Publications by authors named "Jing Miao"

187 Publications

Long non-coding RNA KCNQ1 overlapping transcript 1 promotes the progression of esophageal squamous cell carcinoma by adsorbing microRNA-133b.

Clinics (Sao Paulo) 2021 26;76:e2175. Epub 2021 Apr 26.

Department of Thoracic Surgery, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China.

Objective: The long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) exerts vital regulatory functions in diverse tumors. However, the biological function of KCNQ1OT1 in esophageal squamous cell carcinoma (ESCC) remains unclear.

Methods: KCNQ1OT1 expression was detected in ESCC tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were detected by the CCK-8 assay, EdU assay, flow cytometry analysis, and Transwell experiments, respectively. Bioinformatics analysis, luciferase reporter experiments, and RNA immunoprecipitation assays were used to predict and validate the regulatory relationships between KCNQ1OT1, microRNA-133b (miR-133b) and epidermal growth factor receptor (EGFR).

Results: KCNQ1OT1 expression was remarkably upregulated in ESCC tissues and cell lines. Overexpression of KCNQ1OT1 markedly promoted ESCC cell proliferation, migration, and invasion and enhanced the expression of N-cadherin, MMP-2, and MMP-9, but inhibited apoptosis and E-cadherin expression in ESCC cell lines; KCNQ1OT1 knockdown exerted the opposite effects. KCNQ1OT1 could directly bind to miR-133b and suppress its expression, and miR-133b reversed the effects of KCNQ1OT1 overexpression in ESCC cells. MiR-133b reduced the expression of epidermal growth factor receptor (EGFR); further, KCNQ1OT1 activated the phosphatidylinositol 3-kinase/AKT serine/threonine kinase 1 (PI3K/AKT) signaling pathway by repressing miR-133b repression and indirectly upregulating EGFR. KCNQ1OT1 expression was positively correlated with EGFR mRNA expression and negatively correlated with miR-133b expression.

Conclusion: KCNQ1OT1 facilitates ESCC progression by sponging miR-133b and activating the EGFR/PI3K/AKT pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6061/clinics/2021/e2175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050598PMC
April 2021

Limited Significance of Antifactor H Antibodies in Patients with Membranous Nephropathy.

Clin J Am Soc Nephrol 2021 Apr 15. Epub 2021 Apr 15.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.16631020DOI Listing
April 2021

The Effects of Infection on Microbiota Associated With Gastric Mucosa and Immune Factors in Children.

Front Immunol 2021 24;12:625586. Epub 2021 Mar 24.

Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.

Background: infection is the main cause of chronic gastritis in children. Little is known about the effect of on microbiota and immunity. This study was aimed at characterizing stomach microbiota and immune-regulatory properties of children with colonization.

Methods: We studied 122 children who had undergone gastric endoscopy due to gastrointestinal symptoms, 57 were diagnosed with infection. Endoscopic mucosal biopsy samples were obtained for DNA and RNA extraction. Microbiomes were analyzed by 16S rRNA profiling, with the differentially expressed genes analyzed using RNA sequencing. The RNA-sequencing results of selected genes were validated by qRT-PCR.

Results: Bacterial diversity of -positive gastric specimens were lower than those of negative, and both groups were clearly separated according to beta diversity. -positive group significantly reduced proportions of six phyla and eight genera; only taxa were more abundant in negative group. Gastric tissues RNA sequencing showed increased expression of multiple immune response genes in -infection. -infected children with restructured gastric microbiota had higher levels of FOXP3, IL-10, TGF-β1 and IL-17A expressions, which were consistent with increased CD4T cell and macrophagocyte, compared with non-infected children.

Conclusions: Presence of significantly influences gastric microbiota and results in lower abundance of multiple taxonomic levels in children. Meanwhile, it affects gastric immune environment and promotes the occurrence of gastritis.

Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1800015190].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.625586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024644PMC
March 2021

Anti-inflammatory activity of the Tongmai Yangxin pill in the treatment of coronary heart disease is associated with estrogen receptor and NF-κB signaling pathway.

J Ethnopharmacol 2021 Apr 7;276:114106. Epub 2021 Apr 7.

School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address:

Ethnopharmacological Relevance: The Tongmai Yangxin Pill (TMYX) is a patented traditional Chinese medicine originating from two classic prescriptions, Zhigancao Decoction and Shenmai Yin, which composed of 11 Chinese medicinal herbs: Rehmannia glutinosa (Gaertn.) DC., Spatholobus suberectus Dunn, Ophiopogon japonicus (Thunb.) Ker Gawl., Glycyrrhiza uralensis Fisch., Polygonum multiflorum Thunb., Equus asinus L., Schisandra chinensis (Turcz.) Baill., Codonopsis pilosula (Franch.) Nannf., Chinemys reevesii (Gray), Ziziphus jujuba Mill. and Cinnamomum cassia (L.) J.Presl (Committee of the Pharmacopoeia of PR China, 2015). TMYX has marketed in China for the treatment of chest pain, palpitation, angina, irregular heartbeat and coronary heart disease (CHD) for several decades. Previous studies have confirmed that TMYX can treat CHD by reducing inflammation, but the underlying pharmacological mechanism remains unclear.

Aim Of The Study: This study aimed to declare the underlying pharmacological mechanism of anti-inflammatory activity of TMYX in the treatment of CHD via clinical trial, microarray study, bioinformatics analysis and the vitro assays.

Materials And Methods: Eight CHD patients' serum biochemical indices including coagulation function, lipid metabolism, endothelial injury, metalloprotease, adhesion molecule, inflammatory mediator and homocysteine were measured to investigate the reduction of CHD risk by TMYX oral administration (40 pills/time, 2 times/day) for eight weeks. The expression profile chips and Ingenuity Pathway Analysis (IPA) were assessed to reveal the global transcriptional response and predict related functions, diseases and canonical pathways. The in vitro anti-inflammatory actions of TMYX were evaluated using oxidized low-density lipoprotein (100 μg/mL) induced murine RAW264.7 macrophage with an ethanol extract from TMYX (EETMYX) (25-100 μg/mL).

