Publications by authors named "Ke Hu"

424 Publications

Long noncoding RNA UCA1 promotes high glucose-induced human retinal endothelial cells angiogenesis via regulating miR-624-3p/VEGF-C.

J Diabetes Investig 2021 Jun 17. Epub 2021 Jun 17.

Ophthalmology Department, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Aims/introduction: Emerging evidences have indicated that lncRNAs play important roles in the development and progression of Diabetic retinopathy (DR). It is reported that UCA1 was highly expressed in diabetic lymphoendothelial cells and influences glucose metabolism in rats with DR. The aim of the present study was to explore the role of UCA1 in the mechanism of DR.

Methods: Gene expression analyses in fibrovascular membranes excised from patients with DR using public microarray datasets (GSE60436). RT-PCR was performed to detect UCA1, miR-624-3p and VEGF-C expressions in blood of patients and human retinal endothelial cells (HRECs). Moreover, CCK-8, transwell assay, and tube formation assay were used to identify biological effects of UCA1 on HRECs proliferation, migration ability and angiogenesis in vitro.

Results: UCA1 and VEGF-C was elevated in DR patients and high glucose-induced HRECs cell lines, while miR-624-3p was decreased. UCA1 inhibition inhibited proliferation, angiogenesis and migration of HRECs cells under high glucose condition. Luciferase reporter assay indicated that UCA1 could sponge with miR-624-3p, which could directly target at VEGF-C. Finally, we proved a pathway that UCA1 promoted cell proliferation, migration and angiogenesis through sponging with miR-624-3p thereby upregulating VEGF-C in high glucose-induced HRECs.

Conslusions: We identified UCA1 as an important factor associated with DR, which could regulate the expression of VEGF-C by sponging miR-624-3p in human retinal endothelial cells. Our results pay the way for further studies on diagnostic and therapeutic studies related to UCA1 in DR patients.
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http://dx.doi.org/10.1111/jdi.13617DOI Listing
June 2021

A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway.

Cancer Cell Int 2021 May 30;21(1):285. Epub 2021 May 30.

CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China.

Background: Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity.

Methods: We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro.

Results: The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed.

Conclusion: The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.
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http://dx.doi.org/10.1186/s12935-021-01973-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165811PMC
May 2021

Orexin A improves the cognitive impairment induced by chronic intermittent hypoxia in mice.

Brain Res Bull 2021 Aug 27;173:203-210. Epub 2021 May 27.

Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address:

The orexin neuron in lateral hypothalamus (LH) was involved in the regulation of sleep-wake cycle. However, the effect of orexin A (OXA) on cognitive impairment resulting from diverse diseases remains controversial. In this study, we investigated the effect of OXA on cognitive impairment induced by chronic intermittent hypoxia (CIH) in mice. Adult (10 weeks old) male C57BL/6 mice were randomly divided into the following four groups: normoxia control (NC)+normal saline (NS), NC + OXA, CIH + NS and CIH + OXA group. Following the CIH mice models establishment, OXA was injected into the right lateral ventricles of mice by a micro-injection system. Water maze test was used to assess spatial memory abilities of the mice. The expression of OXA and c-Fos in LH were analyzed by immunofluorescence staining. Apoptotic cell death and oxidative stress in hippocampus were evaluated using multiple methods including TUNEL, western blot and biochemical analysis. Behavioral tests revealed that CIH significantly increased the escape latency and time of arriving platform, of which were markedly decreased by OXA treatment. Similarly, the CIH + NS group was worse than NC + NS group in terms of the number of platform crossing and time in the target quadrant, of which were also significantly improved by OXA treatment. The number of OXA + neuron in LH was decreased, but the percentage of c-Fos+/OXA + neuron in LH was remarkably increased by CIH. Furthermore, we found that micro-injection of OXA attenuated CIH-induced apoptotic cell death and oxidative stress in the hippocampus. Our results suggested that OXA might improve cognitive impairment induced by CIH through inhibiting hippocampal apoptosis and oxidative stress.
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http://dx.doi.org/10.1016/j.brainresbull.2021.05.022DOI Listing
August 2021

Nonlinear response of SIA to emission changes and chemical processes over eastern and central China during a heavy haze month.

Sci Total Environ 2021 Sep 14;788:147747. Epub 2021 May 14.

Wuhan Environmental Monitoring Center, Wuhan 430015, China.

This study used a chemical transport model to investigate the response of secondary inorganic aerosols (SIA) to chemical processes and its precursor emissions over northern and southern city-clusters of China in January 2014. Unexpectedly, SIA concentrations with low levels of precursor emissions were much higher over the southern regions than those over the northern region with high levels of precursor emissions, based on ground observations and high-precision simulations. The sensitivity analysis of chemical processes suggests that the gas-phase chemistry was a critical factor determining the SIA pattern, especially the higher efficiency of nitrogen conversion to nitrate in southern cities controlled by favorable meteorological elements than that in northern city. However, the heterogeneous process led to the decrease of SIA in southern regions by 3% to 36% and the increasing of SIA in NCP by 26.9%, mainly attributing to the impact on nitrate. The reason was that sulfate enhancement by the heterogeneous reactions can compete ammonia (NH) and the excessive nitric acid converted into nitrogen oxide (NO), leading to nitrate decrease in southern regions under NH-deficient regimes. Moreover, through sensitivity experiments of precursor emission reduction by 20%, NH control was found to be the most effective for reducing SIA concentrations comparing to sulfur dioxide (SO) and NO reduction and a more remarkable decrease of SIA was in southern regions by 10% to 15% than that in northern region by 6.7%. The effect of the synergy control of precursors emission varied in different city-clusters, inferring that the control strategy aimed at improving air quality should be implemented based on specific characteristics of precursors emission in different regions of China.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147747DOI Listing
September 2021

Integrated study of circRNA, lncRNA, miRNA, and mRNA networks in mediating the effects of testicular heat exposure.

