Publications by authors named "Chun-yan Wang"

209 Publications

Endoscopic joint capsule and articular process excision to treat lumbar facet joint syndrome: A case report.

World J Clin Cases 2021 Oct;9(28):8545-8551

Department of Radiology, Jinshan Branch, Shanghai Sixth People's Hospital, Shanghai 201599, China.

Background: Lumbar facet joint syndrome (LFJS) is a pain condition arising from lumbar facet joint diseases. Treatments of LFJS includes patient education, oral medication, bed rest, physical therapy, and procedural interventions. For some refractory cases that fail conservative therapies, dorsal ramus medial brunch radiofrequency ablation is warranted. However, as nerve fibers can regenerate, their efficacy is impermanent, and the recurrence rate is relatively high. Considering synovial impingement is a paramount pathogenesis of LFJS, in this case, we removed the culprit hyperplastic articular capsule and the articular process partially through a spinal endoscope. As the culprit hyperplastic joint capsule was excised, it is supposed to generate more prolonged efficacy and a lower recurrence rate than radiofrequency treatment.

Case Summary: A 40-year-old female patient was diagnosed with LFJS. She complained of low back pain and right buttock pain for half a year. The patient was placed in the prone position. After disinfection and draping, a 25-cm 18-gauge needle was inserted into the dorsal surface of the right L5 articular process. Subsequently, a guidewire, dilating tubes, and a working cannula was inserted successively. The spinal endoscope was positioned in the working cannula. Under the endoscope, the microvascular tissue, muscle tissue attached on the L5 inferior articular process and S1 superior articular process, as well as the capsule and minor portion of the inferior articular process were removed. After the joint space was clear and no bleeding points existed, the endoscope and working cannula were shifted, and the incision was sutured. After treatment, the symptoms were completely relieved. The patient was pain-free during the follow-up period of 6 mo.

Conclusion: The endoscopic partial joint capsule and articular process excision is an effective procedure for LFJS, especially for cases caused by synovial impingement.
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http://dx.doi.org/10.12998/wjcc.v9.i28.8545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554426PMC
October 2021

Case Report: A Meningitis in an Immunocompetent Patient Detected Through the Next-Generation Sequencing.

Front Med (Lausanne) 2021 22;8:656066. Epub 2021 Oct 22.

Department of Emergency Intensive Care Unit (EICU), The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China.

Fungal infections of the central nervous system (CNS) are not commonly seen clinically. Clinical diagnosis of fungal infections often depend on the pathogen culture and the clinical features. This method is time-consuming and insensitive, which can lead to misdiagnosis. The authors introduce an adult patient with fungal infections diagnosed by next-generation sequencing (NGS). The patient was a 60-year-old male Chinese who had both hypermyotonia of the lower extremities and fever. The auxiliary examinations such as MRI, CT, and cerebrospinal fluid (CSF) analysis showed obvious abnormalities. Because of the difficulties in diagnosis, it was hard to determine the treatment plan. The NGS detected specific sequences of in 3 days. The patient was then treated with liposomal amphotericin B and fluconazole. About 3 weeks later, the symptoms of the patient improved significantly and he was discharged from the hospital. Compared with the routine cultural method, NGS has made a huge advancement in infection diagnosis and targeting antimicrobial therapy for CNS infection.
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http://dx.doi.org/10.3389/fmed.2021.656066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569226PMC
October 2021

Formaldehyde induces ferritinophagy to damage hippocampal neuronal cells.

Toxicol Ind Health 2021 Nov 13;37(11):685-694. Epub 2021 Oct 13.

The First Affiliated Hospital, Institute of Neurology, Hengyang Medical School, 574417University of South China, Hengyang, P. R. China.

Formaldehyde (FA) causes neurotoxicity and contributes to the occurrence of neurodegenerative diseases. However, the mechanism of FA-induced neurotoxicity has not been fully elucidated. Ferritinophagy, an autophagy process of ferritin mediated by the nuclear receptor coactivator 4 (NCOA4), is a potential mechanism of neurotoxicity. In this study, we explored whether ferritinophagy is associated with the neurotoxicity of FA. Our results showed that FA (50, 100, 200 μM; 24 h) exposure upregulated ferritinophagy in the mouse hippocampal neuronal HT22 cells, which was evidenced by the upregulated autophagic flux, the increased colocalizations of NCOA4 with ferritin heavy chain (FTH1) and NCOA4 with microtubule-associated protein 1 light chain-3B (LC3B), the augmented expression of NCOA4, and the reduced content of FTH1. We also found that FA (0.1, 1, and 10 μmol, i.c.v., 7d) administration boosted ferritinophagy in the hippocampus of Sprague-Dawley (SD) rats, which was demonstrated by the accumulated autophagosomes, the increased expressions of LC3II/I and NCOA4, and the decreased contents of p62 and FTH1 in the hippocampus. Further, we confirmed that inhibition of ferritinophagy by silencing the expression of NCOA4 decreased FA-induced toxic damage in HT22 cells. These results indicated that FA induces neurotoxicity by promoting ferritinophagy. Our findings suggest a potential mechanism insight into the FA-induced neurotoxicity, which in turn provides a new thought for the treatment of FA-related neurodegenerative diseases.
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http://dx.doi.org/10.1177/07482337211048582DOI Listing
November 2021

Sodium hydrosulfide reverses β-microglobulin-induced depressive-like behaviors of male Sprague-Dawley rats: Involving improvement of synaptic plasticity and enhancement of Warburg effect in hippocampus.

Behav Brain Res 2022 Jan 6;417:113562. Epub 2021 Sep 6.

Institute of Neurology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China; Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, PR China. Electronic address:

Background: Our previous works demonstrated that β2-microglobulin (β2m), a systemic pro-aging factor, induce depressive-like behaviors. Hydrogen sulfide (HS) is identified as a potential target for treatment of depression. The aim of the present work is to explore whether HS antagonizes β2m-induced depressive-like behaviors and the underlying mechanisms.

Methods: The depressive-like behaviors were detected using the novelty suppressed feeding test (NSFT), tail suspension test (TST), forced swimming test (FST) and open field test (OFT). The expressions of Warburg-related proteins, including hexokinase II (HK II), pyruvate kinase M2 (PKM2), Lactate dehydrogenase A (LDHA), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase 1(PDK1), and synaptic plasticity-related proteins, including postsynaptic density protein 95 (PSD95) and synaptophysin1 (SYN1), were determined by western blotting.

