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Shanglong Kou

Shenzhen Goodix Technology (China)

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Yanchao Pan

Xinhui People's Hospital

Jing Yuan

Shijiazhuang Yiling Pharmaceutical (China)

Xiaohe Li

Tianjin International Joint Academy of Biomedicine

Yanhua Liang

Guangdong Academy of Medical Sciences

Matthew T.V. Chan

Chinese University of Hong Kong

William K.K. Wu

Chinese University of Hong Kong

Tony Gin

Chinese University of Hong Kong

Idy H. T. Ho

Chinese University of Hong Kong

Lei Liu

General Hospital of Central Theater Command

Jun Yu

Chinese University of Hong Kong

Cooperative Institutions

Chinese University of Hong Kong

Shenzhen Third People’s Hospital

Chinese Academy of Sciences

Southern University of Science and Technology

University of Hong Kong

University of Chinese Academy of Sciences

Sun Yat-sen University

Guangzhou Institutes of Biomedicine and Health

Capital Medical University

Peking University

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Generation of non-integrated induced pluripotent stem cells from a 59-year-old female with multiple endocrine neoplasia type 1 syndrome

Stem Cell Research (2016)

Dongsheng Guo Feima Wu Hai‐Kun Liu Ge Gao Shanglong Kou

Urine resource cells were collected from a 59-year-old female patient with multiple endocrine neoplasia type 1 syndrome (MEN1) for generating iPS cells with episomal plasmids carrying Oct4, Sox2, Klf4 and miR-302-367. The patient sustained a heterozygous G>T transition mutation on the exon 9 of Men1 gene that was confirmed by sequencing analysis on the obtained iPSC lines. Karyotyping indicated the chromosomes with normal appearances and numbers. Their pluripotency was demonstrated by gene expression, as well as their abilities for differentiating into three germ layers. This cell line provides an ideal model for studying MEN1.

MEN1

KLF4

Enteroendocrine cell

Germ layer

10.1016/j.scr.2016.12.009

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Citations (10)

Differences on Pyrexia Related Immune Responses Between COVID-19 and Influenza A Children

Research Square (Research Square) (2020)

Shanglong Kou Senlin Zhan Xiaohe Li Mingxia Zhang Guofang Deng

Abstract Background: Coronavirus disease-2019 has brought rapid challenge to the current health care system raising millions of infected patients globally. The clinical manifestations of asymptomatic patients especially children and young people will contribute to the management of current pandemic. Methods: To provide precise and comprehensive information on the less symptomatic COVID-19 children, total 62 hospitalized children aged 1-14 years with confirmation infection of either SARS-CoV-2 or influenza A were enrolled for past half of year from September 2019 to February 2020. The epidemiological, demographic, clinical, radiologic and laboratory findings were extracted from the electronic medical records of the patients. Results: We reported less fever (43.33% vs 100%, p<0.001) with lower body temperature (p<0.001) and hypoinflammatory responses occurred in COVID-19 children in comparison with influenza infection. We further showed the significant correlations between initial body temperature and multiple immune parameters to imply the role of thermoregulation on asymptomatic COVID-19 children. Conclusions: COVID-19 children were more likely to have mild symptoms and relatively slow progression. Furthermore, correlations between initial body temperature and immunological functional parameters suggested that non-susceptibility of children to SARS-CoV-2 virus may lie in the low sensitivity on thermal regulation of immune activation.

Pandemic

Medical record

10.21203/rs.3.rs-54254/v1

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Citations (0)

The phytochemical polydatin ameliorates non‐alcoholic steatohepatitis by restoring lysosomal function and autophagic flux

Journal of Cellular and Molecular Medicine (2019)

Xiaoting Chen Hung Chan Lin Zhang Xiaodong Liu Idy H. T. Ho

Abstract Impaired autophagic degradation of intracellular lipids is causally linked to the development of non‐alcoholic steatohepatitis (NASH). Pharmacological agents that can restore hepatic autophagic flux could therefore have therapeutic potentials for this increasingly prevalent disease. Herein, we investigated the effects of polydatin, a natural precursor of resveratrol, in a murine nutritional model of NASH and a cell line model of steatosis. Results showed that oral administration of polydatin protected against hepatic lipid accumulation and alleviated inflammation and hepatocyte damage in db / db mice fed methionine‐choline deficient diet. Polydatin also alleviated palmitic acid‐induced lipid accumulation in cultured hepatocytes. In both models, polydatin restored lysosomal function and autophagic flux that were impaired by NASH or steatosis. Mechanistically, polydatin inhibited mTOR signalling and up‐regulated the expression and activity of TFEB, a known master regulator of lysosomal function. In conclusion, polydatin ameliorated NASH through restoring autophagic flux. The polydatin‐regulated autophagy was associated with inhibition of mTOR pathway and restoration of lysosomal function by TFEB. Our study provided affirmative preclinical evidence to inform future clinical trials for examining the potential anti‐NASH effect of polydatin in humans.