Cell Tissue Res 2021 May 20. Epub 2021 May 20.

School of Life Science, Bengbu Medical College, Bengbu, Anhui, China.

The World Health Organization has recognized that testicular function is temperature dependent. Testicular heat exposure caused by occupational factors, lifestyle, and clinical diseases can lead to different degrees of reproductive problems. The aim of this study was to reveal the transcriptional regulatory network and its potential crucial roles in mediating the effects of testicular heat exposure. Testicular tissue was collected from a group of mice subjected to scrotal heat exposure as well as a control group. RNA was isolated from both groups and used for high-throughput sequencing. Using differential transcriptome expression analysis, 172 circRNAs, 279 miRNAs, 465 lncRNAs, and 2721 mRNAs were identified as significantly differentially expressed in mouse testicular tissue after heat exposure compared with the control group. Through Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, differentially expressed lncRNAs and mRNAs were found to have potentially important functions in meiotic cell cycle (GO:0051321), cytoplasm (GO:0005737), membrane raft (GO:0045121), MAPK signaling (mmu04010), purine metabolism (mmu00230), and homologous recombination (mmu03440). Some of the most upregulated and downregulated lncRNAs and circRNAs were predicted to be associated with numerous miRNAs and mRNAs through competing endogenous RNA regulatory network analysis, which were validated with molecular biology experiments. This research provides high-throughput sequencing data of a testicular heat exposure model and lays the foundation for further study on circRNAs, miRNAs, and lncRNAs that are involved in male reproductive diseases related to elevated testicular temperature.
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http://dx.doi.org/10.1007/s00441-021-03474-zDOI Listing
May 2021

Survey on the Progression of Myopia in Children and Adolescents in Chongqing During COVID-19 Pandemic.

Front Public Health 2021 28;9:646770. Epub 2021 Apr 28.

Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, China.

The Covid-19 pandemic restricts children and adolescents from doing normal daily activities such as playing outdoors and going to school. The incidence and prevalence of myopia have increased during the COVID-19 pandemic. The aim of this study was to investigate and evaluate the impact of the home confinement during the COVID-19 pandemic on the progression of myopia among children and adolescents in Chongqing, China. The survey was conducted by using stratified samplings. Samples were randomly selected from the 2019 National Student Physique and Health Survey database, and their visual function and refractive data were compared with those in 2020. Vision-related behavior questionnaire including digital screen exposure was applied to investigate the correlation between eye parameter and eye health-related behavior. A total of 1,733 and 1,728 students were enrolled in 2020 and 2019, respectively. The percentage of myopia students was 55.02% in 2020, which was higher than that in 2019 (44.62%). The mean uncorrected visual acuity (UCVA, LogMAR, 0.35 ± 0.42) in 2020 was higher than that in 2019 (0.27 ± 0.36, < 0.001). The mean spherical equivalent (SE) refraction (-1.94 ± 2.13 D) in 2020 was lower than that in 2019 (-1.64 ± 5.49 D, < 0.001). For students who used digital devices for online courses, the mean SE in the television group (-1.10 ± 1.49 D) was better than that in the computer group (-2.03 ± 2.37 D, = 0.0017) and in the cell phone group (-2.02 ± 2.09 D, = 0.0028). The average duration of online classes ( = -0.27, < 0.0001), the number of online classes per day ( = -0.33, < 0.0001), as well as digital screen exposure time ( = -0.20, < 0.0001) were negatively correlated with SE, and the average time of outdoor activity ( = 0.20, < 0.0001) was positively correlated with SE. Increased digital screen exposure contributes to myopic progression in children and adolescents of Chongqing during the COVID-19 pandemic. Suitable digital devices should be provided for online classes and outdoor activity should be advocated to prevent myopic pandemic.
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http://dx.doi.org/10.3389/fpubh.2021.646770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115404PMC
May 2021

Pure organic quinacridone dyes as dual sensitizers in tandem photoelectrochemical cells for unassisted total water splitting.

Chem Commun (Camb) 2021 Jun;57(46):5634-5637

Key Laboratory for Advanced Materials, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.

Pure organic dye QAP-C8 based on quinacridone (QA) with octyl side chains as the donor and pyridine dicarboxylic acid (PDA) as the acceptor was first used in both the photoanode and the photocathode of photoelectrochemical cells. A tandem device with QAP-C8 as the photosensitizer realized overall water splitting and showed a STH of 0.11% under neutral pH conditions without an external bias.
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http://dx.doi.org/10.1039/d1cc01570bDOI Listing
June 2021

Cell-free DNA copy number variations predict efficacy of immune checkpoint inhibitor-based therapy in hepatobiliary cancers.

J Immunother Cancer 2021 May;9(5)

Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Background: This study was designed to screen potential biomarkers in plasma cell-free DNA (cfDNA) for predicting the clinical outcome of immune checkpoint inhibitor (ICI)-based therapy in advanced hepatobiliary cancers.

