Publications by authors named "Zhang J"

114,184 Publications

Perilipin 2 Impacts Acute Kidney Injury via Regulation of PPAR.

J Immunol Res 2021 9;2021:9972704. Epub 2021 Sep 9.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Renal ischemia-reperfusion (I/R) can induce oxidative stress and injury via the generation of reactive oxygen species (ROS). Renal proximal tubular cells are susceptible to oxidative stress, and the dysregulation of renal proximal tubular cellular homeostasis can damage cells via apoptotic pathways. A recent study showed that the generation of ROS can increase perilipin 2 (Plin2) expression in HepG2 cells. Some evidence has also demonstrated the association between Plin2 expression and renal tumors. However, the underlying mechanism of Plin2 in I/R-induced acute kidney injury (AKI) remains elusive. Here, using a mouse model of I/R-induced AKI, we found that ROS generation was increased and the expression of Plin2 was significantly upregulated. An in vitro study further revealed that the expression of Plin2, and the generation of ROS were significantly upregulated in primary tubular cells treated with hydrogen peroxide. Accordingly, Plin2 knockdown decreased apoptosis in renal proximal tubular epithelial cells treated with hydrogen peroxide, which depended on the activation of peroxisome proliferator-activated receptor (PPAR). Overall, the present study demonstrated that Plin2 is involved in AKI; knockdown of this marker might limit apoptosis via the activation of PPAR. Consequently, the downregulation of Plin2 could be a novel therapeutic strategy for AKI.
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http://dx.doi.org/10.1155/2021/9972704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445733PMC
September 2021

Developmental Angiogenesis Requires the Mitochondrial Phenylalanyl-tRNA Synthetase.

Front Cardiovasc Med 2021 1;8:724846. Epub 2021 Sep 1.

Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi'an, China.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) catalyze the binding of specific amino acids to their cognate tRNAs and play an essential role in the synthesis of proteins encoded by mitochondrial DNA. Defects in mtARSs have been linked to human diseases, but their tissue-specific pathophysiology remains elusive. Here we examined the role of mitochondrial phenylalanyl-tRNA synthetase (FARS2) in developmental angiogenesis and its potential contribution to the pathogenesis of cardiovascular disease. Morpholinos were injected into fertilized zebrafish ova to establish an knock-down model. A visualization of the vasculature was achieved by using transgenic zebrafish. In addition, small interference RNAs (siRNAs) were transferred into human umbilical vein endothelial cells (HUVECs) to establish an knock-down model. Cell motility, proliferation, and tubulogenesis were determined using scratch-wound CCK8, transwell-based migration, and tube formation assays. In addition, mitochondria- and non-mitochondria-related respiration were evaluated using a Seahorse XF24 analyzer and flow cytometry assays. Analyses of the expression levels of transcripts and proteins were performed using qRT-PCR and western blotting, respectively. The knock-down of hampered the embryonic development in zebrafish and delayed the formation of the vasculature in transgenic zebrafish. In addition, the siRNA-mediated knock-down of impaired angiogenesis in HUVECs as indicated by decreased cell motility and tube formation capacity. The knock-down of also produced variable decreases in mitochondrial- and non-mitochondrial respiration in HUVECs and disrupted the regulatory pathways of angiogenesis in both HUVECs and zebrafish. Our current work offers novel insights into angiogenesis defects and cardiovascular diseases induced by deficiency.
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http://dx.doi.org/10.3389/fcvm.2021.724846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440837PMC
September 2021

Chronic Diseases as a Predictor for Severity and Mortality of COVID-19: A Systematic Review With Cumulative Meta-Analysis.

Front Med (Lausanne) 2021 1;8:588013. Epub 2021 Sep 1.

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, United States.

Given the ongoing coronavirus disease 2019 (COVID-19) pandemic and the consequent global healthcare crisis, there is an urgent need to better understand risk factors for symptom deterioration and mortality among patients with COVID-19. This systematic review aimed to meet the need by determining the predictive value of chronic diseases for COVID-19 severity and mortality. We searched PubMed, Embase, Web of Science, and Cumulative Index to Nursing and Allied Health Complete to identify studies published between December 1, 2019, and December 31, 2020. Two hundred and seventeen observational studies from 26 countries involving 624,986 patients were included. We assessed the risk of bias of the included studies and performed a cumulative meta-analysis. We found that among COVID-19 patients, hypertension was a very common condition and was associated with higher severity, intensive care unit (ICU) admission, acute respiratory distress syndrome, and mortality. Chronic obstructive pulmonary disease was the strongest predictor for COVID-19 severity, admission to ICU, and mortality, while asthma was associated with a reduced risk of COVID-19 mortality. Patients with obesity were at a higher risk of experiencing severe symptoms of COVID-19 rather than mortality. Patients with cerebrovascular disease, chronic liver disease, chronic renal disease, or cancer were more likely to become severe COVID-19 cases and had a greater probability of mortality. COVID-19 patients with chronic diseases were more likely to experience severe symptoms and ICU admission and faced a higher risk of mortality. Aggressive strategies to combat the COVID-19 pandemic should target patients with chronic diseases as a priority.
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http://dx.doi.org/10.3389/fmed.2021.588013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440884PMC
September 2021

Corrigendum: ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness.

Front Cell Dev Biol 2021 3;9:758671. Epub 2021 Sep 3.

Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

[This corrects the article DOI: 10.3389/fcell.2021.616887.].
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http://dx.doi.org/10.3389/fcell.2021.758671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448458PMC
September 2021

Cyclohexanone and Phenolic Acid Derivatives from Endophytic Fungus .

Front Chem 2021 1;9:738307. Epub 2021 Sep 1.

Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China.

