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Article ; Online: Obesity-induced blood-brain barrier dysfunction: phenotypes and mechanisms.

Feng, Ziying / Fang, Cheng / Ma, Yinzhong / Chang, Junlei

2024 Volume 21, Issue 1, Page(s) 110

Abstract: Obesity, a burgeoning global health issue, is increasingly recognized for its detrimental effects on the central nervous system, particularly concerning the integrity of the blood-brain barrier (BBB). This manuscript delves into the intricate ... ...

Abstract	Obesity, a burgeoning global health issue, is increasingly recognized for its detrimental effects on the central nervous system, particularly concerning the integrity of the blood-brain barrier (BBB). This manuscript delves into the intricate relationship between obesity and BBB dysfunction, elucidating the underlying phenotypes and molecular mechanisms. We commence with an overview of the BBB's critical role in maintaining cerebral homeostasis and the pathological alterations induced by obesity. By employing a comprehensive literature review, we examine the structural and functional modifications of the BBB in the context of obesity, including increased permeability, altered transport mechanisms, and inflammatory responses. The manuscript highlights how obesity-induced systemic inflammation and metabolic dysregulation contribute to BBB disruption, thereby predisposing individuals to various neurological disorders. We further explore the potential pathways, such as oxidative stress and endothelial cell dysfunction, that mediate these changes. Our discussion culminates in the summary of current findings and the identification of knowledge gaps, paving the way for future research directions. This review underscores the significance of understanding BBB dysfunction in obesity, not only for its implications in neurodegenerative diseases but also for developing targeted therapeutic strategies to mitigate these effects.
MeSH term(s)	Humans ; Blood-Brain Barrier/pathology ; Blood-Brain Barrier/metabolism ; Obesity/pathology ; Obesity/metabolism ; Obesity/complications ; Obesity/physiopathology ; Animals ; Phenotype
Language	English
Publishing date	2024-04-27
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-024-03104-9
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Article: Six Unprecedented Cytochalasin Derivatives from the Potato Endophytic Fungus

Zhang, Xian / Fan, Yinzhong / Ye, Ke / Pan, Xiaoyan / Ma, Xujun / Ai, Honglian / Shi, Baobao / Liu, Jikai

Pharmaceuticals (Basel, Switzerland)

2023 Volume 16, Issue 2

Abstract: Six previously undescribed cytochalasins, Curtachalasins X1-X6 ( ...

Abstract	Six previously undescribed cytochalasins, Curtachalasins X1-X6 (
Language	English
Publishing date	2023-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16020193
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Article ; Online: Advancing stroke therapy: A deep dive into early phase of ischemic stroke and recanalization.

He, Qianyan / Wang, Yueqing / Fang, Cheng / Feng, Ziying / Yin, Meifang / Huang, Juyang / Ma, Yinzhong / Mo, Zhizhun

CNS neuroscience & therapeutics

2024 Volume 30, Issue 2, Page(s) e14634

Abstract: Ischemic stroke, accounting for the majority of stroke events, significantly contributes to global morbidity and mortality. Vascular recanalization therapies, namely intravenous thrombolysis and mechanical thrombectomy, have emerged as critical ... ...