Result: we found that NaHS (the donor of HS) attenuated the depressive-like behaviors in the β2m-exposed rats, as judged by NSFT, TST, FST, and OFT. We also demonstrated that NaHS enhanced the synaptic plasticity, as evidenced by the upregulations of PSD95 and SYN1 expressions in the hippocampus of β2m-exposed rats. Furthermore, NaHS improved the Warburg effect in the hippocampus of β2m-exposed rats, as evidenced by the upregulations of HK II, PKM2, LDHA and PDK1 expressions, and the downregulation of PDH expression.

Conclusion: HS prevents β2m-induced depressive-like behaviors, which is involved in improvement of hippocampal synaptic plasticity as a result of enhancement of hippocampal Warburg effect.
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http://dx.doi.org/10.1016/j.bbr.2021.113562DOI Listing
January 2022

Effects of high pressure and thermal combinations on gel properties and water distribution of pork batters.

J Food Sci Technol 2021 Aug 4;58(8):3243-3249. Epub 2021 Mar 4.

Henan Institute of Science and Technology, Xinxiang, People's Republic of China.

The effects of high pressure (100-500 MPa) and heated (80 °C, 25 min) combinations on gel properties, rheological characteristic and water distribution of pork batters were investigated. Compared to the only-heat, the cooking yield, * value, hardness, cohesiveness, and chewiness of cooked pork batters treated less than 300 MPa were significantly increased ( < 0.05), meanwhile, the * value was significantly decreased ( < 0.05). Opposite, the color and cooking yield were not significant different ( > 0.05) when over 300 MPa, except the * value. At 300 MPa, the cooking yield, hardness, chewiness, and G' value at 80 °C of pork batter were the highest. The initial relaxation time of T was decreased significantly ( < 0.05), and the peak ration of P was increased significantly ( < 0.05) when treated at 200 and 300 MPa, that indicated the water was bound tightly and the ratio of immobilized water was increased. Overall, 300 MPa treatment and thermal combinations could improve the gel properties of pork batters.
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http://dx.doi.org/10.1007/s13197-021-05051-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249663PMC
August 2021

The catalytic activity of PtCu (n = 1-3, m = 0-2) clusters for methanol dehydrogenation to CO.

J Mol Model 2021 Jul 1;27(7):215. Epub 2021 Jul 1.

College of Chemistry and Chemical Engineering, Key laboratory of Hexi Corridor Resources Utilization of Gansu, Hexi University, Zhangye, 734000, People's Republic of China.

A large number of experiments show that PtCu catalyst has a good catalytic effect on methanol decomposition. Therefore, density functional theory (DFT) was used to further study the dehydrogenation of methanol catalyzed by PtCu (n = 1-3, m = 0-2). The energy diagrams of O-adsorption path and H-adsorption path were drawn. By calculation, the Pt is the active site of the whole reaction process, and the barrier energy of the rate-determining step is 11.09 kcal mol by PtCu, which is lower than that of Pt and PtCu. However, the complete dehydrogenation product of methanol, CO, is easier to dissociate from PtCu clusters than from Pt and PtCu clusters. Therefore, Cu doping can improve the catalytic activity and anti-CO toxicity of Pt to a certain extent.
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http://dx.doi.org/10.1007/s00894-021-04836-8DOI Listing
July 2021

Overexpression of retinoid X receptor beta provides protection against oxidized low-density lipoprotein-induced inflammation via regulating PGC1α-dependent mitochondrial homeostasis in endothelial cells.

Biochem Pharmacol 2021 06 17;188:114559. Epub 2021 Apr 17.

Department of Pharmacology, Nantong University Pharmacy College, Nantong 226001, China. Electronic address:

Retinoid X receptor beta (RXRβ) has been poorly studied in atherosclerosis. The aim of the present study is to explore the function of RXRβ in oxidized low density lipoprotein (ox-LDL)-induced inflammation in endothelial cells and the underlying mechanism. The protein expression of RXRβ in the aorta of atherosclerotic mice was detected. A lentivirus vector for RXRβ overexpression and RNA interference for RXRβ downregulation were constructed and transfected into human aortic endothelial cells (HAECs). The results showed that RXRβ protein expression was downregulated in aorta of high fat diet (HFD)-fed LDLr mice and ox-LDL-treated HAECs. The ox-LDL-induced production of pro-inflammatory cytokines and activations of TLR9/NF-κB and NLRP3/caspase-1 inflammasome pathway were significantly decreased by RXRβ overexpression but increased by RXRβ knockdown in HAECs. The ox‑LDL‑induced mitochondrial damage indicated as the increased generation of mitochondrial ROS, decreased mitochondrial membrane potential and increased mitochondrial DNA release was abolished by RXRβ overexpression but aggravated by RXRβ knockdown. Treatment with mito-TEMPO significantly reduced the increased production of pro-inflammatory cytokines and activations of TLR9/NF-κB and NLRP3/caspase-1 inflammasome induced by RXRβ knockdown in ox-LDL treated HAECs. Moreover, peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α) protein expression was reduced in HFD-fed LDLr mice. RXRβ could interact with PGC1α in HAECs. Ox-LDL-induced reduction of PGC1α was significantly inhibited by RXRβ overexpression and aggravated by RXRβ downregulation. Our further study showed that transfection of PGC1α siRNA abrogated the alleviative effects of RXRβ overexpression on mitochondrial damage and inflammation in ox-LDL treated cells. The present study indicates that RXRβ exerted protective effects against the ox-LDL-induced inflammation may through regulating PGC1α-dependent mitochondrial homeostasis.
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http://dx.doi.org/10.1016/j.bcp.2021.114559DOI Listing
June 2021

Efficacy and Side Effects of Combined Capecitabine Plus Intensity Modulated Radiotherapy as an Effective Adjuvant Therapy for Gastric Cancers.

Iran J Pharm Res 2020 ;19(4):365-371

Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Six People's Hospital, No 600, Yishan Road, Shanghai 200233, China.

This study aims to evaluate the clinical outcomes and the toxicities associated with intensity modulated radiotherapy (IMRT) administered in combination with capecitabine for gastric cancer. This study was conducted between July 2009 and October 2011, and included 31 patients (23 female and eight male patients; mean age: 57 years old) with pathologically confirmed gastric cancer (pathological staging T3 or T4 or positive lymph node). All patients underwent D2 surgery and adjuvant chemoradiotherapy, followed by combined treatment with IMRT and capecitabine. All patients received follow-up examinations every 3-6 months by physical examination, magnetic resonance imaging (MRI), and assays for tumor markers. The Kaplan-Meier method was used to calculate the rates for locoregional control (LRC) and disease-free survival (DFS). Only two patients could not complete the planned treatment regimen. Patients treated with IMRT and capecitabine tolerated their treatment well, and displayed few significant side effects. The mean follow-up, disease-free survival (DFS) and survival times were 33.0, 27.5, and 32.9 months, respectively.This study confirmed that the combined administration of IMRT and capecitabine can be used as an adjuvant therapy for gastric cancer patients, with few toxic side effects.
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http://dx.doi.org/10.22037/ijpr.2019.14622.12542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019857PMC
January 2020

Seasonal Changes in Root-Associated Fungal Microbiota Drive N and P Cycling in Terrestrial Ecosystem.