Results: TMYX treatment showed reduced levels of apolipoprotein B, endothelin 1, nuclear factor κB (NF-κB) and homocysteine in CHD patients. In contrast, the treatment increased the ratio of apolipoprotein A/apolipoprotein B. EETMYX restored cell morphology and suppressed the lipid deposition of the induced foam cells. EETMYX exerted anti-inflammatory effects by raising the mRNA and protein expression of Estrogen receptor 1 (ESR1), blocking the reduction of IκBa level and the phosphorylation of IKKα/β, IκBα and NF-κB p65, accompanied by inhibiting MCP-1, TNF-α and IL-6 production, which were consistent with bioinformatics predictions.

Conclusion: TMYX treatment improved the biochemical indices in CHD patients. EETMYX effectively attenuated macrophage foam cell formation and exhibited anti-inflammatory activity is associated with regulating ESR1 and NF-κB signaling pathway activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114106DOI Listing
April 2021

Cholinergic suppression of hippocampal sharp-wave ripples impairs working memory.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Neuroscience Institute, Langone Medical Center, New York University, New York, NY 10016;

Learning and memory are assumed to be supported by mechanisms that involve cholinergic transmission and hippocampal theta. Using G protein-coupled receptor-activation-based acetylcholine sensor (GRAB3.0) with a fiber-photometric fluorescence readout in mice, we found that cholinergic signaling in the hippocampus increased in parallel with theta/gamma power during walking and REM sleep, while ACh3.0 signal reached a minimum during hippocampal sharp-wave ripples (SPW-R). Unexpectedly, memory performance was impaired in a hippocampus-dependent spontaneous alternation task by selective optogenetic stimulation of medial septal cholinergic neurons when the stimulation was applied in the delay area but not in the central (choice) arm of the maze. Parallel with the decreased performance, optogenetic stimulation decreased the incidence of SPW-Rs. These findings suggest that septo-hippocampal interactions play a task-phase-dependent dual role in the maintenance of memory performance, including not only theta mechanisms but also SPW-Rs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2016432118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054002PMC
April 2021

A genetically encoded sensor for measuring serotonin dynamics.

Nat Neurosci 2021 May 5;24(5):746-752. Epub 2021 Apr 5.

State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.

Serotonin (5-HT) is a phylogenetically conserved monoamine neurotransmitter modulating important processes in the brain. To directly visualize the release of 5-HT, we developed a genetically encoded G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB) sensor with high sensitivity, high selectivity, subsecond kinetics and subcellular resolution. GRAB detects 5-HT release in multiple physiological and pathological conditions in both flies and mice and provides new insights into the dynamics and mechanisms of 5-HT signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41593-021-00823-7DOI Listing
May 2021

Design and synthesis of small molecular 2-aminobenzoxazoles as potential antifungal agents against phytopathogenic fungi.

Mol Divers 2021 Apr 3. Epub 2021 Apr 3.

State Key Laboratory of Functions and Applications of Medicinal Plants and College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004, People's Republic of China.

In order to discover novel antifungal agents, three series of simple 2-aminobenzoxazole derivatives were designed, synthesized and evaluated for their antifungal activities against eight phytopathogenic fungi. The in vitro antifungal results showed that most of the target compounds exhibited excellent and broad-spectrum antifungal activities to all the tested fungi. Particularly, the six compounds 3a, 3b, 3c, 3e, 3m and 3v displayed the most potent antifungal activity, with EC value of 1.48-16.6 µg/mL, which were much superior to the positive control hymexazol. The in vivo study further confirmed that compounds 3a, 3c, 3e and 3m displayed good preventative effect against Botrytis cinerea at the concentration of 100 µg/mL. The structure-activity relationships research provides significant reference for the further structural optimization of 2-aminobenzoxazole as potential fungicides. Forty-four 2-aminobenzoxazole derivatives were designed and synthesized as agricultural antifungal agents, the in vitro and in vivo antifungal experiments showed that compounds 3a, 3b, 3c, 3e, 3m and 3v exhibited excellent and broad-spectrum antifungal activities compare with the commercial fungicide hymexazol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11030-021-10213-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019306PMC
April 2021

Manganese salts function as potent adjuvants.

Cell Mol Immunol 2021 May 25;18(5):1222-1234. Epub 2021 Mar 25.

Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China.

Aluminum-containing adjuvants have been used for nearly 100 years to enhance immune responses in billions of doses of vaccines. To date, only a few adjuvants have been approved for use in humans, among which aluminum-containing adjuvants are the only ones widely used. However, the medical need for potent and safe adjuvants is currently continuously increasing, especially those triggering cellular immune responses for cytotoxic T lymphocyte activation, which are urgently needed for the development of efficient virus and cancer vaccines. Manganese is an essential micronutrient required for diverse biological activities, but its functions in immunity remain undefined. We previously reported that Mn is important in the host defense against cytosolic dsDNA by facilitating cGAS-STING activation and that Mn alone directly activates cGAS independent of dsDNA, leading to an unconventional catalytic synthesis of 2'3'-cGAMP. Herein, we found that Mn strongly promoted immune responses by facilitating antigen uptake, presentation, and germinal center formation via both cGAS-STING and NLRP3 activation. Accordingly, a colloidal manganese salt (Mn jelly, MnJ) was formulated to act not only as an immune potentiator but also as a delivery system to stimulate humoral and cellular immune responses, inducing antibody production and CD4/CD8 T-cell proliferation and activation by either intramuscular or intranasal immunization. When administered intranasally, MnJ also worked as a mucosal adjuvant, inducing high levels of secretory IgA. MnJ showed good adjuvant effects for all tested antigens, including T cell-dependent and T cell-independent antigens, such as bacterial capsular polysaccharides, thus indicating that it is a promising adjuvant candidate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41423-021-00669-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093200PMC
May 2021

Hepatocyte-targeting and microenvironmentally responsive glycolipid-like polymer micelles for gene therapy of hepatitis B.