Abstract	Ischemic stroke, accounting for the majority of stroke events, significantly contributes to global morbidity and mortality. Vascular recanalization therapies, namely intravenous thrombolysis and mechanical thrombectomy, have emerged as critical interventions, yet their success hinges on timely application and patient-specific factors. This review focuses on the early phase pathophysiological mechanisms of ischemic stroke and the nuances of recanalization. It highlights the dual role of neutrophils in tissue damage and repair, and the critical involvement of the blood-brain barrier (BBB) in stroke outcomes. Special emphasis is placed on ischemia-reperfusion injury, characterized by oxidative stress, inflammation, and endothelial dysfunction, which paradoxically exacerbates cerebral damage post-revascularization. The review also explores the potential of targeting molecular pathways involved in BBB integrity and inflammation to enhance the efficacy of recanalization therapies. By synthesizing current research, this paper aims to provide insights into optimizing treatment protocols and developing adjuvant neuroprotective strategies, thereby advancing stroke therapy and improving patient outcomes.
MeSH term(s)	Humans ; Ischemic Stroke/therapy ; Stroke/therapy ; Thrombolytic Therapy ; Thrombectomy/methods ; Inflammation ; Brain Ischemia/therapy ; Treatment Outcome
Language	English
Publishing date	2024-04-18
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2423461-8
ISSN	1755-5949 ; 1755-5930
ISSN (online)	1755-5949
ISSN	1755-5930
DOI	10.1111/cns.14634
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Zs.A 4537: Show issues

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Article ; Online: The profile of HIV-1 drug resistance in Shanghai, China: a retrospective study from 2017 to 2021.

Zhang, Min / Ma, Yingying / Wang, Gang / Wang, Zhenyan / Wang, Qianying / Li, Xin / Lin, Feng / Qiu, Jianping / Chen, Daihong / Shen, Yinzhong / Zhang, Chiyu / Lu, Hongzhou

The Journal of antimicrobial chemotherapy

2024 Volume 79, Issue 3, Page(s) 526–530

Abstract: Background: HIV-1 drug resistance is a huge challenge in the era of ART.: Objectives: To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China.: Methods: An epidemiological study was performed ... ...

Abstract	Background: HIV-1 drug resistance is a huge challenge in the era of ART. Objectives: To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. Methods: An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. Results: Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. Conclusions: We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH.
MeSH term(s)	Humans ; HIV-1/genetics ; Retrospective Studies ; China/epidemiology ; HIV Seropositivity ; Alkynes
Chemical Substances	Alkynes
Language	English
Publishing date	2024-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkad370
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Mechanism analysis of humification coupling metabolic pathways based on cow dung composting with ionic liquids.

Yang, Hongxiang / Ma, Liangcai / Fu, Mengxin / Li, Kecheng / Li, Yinzhong / Li, Qunliang

Journal of environmental management

2022 Volume 325, Issue Pt A, Page(s) 116426

Abstract: This study focused on how adding ionic liquids (IL) affects composting humification. During the warming and thermophilic phases, addition of IL increased precursors content, and increased the polymerization of humus (HS) at later stages. Furthermore, the ...

Abstract	This study focused on how adding ionic liquids (IL) affects composting humification. During the warming and thermophilic phases, addition of IL increased precursors content, and increased the polymerization of humus (HS) at later stages. Furthermore, the final HS and humic acid (HA) content of experimental groups (T) groups 129.79 mg/g and 79.91 mg/g were higher than in control group (CK) 118.57 mg/g and 74.53 mg/g, respectively (p < 0.05). IL up-regulated the gene abundance of metabolism for carbohydrate and amino acid (AA), and promoted the contributions of Actinobacteria and Proteobacteria, which affected humification. The redundancy analysis (RDA) results showed that the citrate-cycle (TCA cycle)(ko0020), pentose phosphate pathway (ko00030), pyruvate metabolism (ko00620), glyoxylate and dicarboxylate metabolism (ko00630), propanoate metabolism (ko00640), butanoate metabolism (ko00650) positively correlated with HA and HI. HA and humification index (HI) positively correlated with AA metabolic pathways, and fulvic acid (FA) was negatively correlated with these pathways. Overall, metabolism for carbohydrate and AA metabolism favored compost humification. ILs improved metabolism for carbohydrate and amino acid metabolism, thus enhancing humification.
MeSH term(s)	Animals ; Cattle ; Composting ; Ionic Liquids ; Manure ; Humic Substances/analysis ; Soil ; Amino Acids ; Metabolic Networks and Pathways ; Carbohydrates
Chemical Substances	Ionic Liquids ; Manure ; Humic Substances ; Soil ; Amino Acids ; Carbohydrates
Language	English
Publishing date	2022-10-11
Publishing country	England
Document type	Journal Article
ZDB-ID	184882-3
ISSN	1095-8630 ; 0301-4797
ISSN (online)	1095-8630
ISSN	0301-4797
DOI	10.1016/j.jenvman.2022.116426
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Article: Activation of Wnt/Beta-Catenin Signaling Pathway as a Promising Therapeutic Candidate for Cerebral Ischemia/Reperfusion Injury.