Front Microbiol 2020 18;11:526898. Epub 2021 Jan 18.

College of Forestry, Northwest A&F University, Yangling, China.

In terrestrial ecosystems, mycorrhizal roots play a key role in the cycling of soil carbon (C) and other nutrients. The impact of environmental factors on the mycorrhizal fungal community has been well studied; however, the seasonal variations in the root-associated fungal microbiota affected by environmental changes are less clear. To improve the understanding of how environmental factors shape the fungal microbiota in mycorrhizal roots, seasonal changes in root-associated fungi were investigated. In the present study, the seasonal dynamics of edaphic properties, soil enzymatic activities, root fungal colonization rates, and root-associated fungal microbiota in forests were studied across four seasons during a whole year to reveal their correlations with environmental changes. The results indicate that the soil functions, such as the enzymatic activities related to nitrogen (N) and phosphorus (P) degradation, were varied with the seasonal changes in microclimate factors, resulting in a significant fluctuation of edaphic properties. In addition, the ectomycorrhizal fungal colonization rate in the host pine tree roots increased during warm seasons (summer and autumn), while the fungal colonization rate of dark septate endophyte was declined. Moreover, the present study indicates that the fungal biomass increased in both the pine roots and rhizospheric soils during warm seasons, while the fungal species richness and diversity decreased. While the Basidiomycota and Ascomycota were the two dominant phyla in both root and soil fungal communities, the higher relative abundance of Basidiomycota taxa presented in warm seasons. In addition, the fungal microbial network complexity declined under the higher temperature and humidity conditions. The present study illustrates that the varieties in connectivity between the microbial networks and in functional taxa of root-associated fungal microbiota significantly influence the soil ecosystem functions, especially the N and P cycling.
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http://dx.doi.org/10.3389/fmicb.2020.526898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849022PMC
January 2021

SIRT1 Mediates HS-Ameliorated Diabetes-Associated Cognitive Dysfunction in Rats: Possible Involvement of Inhibiting Hippocampal Endoplasmic Reticulum Stress and Synaptic Dysfunction.

Neurochem Res 2021 Mar 3;46(3):611-623. Epub 2021 Feb 3.

Department of Neurology, Affiliated Nanhua Hospital, University of South China, No. 336, Dongfeng South Road, Hengyang, 421001, Hunan, People's Republic of China.

Diabetes-associated cognitive dysfunction (DACD) characterized by hippocampal injury increases the risk of major cerebrovascular events and death. Endoplasmic reticulum (ER) stress and synaptic dysfunction play vital roles in the pathological process. At present, no specific treatment exists for the prevention and/or the therapy of DACD. We have recently reported that hydrogen sulfide (HS) exhibits therapeutic potential for DACD, but the underlying mechanism has not been fully elucidated. Silent information regulator 1 (SIRT1) has been shown to play a role in regulating the progression of diabetes and is also indispensable for memory formation and cognitive performance. Hence, the present study was performed to explore whether SIRT1 mediates the protective effect of HS on streptozotocin (STZ)-induced cognitive deficits, an in vivo rat model of DACD, via inhibiting hippocampal ER stress and synaptic dysfunction. The results showed that administration of NaHS (an exogenous HS donor) increased the expression of SIRT1 in the hippocampus of STZ-induced diabetic rats. Then, results proved that sirtinol, a special blocker of SIRT1, abrogated the inhibition of NaHS on STZ-induced cognitive deficits, as appraised by Morris water maze test, Y-maze test, and Novel object recognition behavioral test. In addition, administration of NaHS eliminated STZ-induced ER stress as evidenced by the decreases in the expressions of ER stress-related proteins including glucose-regulated protein 78, C/EBP homologous protein, and cleaved caspase-12 in the hippocampus, while these effects of NaHS were also reverted by sirtinol. Furthermore, the NaHS-induced up-regulation of hippocampal synapse-related protein (synapsin-1, SYN1) expression in STZ-induced diabetic rats was also abolished by sirtinol. Taken together, these results demonstrated that SIRT1 mediates the protection of HS against cognitive dysfunction in STZ-diabetic rats partly via inhibiting hippocampal ER stress and synaptic dysfunction.
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http://dx.doi.org/10.1007/s11064-020-03196-8DOI Listing
March 2021

A Prediction Model for Optimal Primary Debulking Surgery Based on Preoperative Computed Tomography Scans and Clinical Factors in Patients With Advanced Ovarian Cancer: A Multicenter Retrospective Cohort Study.

Front Oncol 2020 7;10:611617. Epub 2021 Jan 7.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: This study assessed the predictive value of preoperative computed tomography (CT) scans and clinical factors for optimal debulking surgery (ODS) in patients with advanced ovarian cancer (AOC).

Methods: Patients with AOC in International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent primary debulking surgery (PDS) between 2016 and 2019 from nine tertiary Chinese hospitals were included. Large-volume ascites, diffuse peritoneal thickening, omental cake, retroperitoneal lymph node enlargement (RLNE) below and above the inferior mesenteric artery (IMA), and suspected pelvic bowel, abdominal bowel, liver surface, liver parenchyma and portal, spleen, diaphragm and pleural lesions were evaluated on CT. Preoperative factors included age, platelet count, and albumin and CA125 levels.

Results: Overall, 296 patients were included, and 250 (84.5%) underwent ODS. The prediction model included age >60 years (=0.016; prediction index value, PIV=1), a CA125 level >800 U/ml (=0.033, PIV=1), abdominal bowel metastasis (=0.034, PIV=1), spleen metastasis (<0.001, PIV=2), diaphragmatic metastasis (=0.014, PIV=2), and an RLNE above the IMA (<0.001, PIV=2). This model had superior discrimination (AUC=0.788>0.750), and the Hosmer-Lemeshow test indicated its stable calibration (=0.600>0.050). With the aim of maximizing the accuracy of prediction and minimizing the rate of inappropriate explorations, a total PIV ≥5 achieved the highest accuracy of 85.47% and identified patients who underwent suboptimal PDS with a specificity of 100%.

Conclusions: We developed a prediction model based on two preoperative clinical factors and four radiological criteria to predict unsatisfactory debulking surgery in patients with AOC. The accuracy of this prediction model needs to be validated and adjusted in further multicenter prospective studies.
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http://dx.doi.org/10.3389/fonc.2020.611617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819136PMC
January 2021

Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia.

Liver Int 2021 06 19;41(6):1254-1264. Epub 2021 Jan 19.

Department of Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

Background And Aims: About 20% of patients receiving nucleos(t)ide analogues treatment experienced low-level viraemia (LLV), which is associated with progression of liver fibrosis and high risk of hepatocellular carcinoma. We aimed to evaluate the effectiveness and safety of switching from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in ETV-treated patients with LLV.

Methods: In this prospective study, ETV-treated patients with LLV, presented to our hospital from December 2018 to October 2019, were enrolled. Switching to TAF or continuing ETV was given. The primary effectiveness endpoint was complete virological response (CVR) at 24 weeks, and the safety endpoint was the first occurrence of any clinical adverse event during the treatment.

Results: Totally, 211 patients were recruited and propensity score matching (PSM) generated 75 patients in either TAF or ETV group. After PSM, baseline characteristics were balanced in two groups. After 24-week treatment, the CVR and ALT normalization in TAF group were 62.7% and 47.6%, which were higher than 9.3% and 10.5% in ETV group (OR 16.4, 95% CI 6.6-40.0, P < .001) respectively. Subgroup analysis showed that switching to TAF achieved favours CVR regardless of the status of sex, age, CHB family history, HBV DNA, HBeAg and cirrhosis, whereas alcohol consumption and diabetes mellitus might compromise the CVR of switching to TAF. Both therapies were well tolerated and had satisfying renal safety.

Conclusions: For ETV-treated patients with LLV, switching to TAF is safe enough and superior compared with continuing ETV monotherapy regarding both virological and biochemical benefits.
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http://dx.doi.org/10.1111/liv.14786DOI Listing
June 2021

Formaldehyde induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect.

Toxicology 2021 01 28;448:152650. Epub 2020 Nov 28.

Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, PR China; Institute of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, PR China. Electronic address:

The mechanisms underlying formaldehyde (FA)-induced neurotoxicity have not yet been fully clarified. Ferroptosis is a novel regulatory cell death and the Warburg effect is involved in regulating neural function. In this study, we investigated whether FA-induced neurotoxicity is implicated in neuronal ferroptosis and determined whether the Warburg effect mediates FA-induced neuronal ferroptosis. We found that FA (0.1, 0.5 and 1.0 mM, 6 h) induced cell death in HT22 cells (a cell line of mouse hippocampal neuron), as evidenced by a decrease in cell viability and an increase in cell mortality; enhanced oxidative stress, as evidenced by a decrease in glutathione (GSH) and increases in malondialdehyde (MDA), 4-Hydroxynonenal (4-HNE), as well as reactive oxygen species (ROS); increased the iron content; and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells. Meanwhile, we found that FA (0.1, 1, 10 μmol) decreased the cross-sectional of mitochondria, increased the level of lipid ROS and iron content in primary hippocampal cells. We showed that FA (0.1, 0.5 and 1.0 mM, 6 h) upregulated the Warburg effect in HT22 cells, as evidenced by up-regulations of pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK-1), and lactate dehydrogenase (LDHA) proteins; down-regulation of pyruvate dehydrogenase (PDH); and an increase in lactate production. Also, we found that FA (0.1, 1, 10 μmol, 7 d) upregulated the Warburg effect in hippocampal tissue, as evidenced by up-regulations of PKM2, PDK-1, and LDHA proteins; down-regulation of PDH. Furthermore, the inhibition of the Warburg effect by dichloroacetate (DCA) protected HT22 cells against FA-induced ferroptosis and cell death. Collectively, these data indicated that FA induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect.
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http://dx.doi.org/10.1016/j.tox.2020.152650DOI Listing
January 2021

Effect of Recombinant Human Granulocyte Colony-Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and Lymphopenia: A Randomized Clinical Trial.

JAMA Intern Med 2021 01;181(1):71-78

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

Importance: Lymphopenia is common and correlates with poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19).

Objective: To determine whether a therapy that increases peripheral blood leukocyte and lymphocyte cell counts leads to clinical improvement in patients with COVID-19.

Design, Setting And Participants: Between February 18 and April 10, 2020, we conducted an open-label, multicenter, randomized clinical trial at 3 participating centers in China. The main eligibility criteria were pneumonia, a blood lymphocyte cell count of 800 per μL (to convert to ×109/L, multiply by 0.001) or lower, and no comorbidities. Severe acute respiratory syndrome coronavirus 2 infection was confirmed with reverse-transcription polymerase chain reaction testing.

Exposures: Usual care alone, or usual care plus 3 doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF, 5 μg/kg, subcutaneously at days 0-2).

Main Outcomes And Measures: The primary end point was the time from randomization to improvement of at least 1 point on a 7-category disease severity score.

Results: Of 200 participants, 112 (56%) were men and the median (interquartile range [IQR]) age was 45 (40-55) years. There was random assignment of 100 patients (50%) to the rhG-CSF group and 100 (50%) to the usual care group. Time to clinical improvement was similar between groups (rhG-CSF group median of 12 days (IQR, 10-16 days) vs usual care group median of 13 days (IQR, 11-17 days); hazard ratio, 1.28; 95% CI, 0.95-1.71; P = .06). For secondary end points, the proportion of patients progressing to acute respiratory distress syndrome, sepsis, or septic shock was lower in the rhG-CSF group (rhG-CSF group, 2% vs usual care group, 15%; difference, -13%; 95%CI, -21.4% to -5.4%). At 21 days, 2 patients (2%) had died in the rhG-CSF group compared with 10 patients (10%) in the usual care group (hazard ratio, 0.19; 95%CI, 0.04-0.88). At day 5, the lymphocyte cell count was higher in the rhG-CSF group (rhG-CSF group median of 1050/μL vs usual care group median of 620/μL; Hodges-Lehmann estimate of the difference in medians, 440; 95% CI, 380-490). Serious adverse events, such as sepsis or septic shock, respiratory failure, and acute respiratory distress syndrome, occurred in 29 patients (14.5%) in the rhG-CSF group and 42 patients (21%) in the usual care group.

Conclusion And Relevance: In preliminary findings from a randomized clinical trial, rhG-CSF treatment for patients with COVID-19 with lymphopenia but no comorbidities did not accelerate clinical improvement, but the number of patients developing critical illness or dying may have been reduced. Larger studies that include a broader range of patients with COVID-19 should be conducted.

Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000030007.
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http://dx.doi.org/10.1001/jamainternmed.2020.5503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489414PMC
January 2021

Increases of iASPP-Keap1 interaction mediated by syringin enhance synaptic plasticity and rescue cognitive impairments via stabilizing Nrf2 in Alzheimer's models.

Redox Biol 2020 09 10;36:101672. Epub 2020 Aug 10.

Translational Medicine Laboratory, Basic College of Medicine, Jilin Medical University, Jilin, 132013, China.

Oxidative stress is an important pathogenic manifestation of Alzheimer's disease (AD) that contributes to synaptic dysfunction, which precedes Aβ accumulation and neurofibrillary tangle formation. However, the molecular machineries that govern the decline of antioxidative defence in AD remains to be elucidated, and effective candidate for AD treatment is limited. Here, we showed that the decreases in the inhibitor of apoptosis-stimulating protein of p53 (iASPP) was associated with the vulnerability to oxidative stress in the amyloid precursor protein (APP)/presenilin 1 (PS1) mouse brain. Treatment with an antioxidant, syringin, could ameliorate AD-related pathologic and behavioural impairments. Interestingly, syringin treatment resulted in an upregulation of iASPP and the increase in the interaction of iASPP with Kelchlike ECH-associating protein 1 (Keap1). Syringin reduced neuronal apoptosis independently of p53. We confirmed that syringin-induced enhancement of antioxidant defenses involved the stabilization of Nrf2 in overexpressing human Swedish mutant APP (APPswe) cells in vitro. Syringin-mediated Nrf2 nuclear translocation facilitated the activation of the Nrf2 downstream genes via iASPP/Nrf2 axis. Our results demonstrate that syringin-mediated increases of iASPP-Keap1 interaction restore cellular redox balance. Further study on the syringin-iASPP interactions may help in understanding the regulatory mechanism and designing novel potent modulators for AD treatment.
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http://dx.doi.org/10.1016/j.redox.2020.101672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452088PMC
September 2020

Recommended prophylactic and management strategies for severe acute respiratory syndrome coronavirus 2 infection in transplant recipients.

Chronic Dis Transl Med 2020 Jun 27;6(2):87-97. Epub 2020 Mar 27.

State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.

Since December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.
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http://dx.doi.org/10.1016/j.cdtm.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194659PMC
June 2020

Development of a Real-Time TaqMan PCR Method for Absolute Quantification of the Biocontrol Agent .

Plant Dis 2020 Jun 20;104(6):1694-1700. Epub 2020 Apr 20.

Department of Food Science and Technology, College of Agriculture and Biotechnology, Chungnam National University, Daejeon 34134, South Korea.

has been used as an effective biocontrol agent for the management of the pinewood nematode, . Tools for monitoring the colonization and parasitism patterns of are required for the development of highly effective biocontrol strategies. Because the TaqMan PCR technique is effective for quantification of species in environmental samples, a real-time PCR-based methodology was developed for absolute quantification of via internal standard addition and extrapolation of DNA quantity to hyphal length. Primers and a probe for the 28S ribosomal RNA gene of were designed, and nested TaqMan real-time PCR-based quantification was performed. In addition, internal standard-based yield measurement was correlated to the absolute quantity of target genomic DNA. Moreover, an extrapolation curve obtained by optical microscopy and image analysis of the mycelia was constructed for the measurement of fungal hyphal length. The absolute quantification method developed in the present study provides a sensitive and accurate technique to quantify fungal density in either wood or other substrate samples and can be used as an effective tool for future studies of biocontrol agents.
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http://dx.doi.org/10.1094/PDIS-10-19-2076-REDOI Listing
June 2020

In vivo infection of Bursaphelenchus xylophilus by the fungus Esteya vermicola.

Pest Manag Sci 2020 Aug 19;76(8):2854-2864. Epub 2020 May 19.

Department of Food Science and Technology, College of Agriculture and Biotechnology, Chungnam National University, Daejeon, South Korea.

Background: As the causal agent of pine wilt disease, Bursaphelenchus xylophilus, is a serious pathogen of forest pine trees. Esteya vermicola is a nematophagous fungus of B. xylophilus and exhibits great potential as a biological control agent. However, the in vivo infection mechanism of E. vermicola on B. xylophilus is unclear. Experiments were conducted to study the colonization of host plant and infection of B. xylophilus by E. vermicola inside pine tree xylem.

Results: A green fluorescent protein (GFP)-tagged E. vermicola transformant was constructed as a biomarker to study the in vivo colonization and infection of B. xylophilus in pine trees. The in vitro infection of B. xylophilus by E. vermicola was observed through GFP expression. The bacilloid conidia produced by trophic hyphae in the body of the nematode are described. Additionally, the monitoring of in vivo colonization by GFP-tagged E. vermicola showed the germination and hyphal extension of this fungus after inoculation. Moreover, B. xylophilus infected by this biocontrol agent were extracted from healthy seedlings and observed in the xylem of trees that were wilting due to pine wilt disease.

Conclusion: Evidence of fungal colonization and infection of B. xylophilus by E. vermicola is provided to improve our understanding of the in vivo infection mechanisms used by this nematophagous fungus against B. xylophilus. The infection of B. xylophilus by E. vermicola was inferred to begin with the implantation of propagules, and this inference will require future investigation. The colonization of Esteya vermicola in host pine tree xylem and the in vivo infection of pinewood nematode by E. vermicola were investigated using the green fluorescence protein transformant. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5839DOI Listing
August 2020

Hydrogen Sulfide Prevents Sleep Deprivation-Induced Hippocampal Damage by Upregulation of Sirt1 in the Hippocampus.

Front Neurosci 2020 11;14:169. Epub 2020 Mar 11.

Institute of Neurology, The First Affiliated Hospital, University of South China, Hengyang, China.

Sleep deprivation (SD) induces hippocampal damage. Hydrogen sulfide (HS) is a neuronal protective factor. Silence information regulating factor 1 (Sirt1) plays an important role in neuroprotection. Therefore, this study was aimed at exploring whether HS meliorates SD-induced hippocampal damage and whether Sirt1 mediates this protective role of HS. We found that sodium hydrosulfide (NaHS, a donor of HS) alleviated SD-generated hippocampal oxidative stress, including increases in the activation of SOD and the level of GSH as well as a decrease in the level of MDA. Meanwhile, we found that NaHS reduced SD-exerted hippocampal endoplasmic reticulum (ER) Stress, including downregulations of GRP78, CHOP, and cleaved-caspase-12 expression. Moreover, NaHS reduced the apoptosis in the SD-exposed hippocampus, and this included decreases in the number of apoptotic cells and the activation of caspase-3, downregulation of Bax expression, and upregulation of Bcl-2 expression. NaHS upregulated the expression of Sirt1 in the hippocampus of SD-exposed rats. Furthermore, Sirtinol, the inhibitor of Sirt1, abrogated the protection of NaHS against SD-exerted hippocampal oxidative stress, ER stress, and apoptosis. These results suggested that HS alleviates SD-induced hippocampal damage by upregulation of hippocampal Sirt1.
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http://dx.doi.org/10.3389/fnins.2020.00169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078349PMC
March 2020

Catalpol Exerts a Neuroprotective Effect in the MPTP Mouse Model of Parkinson's Disease.