Chemical investigation of an endophytic fungus SCBG-15, led to the isolation of eight new cyclohexanone derivatives, foeniculins A-H (1-8) and three new phenolic acid derivatives, foeniculins I-K (9-11). Their structures were extensively established on the basis of H and C NMR spectra together with COSY, HSQC, HMBC, and NOESY experiments. The absolute configurations were confirmed by quantum chemical ECD calculations and single-crystal X-ray diffractions. Moreover, the cytotoxic and antibacterial activities of isolated compounds 1-11 were also evaluated.
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http://dx.doi.org/10.3389/fchem.2021.738307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440800PMC
September 2021

Myrislignan Induces Redox Imbalance and Activates Autophagy in .

Front Cell Infect Microbiol 2021 3;11:730222. Epub 2021 Sep 3.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China.

is an important health problem in human and animals, and the highlighting side effects of launched therapeutic chemicals cannot be ignored. Thus, it is urgent to develop new drugs to against the infection. Myrislignan originated from nutmeg exhibited excellent anti- activity and , and was able to destroy mitochondrial function. However, the exact mechanism of action is still unknown. In this study, combining RNAs deep-sequencing analysis and surface plasmon resonance (SPR) analysis, the differentially expressed genes (DEGs) and high affinity proteins suggested that myrislignan may affect the oxidation-reduction process of . Furthermore, the upregulating ROS activity after myrislignan incubation verified that myrislignan destroyed the oxidant-antioxidant homeostasis of tachyzoites. Transmission electron microscopy (TEM) indicated that myrislignan induced the formation of autophagosome-like double-membrane structure. Moreover, monodansyl cadaverine (MDC) staining and western blot further illustrated autophagosome formation. Myrislignan treatment induced a significant reduction in flow cytometry analysis. Together, these findings demonstrated that myrislignan can induce the oxidation-reduction in , lead to the autophagy, and cause the death of
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http://dx.doi.org/10.3389/fcimb.2021.730222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447958PMC
September 2021

Clinical Heterogeneity of Differentiated Thyroid Cancer between Children Less than 10 Years of Age and Those Older than 10 Years: A Retrospective Study of 70 Cases.

Eur Thyroid J 2021 Jul 17;10(5):364-371. Epub 2021 Jun 17.

Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, China.

Objectives: The objectives of this study were to explore the clinical heterogeneity of differentiated thyroid cancer (DTC) between prepubertal children and adolescents and guide clinical treatment.

Methods: A retrospective study included patients with DTC aged ≤19 years in Beijing Children's Hospital from June 2014 to June 2019. All patients were enrolled and divided into 2 subgroups based on the threshold age of 10 years, namely the childhood group (CG) (≤10 years old); and the adolescent group (AG) (between 10 and 19 years old). The χ test and Fisher's exact test were used to estimate the effect of risk factors in the 2 age groups. Multivariate binary logistic regression models were conducted to assess the recurrent risk factors.

Results: Seventy cases of DTC were included with an average age of 9.94 ± 2.88 years, including 35 in CG and 35 in AG. The most common clinical manifestation was a painless mass in the neck, accounting for 77.1% (54/70) of patients. Compared with the AG, the CG was more likely to have lymph node metastasis ( = 0.022) and distant metastasis ( = 0.041). The CG was more likely to have extrathyroidal extension ( = 0.012) and had a significantly higher recurrence rate than the AG ( = 0.040). Age was an independent variable predictive of recurrence ( = 0.0347).

Conclusion: Regional invasiveness, cervical lymph node metastasis, and distant metastasis of DTC were more likely to occur in children ≤10 years old. Meanwhile, children ≤10 years old with DTC were more likely to have recurrence than adolescent's postsurgical treatment. Thus, children younger than 10 years of age with DTC should be treated more aggressively.
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http://dx.doi.org/10.1159/000516830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406248PMC
July 2021

Roles of Histone Deacetylases in Acute Myeloid Leukemia With Fusion Proteins.

Front Oncol 2021 1;11:741746. Epub 2021 Sep 1.

Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University Health Science Center, Shenzhen, China.

Accurate orchestration of gene expression is critical for the process of normal hematopoiesis, and dysregulation is closely associated with leukemogenesis. Epigenetic aberration is one of the major causes contributing to acute myeloid leukemia (AML), where chromosomal rearrangements are frequently found. Increasing evidences have shown the pivotal roles of histone deacetylases (HDACs) in chromatin remodeling, which are involved in stemness maintenance, cell fate determination, proliferation and differentiation, mastering the transcriptional switch of key genes. In abnormal, these functions can be bloomed to elicit carcinogenesis. Presently, HDAC family members are appealing targets for drug exploration, many of which have been deployed to the AML treatment. As the majority of AML events are associated with chromosomal translocation resulting in oncogenic fusion proteins, it is valuable to comprehensively understand the mutual interactions between HDACs and oncogenic proteins. Therefore, we reviewed the process of leukemogenesis and roles of HDAC members acting in this progress, providing an insight for the target anchoring, investigation of hyperacetylated-agents, and how the current knowledge could be applied in AML treatment.
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http://dx.doi.org/10.3389/fonc.2021.741746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440836PMC
September 2021

Regulatory Mechanism and Experimental Verification of Patchouli Alcohol on Gastric Cancer Cell Based on Network Pharmacology.

Front Oncol 2021 1;11:711984. Epub 2021 Sep 1.

Department of Traditional Chinese Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Background: is a traditional Chinese medicine (TCM) that is frequently used to treat various gastrointestinal diseases. Patchouli alcohol (PA), a compound extracted from the , has been shown to have anti-tumor efficacy in human colorectal cancer. However, the mechanism of PA's anticancer effect on gastric cancer (GC) remains unknown.

Methods: We used the public database to obtain the potential targets of PA and genes related to GC. Bioinformatic analyses, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interactions (PPI), were used for analyzing the potential signal pathways and targets. Cell experiments were also conducted to further explain the impact and molecular mechanism of PA on GC, as well as to confirm the findings of network pharmacology.