Steatohepatitis

Steatosis

Lipotoxicity

TFEB

Lipid droplet

10.1111/jcmm.14320

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Citations (54)

Geographic Differences on Clinical Manifestations of COVID-19 Infection Between Overseas Chinese and Local Chinese Patients

Infection and Drug Resistance (2021)

Yanhua Liang Shanglong Kou Xiaohe Li Zhiyi Ke Rongrong Zou

The novel coronavirus (COVID-19) has become a global pandemic with sharp rises in the number of confirmed cases and rapid spread across the world. Here, we looked at the effects of geographic differences on clinical manifestations of SARS-CoV-2 infected patients.A total of 114 confirmed COVID-19 patients were included in this study. The epidemiological, demographic, clinical, as well as laboratory findings were extracted from the electronic medical records of these patients.We report the observation that patients from overseas residents diagnosed with COVID-19 were mildly symptomatic with cough and presented with lower inflammatory response and attenuated virus clearance rate, as well as correspondingly prolonged days of hospital stay than local Chinese patients. Moreover, the receiver-operating characteristic (ROC) analysis, performed to provide a measure of the difference between two groups, showed that serum albumin had the highest area under the curve value (0.81, p < 0.001).Our results suggested that blood albumin level acted as a predictive value in distinguishing clinical features between local and overseas Chinese. This work underscores the need to identify distinguishably prognostic factors of geographical dissimilarity in COVID-19 patients.

Pandemic

2019-20 coronavirus outbreak

Medical record

10.2147/idr.s307238

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Citations (0)

Clinical Characteristics on 25 Discharged Patients with COVID-19 Virus Returning

medRxiv (Cold Spring Harbor Laboratory) (2020)

Jing Yuan Shanglong Kou Yanhua Liang Jianfeng Zeng Yanchao Pan

Abstract Here we report the clinical features of 25 discharged patients with COVID-19 recovery. Our analysis indicated that there was a significant inverse correlation existed between serum D-Dimer level and the duration of antiviral treatment, while lymphocyte concentration significantly positively correlated with the duration of virus reversal.

2019-20 coronavirus outbreak

D-dimer

10.1101/2020.03.06.20031377

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Citations (11)

Generation of non-integrated induced pluripotent stem cells from a 23-year-old male with multiple endocrine neoplasia type 1 syndrome

Stem Cell Research (2016)

Dongsheng Guo Feima Wu Hai‐Kun Liu Ge Gao Shanglong Kou

Urine resource cells were collected from a 23-year-old male with multiple endocrine neoplasia type 1 syndrome (MEN1) for generating iPS cells with episomal plasmids. Two stable iPSC lines with free of episomal plasmid were established. The patient has a heterozygous G>T mutation on the exon 9 of Men1 gene that was confirmed by sequencing analysis on all resulted cell lines. Karyotyping indicated the chromosomes with normal appearances and numbers. Their pluripotency was demonstrated by gene expression and their abilities for differentiating into three germ layers. These iPSC lines provide valuable in vitro resources for pathological study on MEN1 syndrome.

MEN1

Enteroendocrine cell

10.1016/j.scr.2016.12.002

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Citations (7)

A Novel Peptide Interfering with proBDNF-Sortilin Interaction Alleviates Chronic Inflammatory Pain

Theranostics (2019)