Front Aging Neurosci 2019 15;11:316. Epub 2019 Nov 15.

Department of Neurology, the First Hospital of China Medical University, Shenyang, China.

The degeneration of dopaminergic (DA) neurons in Parkinson's disease (PD) is related to inflammation and oxidative stress. Anti-inflammatory agents could reduce the risk or slow the progression of PD. Catalpol, an iridoid glycoside extracted from the roots of radix, has been reported to reduce the release of inflammatory factors and exert neuroprotective effects. 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated mice were used as the PD model and the roles of catalpol on DA neurons and its potential mechanism were investigated in this study. We found that catalpol administration mitigated the loss of DA neurons induced by MPTP and increased exploratory behavior along with tyrosine hydroxylase (TH) expression, which was accompanied by astrocyte and microglia activation. Importantly, catalpol administration significantly inhibited MPTP-triggered oxidative stress, restored growth-associated protein 43 (GAP43) and vascular endothelial growth factor (VEGF) levels. Further, we found that catalpol suppressed the activation of MKK4/JNK/c-Jun signaling, and reduced the pro-inflammatory factors and inflammasome in the mouse model of PD. Our results suggest that catalpol relieves MPTP-triggered oxidative stress, which may benefit to avoid the occurrence of chronic inflammatory reaction. Catalpol alleviates MPTP-triggered oxidative stress and thereby prevents neurodegenerative diseases-related inflammatory reaction, highlighting its therapeutic potential for the management of PD symptoms.
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http://dx.doi.org/10.3389/fnagi.2019.00316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889905PMC
November 2019

BDNF-TrkB pathway mediates antidepressant-like roles of H S in diabetic rats via promoting hippocampal autophagy.

Clin Exp Pharmacol Physiol 2020 02 24;47(2):302-312. Epub 2019 Nov 24.

Department of Neurology, Affiliated Nanhua Hospital, University of South China, Hengyang, China.

Hydrogen sulfide (H S) plays antidepressant-like roles in diabetic rats. However, the underlying mechanisms remain unclear. Brain-derived neurotropic factor (BDNF), a neurotrophic factor, plays important regulatory roles in depression by its high-affinity tropomysin-related kinase B (TrkB) receptor. Autophagy also is implicated in modulation of depression. Previous work confirmed the modulatory roles of H S in BDNF protein expression and autophagy. Thus, in this study, we explored whether the BDNF-TrkB pathway mediates the antidepressant-like effects of H S in diabetic rats and whether this process is achieved via promoting hippocampal autophagy. We demonstrated that H S upregulated the expressions of BDNF and p-TrkB proteins in the hippocampus of streptozotocin (STZ)-induced diabetic rats. K252a (an inhibitor of BDNF-TrkB pathway) reversed the antidepressant-like roles of H S, as evidenced by the tail suspension, forced swimming, novelty suppressed feeding, and elevated plus-maze tests. Furthermore, K252a abolished H S-promoted hippocampal autophagy in diabetic rats, as evidenced by a decrease in the number of autolysosome, downregulation of Beclin-1 (a regulator of autophagy in the early stage of the formation of autophagosomal membranes and its level is positively correlated with autophagic activity) expression, and upregulation of P62 (a substrate of autophagic degradation and its level is inversely correlated with autophagic activity) expression, in the hippocampus of rats co-treated with NaHS and STZ. Taken together, these data indicated that the BDNF-TrkB pathway mediates the antidepressant-like roles of H S in diabetic rats by enhancing hippocampal autophagy.
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http://dx.doi.org/10.1111/1440-1681.13201DOI Listing
February 2020

[Advances in mechanisms of nutrient exchange between mycorrhizal fungi and host plants].

Ying Yong Sheng Tai Xue Bao 2019 Oct;30(10):3596-3604

College of Forestry, Northwest A&F University, Yangling 712100, Shaanxi, China.

Mycorrhizae, formed through the colonization of soil mycorrhizal fungi into the roots of host plants, are common symbiosis in the terrestrial ecosystems. The establishment of mycorrhizae is mainly based on the bidirectional nutrient exchanges between the symbiotic partners. Mycorrhizal fungi can absorb mineral nutrients, such as nitrogen and phosphorus, from soil and transport them to the host plants for their growth. As an exchange, host plants supply mycorrhizal fungi with the carbohydrates in the form of lipids or sugars, which are essential for fungal growth. In recent years, the mechanism of nutrient exchange between the mycorrhizal fungi and host plants has been a hot research topic. Important progresses have been achieved in mechanisms of host plants nutrient uptake and transport mediated by the mycorrhizal fungi. In this review, recent advances in nutrient exchange between arbuscular mycorrhizal fungi, ectomycorrhizal fungi and host plants were summarized, especially in the absorption and bidirectional transfer mechanisms of important nutrients, such as carbon, nitrogen and phosphorus. The potential regulatory effects of nutrient exchange in the mycorrhizal development were also reviewed. In addition, key problems and prospects of related researches were analyzed. This paper would be meaningful for the establishment of mycorrhizal model and the optimization of mycorrhizal effects.
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http://dx.doi.org/10.13287/j.1001-9332.201910.034DOI Listing
October 2019

Dietary inulin decreases circulating ceramides by suppressing neutral sphingomyelinase expression and activity in mice.

J Lipid Res 2020 01 11;61(1):45-53. Epub 2019 Oct 11.