Methods: Three cohorts including 187 patients with hepatobiliary cancers were recruited from clinical trials at the Peking Union Medical College Hospital. Forty-three patients received combination therapy of programmed cell death protein 1 (PD-1) inhibitor with lenvatinib (ICI cohort 1), 108 patients received ICI-based therapy (ICI cohort 2) and 36 patients received non-ICI therapy (non-ICI cohort). The plasma cfDNA and blood cell DNA mutation profiles were assessed to identify efficacy biomarkers by a cancer gene-targeted next-generation sequencing panel.

Results: Based on the copy number variations (CNVs) in plasma cfDNA, the CNV risk score model was constructed to predict survival by using the least absolute shrinkage and selection operator Cox regression methods. The results of the two independent ICI-based therapy cohorts showed that patients with lower CNV risk scores had longer overall survival (OS) and progression-free survival (PFS) than those with high CNV risk scores (log-rank p<0.01). In the non-ICI cohort, the CNV risk score was not associated with PFS or OS. Furthermore, the results indicated that 53% of patients with low CNV risk scores achieved durable clinical benefit; in contrast, 88% of patients with high CNV risk scores could not benefit from combination therapy (p<0.05).

Conclusions: The CNVs in plasma cfDNA could predict the clinical outcome of the combination therapy of PD-1 inhibitor with lenvatinib and other ICI-based therapies in hepatobiliary cancers.
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http://dx.doi.org/10.1136/jitc-2020-001942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112417PMC
May 2021

The combination of intermittent electrical stimulation with acute intermittent hypoxia strengthens genioglossus muscle discharge in chronic intermittent hypoxia-pretreated rats.

Respir Physiol Neurobiol 2021 May 7;291:103680. Epub 2021 May 7.

Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address:

Objective: Exploring whether the genioglossus discharge in chronic intermittent hypoxia(CIH) - pretreated rats could be enhanced by intermittent electrical stimulation combined with acute intermittent hypoxia(AIH).

Methods: Rats were pretreated with CIH for 4 weeks and then were randomly divided into 6 groups: time control, intermittent electric stimulation, AIH, intermittent electric stimulation + AIH, continuous electric stimulation and continuous hypoxia exposure. The genioglossus discharges were recorded and compared before and after stimulation. Normoxic-treated rats were grouped and treated with the same stimulation protocols.

Results: Intermittent electrical stimulation or AIH temporarily increased the activity of the genioglossus discharge, in which the degree of the increase was significantly higher in CIH-pretreated rats than in normoxic rats.After intermittent electrical stimulation, AIH evoked a sustained elevation of genioglossus discharge activities in CIH-pretreated rats, in which the degree of the increase was significantly higher than in rats induced by a single intermittent electric stimulation.

Conclusion: Intermittent electrical stimulation combined with AIH strengthens the genioglossus plasticity in CIH-pretreated rats.
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http://dx.doi.org/10.1016/j.resp.2021.103680DOI Listing
May 2021

Enhanced Peroxidase-mimicking Activity of Plasmonic Gold-modified Mn O Nanocomposites through Photoexcited Hot Electron Transfer.

Chem Asian J 2021 Jun 11;16(12):1603-1607. Epub 2021 May 11.

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433, P. R. China.

Enzyme-mimicking artificial nanomaterials often termed nanozymes have broad applications in many fields, including biosensing, pollutant degradation and cancer diagnosis. Herein, we introduce a plasmonic gold nanoparticle-modified Mn O nanozyme (Mn O -Au). Visible or near infrared light excitation into the plasmonic absorption band of the surface-bound gold nanoparticles enhances the catalytic oxidation of tetramethylbenzidine (TMB). The mechanism of light-enhanced peroxidase activity is proposed based on the Mn O conduction band mediated hot electron transfer from photoexcited gold nanoparticles to H O which undergoes further oxygen-oxygen bond cleavage to yield hydroxyl radical. The surface decoration of plasmonic gold nanoparticles endows Mn O -Au to be a light-regulated nanozyme.
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http://dx.doi.org/10.1002/asia.202100337DOI Listing
June 2021

Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, prospective, randomized controlled trial.

Phytomedicine 2021 May 16;85:153242. Epub 2020 May 16.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong province, 510120 PR China. Electronic address:

Background: Coronavirus disease 2019 (Covid-19) has resulted in a global outbreak. Few existing targeted medications are available. Lianhuaqingwen (LH) capsule, a repurposed marketed Chinese herb product, has been proven effective for influenza.

Purpose: To determine the safety and efficacy of LH capsule in patients with Covid-19.

Methods: We did a prospective multicenter open-label randomized controlled trial on LH capsule in confirmed cases with Covid-19. Patients were randomized to receive usual treatment alone or in combination with LH capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the rate of symptom (fever, fatigue, coughing) recovery.

Results: We included 284 patients (142 each in treatment and control group) in the full-analysis set. The recovery rate was significantly higher in treatment group as compared with control group (91.5% vs. 82.4%, p = 0.022). The median time to symptom recovery was markedly shorter in treatment group (median: 7 vs. 10 days, p < 0.001). Time to recovery of fever (2 vs. 3 days), fatigue (3 vs. 6 days) and coughing (7 vs. 10 days) was also significantly shorter in treatment group (all p < 0.001). The rate of improvement in chest computed tomographic manifestations (83.8% vs. 64.1%, p < 0.001) and clinical cure (78.9% vs. 66.2%, p = 0.017) was also higher in treatment group. However, both groups did not differ in the rate of conversion to severe cases or viral assay findings (both p > 0.05). No serious adverse events were reported.