Mo, Zhizhun / Zeng, Zhongyi / Liu, Yuxiang / Zeng, Linsheng / Fang, Jiansong / Ma, Yinzhong

Frontiers in pharmacology

2022 Volume 13, Page(s) 914537

Abstract: Stroke is one of the leading causes of mortality, and survivors experience serious neurological and motor behavioral deficiencies. Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur because of ... ...

Abstract	Stroke is one of the leading causes of mortality, and survivors experience serious neurological and motor behavioral deficiencies. Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur because of ischemia/reperfusion injury. Wnt signaling is an evolutionarily conserved signaling pathway that has been manifested to play a key role in embryo development and function maintenance in adults. Overactivation of Wnt signaling has previously been investigated in cancer-based research studies. Recently, abnormal Wnt signaling activity has been observed in ischemic stroke, which is accompanied by massive blood-brain barrier (BBB) disruption, neuronal apoptosis, and neuroinflammation within the central nervous system (CNS). Significant therapeutic effects were observed after reactivating the adynamic signaling activity of canonical Wnt signaling in different cell types. To better understand the therapeutic potential of Wnt as a novel target for stroke, we reviewed the role of Wnt signaling in the pathogenesis of stroke in different cell types, including endothelial cells, neurons, oligodendrocytes, and microglia. A comprehensive understanding of Wnt signaling among different cells may help to evaluate its potential value for the development of novel therapeutic strategies based on Wnt activation that can ameliorate complications and improve functional rehabilitation after ischemic stroke.
Language	English
Publishing date	2022-05-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.914537
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Article ; Online: The Role of Immune Cells in Post-Stroke Angiogenesis and Neuronal Remodeling: The Known and the Unknown.

Ma, Yinzhong / Yang, Shilun / He, Qianyan / Zhang, Dianhui / Chang, Junlei

Frontiers in immunology

2021 Volume 12, Page(s) 784098

Abstract: Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur due to ischemia-induced cerebral pathology. Mounting evidence indicates that the robust recruitment of immune cells plays a central role in the ... ...

Abstract	Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur due to ischemia-induced cerebral pathology. Mounting evidence indicates that the robust recruitment of immune cells plays a central role in the acute stage of stroke. Infiltrating peripheral immune cells and resident microglia mediate neuronal cell death and blood-brain barrier disruption by releasing inflammation-associated molecules. Nevertheless, profound immunological effects in the context of the subacute and chronic recovery phase of stroke have received little attention. Early attempts to curtail the infiltration of immune cells were effective in mitigating brain injury in experimental stroke studies but failed to exert beneficial effects in clinical trials. Neural tissue damage repair processes include angiogenesis, neurogenesis, and synaptic remodeling, etc. Post-stroke inflammatory cells can adopt divergent phenotypes that influence the aforementioned biological processes in both endothelial and neural stem cells by either alleviating acute inflammatory responses or secreting a variety of growth factors, which are substantially involved in the process of angiogenesis and neurogenesis. To better understand the multiple roles of immune cells in neural tissue repair processes post stroke, we review what is known and unknown regarding the role of immune cells in angiogenesis, neurogenesis, and neuronal remodeling. A comprehensive understanding of these inflammatory mechanisms may help identify potential targets for the development of novel immunoregulatory therapeutic strategies that ameliorate complications and improve functional rehabilitation after stroke.
MeSH term(s)	Animals ; