Publications by authors named "Mengqi Zhang"

126 Publications

Anticonvulsant activity of melatonin and its success in ameliorating epileptic comorbidity-like symptoms in zebrafish.

Eur J Pharmacol 2021 Oct 23:174589. Epub 2021 Oct 23.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China; Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Ji'nan, 250103, Shandong Province, PR China. Electronic address:

Epilepsy is one of common neurological disorders, greatly distresses the well-being of the sufferers. Melatonin has been used in clinical anti-epileptic studies, but its effect on epileptic comorbidities is unknown, and the underlying mechanism needs further investigation. Herein, by generating PTZ-induced zebrafish seizure model, we carried out interdisciplinary research using neurobehavioral assays, bioelectrical detection, molecular biology, and network pharmacology to investigate the activity of melatonin as well as its pharmacological mechanisms. We found melatonin suppressed seizure-like behavior by using zebrafish regular locomotor assays. Zebrafish freezing and bursting activity assays revealed the ameliorative effect of melatonin on comorbidity-like symptoms. The preliminary screening results of neurobehavioral assays were further verified by the expression of key genes involved in neuronal activity, neurodevelopment, depression and anxiety, as well as electrical signal recording from the midbrain of zebrafish. Subsequently, network pharmacology was introduced to identify potential targets of melatonin and its pathways. Real-time qPCR and protein-protein interaction (PPI) were conducted to confirm the underlying mechanisms associated with glutathione metabolism. We also found that melatonin receptors were involved in this process, which were regulated in response to melatonin exposure before PTZ treatment. The antagonists of melatonin receptors affected anticonvulsant activity of melatonin. Overall, current study revealed the considerable ameliorative effects of melatonin on seizure and epileptic comorbidity-like symptoms and unveiled the underlying mechanism. This study provides an animal model for the clinical application of melatonin in the treatment of epilepsy and its comorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2021.174589DOI Listing
October 2021

Monodispersed Ni active sites anchored on N-doped porous carbon nanosheets as high-efficiency electrocatalyst for hydrogen peroxide sensing.

Anal Chim Acta 2021 Sep 30;1179:338812. Epub 2021 Jun 30.

Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China. Electronic address:

Metal active species combined with N-doped porous carbon nanosheets usually own excellent electrochemical activity and sensing performance owing to its unique microstructure and composition. In this work, monodispersed Ni active sites anchored on N-doped porous carbon nanosheets ([email protected]) were facilely prepared via rational metal-organic frameworks (MOFs) route. Firstly, zeolitic imidazolate frameworks-8 (ZIF-8) was in situ grown on physically-exfoliated graphene nanosheets (GN) with homogeneous sandwich-like structure ([email protected]). Secondly, nickel bonded [email protected] hybrids (Ni/[email protected]) were obtained by ionic exchange reaction, and then transformed into [email protected] by high-temperature pyrolysis. Benefiting from the monodispersed Ni active sites and highly reactive N-doped porous carbon nanosheets (N-PCN), the as-prepared [email protected] hybrids displayed superior catalytic performance toward hydrogen peroxide (HO) sensing. As a result, a highly sensitive electrochemical sensing platform for HO was fabricated with low detection limit (0.032 μM), wide detection linearity (0.2-2332.8 μM), and high sensitivity (6085 μA cm mM). Besides, the as-developed electrochemical sensing platform was successfully applied to detect HO contents in biological medicine and food specimens with satisfied results. This study will provide effective guidance for the preparation of novel metal/N-doped carbon nanomaterials and establishment of high-performance electrochemical sensors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aca.2021.338812DOI Listing
September 2021

Using an exploratory sequential mixed methods design to adapt an Illness Perception Questionnaire for African Americans with diabetes: the mixed data integration process.

Health Psychol Behav Med 2021 13;9(1):796-817. Epub 2021 Sep 13.

School of Nursing, University of Wisconsin-Madison, Madison, WI, USA.

Background: Although qualitative methods have been used to develop quantitative behavioral health measurements, studies rarely report on the exact development process of these questionnaires. In this methodological paper, we highlight the procedure of a mixed data integration process in using qualitative data to create quantitative questionnaire items.

Methods: We used an exploratory sequential mixed methods study design to culturally adapt the Illness Perception Questionnaire-Revised (IPQ-R) and address the sociocultural contexts of African Americans with type 2 diabetes. Forty African Americans with type 2 diabetes taking oral diabetes medication completed the qualitative focus groups and 170 participants completed the quantitative phase (surveys). Using the 'building approach' to integration, qualitative themes from the focus groups were matched to survey domains based on the self-regulatory model. Qualitative themes assessing perceptions of diabetes among African Americans were used to develop new survey items for a culturally adapted IPQ-R, as well as adapt original survey items.

Results: Important themes included the effect on friend/family relationships, lifestyle changes, food experiences (consequences domain), importance of medications (treatment control), comparisons with family members (illness coherence), fear, future worries, and anger (emotional representations). A new domain, 'sociocultural influences' was added to the adapted questionnaire based on qualitative themes of race and racism on provider roles, personal control, and community influences. Merging and integration of the qualitative and quantitative phases, (reported via a joint display) showed evidence of congruence between the illness perceptions from the qualitative focus groups and scores on the survey items.

Conclusion: The use of mixed methods allowed for the development of a robust and patient-centered questionnaire. Future research should consider psychometric testing of the adapted IPQ-R, so that it may be used in addressing illness perceptions among African Americans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21642850.2021.1976650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439214PMC
September 2021

Identification and validation of RNA-binding protein-related gene signature revealed potential associations with immunosuppression and drug sensitivity in glioma.