Conclusion: In light of the safety and effectiveness profiles, LH capsules could be considered to ameliorate clinical symptoms of Covid-19.
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http://dx.doi.org/10.1016/j.phymed.2020.153242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229744PMC
May 2021

Detectable antibodies against SARS-CoV-2 in newborns from mothers infected with COVID-19 at different gestational ages.

Pediatr Neonatol 2021 05 26;62(3):321-323. Epub 2021 Mar 26.

Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China. Electronic address:

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http://dx.doi.org/10.1016/j.pedneo.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997304PMC
May 2021

Vector Competence for DENV-2 Among (Diptera: ) Populations in China.

Front Cell Infect Microbiol 2021 23;11:649975. Epub 2021 Mar 23.

Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, China.

is a vector of over 20 arboviruses that has spread throughout the world, mainly in the second half of the twentieth century. Approximately 50-100 million people are infected with dengue virus (DENV) transmitted by mosquitoes each year, leading to heavy economic burdens for both governments and individuals, among countless other negative consequences. Understanding the vector competence of vector species is critical for effectively preventing and controlling vector-borne diseases. Accordingly, in this study, vector competence was evaluated by quantitative analysis of DENV-2 loads in mosquito tissues (midguts, heads, and salivary glands) and whole mosquitoes through real-time quantitative polymerase chain reaction (RT-qPCR) analysis. and the expression of immune-associated genes (Rel1, Rel2, Dicer2, and STAT) in mosquitoes were also detected by RT-qPCR to explore their impact on vector competence. The amount of DENV-2 in the mosquito midguts, heads, and salivary glands from southern-western China were found to be lower than those from eastern-central-northern China. The DENV-2 loads in whole mosquitoes showed a negative correlation with Rel1 gene ( = -0.285, = 0.011) and STAT gene expression levels ( = -0.289, = 0.009). In terms of strains, the density of the AlbB strain was found to be significantly higher than that of the AlbA strain in the eight populations, and the relative density of the AlbB strain in mosquitoes from southern-western China was higher than those from eastern-central-northern China. The relative density of the AlbB strain showed a negative correlation with the mean loads of DENV-2 in the heads ( = -0.729, = 0.040), salivary glands ( = -0.785, = 0.021), and whole mosquitoes ( = -0.909, = 0.002). Thus, there are lower DENV-2 loads in the mosquitoes from southern-western China, which may be related to the innate immunity of mosquitoes as affected by Rel1 in the Toll pathway, STAT in the JAK-STAT pathway, and the relative density of the AlbB strain.
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http://dx.doi.org/10.3389/fcimb.2021.649975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021855PMC
March 2021

Comparison and clinical characteristics of COVID-19 between January and February 2020 in Wuhan, China.

Ann Palliat Med 2021 Apr 23;10(4):4201-4213. Epub 2021 Mar 23.

Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) continues to make a deadly impact on human life all over the world. Therefore, we aimed to analyze the changes in clinical characteristics of coronavirus disease 2019 (COVID-19) patients over time.

Methods: We recruited 896 patients who were admitted to the Renmin Hospital of Wuhan University between 30th January 2020 and 16st March 2020. We conducted a retrospective study collecting clinical characteristics, radiologic and laboratory findings, treatments administered, and clinical outcomes in the patients. The data collected were compared between patients with onset of illness in January 2020 and patients with onset of illness in February 2020, in Wuhan, China. Categorical data and non-normally distributed continuous data were examined by the χ2 test and the Mann-Whitney-Wilcoxon test respectively, and the Kaplan-Meier plot was used to analyze survival data. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with in-hospital death.

Results: A total of 896 patients were enrolled; the median age was 60 (range, 47-69) years, 685 (76.5%) were categorized into group A (patients with onset of illness in January 2020), and 211 (23.5%) were categorized into group B (patients with onset of illness in February 2020). Compared with group B, group A had a higher incidence of fever (P<0.001), and a lower rate of asymptomatic individuals (P<0.001). Group A patients had a higher incidence of neutrophilia (P=0.043), an elevated D-dimer (P<0.001), and an increased lactate dehydrogenase (LDH) (P=0.002), but a lower incidence of a normal computed tomography (CT) scan (P=0.001). CD3 cell counts (P=0.015) and CD4 cell counts (P=0.04) were significantly reduced in group A patients. Critically ill patients were less frequent (P=0.005) and patients with milder disease were more common (P=0.001) in group B. The fatality rate was significantly less in group B patients (P=0.028). Multivariate regression indicated that older age (odds ratio 1.086, 95% CI: 1.061-1.111, per year increase; P<0.001) increased the risk of in-hospital death. Female sex (odds ratio 0.523, 95% CI: 0.316-0.865; P=0.012) and being in group B (odds ratio 0.423, 95% CI: 0.212-0.844; P=0.015) significantly decreased the risk of in-hospital death.

Conclusions: The condition of patients with onset of illness in January was more serious than that of patients with onset of illness in February 2020. The time of onset of illness was an independent risk factor for in-hospital death comparing January and February 2020. Changing pathogenicity of SARS-CoV-2 and improved healthcare may have contributed to the results, however, more basic research is required to support this hypothesis.
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http://dx.doi.org/10.21037/apm-20-2222DOI Listing
April 2021

Sudden death of COVID-19 patients in Wuhan, China: A retrospective cohort study.

J Glob Health 2021 Mar 27;11:05006. Epub 2021 Mar 27.

Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

Background: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread throughout China. So far, it has caused ~ 4000 deaths in this country. We aimed to systematically characterize clinical features and determine risk factors of sudden death for COVID-19 patients.