Results: Using network pharmacological analysis, 161 possible targets were identified for the treatment of GC. Network analysis and functional enrichment analysis show that PA produced a marked effect in the treatment of GC through multi-targets and multi-pathways, especially the MAPK and PI3K/AKT signal pathways. In addition, PA showed the inhibition of GC cell proliferation, migration and invasion in cell experiments. According to our findings, PA could also cause G0/G1 phase arrest and apoptosis in GC cells.

Conclusion: Using network pharmacology, we aim to uncover the possible molecular mechanism of PA on GC treatment in this research. Cell experiments were also conducted to confirm the therapeutic effect of PA on GC.
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http://dx.doi.org/10.3389/fonc.2021.711984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440821PMC
September 2021

A Comparative Study of Two PET Verification Methods in Clinical Cases.

Front Oncol 2021 3;11:617787. Epub 2021 Sep 3.

Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China.

Purpose: Positron emission tomography (PET) range verification is an important method that can help improve the confidence in proton therapy for clinical applications. Two kinds of verification methods are implemented and compared based on clinical cases in this study.

Method: The study is conducted on 14 breast cancer patients following proton irradiation treatment. Verification is done by calculating the depth error between the numerically predicted values with the measured PET image along the beam direction. Point-based and segment-based methods are applied and compared. The verification results are presented as depth error means and standard deviations in a region of interest (ROI).

Results: The mean value of the depth error of all 14 cases is within the range of [-3, 3] mm for both point-based and segment-based methods, and only one case result calculated by the point-based method is slightly beyond -3 mm. When comparing the mean depth error from the two methods, the paired -test result shows that the -value is 0.541, and the standard deviation of the segment-based method is smaller than that of the point-based method.

Conclusion: In breast cancer case verification application, point-based and segment-based methods show no significant difference in the mean value of results. Both methods can quantify the accuracy of proton radiotherapy to the millimeter level.
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http://dx.doi.org/10.3389/fonc.2021.617787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447881PMC
September 2021

Effect of Ag alloying and trace precipitation on corrosion resistance of Ti-Ta-Ag ternary alloy.

R Soc Open Sci 2021 Sep 15;8(9):210243. Epub 2021 Sep 15.

Faculty of Materials Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan 650093, People's Republic of China.

This work systematically analysed the electrochemical and corrosion behaviour of Ti-Ta-Ag ternary alloy samples in Hank's solution. For the samples with 1.5% and 3% Ag content, the sintering temperature increased from 750 to 950°C, and the corresponding corrosion resistance increased by 100 times due to the increased alloying of Ag; meanwhile for the sample with 4.5% Ag content, the sintering temperature increased from 750 to 950°C, and the corresponding corrosion resistance decreased by six times due to the increased precipitation of Ag. These tests prove that the Ag alloying is beneficial to the enhancement of the corrosion resistance of Ti-Ta-Ag ternary alloy, but the Ag trace precipitation has the opposite effect. A series of electrochemical characterizations and density functional theory calculations explain the mechanism of the above phenomenon. Ag alloying can promote the formation of uniform, complete, dense, stable and thick passivation layer on the surface of Ti-Ta-Ag ternary alloy, which makes Ti-Ta-Ag ternary alloy uniformly corroded without pitting. In addition, Ag alloying can effectively reduce the contact resistance of the solid-liquid interface. However, the trace precipitation of Ag plays the opposite role to the above effect.
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http://dx.doi.org/10.1098/rsos.210243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441115PMC
September 2021

The clinical effects of IABP pumps combined with tirofiban in the treatment of acute myocardial infarction and on patients' serum levels.

Am J Transl Res 2021 15;13(8):9796-9801. Epub 2021 Aug 15.

The Second Department of Cardiology, Lacey People's Hospital Laixi, Qingdao, China.

Objective: To explore the clinical effects of the intra-aortic balloon pump (IABP) combined with tirofiban in the treatment of acute myocardial infarction (AMI) and to analyze the combination's influence on patient serum levels.

Method: 106 patients with AMI admitted to our hospital from February 2017 to February 2018 were recruited as the research cohort. The patients were randomly placed into a control group and an experimental group according to their order of admission, with 53 patients in each group. The patients in the control group were treated with IABP, while the experimental group was treated with IABP combined with tirofiban. The two groups' clinical efficacy and serum levels were compared.

Results: The clinical efficacy in the experimental group was significantly higher than the clinical efficacy in the control group. After the treatment, both groups' serum indexes were significantly better, and the experimental group's indexes were comparatively better than the control group's indexes. The experimental group's thrombolysis and thrombin myocardial infarction (TIMI) glow grades were much better than the glow grades in the control group. The experimental group's left ventricular ejection fraction (LVEF) index was higher than the control group', while the left ventricular end-diastolic dimension (LVEDD) index and the left ventricular end-systolic dimension (LVESD) index in the experimental group exhibited lower levels when compared to the control group. The hemorheological parameters in the experimental group were much lower than the hemorheological parameters in the control group, and the difference between the two groups was statistically significant (P < 0.05).

Conclusion: The clinical effects of an IABP pump combined with tirofiban in treating AMI are significant. The patients' clinical symptoms were alleviated drastically, and their serum levels and cardiac and cardiovascular functions improved significantly. Therefore IABP combined with tirofiban in the treatment of AMI is worthy of clinical application and promotion.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430151PMC
August 2021

The regulatory relationship and function of LncRNA FAM225A-miR-206-ADAM12 in gastric cancer.

Am J Transl Res 2021 15;13(8):8632-8652. Epub 2021 Aug 15.

Cancer Center, Taikang Xianlin Drum Tower Hospital, Nanjing University School of Medicine Nanjing, Jiangsu, China.