Cancer Med 2021 Oct 5;10(20):7418-7439. Epub 2021 Sep 5.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

Background: Glioma is the most common central nervous system tumor in adults, and a considerable part of them are high-degree ones with high malignancy and poor prognosis. At present, the classification and treatment of glioma are mainly based on its histological characteristics, so studies at the molecular level are needed.

Methods: RNA-seq data from The Cancer Genome Atlas (TCGA) datasets (n = 703) and Chinese Glioma Genome Atlas (CGGA) were utilized to find out the differentially expressed RNA-binding proteins (RBPs) between normal cerebral tissue and glioma. A prediction system for the prognosis of glioma patients based on 11 RBPs was established and validated using uni- and multi-variate Cox regression analyses. STITCH and CMap databases were exploited to identify putative drugs and their targets. Single sample gene set enrichment analysis (ssGSEA) was used to calculate scores of specific immune-related gene sets. IC50 of over 20,000 compounds in 60 cancer cell lines was collected from the CellMiner database to test the drug sensitivity prediction value of the RBP-based signature.

Results: We established a reliable prediction system for the prognosis of glioma patients based on 11 RBPs including THOC3, LSM11, SARNP, PABPC1L2B, SMN1, BRCA1, ZC3H8, DZIP1L, HEXIM2, LARP4B, and ZC3H12B. These RBPs were primarily associated with ribosome and post-transcriptional regulation. RBP-based risk scores were closely related to immune cells and immune function. We also confirmed the potential of the signature to predict the drug sensitivity of currently approved or evaluated drugs.

Conclusions: Differentially expressed RBPs in glioma can be used as a basis for prognosis prediction, new drugs screening and drug sensitivity prediction. As RBP-based glioma risk scores were associated with immunity, immunotherapy may become an important treatment for glioma in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.4248DOI Listing
October 2021

Characterization and bioactivities of phospholipids from squid viscera and gonads using ultra-performance liquid chromatography-Q-exactive orbitrap/mass spectrometry-based lipidomics and zebrafish models.

Food Funct 2021 Sep 14;12(17):7986-7996. Epub 2021 Jul 14.

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.

There has been great interest in phospholipids (PLs) from marine by-products due to their long-chain polyunsaturated fatty acids with unique health and functional properties. Here, marine PLs from squid viscera and gonads were comprehensively characterized and compared by UPLC-Q-Exactive Orbitrap/MS-based lipidomics analysis. A total of thirteen phospholipid classes including 1223 molecular species were identified and quantified in both resources. PC, PE and SM were further isolated from the total PLs of squid viscera and gonads, respectively. All isolated squid PL components were first evaluated for anti-inflammatory, antioxidant and cardiovascular effects using in vivo zebrafish models. Our results showed the diversity, content and physiological functions of PLs from squid by-products, which provided a basis for their future application in the nutritional and pharmaceutical industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1fo00796cDOI Listing
September 2021

Identification and Validation of an 11-Ferroptosis Related Gene Signature and Its Correlation With Immune Checkpoint Molecules in Glioma.

Front Cell Dev Biol 2021 23;9:652599. Epub 2021 Jun 23.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

Background: Glioma is the most common primary malignant brain tumor with significant mortality and morbidity. Ferroptosis, a novel form of programmed cell death (PCD), is critically involved in tumorigenesis, progression and metastatic processes.

Methods: We revealed the relationship between ferroptosis-related genes and glioma by analyzing the mRNA expression profiles from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GSE16011, and the Repository of Molecular Brain Neoplasia Data (REMBRANDT) datasets. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct a ferroptosis-associated gene signature in the TCGA cohort. Glioma patients from the CGGA, GSE16011, and REMBRANDT cohorts were used to validate the efficacy of the signature. Receiver operating characteristic (ROC) curve analysis was applied to measure the predictive performance of the risk score for overall survival (OS). Univariate and multivariate Cox regression analyses of the 11-gene signature were performed to determine whether the ability of the prognostic signature in predicting OS was independent. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify the potential biological functions and pathways of the signature. Subsequently, we performed single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status. Finally, seven putative small molecule drugs were predicted by Connectivity Map.

Results: The 11-gene signature was identified to divide patients into two risk groups. ROC curve analysis indicated the 11-gene signature as a potential diagnostic factor in glioma patients. Multivariate Cox regression analyses showed that the risk score was an independent predictive factor for overall survival. Functional analysis revealed that genes were enriched in iron-related molecular functions and immune-related biological processes. The results of ssGSEA indicated that the 11-gene signature was correlated with the initiation and progression of glioma. The small molecule drugs we selected showed significant potential to be used as putative drugs.

Conclusion: we identified a novel ferroptosis-related gene signature for prognostic prediction in glioma patients and revealed the relationship between ferroptosis-related genes and immune checkpoint molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.652599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262596PMC
June 2021

Research on the Structure of Peanut Allergen Protein Ara h1 Based on Aquaphotomics.

Front Nutr 2021 18;8:696355. Epub 2021 Jun 18.