Idy H. T. Ho Xiaodong Liu Yidan Zou Taian Liu Wei Hu

Rationale: Brain-derived neurotrophic factor (BDNF) is a key mediator in the development of chronic pain.Sortilin is known to interact with proBDNF and regulate its activity-dependent secretion in cortical neurons.In a rat model of inflammatory pain with intraplantar injection of complete Freund's adjuvant (CFA), we examined the functional role of proBDNF-sortilin interaction in dorsal root ganglia (DRG).Methods: Expression and co-localization of BDNF and sortilin were determined by immunofluorescence.ProBDNF-sortilin interaction interface was mapped using co-immunoprecipitation and bimolecular fluorescence complementation assay.The analgesic effect of intrathecal injection of a synthetic peptide interfering with proBDNF-sortilin interaction was measured in the CFA model.Results: BDNF and sortilin were co-localized and their expression was significantly increased in ipsilateral L4/5 DRG upon hind paw CFA injection.In vivo adeno-associated virus-mediated knockdown of sortilin-1 in L5 DRG alleviated pain-like responses.Mapping by serial deletions in the BDNF prodomain indicated that amino acid residues 71-100 supported the proBDNF-sortilin interaction.A synthetic peptide identical to amino acid residues 89-98 of proBDNF, as compared with scrambled peptide, was found to interfere with proBDNF-sortilin interaction, inhibit activity-dependent release of BDNF in vitro and reduce CFA-induced mechanical allodynia and heat hyperalgesia in vivo.The synthetic peptide also interfered with capsaicin-induced phosphorylation of extracellular signal-regulated kinases in ipsilateral spinal cord of CFA-injected rats.Conclusions: Sortilin-mediated secretion of BDNF from DRG neurons contributes to CFA-induced inflammatory pain.Interfering with proBDNF-sortilin interaction reduced activity-dependent release of BDNF and might serve as a therapeutic approach for chronic inflammatory pain.

Mediator

Immunoprecipitation

10.7150/thno.29703

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Citations (21)

Ternary Dry Powder Agglomerate Inhalation Formulation of Melatonin With Air Jet Mixing to Improve In Vitro And In Vivo Performance

Journal of Pharmaceutical Sciences (2023)

Qingzhen Zhang Shanglong Kou Yingtong Cui Jie Dong Yuqing Ye

An improved agglomerate formulation with melatonin and fine lactose for dry powder inhalation using Turbuhaler® was developed. Co-grinding lactose with 1 % magnesium stearate prior to air jet mixing served as a key factor to improve the in vitro aerosolization and in vivo efficacy. Elevated mixing pressure facilitated the dispersion and homogenization of the cohesive mixture for even distribution of agglomerate size after spheroidization and subsequent higher emitted dose with lower variation. Magnesium stearate was employed as a tertiary component to adjust the interparticle force for better aerosolization. At optimized mixing pressure, co-grinding lactose with magnesium stearate before jet mixing displayed further improvement of fine particle fraction to 71.6 ± 3.1 %. The superior fine particle deposition efficiency contributed to rapid onset of action and a high bioavailability of 67.0 % after intratracheal administration to rats. Overall, an inhalable melatonin dry powder formulation exhibiting good aerosol property and lung deposition with clinical translation potential was developed.

Aerosolization

Agglomerate

Dry-powder inhaler

10.1016/j.xphs.2023.11.016

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Citations (1)

The correlation between viral clearance and biochemical outcomes of 94 COVID-19 infected discharged patients

Inflammation Research (2020)

Jing Yuan Rougrong Zou Lijiao Zeng Shanglong Kou Jianfeng Lan

This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People's Hospital, enrolled from Jan 5 to Feb 13, 2020. The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected. COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin. Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.

Lopinavir

Ritonavir

Creatine kinase

10.1007/s00011-020-01342-0

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Citations (215)

Cloning and Characterization of a cDNA Encoding Type 1 Diacylglycerol Acyltransferase from Sunflower (Helianthus annuus L.)

Zeitschrift für Naturforschung C (2011)

Li Sun Ouyang Chao Shanglong Kou Shenghua Wang Y. M. Sylvia YAO

A full-length cDNA encoding a putative diacylglycerol acyltransferase (DGAT; EC 2.3.1.20) was obtained from sunflower (Helianthus annuus L.) seeds. The 1524-bp open reading frame of this cDNA, designated as HaDGAT1, encodes a protein of 507 amino acids with a molecular mass of 58.5 kDa showing high homology to DGAT1 enzymes of other plants. The protein characters, such as a predicted structure with a long N-terminal hydrophilic domain followed by 9 transmembrane domains, acyl-CoA-binding signature, diacylglycerol (DAG)-binding and putative endoplasmic reticulum retrieval motifs (ER-DIR), also indicated that HaDGAT belongs to the DGAT1 family. HaDGAT1 is expressed in all plant tissues especially in developing seeds. Expression of recombinant HaDGAT1 in yeast showed an 1.76-fold increase of total fatty acids, especially unsaturated fatty acids such as palmitoleic acid (enhanced by 86.6%) and oleic acid (enhanced by 81.6%).

Helianthus annuus

Acyltransferases

10.1515/znc-2011-1-209

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Citations (8)