Superfund Research Center, University of Kentucky, Lexington, KY 40536; Department of Animal and Food Sciences, College of Agriculture, Food, and Environment, University of Kentucky, Lexington, KY 40536. Electronic address:

Elevated circulating levels of ceramides (Cers) are associated with increased risk of cardiometabolic diseases, and Cers may play a causative role in metabolic dysfunction that precedes cardiac events, such as mortality as a result of coronary artery disease. Although the mechanisms involved are likely complex, these associations suggest that lowering circulating Cer levels could be protective against cardiovascular diseases. Conversely, dietary fibers, such as inulin, have been reported to promote cardiovascular and metabolic health. However, the mechanisms involved in these protective processes also are not well understood. We studied the effects of inulin on lipid metabolism with a model of atherosclerosis in LDL receptor-deficient mice using lipidomics and transcriptomics. Plasma and tissues were collected at 10 days and/or 12 weeks after feeding mice an atherogenic diet supplemented with inulin or cellulose (control). Compared with controls, inulin-fed mice displayed a decreased C16:0/C24:0 plasma Cer ratio and lower levels of circulating Cers associated with VLDL and LDL. Liver transcriptomic analysis revealed that , a gene that encodes neutral SMase (NSMase), was downregulated by 2-fold in inulin-fed mice. Hepatic NSMase activity was 3-fold lower in inulin-fed mice than in controls. Furthermore, liver redox status and compositions of phosphatidylserine and FFA species, the major factors that determine NSMase activity, were also modified by inulin. Taken together, these results showed that, in mice, inulin can decrease plasma Cer levels through reductions in NSMase expression and activity, suggesting a mechanism by which fiber could reduce cardiometabolic disease risk.
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http://dx.doi.org/10.1194/jlr.RA119000346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939596PMC
January 2020

Hydrogen Sulfide Inhibits High Glucose-Induced Neuronal Senescence by Improving Autophagic Flux Up-regulation of SIRT1.

Front Mol Neurosci 2019 20;12:194. Epub 2019 Aug 20.

Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, China.

Hyperglycemia, a key characteristic and risk factor for diabetes mellitus (DM), causes neuronal senescence. Hydrogen sulfide (HS) is a novel neuroprotectant. The present work was to investigate the potential effect of HS on hyperglycemia-induced neuronal senescence and the underlying mechanisms. We found that NaHS, a donor of HS, inhibited high glucose (HG)-induced cellular senescence in HT22 cells (an immortalized mouse hippocampal cell line), as evidenced by a decrease in the number of senescence associated-β-galactosidase (SA-β-gal) positive cells, increase in the growth of cells, and down-regulations of senescence mark proteins, p16 and p21. NaHS improved the autophagic flux, which is judged by a decrease in the amount of intracellular autophagosome as well as up-regulations of LC3II/I and P62 in HG-exposed HT22 cells. Furthermore, blocked autophagic flux by chloroquine (CQ) significantly abolished NaHS-exerted improvement in the autophagic flux and suppression in the cellular senescence of GH-exposed HT22 cells, which indicated that HS antagonizes HG-induced neuronal senescence by promoting autophagic flux. We also found that NaHS up-regulated the expression of silent mating type information regulation 2 homolog 1 (SIRT1), an important anti-aging protein, in HG-exposed HT22 cells. Furthermore, inhibition of SIRT1 by sirtinol reversed the protection of HS against HG-induced autophagic flux blockade and cellular senescence in HT22 cells. These data indicated that HS protects HT22 cells against HG-induced neuronal senescence by improving autophagic flux up-regulation of SIRT1, suggesting HS as a potential treatment strategy for hyperglycemia-induced neuronal senescence and neurotoxicity.
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http://dx.doi.org/10.3389/fnmol.2019.00194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710442PMC
August 2019

Chitin deacetylase 1 and 2 are indispensable for larval-pupal and pupal-adult molts in Heortia vitessoides (Lepidoptera: Crambidae).

Comp Biochem Physiol B Biochem Mol Biol 2019 Nov 24;237:110325. Epub 2019 Aug 24.

College of Forestry and Landscape Architecture, South China Agricultural University, 483 Wushan Road, Guangdong Province, Guangzhou 510642, China. Electronic address:

Heortia vitessoides Moore is a notorious defoliator of Aquilaria sinensis (Lour.) Gilg trees. Chitin deacetylases (CDAs) catalyze the N-deacetylation of chitin, which is a crucial process for chitin modification. Here, we identified and characterized HvCDA1 and HvCDA2 from H. vitessoides. HvCDA1 and HvCDA2 possess typical domain structures of CDAs and belong to the Group I CDAs. HvCDA1 and HvCDA2 were highly expressed before and after the larval-larval molt. In addition, both exhibited relatively high mRNA expression levels during the larval-pupal molt, the pupal stage, and the pupal-adult molt. HvCDA1 and HvCDA2 transcript expression levels were highest in the body wall and relatively high in the larval head. Significant increases in the HvCDA1 and HvCDA2 transcript expression levels were observed in the larvae upon exposure to 20-hydroxyecdysone. RNA interference-mediated HvCDA1 and HvCDA2 silencing significantly inhibited HvCDA1 and HvCDA2 expression, with abnormal or nonviable phenotypes being observed. Post injection survival rates of the larvae injected with dsHvCDA1 and dsHvCDA2 were 66.7% and 46.7% (larval-pupal) during development and 23.0% and 6.7% (pupal-adult), respectively. These rates were significantly lower than those of the control group insects. Our results suggest that HvCDA1 and HvCDA2 play important roles in the larval-pupal and pupal-adult transitions and represent potential targets for the management of H. vitessoides.
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http://dx.doi.org/10.1016/j.cbpb.2019.110325DOI Listing
November 2019

Glial S100A6 Degrades β-amyloid Aggregation through Targeting Competition with Zinc Ions.

Aging Dis 2019 Aug 1;10(4):756-769. Epub 2019 Aug 1.

1Institute of Health Sciences, Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, Shenyang 110122, China.

Evidence has been accumulating that zinc ions can trigger β-amyloid (Aβ) deposition and senile plaque formation in the brain, a pathological hallmark of Alzheimer's disease (AD). Chelating zinc inhibits Aβ aggregation and may hold promise as a therapeutic strategy for AD. S100A6 is an acidic Ca/Zn-binding protein found only in a small number of astrocytes in the normal brain. However, in the AD brain, S100A6 is highly expressed in astrocytes around Aβ plaques. The role of the astrocytic S100A6 upregulation in AD is unknown. In the present study, we examined the effects of S100A6 on Aβ plaques and intracellular zinc levels in a mouse model of AD. Chronic exposure to zinc increased Aβ deposition and S100A6 expression, both reversible by the zinc chelator clioquinol, in the brains of amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice. To examine whether exogenous S100A6 could induce Aβ plaque disaggregation through competition for zinc in vitro, we incubated APP/PS1 mouse brain sections with recombinant human S100A6 protein or co-incubated them with human S100A6-expressing cells. Both treatments efficiently reduced the Aβ plaque burden in situ. In addition, treatment with exogenous S100A6 protected cultured COS-7 cells against zinc toxicity. Our results show for the first time that increased S100A6 levels correlate with both Aβ disaggregation and decrease of Aβ plaque-associated zinc contents in brain sections with AD-like pathology. Astrocytic S100A6 in AD may protect from Aβ deposition through zinc sequestration.
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http://dx.doi.org/10.14336/AD.2018.0912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675528PMC
August 2019

Clinical efficacy of low-dose rituximab on hematological abnormalities in patients with connective tissue disease
.