School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Peanut allergy is becoming a life-threatening disease that could induce severe allergic reactions in modern society, especially for children. The most promising method applied for deallergization is heating pretreatment. However, the mechanism from the view of spectroscopy has not been illustrated. In this study, near-infrared spectroscopy (NIRS) combined with aquaphotomics was introduced to help us understand the detailed structural changes information during the heating process. First, near-infrared (NIR) spectra of Ara h1 were acquired from 25 to 80°C. Then, aquaphotomics processing tools including principal component analysis (PCA), continuous wavelet transform (CWT), and two-dimensional correlation spectroscopy (2D-COS) were utilized for better understanding the thermodynamic changes, secondary structure, and the hydrogen bond network of Ara h1. The results indicated that about 55°C could be a key temperature, which was the structural change point. During the heating process, the hydrogen bond network was destroyed, free water was increased, and the content of protein secondary structure was changed. Moreover, it could reveal the interaction between the water structure and Ara h1 from the perspective of water molecules, and explain the effect of temperature on the Ara h1 structure and hydrogen-bonding system. Thus, this study described a new way to explore the thermodynamic properties of Ara h1 from the perspective of spectroscopy and laid a theoretical foundation for the application of temperature-desensitized protein products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2021.696355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249571PMC
June 2021

Follicle-stimulating hormone worsens osteoarthritis by causing inflammation and chondrocyte dedifferentiation.

FEBS Open Bio 2021 Jun 27. Epub 2021 Jun 27.

Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Previous studies have found follicle-stimulating hormone (FSH) receptors on chondrocytes (cartilage cells), but the mechanism of FSH action on chondrocytes is not clear. The purpose of this experiment is to study whether FSH affects chondrocytes and how it causes changes in these cells. Our results show that osteoarthritis became worse after FSH injection in the knee joint of mice. After the stimulation of chondrocytes by FSH, a total of 664 up-regulated genes, such as Col12a1 and Col1a1, and 644 down-regulated genes, such as MGP, were screened by transcriptomics. A subset of extracellular matrix (ECM)-related genes and pathways underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the downregulation of MGP, the upregulation of EGR1 and Col1a1, and the increase of IL-6 were verified. It was also observed that FSH can inhibit the cAMP/PKA and MKK4/JNK signaling pathway. In conclusion, we demonstrated that FSH can increase cartilage inflammatory response and promote chondrocyte dedifferentiation by inhibiting the cAMP/PKA and MKK4/JNK signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/2211-5463.13238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329950PMC
June 2021

Long non-coding RNAs mediate cerebral vascular pathologies after CNS injuries.

Neurochem Int 2021 09 18;148:105102. Epub 2021 Jun 18.

Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, 15261, USA. Electronic address:

Central nervous system (CNS) injuries are one of the leading causes of morbidity and mortality worldwide, accompanied with high medical costs and a decreased quality of life. Brain vascular disorders are involved in the pathological processes of CNS injuries and might play key roles for their recovery and prognosis. Recently, increasing evidence has shown that long non-coding RNAs (lncRNAs), which comprise a very heterogeneous group of non-protein-coding RNAs greater than 200 nucleotides, have emerged as functional mediators in the regulation of vascular homeostasis under pathophysiological conditions. Remarkably, lncRNAs can regulate gene transcription and translation, thus interfering with gene expression and signaling pathways by different mechanisms. Hence, a deeper insight into the function and regulatory mechanisms of lncRNAs following CNS injury, especially cerebrovascular-related lncRNAs, could help in establishing potential therapeutic strategies to improve or inhibit neurological disorders. In this review, we highlight recent advancements in understanding of the role of lncRNAs and their application in mediating cerebrovascular pathologies after CNS injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuint.2021.105102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286347PMC
September 2021

The Effects of Biological Sex on Sepsis Treatments in Animal Models: A Systematic Review and a Narrative Elaboration on Sex- and Gender-Dependent Differences in Sepsis.

Crit Care Explor 2021 Jun 14;3(6):e0433. Epub 2021 Jun 14.

Clinical Epidemiology Program, Blueprint Translational Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

Preclinical studies provide an opportunity to evaluate the relationship between sex and sepsis, and investigate underlying mechanisms in a controlled experimental environment. The objective of our systematic review was to assess the impact of biological sex on treatment response to fluid and antibiotic therapy in animal models of sepsis. Furthermore, we provide a narrative elaboration of sex-dependent differences in preclinical models of sepsis.

Data Sources: MEDLINE and Embase were searched from inception to March 16, 2020.

Study Selection: All studies reporting sex-stratified data comparing antibiotics and/or fluid resuscitation with a placebo or no treatment arm in an in vivo model of sepsis were included.

Data Extraction: Outcomes of interest were mortality (primary) and organ dysfunction (secondary). Risk of bias was assessed. Study selection and data extraction were conducted independently and in duplicate.

Data Synthesis: The systematic search returned 2,649 unique studies, and two met inclusion criteria. Both studies used cecal ligation and puncture models with imipenem/cilastatin antibiotics. No eligible studies investigated fluids. In one study, antibiotic therapy significantly reduced mortality in male, but not female, animals. The other study reported no sex differences in organ dysfunction. Both studies were deemed to be at a high overall risk of bias.

Conclusions: There is a remarkable and concerning paucity of data investigating sex-dependent differences in fluid and antibiotic therapy for the treatment of sepsis in animal models. This may reflect poor awareness of the importance of investigating sex-dependent differences. Our discussion therefore expands on general concepts of sex and gender in biomedical research and sex-dependent differences in key areas of sepsis research such as the cardiovascular system, immunometabolism, the microbiome, and epigenetics. Finally, we discuss current clinical knowledge, the potential for reverse translation, and directions for future studies.

Registration: PROSPERO CRD42020192738.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCE.0000000000000433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205191PMC
June 2021

RNA methylation and neurovascular unit remodeling.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 May;46(5):536-544

Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.