Objective: To investigate the role and functions of FAM225A in gastric cancer.

Methods: The expressions of FAM225A, miR-206, ADAM12 and epithelial-mesenchymal transition (EMT)-related genes were detected by quantitative real-time PCR and Western blot. Functional experiments including cell counting kit-8, colony formation, wound-healing, and Transwell assays were conducted to analyze the biological characteristics of gastric cancer cells in different groups. Bioinformatics, dual-luciferase reporter assay and Pearson correlation coefficients were performed for determining the regulatory relationship of lncRNA-miRNA-mRNA. nude mouse xenografts and immunohistochemistry were used to verify the results .

Results: In gastric cancer, FAM225A and ADAM12 expressions were up-regulated, while miR-206 expression was down-regulated. Opposite to the regulatory effects of overexpressed FAM225A, blocking FAM225A expression reduced cell viability, migration, invasion and number of cell clones, increased E-Cadherin expression, inhibited N-Cadherin and Vimentin expressions, and ultimately promoted tumor growth. MiR-206 inhibitor partially offset the effects of siFAM225A. Moreover, FAM225A competitively bound to miR-206 to up-regulate ADAM12 expression. Overexpressed ADAM12 partially reversed the effect of miR-206 mimic on the biological characteristics of gastric cancer cells and EMT-related proteins.

Conclusion: Our research revealed that FAM225A-miR-206-ADAM12 axis may be a potential pathway for regulating gastric cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430187PMC
August 2021

Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy.

J Cancer 2021 27;12(20):6198-6208. Epub 2021 Aug 27.

Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Drug resistance is the major cause for disease relapse and patient death in multiple myeloma (MM). It is an urgent need to develop new therapies to overcome drug resistance in MM. Chidamide (CHI), a novel oral HDAC inhibitor targeting HDAC1, 2, 3 and 10, has shown potential therapeutic effect in MM. In this study, we determined that CHI exhibited significant anti-tumor effect on MM cells both and , which was positively correlated with the expression of HDAC1. Meanwhile, CHI enhanced Bortezomib (BTZ) effects synergistically in MM cells and a combination of CHI with BTZ induced myeloma cell apoptosis and G0/G1 arrest and . Mechanistically, the synergistic anti-tumor effect of CHI and BTZ was related with the increased production of reactive oxygen species (ROS) dependent DNA damage and the changes of cell apoptosis and cycle pathways. Our data indicate that CHI may be a suitable drug to sensitize BTZ in MM cells, which provides novel insight into the therapy for MM patients.
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http://dx.doi.org/10.7150/jca.61602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425211PMC
August 2021

Overexpression of Nicotinamide N-methyltransferase mainly covers stroma of colorectal cancer and correlates with unfavorable survival by its product 1-MNA.

J Cancer 2021 26;12(20):6170-6181. Epub 2021 Aug 26.

Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou 310016, Zhejiang, People's Republic of China.

Accumulating evidence indicates that Nicotinamide N-methyltransferase (NNMT) is abnormally expressed in tumor tissues of several cancers including colorectal cancer (CRC) and associated with cancer progression. However, the distribution characteristics and the clinical value of each part of NNMT expression in CRC are still not fully understood. The purpose of this study is to determine the distribution of NNMT expression and its association with survival in CRC. By using the cancer genome atlas (TCGA) and clinical proteomic tumor analysis consortium (CPTAC), we firstly analyzed the difference of gene and protein levels of NNMT between CRC and normal colorectal tissue. Then, NNMT protein expressions were detected in 18 intraepithelial neoplastic samples and 177 CRC tumor samples through immunohistochemistry in our study cohort. Furthermore, the relationship between NNMT expression and clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) of CRC patients were analyzed by Pearson χ2 test and log-rank test, respectively, in public datasets and our study cohort. Lastly, the function of NNMT and its product 1-methyl-nicotinamide (1-MNA) on migration and invasion in colorectal cancer cells was analyzed by wound healing assay and transwell assay. We determined that higher NNMT expression in CRC tissues than normal tissues in both gene and protein level in TCGA and CPTAC datasets (all < 0.05). In addition, the strong relationships of NNMT expression with stromal cells were found in the TCGA cohort. Fortunately, our cohort could validate that the expression of NNMT in tumor stroma cell was significantly higher than that in tumor cell ( < 0.0001), and both of them were significantly higher than that in adjacent normal tissue (ANT) ( < 0.0001 and < 0.0001, respectively). Furthermore, the positive NNMT expression in tumor cell and stromal cell were associated with series of unfavorable clinical characteristics, including advanced TNM stage, lymph node metastasis, distant metastasis (all < 0.05). Also, higher NNMT was associated with unfavorable survival both in our study and public datasets, including TCGA and two Gene Expression Omnibus (GEO) datasets (GSE33113 and GSE17538). Moreover, the functional experiments showed that stromal cells with high NNMT expression can secret 1-MAN to promote migration and invasion of CRC cells . In CRC, NNMT is overexpressed in tumor cells and stroma cells, and then mainly expressed in tumor stroma cells. Overexpression of NNMT in tumor cell and stroma cell both are associated with metastasis and unfavorable survival. Besides, stromal cells with high NNMT expression secrets 1-MAN to promote migration and invasion of CRC cells. Therefore, NNMT may be a potential prognostic indicator in CRC patients.
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http://dx.doi.org/10.7150/jca.56419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425209PMC
August 2021

The contribution of gene rs3738067 A>G to the Wilms tumor susceptibility.

J Cancer 2021 26;12(20):6165-6169. Epub 2021 Aug 26.

Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Biomedical Engineering Research Center, Kunming Medical University, Kunming 650500, Yunnan, China.

