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Neuroprotective effects of erythropoietin on neurodegenerative and ischemic brain diseases: the role of erythropoietin receptor

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Neural Regeneration Research 2017年第9期12卷 1381-1389页

作者： Carolina Castillo Hernández Carlos Felipe Burgos Angela Hidalgo Gajardo Tiare Silva-Grecchi Javiera Gavilan Jorge Roberto Toledo Jorge Fuentealba laboratory of Screening of Neuroactive Compounds Department of Physiology School of Biological Sciences University of Concepción Laboratory of Biotechnology and Biopharmaceutical Department of Pathophysiology School of Biological Sciences University of Concepción

Erythropoietin （Epo） is a fundamental hormone in the regulation of hematopoiesis, and other secondary roles mediated by the binding of the hormone to its specific receptor （EpoR）, which leads to an activation of key signaling pathways that induce an increase in cell differentiation, apoptosis control and neuroprotection. It has been suggested that their ftmction depends on final conformation of glycosylations, related with affinity to the receptor and its half-life. The presence of EpoR has been reported in different tissues including central nervous system, where it has been demonstrated to exert a neuroprotective function against oxidative stress conditions, such as ischemic injury and neurodegenerative diseases. There is also evidence of an increase in EpoR expression in brain cell lysates of Alzheimer＇s patients with respect to healthy patients. These results are related with extensive in vitro experimental data of neuroprotection obtained from cell lines, primary cell cultures and hippocampal slices. Additionally, this data is correlated with in vivo experiments （water maze test） in mouse models of Alzheimer＇s disease where Epo treatment improved cognitive function. These stud- ies support the idea that receptor activation induces a neuroprotective effect in neurodegenerative disorders including dementias, and especially Alzheimer＇s disease. Taken together, available evidence suggests that Epo appears to be a central element for EpoR activation and neuroprotective properties in the central nervous system. In this review, we will describe the mechanisms associated with neuroprotection and its relation with the activation of EpoR in order with identify new targets to develop pharmacological strategies.

关键词： erythropoietin erythropoietin receptor neuroprotection anti-apoptosis Alzheimer＇s disease

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Comparative study of brine shrimp bioassay-based toxic activities of three harmful microalgal species that frequently blooming in aquaculture ponds

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Journal of Oceanology and Limnology 2018年第5期36卷 1697-1706页

作者：杨小倩文欣周成旭朱小娟孟冉骆其君严小军 School of Marine Science Ningbo University Senior High School of Yudu Key laboratory of Marine biotechnology of Zhejiang Province Ningbo University Li Dak Sum Yip Yio Chin Kenneth Li Marine biopharmaceutical Research Center Ningbo University

Typical harmful micro-algal species constantly occurred in high density in marine aquaculture ponds in Xiangshan and Sanmen Bay, Zhejiang Province. Fates of the microalgal cells influenced by activity of the cultured animals largely determined the ef fects of the harmful microalgae. However, it is difficult to detect the in situ process. In this paper, toxic activities of three harmful microalga, namely P rymnesium parvum, Pleurochrysis elongata, Karlodinium veneficum, which were isolated from the local ponds, were comparatively studied based on brine shrimp toxic bioassays. Diff erent lethal activities of live cells, cell debris, cellular extracts, and cell free mediums prepared by different process were analyzed. The results showed that,(1) all of the three microalgal species had density and time dependent lethal ef fects on A rtermia nauplii, while P. parvum was the most toxic one and had acute lethal eff ects in 5 h. No such acute lethal eff ects were observed in P. elongata or K. veneficum;(2) live cells, cell debris and cellular extracts of P. parvum had the same lethal pattern. Prymnesins, toxin from P. parvum, is probably not exotoxic active; For P. elongata, toxic activity mainly came from live cells and cell debris; For K. veneficum, toxic activity was relatively lower compared with the other two species. However, Karlotoxin, toxin from K. veneficum, is exotoxic active. Physical disturbance triggered K. veneficum cells actively releasing toxins, which made it an active predator.