Methods: Deceased patients with COVID-19 in Tongji hospital from January 22 to March 23, 2020 were extracted. Patients who died within 24 hours after admission were identified as sudden deaths, and the others formed non-sudden deaths. The differences in clinical characteristics between the two groups were estimated. Risk factors associated with sudden deaths were explored by logistic regression.

Results: 281 deceased patients were enrolled in this study. Sudden death occurred in 28 (10.0%) patients, including 4 (14.3%) admitted to the intensive care unit. Fatigue was more common in sudden deaths (11, 47.8%) than in non-sudden deaths (40, 17.2%). Both the count and percentage of eosinophils were lower in sudden deaths than that in non-sudden deaths ( = 0.006 and  = 0.004). Compared with non-sudden deaths, sudden deaths had higher plasma levels of procalcitonin, C-reactive protein, D-dimer, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase and N-terminal pro-brain natriuretic peptide. There were not significant differences in gender, age, chest CT image features and comorbidities observed.

Conclusions: The differences between the two groups suggested more severe systemic inflammation, multi-organ dysfunction, especially impaired liver and heart function in COVID-19 patients who died suddenly after admission. More researches are needed to verify these points.
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http://dx.doi.org/10.7189/jogh.11.05006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005311PMC
March 2021

Anti-DLBCL efficacy of DCZ0825 in vitro and in vivo: involvement of the PI3K‒AKT‒mTOR/JNK pathway.

Acta Biochim Biophys Sin (Shanghai) 2021 Apr;53(5):575-583

Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, characterized by high heterogeneity. The poor outcome of a portion of patients who suffer relapsing or resistant to conventional treatment impels the development of novel agents for DLBCL. DCZ0825 is a novel compound derived from pterostilbene and osalmide, whose antitumor activities have drawn our attention. In this study, we found that DCZ0825 exhibited high cytotoxicity toward DLBCL cell lines in a dose- and time-dependent manner, as revealed by cell counting kit-8 assay. Flow cytometry and western blot analysis results showed that DCZ0825 also promoted cell apoptosis via both extrinsic and intrinsic apoptosis pathways mediated by caspase. In addition, DCZ0825 induced cell cycle arrest in the G2/M phase by downregulating Cdc25C, CDK1, and Cyclin B1, thus interfering with cell proliferation. Further investigation showed the involvement of the phosphatidylinositol 3-kinase (PI3K)‒AKT‒mTOR/JNK pathway in the efficacy of DCZ0825 against DLBCL. Remarkably, DCZ0825 also exerted notable cytotoxic effects in vivo as well, with low toxicity to important internal organs such as the liver and kidney. Our results suggest that DCZ0825 may have the potential to become a novel anti-DLBCL agent or to replenish the conventional therapeutic scheme of DLBCL.
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http://dx.doi.org/10.1093/abbs/gmab031DOI Listing
April 2021

Clinical features and risk factors associated with severe COVID-19 patients in China.

Chin Med J (Engl) 2021 Apr 1;134(8):944-953. Epub 2021 Apr 1.

Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.

Background: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines.

Methods: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19.

Results: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004).

Conclusions: The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.
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http://dx.doi.org/10.1097/CM9.0000000000001466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078348PMC
April 2021

Epidemiology and risk factors of candidemia due to Candida parapsilosis in an intensive care unit.

Rev Inst Med Trop Sao Paulo 2021 24;63:e20. Epub 2021 Mar 24.

Wuhan University, Renmin Hospital, Department of Respiratory and Critical Care Medicine, Wuhan, Hubei Province, People's Republic of China.

We analyzed the clinical features and risk factors of candidemia due to C. parapsilosis (n=104) in the intensive care unit of a tertiary hospital over six years. This was a monocentric, retrospective study of candidemia, conducted from January 2013 to March 2019. Epidemiological characteristics, clinical features, invasive procedures, laboratory data and outcomes of 267 patients with candidemia were analyzed to determine risk factors of candidemia due to C. parapsilosis. Sixty-three cases of C. albicans and 204 cases of non-C. albicans Candida (NCAC) species were included, the latter was composed of 104 cases of C. parapsilosis and 100 cases of non-C. albicans species (46 cases of C. tropicalis, 22 cases of C. glabrata, 23 cases of C. guilliermondii, 5 cases of C. krusei and 4 cases of C. lusitaniae), suggesting that C. parapsilosis was the predominant Candida species isolated from cases of candidemia. A binary multivariate logistic regression analysis showed that APACHE II scores, central venous catheterization and the use of broad-spectrum antibiotics were closely related to C. parapsilosis candidemia, with OR values of 1.159, 3.913 and 2.217, respectively. In conclusion, we found that C. parapsilosis was the main pathogen among the NCAC candidemia in the ICU patients. APACHE II scores, central venous catheterization and the use of broad-spectrum antibiotics were independent risk factors for the occurrence of C. parapsilosis candidemia, which may provide data to support the early introduction of anti-fungal therapy.
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http://dx.doi.org/10.1590/S1678-9946202163020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997672PMC
April 2021

The art of the steal.

Authors:
Ke Hu

Nat Microbiol 2021 Apr;6(4):421-422

Biodesign Institute - Center for Mechanisms of Evolution/School of Life Sciences, Arizona State University, Tempe, AZ, USA.

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http://dx.doi.org/10.1038/s41564-021-00886-zDOI Listing
April 2021

A new species of (Anura, Ranidae) from Hunan Province, China.

Zookeys 2021 15;1024:91-115. Epub 2021 Mar 15.