YTHDF2 is responsible for maintaining the dynamic N-methyladenosine (mA) modification balance and influences a variety of cancers. We tested whether gene rs3738067 A>G polymorphism is related to Wilms tumor by genotyping samples of Chinese children (450 cases and 1317 controls). However, the rs3738067 A>G polymorphism showed no statistical significance with Wilms tumor susceptibility. Stratification analysis also revealed that there was no remarkable association of rs3738067 variant AG/GG genotype with Wilms tumor risk in every subgroup (age, gender, and clinical stages). In all, the results indicated gene rs3738067 A>G polymorphism could not alter Wilms tumor risk significantly.
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http://dx.doi.org/10.7150/jca.62154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425210PMC
August 2021

Progress on the study of the anticancer effects of artesunate.

Oncol Lett 2021 Nov 27;22(5):750. Epub 2021 Aug 27.

Department of Pharmacology, The School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, P.R. China.

Artesunate (ART) is a derivative of artemisinin that is extracted from the wormwood plant . ART is an antimalarial drug that has been shown to be safe and effective for clinical use. In addition to its antimalarial properties, ART has been attracting attention over recent years due to its reported inhibitory effects on cancer cell proliferation, invasion and migration. Therefore, ART has a wider range of potential clinical applications than first hypothesized. The aim of the present review was to summarize the latest research progress on the possible anticancer effects of ART, in order to lay a theoretical foundation for the further development of ART as a therapeutic option for cancer.
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http://dx.doi.org/10.3892/ol.2021.13011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436334PMC
November 2021

Knockdown of DLGAP5 suppresses cell proliferation, induces G/M phase arrest and apoptosis in ovarian cancer.

Exp Ther Med 2021 Nov 2;22(5):1245. Epub 2021 Sep 2.

Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441000, P.R. China.

Discs large-associated protein 5 (DLGAP5) is a microtubule-associated protein and is reported to exert oncogenic role in tumorigenesis, including lung cancer and hepatocellular carcinoma. However, the prognostic value and biological function of DLGAP5 in ovarian cancer (OC) still remain unclear. The present study investigated the expression pattern of DLGAP5 by searching the Oncomine microarray database. The correlation between DLGAP5 and survival prognosis of OC patients was analyzed by the online tool KM-plotter. Knockdown of DLGAP5 was achieved by transfection with small interfering RNA targeting DLGAP5 in two OC cell lines (SKOV3 and CAOV3). Cell proliferation was assessed by Cell Counting Kit-8 assay and colony-formation assay. Flow cytometry was utilized to determine the effects of DLGAP5 on cell cycle distribution and apoptosis. The present study data showed that DLGAP5 was significantly upregulated in OC and its higher expression was associated with poor survival prognosis. Knockdown of DLGAP5 significantly suppressed cell proliferation, induced cell cycle G/M phase arrest and apoptosis. Western blot analysis further demonstrated that DLGAP5 knockdown downregulated the expression of CDK1, Cyclin B1 and Bcl-2, but upregulated Bax expression. Collectively, these data demonstrate that DLGAP5 might be a promising prognostic therapeutic target for OC treatment.
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http://dx.doi.org/10.3892/etm.2021.10680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438692PMC
November 2021

Molecular Characterization and Expression Analysis of the Na/H Exchanger Gene Family in L.

Front Genet 2021 2;12:680457. Epub 2021 Sep 2.

Department of Modern Agriculture, Zunyi Vocational and Technical College, Zunyi, China.

The Na/H exchangers () are a class of transporters involved in ion balance during plant growth and abiotic stress. We performed systematic bioinformatic identification and expression-characteristic analysis of genes in pepper to provide a theoretical basis for pepper breeding and practical production. At the whole-genome level, the members of the gene family of cultivated and wild pepper were systematically identified using bioinformatics methods. Sequence alignment and phylogenetic tree construction were performed using MEGA X software, and the gene functional domain, conserved motif, and gene structure were analyzed and visualized. At the same time, the co-expression network of genes was analyzed, and salt-stress analysis and fluorescence quantitative verification of the Zunla-1 cultivar under stress conditions were performed. A total of 9 genes were identified, which have typical functional domains of the Na/H exchanger gene. The physical and chemical properties of the protein showed that the protein was hydrophilic, with a size of 503-1146 amino acids. Analysis of the gene structure showed that Chr08 was the most localized chromosome, with 8-24 exons. -acting element analysis showed that it mainly contains -acting elements such as light response, salicylic acid response, defense, and stress response. Transcriptom and co-expression network analysis showed that under stress, the co-expressed genes of genes in roots and leaves were more obvious than those in the control group, including ABA, IAA, and salt. The transcriptome and co-expression were verified by qRT-PCR. In this study, the genes were identified at the genome level of pepper, which provides a theoretical foundation for improving the stress resistance, production, development, and utilization of pepper in genetic breeding.
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http://dx.doi.org/10.3389/fgene.2021.680457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444994PMC
September 2021

Identification of Key Genes Associated With the Process of Hepatitis B Inflammation and Cancer Transformation by Integrated Bioinformatics Analysis.

Front Genet 2021 1;12:654517. Epub 2021 Sep 1.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Background: Hepatocellular carcinoma (HCC) has become the main cause of cancer death worldwide. More than half of hepatocellular carcinoma developed from hepatitis B virus infection (HBV). The purpose of this study is to find the key genes in the transformation process of liver inflammation and cancer and to inhibit the development of chronic inflammation and the transformation from disease to cancer.

Methods: Two groups of GEO data (including normal/HBV and HBV/HBV-HCC) were selected for differential expression analysis. The differential expression genes of HBV-HCC in TCGA were verified to coincide with the above genes to obtain overlapping genes. Then, functional enrichment analysis, modular analysis, and survival analysis were carried out on the key genes.