关键词：海水养殖藻类植物植物学海洋学

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Changes of pigments and lipids composition in Haematococcus pluvialis vegetative cell as affected by monochromatic red light compared with white light

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Journal of Oceanology and Limnology 2018年第6期36卷 2257-2267页

作者：朱小娟罗杰周成旭王建沅孟冉徐继林陈娟娟骆其君严小军 School of Marine Science Ningbo University Department of Marine Drug and Biological Products Ningbo Institute of Oceanography Li Dak Sum Yip Yio Chin Kenneth Li Marine biopharmaceutical Research Center Ningbo University Key laboratory of Marine biotechnology of Zhejiang Province Ningbo University

Much attention has been paid on studies of astaxanthin accumulation process in H aematococcus pluvialis industry. However, growth of H. pluvialis in motile vegetative stage is still the most important and problematic part in the whole cultivation process, such as low growth rate and cell yields. Motile vegetative cells are extremely sensitive to various stresses which make it difficult to maintain the cells of this state to grow. Previous reports showed that motile vegetative cells may have higher biomass yields ifapplied monochromatic red light. However, metabolic responses of these cells are not completely understood, which constraints application of this illumination protocol in industry. The aim of this study was to examine how critical biochemical changes of H. pluvialis motile vegetative cells were af fected by red light when compared with white light. Variation of photosynthetic pigments composition and lipids were mainly studied. By comparing growth process of cultures in red light and white light, prominent variation of pigments composition and lipids changes were observed. The results showed that, even though cell proliferation was the same during exponential growth phase, variation of photosynthetic pigment composition and lipids occurred. The final biomass of cell number was higher in red light group than in white light group. The variations were significant different. Increase or decrease of major photosynthetic membrane lipids to some extent did not influence photosynthesis of the vegetative cells during this phase. However, vegetative cells under polychromatic white light other than monochromatic red light need further metabolic process to adjust its pigment composition and lipids, possibly this is energetically and biochemically unfavorable for motile vegetative cells to growth under white light, a light condition normally not considered as a stress.

关键词： Haematococcus pluvialis light quality photosynthetic pigments neutral lipid photosynthetic membrane lipids

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Targeted hyperalkalization with NaOH-loaded starch implants enhances doxorubicin efficacy in tumor treatment

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Asian Journal of Pharmaceutical Sciences 2023年第5期18卷 185-195页

作者： Changkyu Lee Department of biopharmaceutical Engineering Division of Chemistry and BiotechnologyDongguk UniversityGyeongju 38066Korea

High-alkali treatment using sodium hydroxide(NaOH)injection can be a therapeutic approach for killing tumor cells.Alkalization can damage cellular structures and lead to cell death.Increased alkalinity can also enhance the efficacy of certain chemotherapeutic drugs such as doxorubicin(DOX).In this study,NaOH-loaded starch implants(NST implants)were used to induce hyperalkalization(increase pH)in the tumor environment,thereby inducing necrosis and enhancing the effects of DOX.NaOH is a strongly alkaline substance that can increase the pH when injected into a tumor.However,the administration of NaOH can have toxic side effects because it increases the pH of the entire body,not just at the tumor site.To overcome this problem,we developed an injectable NST implant,in which NaOH can be delivered directly into the tumor.This study showed that NST implants could be easily administered intratumorally in mice bearing 4T1 tumors and that most of the NaOH released from the NST implants was delivered to the tumors.Although some NaOH from NST implants can be systemically absorbed,it is neutralized by the body’s buffering effect,thereby reducing the risk of toxicity.This study also confirmed both in vitro and in vivo that DOX is more effective at killing 4T1 cells when alkalized.It has been shown that administration of DOX after injection of an NST implant can kill most tumors.Systemic absorption and side effects can be reduced using an NST implant to deliver NaOH to the tumor.In addition,alkalinization induced by NST implants not only exerts anticancer effects but can also enhance the effect of DOX in killing cancer cells.Therefore,the combination of NaOH-loaded starch implants and DOX treatment has the potential to be a novel therapy for tumors.

关键词： NaOH Starch Implant Doxorubicin Alkalinization Tumor

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MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4234-4252页

作者： Chao Hou Dong Wang Mingxia Zhao Petek Ballar Xinru Zhang Qiong Mei Wei Wang Xiang Li Qiang Sheng Jun Liu Chuansheng Wei Yujun Shen Yi Yang Peng Wang Juntang Shao Sa Xu Fuyan Wang Yang Sun Yuxian Shen School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China biopharmaceutical Research Institute Anhui Medical UniversityHefei 230032China Department of Biochemistry Faculty of PharmacyEge UniversityIzmir 35100Turkey State Key laboratory of Pharmaceutical biotechnology School of Life SciencesNanjing UniversityNanjing 210023China

The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

关键词： Hepatic fibrosis Mesencephalic astrocyte-derived neurotrophic factor Macrophage differentiation Ly6C^(high)macrophages S100A8/S100A9 TLR4 NF-κB pathway HSCs activation

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Purification and characterization of an extracellular chitinase from a newly isolated chitinolyticbacter meiyuanensis SYBC-H1

Purification and characterization of an extracellular chitin...

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中国生物化学与分子生物学会第十一次会员代表大会暨201...

作者： Zhikui Hao Hangui Wu Meiling Yang Jianjun Chen Xiangru Liao biopharmaceutical R & D Center Taizhou Vocational & Technical College The Key laboratory of Industrial B iotechnology Ministry of Education School of Biotechnology Jiangnan University

Chitinase was purified from the bacterium C.Meiyuanensis SYBC-H1 isolated from the soilsamples collected from Meiyuan Park.The chitinase was purified by ammonium sulphateprecipitation followed by DEAE-cellulose column and than Sephadex G-100.Enzyme waspurified by 10.16 folds with 20.9%yield.Molecular characterization through SDS-PAGEanalysis showed that it has molecular weight of about 39 kDa.The enzyme kinetics studiesof purified chitinase revealed the following characteristics,Km 6.25 mg/ml and Vmax 9.066U/mg for 4-Nitrophenyl-N-acetyl-α-D-glucopyranoside as a substrate.The optimum chitinaseactivity was observed at 40°C.The optimum pH for chitinase is 6.5,with appreciableactivity between 3.5and 9.0.Activity staining show two kinds of chitinase isoenzyme wereproduced.β-mercaptoethanol has worked a lot for the stability of Chitinase.

关键词： Chitinase purification stability β-mercaptoethanol C.Meiyuanensis SYBC-H1

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Insight into the distribution of metallic elements in membrane bioreactor: Influence of operational temperature and role of extracellular polymeric substances

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Journal of Environmental Sciences 2019年第2期31卷 111-120页

作者： He Wang Xiufen Li Xinhua Wang Yueping Ren laboratory of Environmental biotechnology School of Environmental and Civil EngineeringJiangnan University Jiangsu Key laboratory of Anaerobic biotechnology

The distribution of metallic elements in a submerged membrane bioreactor(MBR) was revealed at different temperatures using inductively coupled plasma-optical emission spectrometry(ICP-OES), and the role of extracellular polymeric substances(EPS) was probed by integrating scanning electron microscopy(SEM) with confocal laser scanning microscopy(CLSM) over long-term operation. More metallic elements in the influent were captured by suspended sludge and built up in the fouling layer at lower temperature. The concentration of metallic elements in the effluent was 5.60 mg/L at 10°C operational temperature, far lower than that in the influent(51.35 mg/L). The total contents of metallic elements in suspended sludge and the membrane fouling layer increased to 40.20 and 52.19 mg/g at 10°C compared to 35.14 and 32.45 mg/g at 30°C, and were dominated by the organically bound fraction. The EPS contents in suspended sludge and membrane fouling layer sharply increased to 37.88 and 101.51 mg/g at 10°C, compared to 16.87 and 30.03 mg/g at 30°C. The increase in EPS content at lower temperature was responsible for the deposition of more metallic ions. The strong bridging between EPS and metallic elements at lower temperature enhanced the compactness of the fouling layer and further decreased membrane flux. This was helpful for understanding the mechanism of membrane fouling at different operational temperatures and the role of EPS, and also of significance for the design of cleaning strategies for fouled membranes after long-term operation.

关键词： Membrane bioreactor Metallic elements Extracellular polymeric substances

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Molecular basis of COVID-19,ARDS and COVID-19-associated ARDS:Diagnosis pathogenesis and therapeutic strategies

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BIOCELL 2023年第11期47卷 2335-2350页

作者： PRIYADHARSHINI THANJAVUR SRIRAMAMOORTHI GAYATHRI GOPAL SHIBI MURALIDAR SAI RAMANAN ESWARAN DANUSH NARAYAN PANNEERSELVAM BHUVANESWARAN MEIYANATHAN SRICHANDRASEKAR THUTHIKKADU INDHUPRAKASH SENTHIL VISAGA AMBI biopharmaceutical Research Lab Anusandhan Kendra-1SASTRA Deemed-to-be UniversityThanjavur613401India School of Chemical and biotechnology SASTRA Deemed-to-be UniversityThanjavur613401India