Int J Clin Pharmacol Ther 2019 Oct;57(10):500-505

Objective: To evaluate the efficacy and safety of low-dose rituximab in the treatment of hematologic abnormalities in patients with connective tissue disease.

Materials And Methods: A total of 13 patients with connective tissue disease who did not respond to prednisolone and multiple immunosuppressive agents, or their disease recurred after treatment, were given 100 mg of rituximab only combined with prednisolone once a week for 4 weeks. Then, the therapeutic effects and adverse reactions were respectively observed in the 13 patients.

Results: Rituximab showed good and rapid efficacy in the treatment of refractory thrombocytopenia and autoimmune hemolytic anemia caused by systemic lupus erythematosus, Sjögren's syndrome, and mixed connective tissue disease. Only 1 patient had urinary tract infection. During 24-month follow-up, disease recurred in 7 patients who still responded to azathioprine/.

Conclusion: Low-dose rituximab has good efficacy and safety in the treatment of hematologic abnormalities in patients with connective tissue disease.
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http://dx.doi.org/10.5414/CP203453DOI Listing
October 2019

Refractory adult-onset Still disease treated by tocilizumab combined with methotrexate: A STROBE-compliant article.

Medicine (Baltimore) 2019 Aug;98(32):e16682

Department of Rheumatology and Immunology, Lanzhou University Second Hospital, Lanzhou, China.

Some patients have poor response to adult-onset Still disease (AOSD) traditional treatment, which easily recurs during the reduction of prednisone. We observed the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory AOSD, and to explore the possibility of reducing the dosage of tocilizumab after disease control.A total of 28 refractory AOSD cases who had an inadequate response to corticosteroids combined with at least 1 traditional immunosuppressive agent, and even large-dose prednisone could not relieve their conditions after recurrence, were selected in this study. They were treated with tocilizumab (intravenous 8 mg/kg) combined with MTX (oral 12.5 mg once a week). In detail, tocilizumab was firstly given every 4 weeks and after 6-month remission, it was then given every 8 weeks. Some items including body temperature, skin rash, joint swelling and pain, hepatosplenomegaly, blood routine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and dosage of prednisone were observed before treatment as well as 2, 4, 8, 12, 24, 36, and 48 weeks after treatment. The adverse reactions occurring during the treatment were recorded.The body temperature was normal, the skin rash as well as joint swelling and pain disappeared, and laboratory indexes including CRP, ESR, white blood cell, neutrophilic granulocyte, platelet, hemoglobin, and ferritin were significantly improved after 8-week treatment (all P < .05). The clinical symptoms and laboratory indexes above mentioned were continuously improved 12, 24, 36, and 48 weeks after treatment. The mean dosage of prednisone was reduced from 71.4 ± 20.7 mg/day to 55.0 ± 11.1 mg/day after 2-week treatment, and to 3.3 ± 2.1 mg/day after 48-week treatment (all P < .05). Prednisone was discontinued in 5 cases after 36-week treatment and in 7 cases after 48-week treatment. No serious adverse reactions occurred during the treatment.Tocilizumab can rapidly and markedly improve the clinical symptoms and laboratory indexes and contribute to reduction and discontinuation of prednisone in refractory AOSD. The patients' conditions are stable after reduction or discontinuation of prednisone and the tocilizumab possesses good safety.
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http://dx.doi.org/10.1097/MD.0000000000016682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708626PMC
August 2019

Liquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: A case report.

World J Clin Cases 2019 May;7(10):1200-1205

Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.

Background: Licorice-induced severe hypokalemic rhabdomyolysis is clinically rare. Gitelman syndrome (GS) is the most common inherited renal tubular disease, while diabetes is one of the most prevalent diseases in the world. Recently, some studies have found that GS patients had higher diabetic morbidity. However, the coexistence of these three diseases has yet to be reported.

Case Summary: We report the case of a 62-year-old Chinese man who was admitted with weakness in the extremities, muscle pain, and dark-colored urine. He had consumed liquorice water daily for seven days prior to admission. The laboratory tests revealed a serum potassium level of 1.84 mmol/L, magnesium 0.68 mmol/L, creatinine phosphokinase (CK) 10117 IU/L, and marked hemoglobinuria. Fractional chloride excretion and fractional magnesium excretion were increased. Plasma renin activity and aldosterone concentration were within the normal ranges. Sequence analysis of the gene revealed that he had compound heterozygous mutations. The diagnosis of liquorice-induced severe hypokalemic rhabdomyolysis with GS and diabetes was thus genetically confirmed. Serum potassium and CK quickly improved with potassium replacement therapy, hydration, and discontinuation of liquorice ingestion. Upon follow-up at 3 mo, the levels of CK, myoglobin, and potassium remained normal, and magnesium was above 0.6 mmol/L.

Conclusion: This case emphasizes that liquorice consumption and GS should be considered causes of hypokalemia and that the diabetic status of GS patients should be noted in the clinic.
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http://dx.doi.org/10.12998/wjcc.v7.i10.1200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547317PMC
May 2019

Enhancing autophagy protects platelets in immune thrombocytopenia patients.

Ann Transl Med 2019 Apr;7(7):134

Department of Hematology, Qilu Hospital, Shandong University, Ji'nan 250012, China.

Background: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder and involves increased apoptosis of platelets. Autophagy is an essential process for platelets to maintain their life and physiological functions. However, the role of autophagy in ITP platelets was previously unclear.

Methods: In the present study, the expression of autophagy-related protein and autophagy flux were detected in platelets from ITP patients and healthy controls by immunofluorescence staining and immunoblotting, and the influence of autophagy on the viability and apoptosis of ITP platelets was further explored.

Results: We found that platelet autophagy was diminished in ITP patients. Platelet autophagy in ITP was regulated by the PI3K/AKT/mTOR pathway, with mTOR (mammalian target of rapamycin) as a negative regulator and class III PtdIns3K playing a crucial role in the process. Importantly, the small-molecule compound ABO (6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine) enhanced autophagy in ITP platelets. Enhancing platelet autophagy alleviated platelet destruction by inhibiting apoptosis and improving platelet viability.

Conclusions: These results suggest a role for autophagy regulation in the pathogenesis of ITP, and offer a novel treatment for these patients.
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http://dx.doi.org/10.21037/atm.2019.03.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511561PMC
April 2019
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