Results: We identified nine central genes (CDK1, MAD2L1, CCNA2, PTTG1, NEK2) that may be closely related to the transformation of hepatitis B. The survival and prognosis gene markers composed of PTTG1, MAD2L1, RRM2, TPX2, CDK1, NEK2, DEPDC1, and ZWINT were constructed, which performed well in predicting the overall survival rate.

Conclusion: The findings of this study have certain guiding significance for further research on the transformation of hepatitis B inflammatory cancer, inhibition of chronic inflammation, and molecular targeted therapy of cancer.
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http://dx.doi.org/10.3389/fgene.2021.654517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440810PMC
September 2021

Transcriptomic, Metabolomic, and Physiological Analyses Reveal That the Culture Temperatures Modulate the Cryotolerance and Embryogenicity of Developing Somatic Embryos in .

Front Plant Sci 2021 1;12:694229. Epub 2021 Sep 1.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, College of Biological Science and Biotechnology, Beijing Forestry University, Beijing, China.

Cryopreservation is one of the key technologies for the mass propagation of conifers via somatic embryogenesis. Cryotolerance and embryogenecity of conifer somatic embryos (SEs) could be affected by different temperature treatments, for which the underlying mechanisms were unknown. In this study, the developing SEs of obtained their cryotolerance with a survival rate of 100% when cultured on maturation medium at either 23°C for 4 weeks or 4°C for 10 weeks. However, only the embryos that underwent 4°C acclimation remained high embryogenicity, i.e., 91.7% based on cryovials or 29.3% on the plant tissue. Analysis of differentially expressed genes (DEGs) revealed that both 23 and 4°C treatments led to drastic changes in the gene expression, i.e., 21,621 and 14,906 genes, respectively, and the general increase in many oligosaccharides and flavonoids, in addition to the content change of proline (1.9- and 2.3-fold at 23 or 4°C) and gallic acid (6,963- and 22,053-fold). There were 249 significantly different metabolites between the samples of 23 and 4°C treatments and the changing trend of the sorbitol, fatty acids, and monosaccharides differed between these samples. During 4°C-acclimation, the metabolites of the arginine biosynthesis pathway increased between 2.4- and 8.1-fold, and the expression of antioxidant genes was up-regulated significantly. At 4°C, the up-regulated genes were for germ-like proteins, instead of seed storage proteins at 23°C. Concentrations of abscisic acid and jasmonic acid increased up to 2- and 1.5-fold, respectively, in the cold-acclimated embryos. After 10 weeks at 4°C, the embryos stayed at pre-cotyledonary stage with 17.1% less DNA methylation and fewer storage substances than those at 23°C for 4 weeks, which developed cotyledons. This research provides new insights into mechanisms underlying the response of SEs to different culture temperatures and benefits method development for germplasm conservation in conifers.
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http://dx.doi.org/10.3389/fpls.2021.694229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440983PMC
September 2021

Applications of Multi-Omics Technologies for Crop Improvement.

Front Plant Sci 2021 3;12:563953. Epub 2021 Sep 3.

Hainan Key Laboratory of Tropical Oil Crops Biology/Coconut Research Institute, Chinese Academy of Tropical Agricultural Sciences, Wenchang, China.

Multiple "omics" approaches have emerged as successful technologies for plant systems over the last few decades. Advances in next-generation sequencing (NGS) have paved a way for a new generation of different omics, such as genomics, transcriptomics, and proteomics. However, metabolomics, ionomics, and phenomics have also been well-documented in crop science. Multi-omics approaches with high throughput techniques have played an important role in elucidating growth, senescence, yield, and the responses to biotic and abiotic stress in numerous crops. These omics approaches have been implemented in some important crops including wheat ( L.), soybean (), tomato (), barley ( L.), maize ( L.), millet ( L.), cotton ( L.), , and rice ( L.). The integration of functional genomics with other omics highlights the relationships between crop genomes and phenotypes under specific physiological and environmental conditions. The purpose of this review is to dissect the role and integration of multi-omics technologies for crop breeding science. We highlight the applications of various omics approaches, such as genomics, transcriptomics, proteomics, metabolomics, phenomics, and ionomics, and the implementation of robust methods to improve crop genetics and breeding science. Potential challenges that confront the integration of multi-omics with regard to the functional analysis of genes and their networks as well as the development of potential traits for crop improvement are discussed. The panomics platform allows for the integration of complex omics to construct models that can be used to predict complex traits. Systems biology integration with multi-omics datasets can enhance our understanding of molecular regulator networks for crop improvement. In this context, we suggest the integration of entire omics by employing the "phenotype to genotype" and "genotype to phenotype" concept. Hence, top-down (phenotype to genotype) and bottom-up (genotype to phenotype) model through integration of multi-omics with systems biology may be beneficial for crop breeding improvement under conditions of environmental stresses.
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http://dx.doi.org/10.3389/fpls.2021.563953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446515PMC
September 2021

Cytotoxic T-Cell Trafficking Chemokine Profiles Correlate With Defined Mucosal Microbial Communities in Colorectal Cancer.

Front Immunol 2021 1;12:715559. Epub 2021 Sep 1.

Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China.