RNA methylation is of great significance in the regulation of gene expression, among which the more important methylation modifiers are N6-methyladenosine (m6A) and 5-methylcytosine (m5C). The methylation process is mainly regulated by 3 kinds of proteins: methyltransferase, demethylase, and reader. m6A, m5C, and their related proteins have high abundance in the brain, and they have important roles in the development of the nervous system and the repair and remodeling of the vascular system. The neurovascular unit (NVU) is a unit of brain structure and function composed of neurons, capillaries, astrocytes, supporting cells, and extracellular matrix. The local microenvironment for NVU has an important role in nerve cell function repair, and the remodeling of NVU is of great significance in the prognosis of various neurological diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200246DOI Listing
May 2021

Long non-coding RNA: An underlying bridge linking neuroinflammation and central nervous system diseases.

Neurochem Int 2021 09 15;148:105101. Epub 2021 Jun 15.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. Electronic address:

Central nervous system (CNS) diseases are responsible for a large proportion of morbidity and mortality worldwide. CNS diseases caused by intrinsic and extrinsic stimuli stimulate the resident immune cells including microglia and astrocyte, resulting in neuroinflammation that exacerbates the progression of diseases. Recent evidence reveals the aberrant expression patterns of long non-coding RNAs (lncRNAs) in the damaged tissues following CNS diseases. It was also proposed that lncRNAs possessed immune-modulatory activities by directly or indirectly affecting various effector proteins including transcriptional factor, acetylase, protein kinase, phosphatase, etc. In addition, lncRNAs can form a sophisticated network by interacting with other molecules to regulate the expression or activation of downstream immune response pathways. However, the major roles of lncRNAs in CNS pathophysiologies are still elusive, especially in neuroinflammation. Herein, we tend to review some potential roles of lncRNAs in modulating neuroinflammation based on current evidence in various CNS diseases, in order to provide novel explanations for the initiation and progression of CNS diseases and help to establish therapeutic strategies targeting neuroinflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuint.2021.105101DOI Listing
September 2021

Study on the Mechanism of the Danggui-Chuanxiong Herb Pair on Treating Thrombus through Network Pharmacology and Zebrafish Models.

ACS Omega 2021 Jun 25;6(22):14677-14691. Epub 2021 May 25.

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250103, China.

Danggui-Chuanxiong (DC) is a commonly used nourishing and activating blood medicine pair in many gynecological prescriptions and modern Chinese medicine. However, its activating blood mechanism has not been clearly elucidated. Our research aimed at investigating the activating blood mechanisms of DC using network pharmacology and zebrafish experiments. Network pharmacology was used to excavate the potential targets and mechanisms of DC in treating thrombus. The antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities of DC and the main components of DC, ferulic acid (DC2), ligustilide (DC7), and levistilide A (DC17), were evaluated by zebrafish models in vivo. A total of 24 compounds were selected as the active ingredients with favorable pharmacological parameters for this herb pair. A total of 89 targets and 18 pathways related to the thrombus process were gathered for active compounds. The genes, TNF, CXCR4, IL2, ESR1, FGF2, HIF1A, CXCL8, AR, FOS, MMP2, MMP9, STAT3, and RHOA, might be the main targets for this herb pair to exert cardiovascular activity from the analysis of protein-protein interaction and KEGG pathway results, which were mainly related to inflammation, vasculogenesis, immunity, hormones, and so forth. The zebrafish experiment results showed that DC had antithrombotic, anti-inflammatory, antioxidant, and vasculogenesis activities. The main compounds had different effects of zebrafish activities. Especially, the antithrombotic activity of the DC17H group, anti-inflammatory activities of DCH and DC2H groups, antioxidant activities of DCM, DCH, DC2, DC7, and DC17 groups, and vasculogenesis activities of DCM, DCH, and DC2 groups were stronger than those of the positive group. The integrated method coupled zebrafish models with network pharmacology provided the insights into the mechanisms of DC in treating thrombus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.1c01847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190889PMC
June 2021

FSH modulated cartilage ECM metabolism by targeting the PKA/CREB/SOX9 pathway.

J Bone Miner Metab 2021 Sep 14;39(5):769-779. Epub 2021 May 14.

School of Medicine, Shandong University, jinan, 250021, shandong, China.

Introduction: Osteoarthritis (OA) is a common joint disease characterized by articular cartilage degeneration. The prevalence of OA is higher among women than men, and this prevalence is closely related to menopause. The classic view assumes that the underlying mechanism of postmenopausal OA is attributed to declining estrogen levels. Although follicle-stimulating hormone (FSH) levels become elevated in parallel, the effects of FSH on OA have been poorly explored. The present study aimed to study the effect of FSH on cartilage metabolism.

Methods: Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections.

Results: We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice.

Conclusions: Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00774-021-01232-3DOI Listing
September 2021

DHCR24 Knock-Down Induced Tau Hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, Ser396 Epitopes and Inhibition of Autophagy by Overactivation of GSK3β/mTOR Signaling.

Front Aging Neurosci 2021 21;13:513605. Epub 2021 Apr 21.

Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, China.