The novel coronavirus pneumonia(COVID-19)is spreading worldwide and threatening people greatly.The routes by which SARS-CoV-2 causes lung injury have grown to be a major concern in the scientific community since patients with new Coronavirus,severe acute respiratory syndrome coronavirus(SARS-CoV-2)have a high likelihood of developing acute respiratory distress syndrome(ARDS)in severe cases.The mortality rate of COVID-19 has increased over the period due to rapid spread,and it becomes crucial to understand the disease epidemiology,pathogenic mechanisms,and suitable treatment strategies.ARDS is a respiratory disorder and is one of the clinical manifestations observed in patients with severe COVID-19.In this scenario,it is important to address this problem to develop suitable treatment strategies.This review attempts to present the prevalence of ARDS in COVID-19 patients and their predictive causes and risk factors,highlighting the contrasting features of COVID-19-induced ARDS with typical ARDS.This review also presents insights into the association between SARS-CoV-2 and lung damage while exploring the potential COVID-19 mechanisms in ARDS from the perspective of the angiotensin-converting enzyme 2 protein,cytokine storm,immune responses,and other signaling pathways.The review also discusses the diagnosis strategies,pathogenesis,risk factors,and treatment options of COVID-19-related ARDS.

关键词： ARDS SARS-CoV-2 Variants Pathogenesis Risk factors Vaccines

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Systematic bio‑fabrication of aptamers and their applications in engineering biology

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Systems Microbiology and Biomanufacturing 2023年第2期3卷 223-245页

作者： Rongfeng Cai Xin Chen Yuting Zhang Xiaoli Wang Nandi Zhou The Key laboratory of Carbohydrate Chemistry and biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China

Aptamers are single-stranded DNA or RNA molecules that have high affinity and selectivity to bind to specific targets.Compared to antibodies,aptamers are easy to in vitro synthesize with low cost,and exhibit excellent thermal stability and programmability.With these features,aptamers have been widely used in biology and medicine-related fields.In the meantime,a variety of systematic evolution of ligands by exponential enrichment(SELEX)technologies have been developed to screen aptamers for various targets.According to the characteristics of targets,customizing appropriate SELEX technology and post-SELEX optimization helps to obtain ideal aptamers with high affinity and specificity.In this review,we first summarize the latest research on the systematic bio-fabrication of aptamers,including various SELEX technologies,post-SELEX optimization,and aptamer modification technology.These procedures not only help to gain the aptamer sequences but also provide insights into the relationship between structure and function of the aptamers.The latter provides a new perspective for the systems bio-fabrication of aptamers.Furthermore,on this basis,we review the applications of aptamers,particularly in the fields of engineering biology,including industrial biotechnology,medical and health engineering,and environmental and food safety monitoring.And the encountered challenges and prospects are discussed,providing an outlook for the future development of aptamers.

关键词： Aptamer SELEX Engineering biology Biosensors

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Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics

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Acta Pharmaceutica Sinica B 2022年第1期12卷 149-166页

作者： Jian Gao Zhigui Wu Mingxia Zhao Rui Zhang Manru Li Dongdong Sun Haibo Cheng Xianjia Qi Yuxian Shen Qiang Xu Hongqi Chen Dijun Chen Yang Sun State Key laboratory of Pharmaceutical biotechnology Chemistry and Biomedicine Innovation Center(Chem BIC)School of Life SciencesNanjing UniversityNanjin 210023China biopharmaceutical Research Institute School of Basic Medical SciencesAnhui Medical UniversityHefei 230032China Department of Colorectal Surgery Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital&InstituteShenyang 110042China The First Clinical College of Nanjing University of Chinese Medicine Nanjing 210023China Shanghai Xu Ran biotechnology Co. Ltd.Shanghai 201109China Jiangsu Key laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China Department of General Surgery Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China

Colorectal cancer(CRC), a malignant tumor worldwide consists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing wasperformed to explore the role of SHP2 in all cell types of tumor microenvironment(TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68;macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

关键词： Tumor microenvironment PTPN11 SHP099 STING Type I interferon Colorectal cancer scRNA-seq Macrophage

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