Mol Ther Nucleic Acids 2021 Jun 18;24:127-139. Epub 2021 Feb 18.

College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China.

Hepatitis B (HB) is a viral infectious disease that seriously endangers human health, and since there are no radical drugs to counter this, effective and safe therapies urgently need to be developed. HB virus (HBV) mainly infects hepatocytes (HCs), while the drugs are easily phagocytosed by Kupffer cells (KCs). In this study, the glutathione concentration difference between HCs and KCs was examined and utilized in an ideal drug-release strategy. Here, galactosylated chitosan-oligosaccharide-SS-octadecylamine (Gal-CSSO) was prepared to accurately deliver 10-23 DNAzyme DrzBC (blocking HBeAg expression) or DrzBS (blocking HBsAg expression) in targeted HB therapy. Gal-CSSO systems exhibited low cytotoxicity, endosomal escape, and glutathione responsiveness. The HBeAg and HBsAg secretion of HepG2.2.15 was significantly decreased by Gal-CSSO systems, and the maximum inhibition rates were 1.82-fold and 2.38-fold greater than those of commercial Lipofectamine 2000 (Lipo2000) systems. Gal-CSSO systems exhibited HC targeting and HC microenvironmental responsiveness without noticeable hepatotoxicity or systemic toxicity. The HBeAg and HBsAg titers of the HBV-infected mice were evidently decreased by Gal-CSSO systems, and the inhibition rates were 1.52-fold and 1.22-fold greater than those of Lipo2000 systems. This study presents a kind of glycolipid-like polymer micelles that promise efficient and safe gene therapy of HB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtn.2021.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943969PMC
June 2021

Rapid multi-directed cholinergic transmission in the central nervous system.

Nat Commun 2021 03 2;12(1):1374. Epub 2021 Mar 2.

Department of Biology, University of Victoria, Victoria, BC, Canada.

In many parts of the central nervous system, including the retina, it is unclear whether cholinergic transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale 'non-synaptic' mechanisms. Here, we characterized the ultrastructural features of cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a 'tripartite' structure facilitates a 'multi-directed' form of transmission, in which ACh released from a single vesicle rapidly (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 µm of the release site. Cholinergic signals are direction-selective at a local, but not global scale, and facilitate the transfer of information from starburst to ganglion cell dendrites. These results suggest a distinct operational framework for cholinergic signaling that bears the hallmarks of synaptic and non-synaptic forms of transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21680-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925691PMC
March 2021

Membranous nephropathy in a patient with coronavirus disease 2019 (COVID-19): A case report.

Clin Nephrol Case Stud 2021 19;9:11-18. Epub 2021 Feb 19.

Division of Nephrology and Hypertension.

Introduction: Though respiratory, immune, and coagulation systems are major targets of coronavirus disease 2019 (COVID-19), kidney dysfunction, presenting with acute kidney injury (AKI), is also common. Most AKI cases in COVID-19 manifest as acute tubular injury (ATI) in conjunction with multiorgan failure. While initial renal pathological findings were limited to acute tubular necrosis and collapsing glomerulopathy, a recent case series reported a larger spectrum of findings.

Case Report: Here, we report a case of membranous nephropathy (MN) in an 81-year-old Hispanic man with underlying chronic kidney disease (CKD) stage 3 who developed ATI in the setting of COVID-19. The patient was hospitalized for hypoxic respiratory failure in the setting of AKI stage 3 with serum creatinine 7.1 mg/dL 6 days after a positive-SARS-CoV-2 screening. He was found to have nephrotic range proteinuria, glycosuria (with normal serum glucose), anemia, and hypoalbuminemia. Kidney biopsy showed ATI and early MN. Workup for primary and secondary MN was unrevealing, and serum PLA2R antibody was negative. No viral particles were observed in podocytes.

Conclusion: Although the MN could be incidental, this observation raises the question of whether SARS-CoV-2 infection can trigger or worsen an underlying MN from an exaggerated immune response associated with COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5414/CNCS110379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901357PMC
February 2021

A Challenging Diagnosis of Atypical Glut1-DS: A Case Report and Literature Review.

Front Neurol 2020 28;11:549331. Epub 2021 Jan 28.

Department of Neurology and Neuroscience Center, First Hospital of Jilin University, Changchun, China.

Glucose transporter type 1 deficiency syndrome (Glut1-DS) is a rare neurometabolic disorder caused by mutations of the SLC2A1 gene. Paroxysmal exercise-induced dyskinesia is regarded as a representative symptom of Glut1-DS. Paroxysmal non-kinesigenic dyskinesia is usually caused by aberrations of the MR1 and KCNMA1 genes, but it also appears in Glut1-DS. We herein document a patient with Glut1-DS who suffered first from paroxysmal exercise-induced dyskinesia and subsequently paroxysmal non-kinesigenic dyskinesia and experienced a recent worsening of symptoms accompanied with a low fever. The lumbar puncture result showed a decreased glucose concentration and increased white blood cell (WBC) count in cerebrospinal fluid (CSF). The exacerbated symptoms were initially suspected to be caused by intracranial infection due to a mild fever of <38.0°C, decreased CSF glucose, and increased CSF WBC count. However, the second lumbar puncture result indicated a decreased glucose concentration and normal WBC count in CSF with no anti-infective agents, and the patient's symptoms were not relieved apparently. The continuous low glucose concentration attracted our attention, and gene analysis was performed. According to the gene analysis result, the patient was diagnosed with Glut1-DS finally. This case indicates that the complex paroxysmal dyskinesia in Glut1-DS may be confusing and pose challenges for accurate diagnosis. Except intracranial infection, Glut1-DS should be considered as a differential diagnosis upon detection of a low CSF glucose concentration and dyskinesia. The case presented here may encourage clinicians to be mindful of this atypical manifestation of Glut1-DS in order to avoid misdiagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.549331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876440PMC
January 2021

[Study on the application value of MELD-Na, CLIF-C OFs, COSSH-ACLFs and NLR scoring systems in patients with hepatitis B virus related acute-on-chronic liver failure].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Dec;32(12):1496-1501

Tianjin Second People's Hospital, Tianjin 300192, China.