Accumulating evidences supported that knock-down of DHCR24 is linked to the pathological risk factors of AD, suggesting a potential role of DHCR24 in AD pathogenesis. However, the molecular mechanism link between DHCR24 and tauopathy remains unknown. Here, in order to elucidate the relationship between DHCR24 and tauopathy, we will focus on the effect of DHCR24 on the tau hyperphosphorylation at some toxic sites. In present study, we found that DHCR24 knock-down significantly lead to the hyperphosphorylation of tau sites at Thr181, Ser199, Thr231, Ser262, Ser396. Moreover, DHCR24 knock-down also increase the accumulation of p62 protein, simultaneously decreased the ratio of LC3-II/LC3-I and the number of autophagosome compared to the control groups, suggesting the inhibition of autophagy activity. In contrast, DHCR24 knock-in obviously abolished the effect of DHCR24 knock-down on tau hyperphosphrylation and autophagy. In addition, to elucidate the association between DHCR24 and tauopathy, we further showed that the level of plasma membrane cholesterol, lipid raft-anchored protein caveolin-1, and concomitantly total I class PI3-K (p110α), phospho-Akt (Thr308 and Ser473) were significantly decreased, resulting in the disruption of lipid raft/caveola and inhibition of PI3-K/Akt signaling in silencing DHCR24 SH-SY5Y cells compared to control groups. At the same time, DHCR24 knock-down simultaneously decreased the level of phosphorylated GSK3β at Ser9 (inactive form) and increased the level of phosphorylated mTOR at Ser2448 (active form), leading to overactivation of GSK3β and mTOR signaling. On the contrary, DHCR24 knock-in largely increased the level of membrane cholesterol and caveolin-1, suggesting the enhancement of lipid raft/caveola. And synchronously DHCR24 knock-in also abolished the effect of DHCR24 knock-down on the inhibition of PI3-K/Akt signaling as well as the overactivation of GSK3β and mTOR signaling. Collectively, our data strongly supported DHCR24 knock-down lead to tau hyperphosphorylation and the inhibition of autophagy by a lipid raft-dependent PI3-K/Akt-mediated GSK3β and mTOR signaling. Taking together, our results firstly demonstrated that the decrease of plasma membrane cholesterol mediated by DHCR24 deficiency might contribute to the tauopathy in AD and other tauopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2021.513605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098657PMC
April 2021

Detection of chlorpyrifos and carbendazim residues in the cabbage using visible/near-infrared spectroscopy combined with chemometrics.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Aug 1;257:119759. Epub 2021 Apr 1.

College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China; Key Laboratory of Spectroscopy Sensing, Ministry of Agriculture and Rural Affairs, Hangzhou 310058, China. Electronic address:

Contamination of agricultural plants and food in the environment caused by pesticide residues has gained great attention of the world. Pesticide residues on vegetables constitute a potential risk to human health. A visible/near-infrared (Vis/NIR) spectroscopy combined with chemometric methods was employed to quantitatively determine chlorpyrifos and carbendazim residues in the cabbage (Brassica chinensis L.). Preprocessing methods were used for spectra denoising. Partial least squares regression (PLSR) and least squares-support vector machine (LS-SVM) were applied as the quantification models. Feature variables were selected by successive projection algorithms (SPA), random frog and regression coefficients in PLSR. As for the samples with chlorpyrifos residues, LS-SVM models based on the global spectra achieved best model performance. The best performance for carbendazim content prediction was achieved by the LS-SVM models based on the original global spectra. And modeling with SPA selected feature variables for carbendazim determination was as good as modeling with the global spectra. The results indicated that Vis/NIR spectroscopy coupled with chemometrics could be an efficient way for the assessment of the pesticide residues in vegetables, and was significant for detection of environmental pollution and ensuring food safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.saa.2021.119759DOI Listing
August 2021

Preparation and characterization of young fruit fraction and its anti-inflammatory effect on a transgenic zebrafish model.

Nat Prod Res 2021 Apr 16:1-6. Epub 2021 Apr 16.

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, P.R.China.

Young fruits (YPF) contain substances that are distinct from those found in the mature fruits. Response surface methodology was used to explore the influences of extraction conditions including ultrasonic time (X), ethanol proportion (X), liquid-to-solid ratio (X) and temperature (X) on UV-absorbing components from YPF. To purify the extract, the adsorption/desorption properties of 280 nm-absorbing components on AB-8 resin were investigated. A total of 11 metabolites (amino acids, glycosylated amino acids and phenolics) were identified in the UV-absorbing fraction of YPF (YPF-F) based on LC-MS/MS assays. In a study of anti-inflammatory activity, YPF-F significantly decreased the number of inflammatory cells that migrated to the lateral line location in CuSO-induced transgenic fluorescent zebrafish. YPF should be utilized as a high value resource of functional foods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2021.1912748DOI Listing
April 2021

Long Noncoding RNA X-Inactive-Specific Transcript Promotes the Secretion of Inflammatory Cytokines in LPS Stimulated Astrocyte Cell Via Sponging miR-29c-3p and Regulating Nuclear Factor of Activated T cell 5 Expression.

Front Endocrinol (Lausanne) 2021 12;12:573143. Epub 2021 Mar 12.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

Background: Astrocyte activation promotes glutamate accumulation and secretion of inflammatory factors, mainly responsible for epilepsy. Long noncoding RNA (lncRNA) X-inactive-specific transcript (XIST) regulates inflammation; however, the biological role and regulatory mechanism of XIST during astrocyte activation remain unclear.

Methods: In the present study, rat epilepsy model and lipopolysaccharide (LPS)-treated CTX-TNA2 were established. XIST and miR-29c-3p expression were evaluated using quantitative real-time polymerase chain reaction. Nuclear factor of activated T cells 5 (NFAT5) was measured using western blot analysis. Interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and L-glutamate levels in the culture supernatants were assessed using enzyme-linked immunosorbent assay. The binding between XIST and miR-29c-3p and between miR-29c-3p and the 3'-UTR of NFAT5 was analyzed using dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and Biotin pull-down assay. The proliferation and apoptosis were evaluated using CCK8 and flow cytometry, respectively.