The involvement of gut microbiota in T-cell trafficking into tumor tissue of colorectal cancer (CRC) remains to be further elucidated. The current study aimed to evaluate the expression of major cytotoxic T-cell trafficking chemokines (CTTCs) and chemokine-associated microbiota profiles in both tumor and adjacent normal tissues during CRC progression. We analyzed the expression of chemokine C-X-C motif ligands 9, 10, and 11 (, , and ), and C-C motif ligand 5 (), characterized gut mucosa-associated microbiota (MAM), and investigated their correlations in CRC patients. Our results showed that the expression of , and was significantly higher in tumor than in adjacent normal tissues in 136 CRC patients. Notably, the high expression of in tumor tissues was associated with enhanced CD8 T-cell infiltration and improved survival. Moreover, the MAM in tumor tissues showed reduction of microbial diversity and increase of oral bacteria. Microbial network analysis identified differences in microbial composition and structure between tumor and adjacent normal tissues. In addition, stronger associations between oral bacteria and other gut microbes were observed. Furthermore, the correlation analysis between the defined MAM and individual CTTCs showed that the CTTCs' correlated operational taxonomic units (OTUs) in tumor and adjacent normal tissues rarely overlap with each other. Notably, all the enriched OTUs were positively correlated with the CTTCs in either tumor or adjacent normal tissues. Our findings demonstrated stronger interactions between oral bacteria and gut microbes, and a shifted correlation pattern between MAM and major CTTCs in tumor tissues, underlining possible mechanisms of gut microbiota-host interaction in CRC.
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http://dx.doi.org/10.3389/fimmu.2021.715559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442671PMC
September 2021

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer.

Front Immunol 2021 3;12:709493. Epub 2021 Sep 3.

Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.

Predictive models could indicate the clinical outcome of patients with carcinoma. Cervical cancer is one of the most frequently diagnosed female malignancies. Herein, we proposed an immune infiltration-related gene signature that predicts prognosis of patients with cervical cancer and depicts the immune landscape as well. We utilized the transcriptome data of The Cancer Genome Atlas (TCGA) and estimated the infiltration level of 28 immune cell types. We screened out four immune cell types conducive to patient survival and recognized their shared differentially expressed genes (DEGs). Four core genes (CHIT1, GTSF1L, PLA2G2D, and GNG8) that composed the ultimate signature were identified univariate and multivariate Cox regression. The optimal model we built up could distinguish patients with cervical cancer into high-score and low-score subgroups. These two subgroups showed disparity in aspects of patient survival, immune infiltration landscape, and response to immune checkpoint inhibitors. Additionally, we found that GTSF1L was decreased gradually along with the severity of cervical lesions, and its potential role in immune contexture and clinical practice were also demonstrated. Our results suggested that the Immunoscore based on four immune-related genes could serve as a supplementary criterion to effectively foresee the survival outcome, tumor infiltration status, and immunotherapy efficacy of cervical cancer patients.
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http://dx.doi.org/10.3389/fimmu.2021.709493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446628PMC
September 2021

Anthraquinones as Potential Antibiofilm Agents Against Methicillin-Resistant .

Front Microbiol 2021 3;12:709826. Epub 2021 Sep 3.

Shenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.

Biofilms formed by methicillin-resistant (MRSA) are one of the contributing factors to recurrent nosocomial infection in humans. There is currently no specific treatment targeting on biofilms in clinical trials approved by FDA, and antibiotics remain the primary therapeutic strategy. In this study, two anthraquinone compounds isolated from a rare actinobacterial strain R62, 3,8-dihydroxy-l-methylanthraquinon-2-carboxylic acid () and 3,6,8-trihydroxy-1-methylanthraquinone-2-carboxylic acid (), together with their 10 commercial analogs - were evaluated for antibacterial and antibiofilm activities against MRSA, which led to the discovery of two potential antibiofilm anthraquinone compounds anthraquinone-2-carboxlic acid () and rhein (). The structure-activity relationship analysis of these anthraquinones indicated that the hydroxyl group at the C-2 position of the anthraquinone skeleton played an important role in inhibiting biofilm formation at high concentrations, while the carboxyl group at the same C-2 position had a great influence on the antibacterial activity and biofilm eradication activity. The results of crystal violet and methyl thiazolyl tetrazolium staining assays, as well as scanning electron microscope and confocal scanning laser microscopy imaging of compounds and treatment groups showed that both compounds could disrupt preformed MRSA biofilms possibly by killing or dispersing biofilm cells. RNA-Seq was subsequently used for the preliminary elucidation of the mechanism of biofilm eradication, and the results showed upregulation of phosphate transport-related genes in the overlapping differentially expressed genes of both compound treatment groups. Herein, we propose that anthraquinone compounds and could be considered promising candidates for the development of antibiofilm agents.
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http://dx.doi.org/10.3389/fmicb.2021.709826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446625PMC
September 2021

Development and Application of a Novel Rapid and Throughput Method for Broad-Spectrum Anti-Foodborne Norovirus Antibody Testing.

Front Microbiol 2021 3;12:670488. Epub 2021 Sep 3.

Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

Foodbone norovirus (NoV) is the leading cause of acute gastroenteritis worldwide. Candidate vaccines are being developed, however, no licensed vaccines are currently available for managing NoV infections. Screening for stimulated antibodies with broad-spectrum binding activities can be performed for the development of NoV polyvalent vaccines. In this study, we aimed to develop an indirect enzyme-linked immunosorbent assay (ELISA) for testing the broad spectrum of anti-NoV antibodies. Capsid P proteins from 28 representative NoV strains (GI.1-GI.9 and GII.1-GII.22 except GII.11, GII.18, and GII.19) were selected, prepared, and used as coating antigens on one microplate. Combined with incubation and the horseradish peroxidase chromogenic reaction, the entire process for testing the spectrum of unknown antibodies required 2 h for completion. The intra-assay and inter-assay coefficients of variation were less than 10%. The new method was successfully performed with monoclonal antibodies and polyclonal antibodies induced by multiple antigens. In conclusion, the indirect ELISA assay developed in this study had a good performance of reliability, convenience, and high-throughput screening for broad-spectrum antibodies.
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http://dx.doi.org/10.3389/fmicb.2021.670488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446669PMC
September 2021

The Effects of Repetitive Use and Pathological Remodeling on Channelrhodopsin Function in Cardiomyocytes.

Front Physiol 2021 23;12:710020. Epub 2021 Aug 23.

Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands.