Institute of Wildlife Conservation, Central South University of Forestry and Technology, Changsha 410004, China Central South University of Forestry and Technology Changsha China.

A new species, , is described, based on five specimens from Sangzhi County, Zhangjiajie City, Hunan Province, China. Molecular phylogenetic analyses, based on mitochondrial 12S rRNA and 16S rRNA gene sequences, strongly support the new species as a monophyletic group nested into the species complex. The new species can be distinguished from its congeners by a combination of the following characters: (1) body size medium (SVL: 42.1-45.1 mm in males, 83.3-92.7 mm in females); (2) dorsolateral folds absent; (3) tympanum diameter 1.53 times as long as the width of the disc of finger III in females; 2.3 times in males; (4) dorsal skin green with dense granules and sparse irregular brown spots; males with several large warts on dorsum; (5) two metacarpal tubercles; (6) relative finger lengths: I ≤ II < IV < III; (7) tibiotarsal articulation beyond the tip of the snout; (8) ventral surface smooth in females; throat and chest having pale spinules in adult males; (9) dorsal limbs green or yellow green with brown transverse bands; and (10) paired external vocal sacs located at corners of the throat, finger I with light yellow nuptial pad in males. This discovery increases the number of species to 59 and those known from China to 37.
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http://dx.doi.org/10.3897/zookeys.1024.56399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985132PMC
March 2021

Survival Analysis and Risk Factors in COVID-19 Patients.

Disaster Med Public Health Prep 2021 Mar 25:1-6. Epub 2021 Mar 25.

Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China.

Objective: The aim of this study is to evaluate the clinical characteristics and outcomes in 2019 coronavirus disease (COVID-19) patients and to help clinicians perform correct treatment and evaluate prognosis and guide the treatment.

Methods: Patients totaling 239 were diagnosed with COVID-19 and were included in this study. Patients were divided into the improvement group and the death group according to their outcome (improvement or death). Clinical characteristics and laboratory parameters were collected from medical records. Continuous variables were tested by an independent sample T test, and categorical variables were analyzed by the chi-square test or Fisher's exact test. The Cox proportional hazard regression model was used for survival analysis in death patients. The time-dependent area under curves (AUC) based on white blood cell count, lymphocyte count, neutrophil count by age, blood urea nitrogen, and C-reactive protein were plotted.

Results: Efficacy evaluation indicated that 99 (41.4%) patients had deteriorated, and 140 (58.6%) patients had improved. Oxygen saturation, hemoglobin levels, infection-related indicators, lymphocyte and platelet counts, C-reactive protein, serum albumin, liver and kidney function, and lactate dehydrogenase in improvement group were statistically significant between the improvement and death groups. A survival analysis revealed that comorbidities, lymphocyte counts, platelet count, serum albumin, C-reactive protein level, and renal dysfunction may be risk factors in patients with COVID-19.

Conclusion: Patients with comorbidities, lower lymphocyte counts in hemogram, platelet count and serum albumin, high C-reactive protein level, and renal dysfunction may have higher risk for death. More attention should be given to risk management in the progression of COVID-19.
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http://dx.doi.org/10.1017/dmp.2021.82DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144806PMC
March 2021

Mutational spectrum and precision oncology for biliary tract carcinoma.

Theranostics 2021 4;11(10):4585-4598. Epub 2021 Mar 4.

Department of Liver Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Wangfujing, Beijing 100730, China.

The genomic spectrum of biliary tract carcinoma (BTC) has been characterized and is associated with distinct anatomic and etiologic subtypes, yet limited studies have linked genomic alterations with personalized therapies in BTC patients. This study analyzed 803 patients with BTC:164 with gallbladder cancer, 475 with intrahepatic cholangiocarcinoma (ICC) and 164 with extrahepatic cholangiocarcinoma. We determined genomic alterations, mutational signatures related to etiology and histopathology and prognostic biomarkers. Personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. The median tumor mutation burden (TMB) was 1.23 Mut/Mb, with 4.1% of patients having hypermutated BTCs. Unlike the results obtained from the Western population, the most frequently altered cancer-related genes in our cohort included (53%), (26%), (18%), (14%) and (14%). Germline mutations occurred mostly in DNA damage repair genes. Notably, 35.8% of the ICCs harbored aristolochic acid related signatures and an elevated TMB. and mutations and amplified 7q31.2 were demonstrated to negatively affect patient prognosis. Moreover, 19 genes were proposed to be PATs in BTCs, with 25.4% of patients harboring these PATs. Forty-six patients received PAT-matched targeted therapies, achieving a 26.1% objective response rate; the median progression-free survival (PFS) was 5.0 months, with 56.8% of patients obtaining PFS benefits. Extensive genomic diversity and heterogeneity were observed among BTC patients, with contributions according to potential etiology exposures, anatomical subtypes and clinicopathological characteristics. We also demonstrated that patients with refractory BTCs who have PATs can derive considerable benefit from receiving a matched therapy, initiating further prospective clinical trials guided by molecular profiling among this aggressive cancer.
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http://dx.doi.org/10.7150/thno.56539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978308PMC
March 2021

Effects of Toluene on the Development of the Inner Ear and Lateral Line Sensory System of Zebrafish.

Biomed Environ Sci 2021 Feb;34(2):110-118

Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, China.

Objective: The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.

Methods: Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.

Results: The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml ) neuromasts in 3 days post fertilization larvae in a concentration-dependent manner. Toluene altered the expression level of genes involved in ear development/function in zebrafish, among which the mRNA levels of , , and were upregulated, while the level of was downregulated, according to the qPCR results.

Conclusion: This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.
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http://dx.doi.org/10.3967/bes2021.016DOI Listing
February 2021

Stilbene glycoside upregulates SIRT3/AMPK to promotes neuronal mitochondrial autophagy and inhibit apoptosis in ischemic stroke.

Adv Clin Exp Med 2021 Feb;30(2):139-146

Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.

Background: Ischemic stroke, also known as cerebrovascular accident or cerebral stroke, occupies the first place in the world's top 10 causes of death, with high incidence, mortality and disability rates.

Objectives: To investigate the effect of stilbene glycoside upregulated SIRT3/AMPK expression on neuronal mitochondrial autophagy and neuronal apoptosis in ischemic stroke.

Material And Methods: The PC12 cells were cultured without serum to construct an ischemic neuron model. The cells were divided into 6 groups: normal group (untreated cells), model group (ischemic treated cells), TSG group (stilbene glycoside treatment), NC group (SIRT3 and AMPK negative control treatment), si-SIRT3 group (SIRT3 silencing treatment), TSG+si-SIRT3 group (joint treatment), and TSG+si-SIRT3+oe-AMPK group (joint treatment). Cell survival and the expression of related molecules were detected.

Results: Compared with normal group, the model group had significantly decreased cell survival rate, mitochondrial membrane potential, as well as the expression of Bcl-2, LC3II/I, P62, PINK1, Parkin, SIRT3, AMPK, and p-AMPK, while showing significantly increased proportion of apoptosis and the expression of caspase 3 and Bax. Compared with the model group, TSG treatment promoted cell survival rate and mitochondrial autophagy, and inhibited apoptosis, while SIRT3 silencing treatment reduced cell survival rate and mitochondrial autophagy, and increased apoptosis. The SIRT3 silencing could block the inhibitory effect of TSG on the apoptosis of ischemic PC12 cells and promote mitochondrial autophagy, and AMPK overexpression could save the apoptosis of ischemic PC12 cells caused by SIRT3 silencing, and promote mitochondrial autophagy.

Conclusions: By promoting the expression of SIRT3/AMPK, TSG promotes mitochondrial autophagy in ischemic neurons and inhibits their apoptosis.
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http://dx.doi.org/10.17219/acem/130608DOI Listing
February 2021

Differentially expressed genes accompanying neurobehavioral deficits in a modified rat model of vascular dementia.

Neurosci Lett 2021 04 25;750:135774. Epub 2021 Feb 25.

School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China. Electronic address:

Vascular dementia refers to the progressive loss of memory and other cognitive functions. The heterogeneity of cerebrovascular disease renders it challenging to elucidate the neuropathological substrates and mechanisms underlying vascular dementia. In this study, we performed neurobehavioral tests, RNA sequencing (RNA-seq), and quantitative real-time polymerase chain reaction (qRT-PCR) tests to evaluate a rat model of modified two-vessel occlusion (2-VO) and identify the differentially expressed genes in the hippocampus of 2-VO versus sham rats by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. Compared with the sham group, the 2-VO group revealed significantly reduced spontaneous motor behaviors, a lack of exploration for new objects, and varying degrees of spatial memory impairment. Although the genetic background of vascular dementia is well established for monogenic disorders, the relationship between key regulatory genes and signaling pathways remains obscure. Using RNA-seq and bioinformatic analyses, we identified 58 upregulated genes and 137 downregulated genes in the hippocampus of 2-VO rats compared to sham rats. Results were confirmed by qRT-PCR. ErbB3, a gene mainly involved in cranial nervous system development, negative regulation of neuronal apoptosis, and signal transduction, was downregulated in the hippocampus of 2-VO rats compared to sham rats. Moreover, ERBB3 plays an important role in neuron-protecting ERBB and PI3K-AKT signaling pathways, both of which were found to be enriched by GO and KEGG functional pathway analyses. Understanding the molecular mechanisms of vascular dementia may help establish potential treatment targets for cognitive deficits.
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http://dx.doi.org/10.1016/j.neulet.2021.135774DOI Listing
April 2021

Association of different Candida species with catheter-related candidemia, and the potential antifungal treatments against their adhesion properties and biofilm-forming capabilities.

J Clin Lab Anal 2021 Apr 19;35(4):e23738. Epub 2021 Feb 19.

Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China.

Background: To compare the adhesion properties and biofilm-forming capabilities of 27 Candida isolates obtained from catheter-related candidemia patients and to evaluate the inhibitory effects of antifungal agents on different Candida species.

Material And Methods: Seven C. albicans, six C. parapsilosis, five C. guilliermondii, five C. tropicalis, and four C. glabrata clinical isolates were investigated. We quantified the adherence of these Candida species by flow cytometric method and evaluated the formation of biofilms by XTT reduction and crystal violet methods. Actions of micafungin (MF), fluconazole (FZ), and N-acetylcysteine (NAC) on the adhesion and biofilm formation of different Candida species were determined.

Results: Non-albicans Candida species were demonstrated to have stronger adhesion abilities compared with C. albicans. The biofilm-forming capabilities of different Candida species were varied considerably, and the degree of biofilm formation might be affected by different assay approaches. Interestingly, C. parapsilosis displayed the highest biofilm formation abilities, while C. glabrata exhibited the lowest total biomass and metabolic activity. Furthermore, the inhibitory activities of MF, FZ, and NAC on fungal adhesion and biofilm formation were evaluated, and the results indicated that MF could reduce the adhesion ability and biofilm metabolism more significantly (p < 0.05), and its antifungal activity was elevated in a dose-dependent manner.

Conclusion: Non-albicans Candida species, especially C. guilliermondii, C. tropicalis, and C. parapsilosis, exhibited higher adhesion ability in catheter-related candidemia patients. However, these Candida species had varied biofilm-forming capabilities. MF tended to have stronger inhibitory effects against both adhesion and biofilm formation of different Candida species.
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http://dx.doi.org/10.1002/jcla.23738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059721PMC
April 2021

Expression and Clinical Significance of Microtubule-Actin Cross-Linking Factor 1 in Serous Ovarian Cancer.

Recent Pat Anticancer Drug Discov 2021 ;16(1):66-72

Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou 511442, China.

Background: Ovarian Cancer (OC) remains the first leading cause of gynecologic malignancy. The survival rate from Serous Ovarian Cancer (SOC) is very low, and the present prognostic predictors of SOC are not very sensitive or specific.

Objective: The present study aimed to investigate Microtubule-Actin Cross-Linking Factor 1 (MACF1) expression in SOC tissues (including paraffin-embedded and fresh tissues) and to assess its expression and significant value in patients with SOC.

Methods: A total of 18 fresh SOC tissues and their paired paratumor tissues were performed with reverse-transcription quantitative PCR analysis to detect MACF1 mRNA expression. Moreover, 175 paraffin-embedded SOC tissues and 41 paratumor tissues were assessed for MACF1 expression using immunohistochemistry.

Results: The mRNA and protein expression of MACF1, both were higher in cancer tissues than that in paratumor tissues, and the high expression of MACF1 was associated with shorter Recurrence Free Survival (RFS) and Overall Survival (OS) in patients with SOC. Furthermore, multivariate regression analysis showed that high MACF1 expression was an independent poor survival predictor of patients with SOC.

Conclusion: MACF1 is upregulated in SOC, and it may be used as a useful prognostic biomarker in SOC.
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http://dx.doi.org/10.2174/1574892816666210211091543DOI Listing
January 2021

Spatial regulation of MCAK promotes cell polarization and focal adhesion turnover to drive robust cell migration.

Mol Biol Cell 2021 04 10;32(7):590-604. Epub 2021 Feb 10.

Medical Sciences, Indiana University School of Medicine-Bloomington, Bloomington, IN 47405.

The asymmetric distribution of microtubule (MT) dynamics in migrating cells is important for cell polarization, yet the underlying regulatory mechanisms remain underexplored. Here, we addressed this question by studying the role of the MT depolymerase, MCAK (mitotic centromere-associated kinesin), in the highly persistent migration of RPE-1 cells. MCAK knockdown leads to slowed migration and poor directional movement. Fixed and live cell imaging revealed that MCAK knockdown results in excessive membrane ruffling as well as defects in cell polarization and the maintenance of a major protrusive front. Additionally, loss of MCAK increases the lifetime of focal adhesions by decreasing their disassembly rate. These functions correlate with a spatial distribution of MCAK activity, wherein activity is higher in the trailing edge of cells compared with the leading edge. Overexpression of Rac1 has a dominant effect over MCAK activity, placing it downstream of or in a parallel pathway to MCAK function in migration. Together, our data support a model in which the polarized distribution of MCAK activity and subsequent differential regulation of MT dynamics contribute to cell polarity, centrosome positioning, and focal adhesion dynamics, which all help facilitate robust directional migration.
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http://dx.doi.org/10.1091/mbc.E20-05-0301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101467PMC
April 2021

Ultraviolet B irradiation up-regulates MM1 and induces photoageing of the epidermis.

Photodermatol Photoimmunol Photomed 2021 Feb 10. Epub 2021 Feb 10.

Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.

Background: ΔNp63α and c-Myc are key transcription factors controlling proliferation and senescence in epithelial cells. We previously reported that the c-Myc modulator MM1 and its E3 ligase, HERC3, together with the transcription factor ΔNp63α, compose a feedback loop, which regulates proliferative senescence in MCF-10A mammary epithelial cells. However, it is unknown whether this loop is involved in skin ageing. On the other hand, ultraviolet B (UVB) rays are assumed to be the main culprits for photoageing of the epidermis, but the underlying mechanisms are obscure.

Aims: To investigate whether MM1/ΔNp63α axis is involved in UVB-induced photoageing of the epidermis.

Materials And Methods: HaCaT human immortalized keratinocytes overexpressed with MM1, knocked down with c-Myc or irradiated with UVB, were subjected to MTT assays to measure cell proliferation, as well as RT-qPCR or immunoblot to detect the members of MM1/ΔNp63α loop and the cellular senescence markers. Meanwhile, primary normal human keratinocytes (NHKs) or mice were irradiated with UVB, followed by immunoblot analysis, SA-β-gal, haematoxylin-eosin or immunohistochemistry staining.

Results: Overexpression of MM1 down-regulated ΔNp63α and induced proliferative senescence in the HaCaT cells. In the HaCaT cells, NHKs and the mouse epidermis, UVB irradiation increased MM1 mRNA level and led to a down-regulation of ΔNp63α, HERC3 and c-Myc, concomitant with cellular senescence or photoageing. Additionally, knock-down of c-Myc induced proliferative senescence in the HaCaT cells and abrogated UVB-induced cellular senescence.

Conclusions: UVB up-regulates MM1 and consequently modulates ΔNp63α and c-Myc, which may account for the proliferative senescence of keratinocytes and photoageing of the epidermis.
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http://dx.doi.org/10.1111/phpp.12670DOI Listing
February 2021