Results: XIST expression and NFAT5 protein level was increased, whereas miR-29c-3p expression was decreased in the epilepsy rat model and LPS-treated CTX-TNA2 cells. Silenced XIST expression, miR-29c-3p overexpression, or silenced NFAT5 expression inhibited the secretion of IL-1β, IL-6, and TNF-α and promoted glutamate transport in LPS-treated CTX-TNA2 cells. miR-29c-3p was the potential miRNA sponged by XIST. NFAT5 acted as a direct binding target of miR-29c-3p. Silenced miR-29c-3p expression or NFAT5 overexpression reversed the effect of silenced XIST expression on LPS-treated CTX-TNA2.XIST and miR-29c-3p treatment does not affect NFAT5 mRNA expression, but affects NFAT5 protein level. Furthermore, underexpressed XIST or overexpressed miR-29c-3p in LPS-stimulated CTX-TNA2 can attenuate neuronal apoptosis induced by LPS-stimulated CTX-TNA2.

Conclusion: LncRNA XIST promotes the secretion of inflammatory cytokines in LPS- treated CTX-TNA2 sponging miR-29c-3p and regulating NFAT5 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.573143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995889PMC
March 2021

Thyroid-stimulating hormone decreases the risk of osteoporosis by regulating osteoblast proliferation and differentiation.

BMC Endocr Disord 2021 Mar 16;21(1):49. Epub 2021 Mar 16.

Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, China.

Background: As the incidence of secretory osteoporosis has increased, bone loss, osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and its possible underlying mechanisms were investigated.

Methods: We analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH and the bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different lengths of time. The related gene and protein expression levels were investigated.

Results: A comparison of the BMD between the high-level and low-level serum TSH groups showed that the TSH serum concentration was positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P < 0.05, P < 0.01). Bone morphogenetic protein (BMP)2 activity was enhanced with both increased TSH concentration and increased time. The protein levels of Runx2 and osterix were increased in a dose-dependent manner.

Conclusions: The circulating concentrations of TSH and BMD were positively correlated with normal thyroid function in males. TSH promoted osteoblast proliferation and differentiation in rat primary osteoblasts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12902-021-00715-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968288PMC
March 2021

Segmental resection is associated with decreased survival in patients with stage IA non-small cell lung cancer with a tumor size of 21-30 mm.

Transl Lung Cancer Res 2021 Feb;10(2):900-913

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: The feasibility of segmental resection for early-stage non-small cell lung cancer (NSCLC) is still controversial. This study aimed to compare survival outcomes following lobectomy and segmental resection in patients with pathological T1cN0M0 (tumor size 21-30 mm) NSCLC.

Methods: Patients diagnosed between 1998 and 2016 with pathological stage IA NSCLC and with tumors measuring 21-30 mm were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The observational outcomes were cancer-specific survival (CSS) and overall survival (OS) at 5 years. Univariate survival analysis was carried out to identify potential prognostic factors of prolonged survival. Cox proportional hazards model was used to adjust for confounding factors. Additionally, pairwise comparisons were conducted between lobectomy and segmental resection for CSS and OS, and forest plots were drawn.

Results: Of the 9,580 patients analyzed, 400 patients (4.2%) underwent segmental resections. Patients with older age (P<0.001), smaller tumors (P<0.001), and left-sided tumors (P=0.002) were more likely to receive segmental resection. No difference was found in the operative mortality rates between the segmental resection group and the lobectomy group (1.0% . 1.2%, P=0.707). The CSS (HR, 1.429; 95% CI, 1.166-1.752; P=0.001) and OS (HR, 1.348; 95% CI, 1.176-1.544; P<0.001) in the segmental resection group were significantly worse than those in the lobectomy group. Subgroup analyses by age, year of diagnosis, sex, tumor size, histology, grade, and the number of dissected lymph nodes also confirmed that lobectomy was associated with improved CSS and OS.

Conclusions: Lobectomy and thorough removal of lymph nodes should continue to be the recommended standard of care for patients with surgically resectable stage IA NSCLC with tumor size of 21-30 mm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tlcr-20-1217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947415PMC
February 2021

DHCR24 Knockdown Lead to Hyperphosphorylation of Tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites by Membrane Lipid-Raft Dependent PP2A Signaling in SH-SY5Y Cells.

Neurochem Res 2021 Jul 12;46(7):1627-1640. Epub 2021 Mar 12.

Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, 201508, China.

Accumulating data suggest that the downregulation of DHCR24 is linked to the pathological risk factors of AD, denoting a potential role of DHCR24 in AD pathogenesis. However, it remains unclear whether the downregulation of DHCR24 affects the abnormal heper-phosphorylation of tau protein, which is involved in tauopathy. In present papers, immunofluorescence and Filipin III fluorescence results showed that DHCR24 knockdown significantly lowered the level of plasma membrane cholesterol and expression level of membrane lipid-raft structural protein caveolin-1; and overexpression of DHCR24 could increase the plasma membrane cholesterol levels and facilitating caveolae structure through increase the expression of caveolin-1. PP2A is the key phosphatase involving in tau phosphorylation, which is localized in cholesterol-dependent caveola/raft lipid domains. Here, the PP2A activity was detected by western blot assay. Interestingly, the level of p-PP2Ac at Y307 (inactive) and p-GSK3β at Y216 (active) in the downstream of the PP2A signal pathway were both significantly increased in silencing DHCR24 SH-SY5Y cells, which denoted an inhibition of the PP2A and activation of GSK3β signaling. Conversely, overexpression of DHCR24 blunted the inhibition effect of PP2A and activation of GSK3β. Besides, in the SH-SY5Y cell lines we demonstrated that DHCR24 knockdown obviously induced hyperphosphorylation of tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites. In contrast, DHCR24 overexpression protects neuronal SH-SY5Y cells against the hyperphosphorylation of tau at Thr181, Thr231, Ser262, Ser396, and Ser422 Sites. Furthermore, PP2A activator D-erythro-Sphingosine (DES) also obviously inhibited the hyperphosphorylation of tau induced by DHCR24 knockdown. Collectively, our findings firstly confirmed that DHCR24 knockdown obviously induced abnormal hyperphosphorylation of tau by a novel lipid raft-dependent PP2A signaling. We propose that DHCR24 downregulation led to altered cholesterol synthesis as a potential mechanism in the progression of tau hyperphosphorylation involving in AD and other tauopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-021-03273-6DOI Listing
July 2021

Alleviative effects of nitric oxide on Vigna radiata seedlings under acidic rain stress.

