rate (22%). These results were validated using the data from the validation cohort (n = 3670) and three RCTs (n = 2289) and had reproducibility. Patients with these ARDS phenotypes had different treatment responses to randomized interventions. Specifically, in the ALVEOLI cohort, the effects of ventilation strategy (high PEEP vs low PEEP) on ventilator-free days differed by phenotype (p = 0.001); in the FACTT cohort, there was a significant interaction between phenotype and fluid-management strategy for 60-day mortality (p = 0.01). The fluid-conservative strategy was associated with improved mortality in phenotype II but had the opposite effect in phenotype III.

Conclusion: Three clinical phenotypes of ARDS were identified and had different clinical characteristics and outcomes. The analysis shows evidence of a phenotype-specific treatment benefit in the ALVEOLI and FACTT trials. These findings may improve the identification of distinct subsets of ARDS patients for exploration in future RCTs.
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http://dx.doi.org/10.1186/s13054-021-03734-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404019PMC
August 2021

Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

Am J Hematol 2021 Aug 27. Epub 2021 Aug 27.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p <  0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.
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http://dx.doi.org/10.1002/ajh.26335DOI Listing
August 2021

Prognostication of Primary Tumor Location in Early-Stage Nodal Diffuse Large B-Cell Lymphoma: An Analysis of the SEER Database.

Cancers (Basel) 2021 Aug 5;13(16). Epub 2021 Aug 5.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dong Feng East Road, Guangzhou 510060, China.

The prognostic role of primary tumor location for clinical outcomes of patients with early-stage nodal diffuse large B-cell lymphoma (DLBCL) remains uncertain. We evaluated the relationship between primary tumor site and overall survival (OS) in 9738 early-stage nodal DLBCL patients from the Surveillance, Epidemiology, and End Results (SEER) database. The primary site of the tumors was characterized as supradiaphragm and subdiaphragm according to the definition of lymph node distribution in the Ann Arbor staging. The OS was significantly better for patients of the supradiaphragm group ( = 6038) compared to the ones from the subdiaphragm group ( = 3655) (hazard ratio (HR) 1.24; 95%CI: 1.16-1.33; < 0.001), and it was preserved after propensity score matching (PSM) (HR 1.15; 95% CI: 1.07-1.24; < 0.001). Gene enrichment analyses demonstrated that the subdiaphragm group has an upregulated extracellular matrix (ECM)-related signaling, which reportedly can promote growth, invasion, and metastasis of the cancer, and downregulated interferon response, which is considered to have anti-tumor function. Our results indicate the two tumor locations (supradiaphragm and subdiaphragm) presented different prognostic implications for the overall survival, suggesting that the tumor's location could serve as a prognostic biomarker for early-stage nodal DLBCL patients.
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http://dx.doi.org/10.3390/cancers13163954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392260PMC
August 2021

The Role of AMPARs Composition and Trafficking in Synaptic Plasticity and Diseases.

Cell Mol Neurobiol 2021 Aug 26. Epub 2021 Aug 26.

Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

AMPA receptors are tetrameric ionic glutamate receptors, which mediate 90% fast excitatory synaptic transmission induced by excitatory glutamate in the mammalian central nervous system through the activation or inactivation of ion channels. The alternation of synaptic AMPA receptor number and subtype is thought to be one of the primary mechanisms that involve in synaptic plasticity regulation and affect the functions in learning, memory, and cognition. The increasing of surface AMPARs enhances synaptic strength during long-term potentiation, whereas the decreasing of AMPARs weakens synaptic strength during the long-term depression. It is closely related to the AMPA receptor as well as its subunits assembly, trafficking, and degradation. The dysfunction of any step in these precise regulatory processes is likely to induce the disorder of synaptic transmission and loss of neurons, or even cause neuropsychiatric diseases ultimately. Therefore, it is useful to understand how AMPARs regulate synaptic plasticity and its role in related neuropsychiatric diseases via comprehending architecture and trafficking of the receptors. Here, we reviewed the progress in structure, expression, trafficking, and relationship with synaptic plasticity of AMPA receptor, especially in anxiety, depression, neurodegenerative disorders, and cerebral ischemia.
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http://dx.doi.org/10.1007/s10571-021-01141-zDOI Listing
August 2021

A Meta-Analysis of Randomized Controlled Trials Concerning the Efficacy of Transversus Abdominis Plane Block for Pain Control After Laparoscopic Cholecystectomy.

Front Surg 2021 4;8:700318. Epub 2021 Aug 4.

Department of Thoracic Surgery, Weifang Second People's Hospital, Weifang, China.

Transverse abdominis plane (TAP) block has been suggested to reduce post-operative pain after laparoscopic cholecystectomy (LC). However, the literature is divided on whether ultrasound (USG)-guided TAP block is effective for pain control after LC. The present meta-analysis therefore evaluated the efficacy of USG-guided TAP block vs. controls and port site infiltration for pain control after LC. A comprehensive literature search of online academic databases was performed for published randomized controlled trials (RCTs) for studies published to January 31, 2021. The primary outcome analyzed was post-operative pain score at 0, 6, 12, and 24 h post-surgery, both during rest and while coughing. Secondary outcomes included morphine consumption and post-operative nausea and vomiting (PONV) incidence. A total of 23 studies with data on 1,450 LC patients were included in our meta-analysis. A reduction in pain intensity at certain post-operative timepoints was observed for USG-guided TAP block patients compared to control group patients. No reduction in pain intensity was observed for patients receiving USG-guided TAP block patients vs. conventional Port site infiltration. This meta-analysis concludes that TAP block is more effective than a conventional pain control, but not significatively different from another local incisional pain control that is port site infiltration. Additional prospective randomized controlled trials are required to further validate our findings.
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http://dx.doi.org/10.3389/fsurg.2021.700318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371254PMC
August 2021

Cytokine levels in sputum, not serum, may be more helpful for indicating the damage in the lung and the prognosis of severe COVID-19 - A case series.

J Infect 2021 Aug 19. Epub 2021 Aug 19.

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China. Electronic address:

Purpose: To describe the relationship between the severity of lung damage and cytokine levels in sputum, bronchoalveolar lavage fluid (BALF), serum.

Method: Eight severe patients infected with coronavirus disease 2019 (COVID-19) were admitted and their cytokines and chest computed tomography (CT) were analyzed.

Results: Compared with in serum, IL-6 and TNF-α in sputum and in BALF show more directly reflect the severity of COVID-19 critical patients. The gradient ratio of IL-6 levels may predict the prognosis of severe patients.

Conclusion: Cytokine levels in the sputum may be more helpful for indicating lung damage. Local intervention through the respiratory tract is expected to benefit patients with severe COVID-19.
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http://dx.doi.org/10.1016/j.jinf.2021.08.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375249PMC
August 2021

A review of cutting-edge therapies for hepatocellular carcinoma (HCC): Perspectives from patents.

Int J Med Sci 2021 18;18(14):3066-3081. Epub 2021 Jun 18.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.

Hepatocellular carcinoma (HCC) is a challenging disease due to its heterogenous etiology. Several breakthroughs have occurred in treatment of HCC, associated with an enormous number of patent publications for a variety of HCC treatment modalities. As patents can provide valuable information for academic research and commercial development, this study aims to unravel the cutting-edge therapies for HCC by using patents as an indicator. The outcome from this analysis may offer meaningful insights for respective policymaking, strategic plan and research and development (R&D) prioritization. Derwent Innovation platform was employed to collect the sample data of patents related to HCC treatment technologies worldwide as of December 31, 2019. Data inclusion, screening and exclusion were according to the rules of preferred reporting items for systematic reviews and meta-analyses (PRISMA). Technologies were classified based on Barcelona Clinic Liver Cancer (BCLC) staging system and recent clinical publications. Patent citation network analysis was carried out to identify and understand HCC therapeutic technology flow. A dataset of 2543 patent documents and 528 patent families was generated. 11 technological categories were classified. Numerous researches were focalized on refinements in technologies and innovations within the field of HCC therapy, and the major achievements are technology advancement on molecular target therapy, chemotherapy, locoregional therapy, combination therapy and immunotherapy with demonstrated clinical benefits. In patent citation network, Notch pathway investigation, antibody drug conjugate (ADC) technology development and drug eluting beads trans artery chemoembolization (DEB-TACE) advancement are the major technological communities involving patents with the greatest future exploratory potential. Numerous emerging technologies have been identified in this study, in which exploring novel therapeutic targets in molecular target therapy, more localized and visible locoregional therapy and combination of immunotherapy with target therapy or other traditional therapies are highlighted as the future trends in treating HCC.
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http://dx.doi.org/10.7150/ijms.59930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364461PMC
June 2021

Temperature-sensitive poly(N-isopropylacrylamide)-chitosan hydrogel for fluorescence sensors in living cells and its antibacterial application.

Int J Biol Macromol 2021 Aug 12;189:316-323. Epub 2021 Aug 12.

College of Chemistry, Jilin University, Changchun 130012, PR China; Weihai Institute for Bionics-Jilin University, Weihai 264400, PR China. Electronic address:

It is meaningful and challenging to design and develop a fluorescent probe for living cell temperature sensors since it should have good cell compatibility and high-resolution features. In this work, the temperature-sensitive polymer of PA-loaded cysteine (Cys) modified chitosan (Cs) grafted PNIPAM (Cs-Cys-PN/PA) with aggregation-induced emission enhancement (AIEE) properties that reversible hydrogel in an aqueous solution is synthesized. Here, we interpret the temperature stimulus as a monochromatic signal through the AIEE active reversible hydrogel of Cs-Cys-PN. In addition, the cytotoxicity test shown that Cs-Cys-PN has good biocompatibility. Cs-Cys-PN can be used to build antibacterial drugs carrier, thereby providing a new platform of self-released drugs for the treatment of bacterial infections.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.057DOI Listing
August 2021

Metabolic signatures in the conversion from gestational diabetes mellitus to postpartum abnormal glucose metabolism: a pilot study in Asian women.

Sci Rep 2021 Aug 12;11(1):16435. Epub 2021 Aug 12.

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.

We aimed to identify serum metabolites related to abnormal glucose metabolism (AGM) among women with gestational diabetes mellitus (GDM). The study recruited 50 women diagnosed with GDM during mid-late pregnancy and 50 non-GDM matchees in a Singapore birth cohort. At the 5-year post-partum follow-up, we applied an untargeted approach to investigate the profiles of serum metabolites among all participants. We first employed OPLS-DA and logistic regression to discriminate women with and without follow-up AGM, and then applied area under the curve (AUC) to assess the incremental indicative value of metabolic signatures on AGM. We identified 23 candidate metabolites that were associated with postpartum AGM among all participants. We then narrowed down to five metabolites [p-cresol sulfate, linoleic acid, glycocholic acid, lysoPC(16:1) and lysoPC(20:3)] specifically associating with both GDM and postpartum AGM. The combined metabolites in addition to traditional risks showed a higher indicative value in AUC (0.92-0.94 vs. 0.74 of traditional risks and 0.77 of baseline diagnostic biomarkers) and R (0.67-0.70 vs. 0.25 of traditional risks and 0.32 of baseline diagnostic biomarkers) in terms of AGM indication, compared with the traditional risks model and traditional risks and diagnostic biomarkers combined model. These metabolic signatures significantly increased the AUC value of AGM indication in addition to traditional risks, and might shed light on the pathophysiology underlying the transition from GDM to AGM.
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http://dx.doi.org/10.1038/s41598-021-95903-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361021PMC
August 2021

Disturbed mitochondrial acetylation in accordance with the availability of acetyl groups in hepatocellular carcinoma.

Mitochondrion 2021 Aug 8;60:150-159. Epub 2021 Aug 8.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address:

As an essential post-translational modification, acetylation participates in various cellular processes and shows aberrances during tumorigenesis. Owing to its modification substrate, acetyl-CoA, acetylation is postulated as a depot for acetyl groups and evolve to build a connection between epigenetics and metabolism. Here we depict a distinct acetylome atlas of hepatocellular carcinoma from the perspectives of both protein acetylation and acetyl-CoA metabolism. We found that tumor acetylome demonstrated a compartment-dependent alteration that the acetylation level of mitochondrial proteins tended to be decreased while nuclear proteins were highly acetylated. In addition, elevated expression of ATP-citrate synthase (ACLY) was observed in tumors, which would facilitate histone acetylation by transporting mitochondrial acetyl coenzyme A to the nucleus. A hypothetical model of the oncogenic acetylome was proposed that growing demands for histone acetylation in tumor cells would drive the relocalization of acetyl-CoA to the nucleus, which may contribute to the global deacetylation of mitochondrial proteins to support the nuclear acetyl-CoA pool in an ACLY-dependent manner. Our findings are thought-provoking on the potential linkage between epigenetics and metabolism in the progression of tumorigenesis.
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http://dx.doi.org/10.1016/j.mito.2021.08.004DOI Listing
August 2021

Treatment of Melanoma by Nano-conjugate-Delivered Wee1 siRNA.

Mol Pharm 2021 Sep 10;18(9):3387-3400. Epub 2021 Aug 10.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, People's Republic of China.

Small interfering RNA (siRNA)-based drugs have shown tremendous potential to date in cancer gene therapy. Despite the considerable efforts in siRNA design and manufacturing, unsatisfactory delivery systems persist as a limitation for the application of siRNA-based drugs. In this work, the cholesterol, cell-penetrating peptide conjugate cRGD (R8-cRGD), and polyethylene glycol (PEG) were introduced into low-molecular-weight polyethyleneimine (LMW PEI) to form cRGD-R9-cholesterol-PEI-PEG (RRCPP) nanoparticles with specific targeting and highly penetrating abilities. The enhanced siRNA uptake efficiency of the RRCPP delivery system benefited from R8-cRGD modification. Wee1 is an oncogenic nuclear kinase that can regulate the cell cycle as a crucial G2/M checkpoint. Overexpression of Wee1 in melanoma may lead to a poor prognosis. In the present study, RRCPP nanoparticles were designed for Wee1 siRNA delivery to form an RRCPP/siWee1 complex, which significantly silenced the expression of the gene (>60% inhibition) and induced B16 tumor cell apoptosis by abrogating the G2M checkpoint and DNA damage . Furthermore, the RRCPP/siWee1 complex suppressed B16 tumor growth in a subcutaneous xenograft model (nearly 85% inhibition rate) and lung metastasis (nearly 66% inhibition rate) with ideal safety. Briefly, our results support the validity of RRCPP as a potential Wee1 siRNA carrier for melanoma gene therapy.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00316DOI Listing
September 2021

Endophytic OsiSh-2-Mediated Balancing between Growth and Disease Resistance in Host Rice.

mBio 2021 Aug 10;12(4):e0156621. Epub 2021 Aug 10.

State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, College of Biology, Hunan Universitygrid.67293.39, Changsha, Hunan, China.

Plants fine-tune the growth-defense trade-off to survive when facing pathogens. Meanwhile, plant-associated microbes, such as the endophytes inside plant tissues, can benefit plant growth and stress resilience. However, the mechanisms for the beneficial microbes to increase stress resistance with little yield penalty in host plants remain poorly understood. In the present study, we report that endophytic Streptomyces hygroscopicus OsiSh-2 can form a sophisticated interaction with host rice, maintaining cellular homeostasis under pathogen-infection stress, and optimize plant growth and disease resistance in rice. Four-year field trials consistently showed that OsiSh-2 could boost host resistance to rice blast pathogen Magnaporthe oryzae while still maintaining a high yield. The integration of the proteomic, physiological, and transcriptional profiling analysis revealed that OsiSh-2 induced rice defense priming and controlled the expression of energy-consuming defense-related proteins, thus increasing the defense capability with the minimized costs of plant immunity. Meanwhile, OsiSh-2 improved the chloroplast development and optimally maintained the expression of proteins related to plant growth under pathogen stress, thus promoting the crop yield. Our results provided a representative example of an endophyte-mediated modulation of disease resistance and fitness in the host plant. The multilayer effects of OsiSh-2 implicate a promising future of using endophytic actinobacteria for disease control and crop yield promotion. Under disease stress, activation of defense response in plants often comes with the cost of a reduction in growth and yield, which is referred as the growth-defense trade-off. The microorganisms which can be recruited by plants to mitigate the growth-defense trade-off are of great value in crop breeding. Here, we reported a rice endophytic actinomycetes Streptomyces hygroscopicus OsiSh-2, which can improve host performances on resistance to rice blast while still sustaining high yield in the 4-year field trials. The proteomic, physiological, and transcriptional profiling data offer insights into the molecular basis underlying the balancing between defense and growth in OsiSh-2-rice symbiont. The findings provide an example for the endophyte-mediated modulation of growth-defense trade-offs in plants and indicated the promising application of endophytic actinobacterial strains in agriculture to breed "microbe-optimized crops."
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http://dx.doi.org/10.1128/mBio.01566-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406269PMC
August 2021
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