Objective: To verify the accuracy of the model for end-stage liver disease-sodium (MELD-Na), chronic liver failure consortium organ failure score (CLIF-C OFs), Chinese Group on the Study of Severe Hepatitis B-Acute-on-chronic Liver Failure score (COSSH-ACLFs) and neutrophil-to-lymphocyte ratio (NLR) scoring systems in patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) and to explore its value in clinical application.

Methods: The clinical data (gender, age, disease stage) and laboratory indicators [alanine transferase (ALT), glutamate transaminase (AST), total bilirubin (TBil), albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), serum sodium (Na), prothrombin activity (PTA), international standardized ratio (INR), neutrophils count (NEU) and lymphocytes count (LYM)] of 163 patients with HBV-ACLF from July 2010 to July 2018 in Tianjin Second People's Hospital were retrospectively analyzed. After 8 weeks of admission, the patients were divided into death group (90 cases) and survival group (73 cases) according to survival status. The MELD-Na, CLIF-C OFs, COSSH-ACLFs scores and NLR of death group and survival group were compared, and a multivariate Logistic regression analysis was used to analyze the independent risk factors for HBV-ACLF. Propensity score analysis was used to demonstrate the accuracy of the method and receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of the independent risk factors.

Results: There were no significant differences in gender, disease stage, ALB, BUN, Cr, Na, NEU on admission between the two groups (all P > 0.05). The age [years old: 43.00 (34.00, 53.00) vs. 50.00 (42.50, 55.00)] and serum levels of ALT [U/L: 252.90 (61.43, 613.33) vs. 359.10 (115.15, 784.70)], AST [U/L: 146.15 (90.88, 449.30) vs. 237.80 (109.00, 635.05)], TBil [μmol/L: 265.10 (183.10, 347.60) vs. 307.50 (229.90, 405.55)] and INR [2.13 (1.91, 2.46) vs. 2.29 (2.02, 2.94)] in survival group were lower than those in death group and the PTA [%: 34.00 (28.00, 38.00) vs. 31.00 (24.00, 36.00)] and LYM [×10/L: 1.37 (0.72, 1.79) vs. 0.85 (0.51, 1.39)] levels were significantly higher than those in death group (both P < 0.05). The MELD-Na [17.99 (16.60, 19.63) vs. 19.16 (17.43, 20.80)], CLIF-C OFs [9.00 (8.00, 9.00) vs. 9.00 (9.00, 10.00)], COSSH-ACLFs [4.87 (4.63, 5.48) vs. 5.47 (5.07, 5.80)] and NLR [2.86 (2.21, 5.19) vs. 4.38 (2.54, 8.46)] were lower in survival group than those of the death group (all P < 0.05). Logistic regression analysis showed that CLIF-C OFs [odds ratio (OR) = 0.532, 95% confidence interval (95%CI) was 0.380-0.744, P < 0.05] and NLR (OR = 0.901, 95%CI was 0.835-0.972, P < 0.05) were the independent risk factors for the prognosis of HBV-ACLF. After propensity score matching, the data of 59 cases in each group were successfully matched, there were no significant differences in age, gender, disease stage, ALT, AST, TBil, ALB, BUN, Cr, Na, PTA, INR and NEU between the two groups (all P > 0.05), and statistically significant difference in the baseline LYM [×10/L: 1.35 (0.74, 1.73) vs. 0.81 (0.51, 1.30)] were found between the survival group and the death group. The CLIF-C OFs, COSSH-ACLFs scores and NLR were lower in survival group compared with those of the death group [CLIF-C OFs: 9.00 (8.00, 9.00) vs. 9.00 (8.00, 10.00), COSSH-ACLFs: 4.99 (4.69, 5.64) vs. 5.34 (5.03, 5.81), NLR: 2.85 (2.21, 5.72) vs. 4.38 (2.47, 10.20), all P < 0.05] and CLIF-C OFs (OR = 0.593, 95%CI was 0.401-0.878, P < 0.05) and NLR (OR = 0.593, 95%CI was 0.401-0.878, P < 0.05) were still as the independent risk factors for the prognosis of HBV-ACLF. The sensitivity of CLIF-C OFs ≥ 9 and NLR ≥ 3.14 to forecast the 8-week clinical outcome of HBV-ACLF patients were 76.7% and 67.1%, the specificity were 48.9% and 56.7%, and AUC were 0.662 and 0.623. CLIF-C OFs was combined with NLR to increase the specificity of forecasting the 8-week clinical outcome of HBV-ACLF patients to 77.8%.

Conclusions: CLIF-C OFs and NLR scores are independent risk factors affecting the clinical outcome of HBV-ACLF, and have better clinical value in predicting the prognosis of HBV-ACLF. Combined application of the two scores will be more beneficial to the prognosis of HBV-ACLF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.cn121430-20200720-00536DOI Listing
December 2020

Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction.

Nat Commun 2021 01 25;12(1):581. Epub 2021 Jan 25.

Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 100871, Beijing, China.

Formaldehyde (FA) has long been considered as a toxin and carcinogen due to its damaging effects to biological macromolecules, but its beneficial roles have been increasingly appreciated lately. Real-time monitoring of this reactive molecule in living systems is highly desired in order to decipher its physiological and/or pathological functions, but a genetically encoded FA sensor is currently lacking. We herein adopt a structure-based study of the underlying mechanism of the FA-responsive transcription factor HxlR from Bacillus subtilis, which shows that HxlR recognizes FA through an intra-helical cysteine-lysine crosslinking reaction at its N-terminal helix α1, leading to conformational change and transcriptional activation. By leveraging this FA-induced intra-helical crosslinking and gain-of-function reorganization, we develop the genetically encoded, reaction-based FA sensor-FAsor, allowing spatial-temporal visualization of FA in mammalian cells and mouse brain tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20754-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835342PMC
January 2021

A novel homozygous exon2 deletion of TRIM32 gene in a Chinese patient with sarcotubular myopathy: A case report and literature review.

Bosn J Basic Med Sci 2020 Dec 29. Epub 2020 Dec 29.

Department of Neurology and Neuroscience Center, The First Affiliated Hospital of Jilin University, Jilin, China.

Sarcotubular myopathy (STM) is a rare autosomal recessive myopathy caused by TRIM32 gene mutations. It is predominantly characterized by the weakness of the proximal limb and mild to moderate elevation of creatine kinase (CK) levels. In this study, we describe a 50-year-old Chinese man who exhibited a proximal-to-distal weakness in the muscles of the lower limbs and who had difficulty standing up from a squat position. The symptoms gradually became more severe. He denied a history of cognitive or cardiological problems. The patient's parents and children were healthy. Histopathological examination revealed dystrophic changes and irregular slit-shaped vacuoles containing amorphous materials. Whole-exome sequencing consisting of protein-encoding regions of 19,396 genes was performed, the results of which identified one novel homozygous 2kb deletion chr9.hg19: g.119460021_119461983del (exon2) in the TRIM32 gene. This was confirmed at the homozygous state with quantitative real-time PCR. Here, we present a Chinese case of STM with one novel mutation in TRIM32 and provide a brief summary of all known pathogenic mutations in TRIM32.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17305/bjbms.2020.5288DOI Listing
December 2020

The complete chloroplast genome sequence of (Lindl.) Schott (Fagaceae).

Mitochondrial DNA B Resour 2020 Jul 15;5(3):2848-2849. Epub 2020 Jul 15.

Co-Innovation Center for Sustainable Forestry in Southern China, College of Biology and the Environment, Key Laboratory of State Forestry and Grassland Administration on Subtropical Forest Biodiversity Conservation, Nanjing Forestry University, Nanjing, PR China.

(Lindl.) Schott is one of the National Class II protected plants, and an important species in subtropical evergreen forests in China. The object of this work was to thoroughly explore the complete chloroplast (cp) genome of . using next-generation sequencing. The circular complete cp genome of . is 160,519 bp in length, containing a large single-copy (LSC) region of 90,243 bp, and a small single-copy (SSC) region of 18,976 bp. It comprises 131 genes, including 8 rRNA genes, 37 tRNAs genes, and 85 protein-coding genes. The GC content of cp genome is 36.81%. The phylogenetic analysis suggests that . is a sister species to . in Fagaceae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2020.1790324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781992PMC
July 2020

Rather Unusual Cause of Seizures.

Am J Med 2021 Jan 14. Epub 2021 Jan 14.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjmed.2020.11.015DOI Listing
January 2021

Evaluation of an Element-Tagged Duplex Immunoassay Coupled with Inductively Coupled Plasma Mass Spectrometry Detection: A Further Study for the Application of the New Assay in Clinical Laboratory.

Molecules 2020 Nov 17;25(22). Epub 2020 Nov 17.

Department of Clinical Laboratory Medicine, Chinese People's Liberation Army General Hospital & Postgraduate Medical School, Beijing 100853, China.

Background: Element-tagged immunoassay coupled with inductively coupled plasma mass spectrometry (ICP-MS) detection has the potential to revolutionize immunoassay analysis for multiplex detection. However, a further study referring to the standard evaluation and clinical sample verification is needed to ensure its reliability for simultaneous analysis in clinical laboratories.

Methods: Carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) were chosen for the duplex immunoassay. The performance of the assay was evaluated according to guidelines from the Clinical and Laboratory Standards Institute (CLSI). Moreover, reference intervals (RIs) of CEA and AFP were established. At last, 329 clinical samples were analyzed by the proposed method and results were compared with those obtained with electrochemiluminescent immunoassay (ECLIA) method.

Results: The measurement range of the assay was 2-940 ng/mL for CEA and 1.5-1000 ng/mL for AFP, with a detection limit of 0.94 ng/mL and 0.34 ng/mL, respectively. The inter-assay and intra-assay imprecision were all less than 6.58% and 10.62%, respectively. The RI of CEA and AFP was 0-3.84 ng/mL and 0-9.94 ng/mL, respectively. Regarding to clinical sample detection, no significant difference was observed between the proposed duplex assay and the ECLIA method.

Conclusions: The ICP-MS-based duplex immunoassay was successfully developed and the analytical performance fully proved clinical applicability. Well, this could be different with other analytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25225370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698432PMC
November 2020

Development and Evaluation of a Combined Immunoassay Method Based on a Stable Isotope Tagging Strategy and Inductively Coupled Plasma Mass Spectrometry for Detecting Human Chorionic Gonadotropin.

Clin Lab 2020 Nov;66(11)

Background: The development of a combined immunoassay method, based on a stable isotope tagging strategy and inductively coupled plasma mass spectrometry (ICP-MS), has created options for quantitative bioanalysis. The aim of the study was to develop a combined immunoassay, featuring ICP-MS and a stable element labeling strategy, for the detection of human chorionic gonadotropin (HCG), and developed methodology applicable for clinical practice.

Methods: In accordance with guidelines published by the Clinical and Laboratory Standards Institute (CLSI), we developed our assay and then evaluated its analytical performance, including the limit of detection (LOD), the upper limit of quantification (ULoQ), linearity, precision, recovery, cross reactivity, and interference. Next, we collected 130 clinical samples for analysis with the new assay. The data derived from our assay were then compared with those derived by an existing electrochemiluminescence immunoassay (ECLIA).

Results: The LOD of the assay was 0.33 mIU/mL and the ULoQ was 11,300 mIU/mL. The coefficient of determina-tion of linearity was higher than 0.99 in the range of 1 to 8,917 mIU/mL (R2 = 0.9964). The obtained recoveries ranged from 97.08% to 103.50%, while the intra-assay imprecision of high value samples and low value samples were 2.97% and 6.08%, respectively. The inter-assay imprecision of high value samples and low value samples were 3.98% and 7.08%, respectively. Interference test results deviated by less than ± 10% in the presence of hemoglobin ≤ 2 g/L, bilirubin ≤ 274 mol/L, or triglycerides ≤ 37 mmol/L. Compared with the commercial ECLIA method for clinical sample detection, the proposed method showed a significant correlation (R2 = 0.9770) and satisfactory agreement.

Conclusions: The combination of ICP-MS and a stable element labeling based immunoassay for HCG detection was established successfully and the general performance of this system was acceptable, thus indicating that the assay has potential for the clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2020.191207DOI Listing
November 2020

Kang-Xian Pills Inhibit Inflammatory Response and Decrease Gut Permeability to Treat Carbon Tetrachloride-Induced Chronic Hepatic Injury through Modulating Gut Microbiota.

Evid Based Complement Alternat Med 2020 20;2020:8890182. Epub 2020 Oct 20.

Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Kang-Xian (KX) pills have been clinically used for the treatment of chronic hepatic injury (CHI). However, the mechanisms of KX on CHI remain unknown. The aim of this study mainly focused on the anti-inflammatory effects of KX in a CHI mouse model based on modulating gut microbiota and gut permeability. We first established a CHI model using carbon tetrachloride (CCl) and treated it with KX. The anti-inflammatory effects of KX on CHI model mice and the changes in gut permeability after KX treatment were also investigated. 16S rRNA analysis was used to study the changes of gut microbiota composition after KX treatment. In addition, gut microbiota was depleted using a combination of antibiotics in order to further confirm that KX could inhibit the inflammatory response and decrease gut permeability to treat CHI by modulating the gut microbiota. Results showed that KX treatment significantly improved liver function in CHI model mice. KX could also increase the levels of tight junction proteins in the colon and decrease the expression of proinflammatory cytokines in the liver. 16S rRNA analysis indicated that KX treatment affected the alpha and beta diversities in CHI model mice. Further analysis of 16S rRNA sequencing indicated that KX treatment increased the ratio of Firmicutes to Bacteroidetes at the phylum level. At the genus level, KX treatment increased the relative abundance of and and decreased the relative abundance of and . However, KX could not alleviate CHI after depleting the gut microbiota. The effects of KX on gut permeability and inflammatory response in the liver were also decreased following the depletion of gut microbiota. In conclusion, our current study demonstrated that gut microbiota was significantly affected during CHI progression. KX could inhibit the inflammatory response and decrease the gut permeability in CHI model mice through modulating the gut microbiota.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8890182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596455PMC
October 2020

Ethnic preference distribution of inborn errors of metabolism: A 4-year study in a multi-ethnic region of China.

Clin Chim Acta 2020 Dec 12;511:160-166. Epub 2020 Oct 12.

Maternal and Child Health Care Hospital of Ningxia Hui Autonomous Region, Yinchuan 750011, Ningxia, China.

Chinese newborns have been screened for inborn errors of metabolism (IEM) for over 20 years. Although China features 56 different ethnic groups, there are no specific data describing the incidence of such genetic errors across difference ethnicities. To understand the ethnic preference distribution of the incidence and variants of IEM in the Ningxia Hui Autonomous Region of China, 189,354 newborns from 2016 to 2019 were screened by tandem mass spectrometry, including 87,482 from the Han ethnic population, 88,229 from the Hui population, 1,103 from other ethnicities, and 12,540 infants without ethnic registration. Suspected cases then underwent specific genetic profiling by targeted next generation sequencing. In total, 160 patients were diagnosed with 17 types of IEM, with a significant higher incidence in Hui infants (1/1,003) than in Han infants (1/1,232). Five diseases (eight patients) were specifically detected in Han infants, while three were exclusively diagnosed in six Hui infants. For shared diseases, the variants of keys genes also showed ethnic preference. Our findings enhance our understanding of the genetics underlying IEM, thus promoting the development of treatment plans for patients from different areas or ethnicities in China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2020.10.003DOI Listing
December 2020

A case report: identification of a novel exon 1 deletion mutation in the GNE gene in a Chinese patient with GNE myopathy.

Medicine (Baltimore) 2020 Oct;99(41):e22663

Department of Neurology and Neuroscience Center, the First Affiliated Hospital of Jilin University, Changchun, Jilin, People's Republic of China.

Rationale: GNE myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase(GNE) gene and is clinically characterized by progressive weakness and atrophy of the lower-limb muscles with quadriceps sparing. Nearly all GNE mutations that have been reported thus far in various ethnic populations around the world have been missense or nonsense mutations.

Patient Concerns: We describe the case of a 32-year-old woman with GNE myopathy. The patient presented with progressive weakness of the lower-limb muscles that had spread to her legs. Her serum creatine kinase level was higher than the normal range. Mild myogenic changes were detected in the tibialis anterior muscles on electromyography, and moderate fatty infiltration was observed in various lower-limb muscles on magnetic resonance imaging. Histopathological examination of a skeletal muscle biopsy specimen revealed variation in muscle fiber size, rimmed vacuoles, and disorganized intermyofibrillar networks. DNA sequencing testing revealed a compound heterozygous mutation consisting of a known mutation (c.620A > T in exon 3) and a novel (exon 1 deletion) mutation.

Diagnoses: Taken together, the clinical features, laboratory testing and DNA findings eventually made the diagnosis of GNE myopathy.

Interventions And Outcomes: Based on the diagnosis of the GNE myopathy, the patient was administered sialic acid 6 g a day for 1 year, and up to now, her symptoms did not progress further.

Lessons: We have reported the case of a GNE myopathy patient with compound heterozygous GNE gene mutations. This case expands the genotypic spectrum of GNE myopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000022663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544422PMC
October 2020

Composition of "gold juice" using an ancient method based on intestinal microecology.

J Int Med Res 2020 Sep;48(9):300060520931288

Integrative Medicine Institute, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Objective: To identify potentially effective bacterial components of gold juice, a traditional Chinese medicine treatment used for fecal microbiota transplantation.

Methods: Fecal samples were collected from five healthy children (two boys and three girls; mean age, 7.52 ± 2.31 years). The children had no history of antibiotic use or intestinal microecological preparation in the preceding 3 months. Fresh fecal samples were collected from children to prepare gold juice in mid-to-late November, in accordance with traditional Chinese medicine methods, then used within 7 days. Finally, 16S rDNA sequence analysis was used to identify potentially effective bacterial components of gold juice. QIIME software was used for comparisons of microbial species among gold juice, diluent, filtrate, and loess samples.

Results: Microflora of gold juice exhibited considerable changes following "ancient method" processing. Microbial components significantly differed between gold juice and filtrate samples. The gold juice analyzed in our study consisted of microbes that synthesize carbohydrates and amino acids by degrading substances, whereas the filtrate contained probiotic flora, , and 9.

Conclusions: This study of microbial components in gold juice and filtrate provided evidence regarding effective bacterial components in gold juice, which may aid in clinical decisions concerning fecal microbiota transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300060520931288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545780PMC
September 2020

An optimized acetylcholine sensor for monitoring in vivo cholinergic activity.

Nat Methods 2020 11 28;17(11):1139-1146. Epub 2020 Sep 28.

State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.

The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRAB (GPCR-activation-based ACh) sensor to achieve substantially improved sensitivity in ACh detection, as well as reduced downstream coupling to intracellular pathways. The improved version of the ACh sensor retains the subsecond response kinetics, physiologically relevant affinity and precise molecular specificity for ACh of its predecessor. Using this sensor, we revealed compartmental ACh signals in the olfactory center of transgenic flies in response to external stimuli including odor and body shock. Using fiber photometry recording and two-photon imaging, our ACh sensor also enabled sensitive detection of single-trial ACh dynamics in multiple brain regions in mice performing a variety of behaviors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41592-020-0953-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606762PMC
November 2020

Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances the learning of cue-reward contingency.

Elife 2020 09 18;9. Epub 2020 Sep 18.

Department of Psychiatry, Yale University, New Haven, United States.

The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and nucleus basalis of Meynert (NBM) cholinergic terminal activity in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the cue-reward contingency. BLA CaMKIIα neuron activity followed reward retrieval and moved to the reward-predictive cue after task acquisition. Optical stimulation of cholinergic NBM-BLA terminal fibers led to a quicker acquisition of the cue-reward contingency. These results indicate BLA ACh signaling carries important information about salient events in cue-reward learning and provides a framework for understanding how ACh signaling contributes to shaping BLA responses to emotional stimuli.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.57335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529459PMC
September 2020

Levels of human Rotaviruses and Noroviruses GII in urban rivers running through the city mirror their infection prevalence in populations.

Sci Total Environ 2021 Feb 3;754:142203. Epub 2020 Sep 3.

Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin Institute of Environmental & Operational Medicine, No.1, Dali Road, Tianjin 300050, China. Electronic address:

Enteric viruses exposed to water pose a huge threat to global public health and can lead to waterborne disease outbreaks. A sudden increase in enteric viruses in some water matrices also underpins the prevalence of corresponding waterborne diseases in communities over the same time period. However, few efforts have been focused on water matrices whose viral pollution may best reflect the clinical prevalence in communities. Here, a one-year surveillance of human enteric viruses including Enteroviruses (EnVs), Rotaviruses (HRVs), Astroviruses (AstVs), Noroviruses GII (HuNoVsGII) and Mastadenoviruses (HAdVs) in four representative water matrices: an urban river (UR) running through city, effluent from Wastewater Treatment Plant (EW), raw water for Urban Water Treatment Plant (RW), and tap water (TW) were performed by qPCR. The relationship between the virus detection frequency at each site and their prevalence in clinical PCR assay was further analyzed. We found that the detection frequencies of HRVs, HuNoVsGII, and AstVs in stools peaked in winter, while EnVs peaked in autumn. No EnVs occurred in EW, RW, or TW, but HuNoVsGII and AstVs occurred intensively in winter. For UR, all types of enteric viruses could be detected and the levels of acute gastroenteritis viruses (HRVs, HuNoVsGII, AstVs, and HAdVs) were highest in autumn or winter, whereas EnVs peaked in summer. In terms of correlation analyses, only HRVs and HuNoVsGII levels in UR showed a strong positive correlation with their prevalence in clinical stool samples. This study indicated that HRVs and HuNoVsGII levels in URs may mirror the local virus prevalence, thereby implying the possibility of revealing their local epidemiology by monitoring them in the URs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.142203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470703PMC
February 2021

[Value of a new predictive model in evaluating short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Aug;32(8):988-993

First Department of Combined Chinese and Western Medicine, Tianjin Second People's Hospital, Tianjin 300192, China. Corresponding author: Jia Jianwei, Email:

Objective: To establish a predictive model and investigate its value in evaluating short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF).

Methods: Patients with HBV-ACLF admitted to Tianjin Second People's Hospital and Beijing Youan Hospital, Capital Medical University from May 2015 to October 2018 were enrolled. The data of gender, age, laboratory markers at admission, model for end-stage liver disease (MELD) score and clinical complications were collected for analysis. According to the prognosis on 12-week, patients were divided into survival group and death group. Univariate analysis and binary Logistic regression analysis were used to test the risk factors for short-term prognosis of the patients with HBV-ACLF, and a prediction model was established. The accuracy of each index and the established model were verified by the receiver operating characteristic (ROC) curve.

Results: A total of 148 patients with HBV-ACLF were enrolled in the study, 91 cases survived while 57 cases died during the 12-week period. The age, total bilirubin (TBIL), neutrophil percentage (NEUT%), hepatitis B surface antigen (HBsAg), MELD score of death group were higher than those of survival group [age (years old): 50.00 (44.50, 55.00) vs. 43.00 (34.00, 53.00), TBIL (μmol/L): 310.30 (240.70, 405.70) vs. 266.40 (184.20, 360.20), NEUT%: (74.52±13.05)% vs. (66.64±12.35)%, lgHBsAg (kU/L): 3.72 (3.29, 3.92) vs. 2.97 (2.49, 3.78), MELD score: 24.27 (19.71, 27.40) vs. 21.88 (18.83, 24.38), all P < 0.05], while albumin (ALB), total cholesterol (CHO), prothrombin activity (PTA) and alpha-fetoprotein (AFP) were lower than those of survival group [ALB (g/L): 29.80 (27.05, 31.05) vs. 30.80 (28.00, 33.90), CHO (mmol/L): 1.98 (1.50, 2.38) vs. 2.49 (2.05, 3.01), PTA: (30.37±7.09)% vs. (32.94±6.03)%, AFP (μg/L): 21.54 (9.28, 51.54) vs. 66.16 (24.50, 152.80), all P < 0.05]. Logistic regression analysis showed that NEUT%, HBsAg and AFP were independent risk factors for short-term prognosis of patients with HBV-ACLF [odds ratio (OR) was 77.843, 1.439, 0.995, respectively, all P < 0.05]. According to the results of regression analysis, the NHA-ACLF model (NEUT%+HBsAg+AFP) was established. The formula was logit (NHA-ACLF) = -5.441+5.688×NEUT%+0.430×lgHBsAg-0.005×AFP. The area under the ROC curve (AUC) of the NHA-ACLF model for pred HBV-ACLF patients was 0.790, which was better than NEUT% (AUC = 0.696), lgHBsAg (AUC = 0.670), AFP (AUC = 0.703) and MELD score (AUC = 0.640). When the cut-off value of NHA-ACLF model score was 0.459, the sensitivity was 73.7%, and the specificity was 79.1%.

Conclusions: NEUT%, HBsAg and AFP are independent predictive indicator for short-term prognosis in patients with HBV-ACLF. Compared with MELD score, the risk assessment model NHA-ACLF has a greater value in predicting the short-term prognosis of patients with HBV-ACLF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.cn121430-20200102-00075DOI Listing
August 2020

Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy.

Cell Res 2020 11 24;30(11):966-979. Epub 2020 Aug 24.

Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, 100871, China.

CD8 T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1, an interaction acts like brakes to prevent T cell overreaction under normal conditions but is exploited by tumor cells to escape the immune surveillance. Immune checkpoint inhibitors have revolutionized cancer therapeutics by removing such brakes. Unfortunately, only a minority of cancer patients respond to immunotherapies presumably due to inadequate immunity. Antitumor immunity depends on the activation of the cGAS-STING pathway, as STING-deficient mice fail to stimulate tumor-infiltrating dendritic cells (DCs) to activate CD8 T cells. STING agonists also enhance natural killer (NK) cells to mediate the clearance of CD8 T cell-resistant tumors. Therefore STING agonists have been intensively sought after. We previously discovered that manganese (Mn) is indispensable for the host defense against cytosolic dsDNA by activating cGAS-STING. Here we report that Mn is also essential in innate immune sensing of tumors and enhances adaptive immune responses against tumors. Mn-insufficient mice had significantly enhanced tumor growth and metastasis, with greatly reduced tumor-infiltrating CD8 T cells. Mechanically, Mn promoted DC and macrophage maturation and tumor-specific antigen presentation, augmented CD8 T cell differentiation, activation and NK cell activation, and increased memory CD8 T cells. Combining Mn with immune checkpoint inhibition synergistically boosted antitumor efficacies and reduced the anti-PD-1 antibody dosage required in mice. Importantly, a completed phase 1 clinical trial with the combined regimen of Mn and anti-PD-1 antibody showed promising efficacy, exhibiting type I IFN induction, manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors. We propose that this combination strategy warrants further clinical translation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41422-020-00395-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785004PMC
November 2020

Apigenin suppresses influenza A virus-induced RIG-I activation and viral replication.

J Med Virol 2020 Aug 10. Epub 2020 Aug 10.

Department of Hematology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.

Apigenin is a flavonoid of low toxicity and multiple beneficial bioactivities, including the properties of antitumor, antioxidant, anti-inflammatory, and antiviral activities. However, the effects of Apigenin on influenza virus infection remain poorly understood. Thus, the aim of this study is to investigate the effect of Apigenin on influenza A virus (IAV)-induced inflammation and viral replication. This study demonstrated that Apigenin treatment significantly suppressed IAV-induced upregulation of retinoic acid-inducible gene-I (RIG-I) expression, as well as the production of proinflammatory cytokines and interferons (IFN-β and IFN-λ1). Meanwhile, Apigenin also protected cells from IAV-induced cell death. In addition, Apigenin specifically inhibited the activation of RIG-I signaling via promoting the ubiquitin-mediated degradation of RIG-I, which may cause by the disrupting its interaction with heat shock protein 90α. Interestingly, instead of enhancing viral replication due to the inhibitory effects of Apigenin on the activation of RIG-I and expression of IFNs, Apigenin inhibited IAV replication in vitro. Further study demonstrated that Apigenin inhibited the influenza viral neuraminidase (NA) activity. Thus, Apigenin may serve as a promising supplementary approach for treatment of influenza because it protected cells from IAV-induced cell death and inhibited viral NA activity to suppress viral replication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.26403DOI Listing
August 2020