Mol Biol Rep 2021 Mar 10;48(3):2243-2251. Epub 2021 Mar 10.

Biological Sciences Department, Dezhou University, Dezhou, Shandong, China.

Although nitric oxide (NO) is a key regulatory molecule in plants, its function in plants under conditions of simulated acid rain (SAR) has not been fully established yet. In this study, exogenous sodium nitroprusside (SNP) at three different concentrations were applied to mung bean seedlings. Malondialdehyde (MDA), NO, hydrogen peroxide (HO), antioxidant enzyme activities, and nitrate reductases (NR) were measured. Real time PCR was used to measure the NR expression. Compared to the control, the NR activity and NO content under the pH 2 SAR decreased by 79% and 85.6% respectively. Meanwhile, the SAR treatment reduced the activities of superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), while increased MDA content. Application of SNP could potentially reverse the adverse impact of SAR, depending on its concentration. For plants under the pH 2 SAR and 0.25 mM SNP condition, the activities of SOD, POD, APX increased by 123%, 291%, and 135.7% respectively, meanwhile, MDA concentration decreased by 43%, NR activities increased by 269%, and NO concentration increased by 123.6% compared with plants undergoing only pH 2 SAR. The relative expression of the NR1 gene was 2.69 times higher than that of pH 2 SAR alone. Overall, the application of 0.25 mM SNP eliminated reactive oxygen species (ROS) by stimulating antioxidant enzyme activities, reducing oxidative stress and mitigating the toxic effects of SAR on mung bean seedlings. This research provides a foundation for further research on the mechanism of NO on plants under SAR conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-021-06244-wDOI Listing
March 2021

Machine learning techniques based on security management in smart cities using robots.

Work 2021 ;68(3):891-902

Department of Computer Science & Engineering, Vel Tech Rangarajan Dr Sagunthala R&D Institute of Science and Technology, Avadi, Chennai, India.

Background: Nowadays, the growth of smart cities is enhanced gradually, which collects a lot of information and communication technologies that are used to maximize the quality of services. Even though the intelligent city concept provides a lot of valuable services, security management is still one of the major issues due to shared threats and activities. For overcoming the above problems, smart cities' security factors should be analyzed continuously to eliminate the unwanted activities that used to enhance the quality of the services.

Objectives: To address the discussed problem, active machine learning techniques are used to predict the quality of services in the smart city manages security-related issues. In this work, a deep reinforcement learning concept is used to learn the features of smart cities; the learning concept understands the entire activities of the smart city. During this energetic city, information is gathered with the help of security robots called cobalt robots. The smart cities related to new incoming features are examined through the use of a modular neural network.

Results: The system successfully predicts the unwanted activity in intelligent cities by dividing the collected data into a smaller subset, which reduces the complexity and improves the overall security management process. The efficiency of the system is evaluated using experimental analysis.

Conclusion: This exploratory study is conducted on the 200 obstacles are placed in the smart city, and the introduced DRL with MDNN approach attains maximum results on security maintains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/WOR-203423DOI Listing
June 2021

Separation, identification and cardiovascular activities of phospholipid classes from the head of by lipidomics and zebrafish models.

Food Funct 2021 Mar;12(5):2282-2291

Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250103, China. and Bioengineering Technology Innovation Center of Shandong Province, Heze, 274000, China.

Phospholipids not only have high nutritional value, but also have a positive effect on cardiovascular disease, cancer and nervous system diseases. However, the activity of individual phospholipid classes of shrimp phospholipids is rarely studied. This paper researched phospholipids in the by-products of Penaeus vannamei processing. The phospholipid classes of the head from P. vannamei (PV) were separated by column chromatography, analyzed with UHPLC-Q-Exactive HF/MS, and quantified using ammonium ferrothiocyarate spectrophometry. In addition, their cardiovascular activities in zebrafish models were evaluated. A total of 5 phospholipid classes were obtained, including PV-PC, PV-PE, PV-PI, PV-PS and PV-SM, and identified as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and sphingomyelin (SM), respectively. In the phospholipid profiling analysis, PV-PC (308 molecules) had the highest proportion with 85.24%, followed by PV-PE (139 types) with 9.32%, PV-SM (41 structures) with 4.75%, PV-PS (24 types) with 0.16%, and PV-PI (6 molecules) with 0.03%. In the quantitative analysis, the content of PV was 45.7%, and the purity of phospholipid classes was 75.5-88.1%. In the cardiovascular activity assays, the effects of different phospholipid classes were different. For example, PV-PC groups had strong angiogenesis activity, but PV-PE groups showed the opposite property. Our comprehensive profiling analysis and in vivo bioactivity evaluation of phospholipids from the head of P. vannamei can provide evidence for their targeted applications in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0fo03017aDOI Listing
March 2021

Advice for COVID-19 vaccination: get some sleep.

Sleep Breath 2021 Feb 17. Epub 2021 Feb 17.

Sleep Medicine Center, Department of Respiratory and Critical Care Medicine, Mental Health Center, West China Hospital, Sichuan University, Chengdu, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11325-021-02313-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889055PMC
February 2021

New Prenylated Indole Homodimeric and Pteridine Alkaloids from the Marine-Derived Fungus Y32-2.