Channelrhodopsins (ChRs) are a large family of light-gated ion channels with distinct properties, which is of great importance in the selection of a ChR variant for a given application. However, data to guide such selection for cardiac optogenetic applications are lacking. Therefore, we investigated the functioning of different ChR variants in normal and pathological hypertrophic cardiomyocytes subjected to various illumination protocols. Isolated neonatal rat ventricular cardiomyocytes (NRVMs) were transduced with lentiviral vectors to express one of the following ChR variants: H134R, CatCh, ReaChR, or GtACR1. NRVMs were treated with phenylephrine (PE) to induce pathological hypertrophy (PE group) or left untreated [control (CTL) group]. In these groups, ChR currents displayed unique and significantly different properties for each ChR variant on activation by a single 1-s light pulse (1 mW/mm: 470, 565, or 617 nm). The concomitant membrane potential ( ) responses also showed a ChR variant-specific profile, with GtACR1 causing a slight increase in average during illumination ( : -38 mV) as compared with a > -20 mV for the other ChR variants. On repetitive activation at increasing frequencies (10-ms pulses at 1-10 Hz for 30 s), peak currents, which are important for cardiac pacing, decreased with increasing activation frequencies by 17-78% ( < 0.05), while plateau currents, which are critical for arrhythmia termination, decreased by 10-75% ( < 0.05), both in a variant-specific manner. In contrast, the corresponding remained largely stable. Importantly, current properties and responses were not statistically different between the PE and CTL groups, irrespective of the variant used ( > 0.05). Our data show that ChR variants function equally well in cell culture models of healthy and pathologically hypertrophic myocardium but show strong, variant-specific use-dependence. This use-dependent nature of ChR function should be taken into account during the design of cardiac optogenetic studies and the interpretation of the experimental findings thereof.
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http://dx.doi.org/10.3389/fphys.2021.710020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448166PMC
August 2021

Hordenine Protects Against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Inflammation.

Front Pharmacol 2021 1;12:712232. Epub 2021 Sep 1.

Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, China.

Acute lung injury (ALI) is a respiratory disease that leads to death in severe cases. Hordenine (Hor), a barley-derived natural product, has various biological activities, including anti-inflammatory, and anti-oxidation activities. We investigated the effect of Hor on lipopolysaccharide-induced ALI and its potential mechanism. The anti-inflammatory effects of Hor were detected using and models by enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blotting, and molecular docking simulations. Hor inhibited increases in the levels of inflammatory factors both and , and its anti-inflammatory effect inhibited activation of protein kinase B, nuclear factor-κB, and mitogen-activated protein kinase signaling. Hor alleviated lipopolysaccharide-induced ALI by inhibiting inflammatory cytokine increases and and shows potential for preventing inflammatory disease.
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http://dx.doi.org/10.3389/fphar.2021.712232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440820PMC
September 2021

Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial.

Front Pharmacol 2021 2;12:683296. Epub 2021 Sep 2.

Clinical Trial Center, Zhongnan Hospital of Wuhan University, Wuhan, China.

In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19). To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients. We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days. A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) ( = 0.1396, difference in recovery rate: 0.0954; 95% CI: -0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, < 0.0001) and cough (difference: 1.75 days, < 0.0001). No difference was observed in the AOT or NMV/MV rate (both > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, = 0.0014). Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.
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http://dx.doi.org/10.3389/fphar.2021.683296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443786PMC
September 2021

Risk Factors for Atorvastatin as a Monotherapy for Chronic Subdural Hematoma: A Retrospective Multifactor Analysis.

Front Aging Neurosci 2021 1;13:726592. Epub 2021 Sep 1.

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.

Chronic subdural hematoma (CSDH) is a common form of intracranial hemorrhage in the aging population. We aimed to investigate the predictive factors for atorvastatin efficacy as a monotherapy for moderate CSDH. We retrospectively reviewed the medical records of patients who were diagnosed with moderate CSDH and received atorvastatin monotherapy between February 5, 2014, and November 7, 2015, in multiple neurosurgical departments. Univariate, multivariate and receiver operating characteristic curve analyses were performed to identify the potential significant factors indicative of the good therapeutic efficacy or poor therapeutic efficacy of atorvastatin for mild CSDH, such as age, sex, history of injury, Markwalder grading scale-Glasgow Coma Scale (MGS-GCS), Activities of Daily Life-the Barthel Index scale (ADL-BI), American Society of Anesthesiologists Physical Status classification system (ASA-PS), blood cell counts, serum levels and computed tomography findings. A total of 89 patients (75 men and 14 women) aged 24-88 years (mean age 61.95 ± 15.30 years) were followed-up for 24 weeks. Computed tomography findings at admission showed mixed-density hematoma in 22 patients, isodense hematoma in 13 patients, high-density hematoma in 26 patients, and low-density hematoma in 28 patients. In total, 3, 80, and 6 patients had MGS-GCS grades of 0, 1, and 2, respectively. The efficacy rate at 6 months was 87.6% (78/89). Eleven patients were switched to surgery due to a worsened neurological condition, of whom 8, 1, 1, and 1 had high-density, low-density, isodense and mixed-density hematomas, respectively. These patients were switched to surgery over a range of 2-27 days, with a median interval of 12 days after the medication treatment. Univariate and multivariate analyses, confirmed by ROC curves, revealed that high-density hematoma, basal cistern compression, and hematoma volume to be independent risk factors for the efficacy of atorvastatin monotherapy in patients with moderate CSDH. Atorvastatin is an effective monotherapy for the treatment of mild CSDH. High-density hematoma, basal cistern compression, and hematoma volume are independent predictors of the efficacy of atorvastatin as a non-surgical treatment. The results suggested that ADL-BI was more sensitive than the MGS-GCS and ASA-PS for determining patient outcomes in our moderate CSDH cohort.
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http://dx.doi.org/10.3389/fnagi.2021.726592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440973PMC
September 2021
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