Mar Drugs 2021 Feb 9;19(2). Epub 2021 Feb 9.

Key Laboratory of Marine Bioactive Substances, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China.

Chemical investigation of secondary metabolites from the marine-derived fungus Y32-2 resulted in the isolation of two new prenylated indole alkaloid homodimers, di-6-hydroxydeoxybrevianamide E () and dinotoamide J (), one new pteridine alkaloid asperpteridinate A (), with eleven known compounds (-). Their structures were elucidated by various spectroscopic methods including HRESIMS and NMR, while their absolute configurations were determined by ECD calculations. Each compound was evaluated for pro-angiogenic, anti-inflammatory effects in zebrafish models and cytotoxicity for HepG2 human liver carcinoma cells. As a result, compounds , , , , exhibited pro-angiogenic activity in a PTK787-induced vascular injury zebrafish model in a dose-dependent manner, compounds , , , displayed anti-inflammatory activity in a CuSO-induced zebrafish inflammation model, and compound showed significant cytotoxicity against HepG2 cells with an IC value of 30 µg/mL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/md19020098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916005PMC
February 2021

The role of pro- and mature neurotrophins in the depression.

Behav Brain Res 2021 04 4;404:113162. Epub 2021 Feb 4.

Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address:

Neurotrophic factors, which can provide nutritional support to neurons and neuronal cells, also played an important role in their proliferation and survival. As signaling molecules, it also mediated the learning, memory and other activities in the brain. The latest study shows that neurotrophic factors have diametrically opposing effects of the pro- and mature form through distinct receptors. In this review, we summarize the different forms of neurotrophic factors, related receptors, and the corresponding biological effects. More importantly, we expounded the physiology and pathology mechanisms of brain-derived neurotrophic factor(BDNF)in depression. It is hopefully to provide new idea on the relationship of neurotrophic factors and depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2021.113162DOI Listing
April 2021

Correction to: Lynch syndrome-associated repeated stroke with MLH1 frame-shift mutation.

Neurol Sci 2021 Apr;42(4):1641

Department of Neurology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05098-1DOI Listing
April 2021

Regulation of ROS in myeloid-derived suppressor cells through targeting fatty acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy.

Cell Immunol 2021 04 19;362:104286. Epub 2021 Jan 19.

Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of Chinese Academy of Sciences, Beijing 100864, China; Shenzhen BinDeBioTech Co., Ltd, Shenzhen 518055, China. Electronic address:

Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy against the PD-1/PD-L1 axis, it induces sustained responses in a sizeable minority of cancer patients due to the activation of immunosuppressive factors such as myeloid-derived suppressor cells (MDSCs). Inhibiting the immunosuppressive function of MDSCs is critical for successful cancer ICB therapy. Interestingly, lipid metabolism is a crucial factor in modulating MDSCs function. Fatty acid transport protein 2 (FATP2) conferred the function of PMN-MDSCs in cancer via the upregulation of arachidonic acid metabolism. However, whether regulating lipid accumulation in MDSCs by targeting FATP2 could block MDSCs reactive oxygen species (ROS) production and enhance PD-L1 blockade-mediated tumor immunotherapy remains unexplored. Here we report that FATP2 regulated lipid accumulation, ROS, and immunosuppressive function of MDSCs in tumor-bearing mice. Tumor cells-derived granulocyte macrophage-colony stimulating factor (GM-CSF) induced FATP2 expression in MDSCs by activation of STAT3 signaling pathway. Pharmaceutical blockade of FATP2 expression in MDSCs by lipofermata decreased lipid accumulation, reduced ROS, blocked immunosuppressive activity, and consequently inhibited tumor growth. More importantly, lipofermata inhibition of FATP2 in MDSCs enhanced anti-PD-L1 tumor immunotherapy via the upregulation of CD107a and reduced PD-L1 expression on tumor-infiltrating CD8T-cells. Furthermore, the combination therapy blocked MDSC's suppressive role on T- cells thereby enhanced T-cell's ability for the production of IFN-γ. These findings indicate that FATP2 plays a key role in modulating lipid accumulation-induced ROS in MDSCs and targeting FATP2 in MDSCs provides a novel therapeutic approach to enhance anti-PD-L1 cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellimm.2021.104286DOI Listing
April 2021

Knowledge, attitudes and anxiety toward COVID-19 among domestic and overseas Chinese college students.

J Public Health (Oxf) 2021 09;43(3):466-471

Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.

Background: To investigate the knowledge, attitudes and anxiety toward COVID-19 among Chinese college students studying in China and abroad.

Method: A structured questionnaire, comprised of demographic characteristics, knowledge and attitudes toward COVID-19 and the State-Trait Anxiety Inventory (STAI), was used to collect data for 566 domestic students and 126 students studying abroad.

Results: Domestic students were better than students abroad in knowledge of epidemiology and manifestations. Domestic students showed a significant higher enthusiasm for voluntary services than students abroad, including medical science popularization, community services, traffic dispersion, logistics transportation and being volunteers for vaccine trials. The scores (Mean ± SD) of S-AI and T-AI among students abroad were 59.48 ± 8.63 and 54.10 ± 7.20, respectively, which were significantly higher than those of domestic students (39.46 ± 8.16 and 39.25 ± 7.72).

Conclusions: Our study showed a better understanding of knowledge, more positive attitudes and less anxiety toward COVID-19 among domestic students, compared with students studying abroad. In light of this information, more attention and appropriate psychological and social intervention should be paid to college students with anxiety, especially those studying abroad.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pubmed/fdaa268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928746PMC
September 2021
-->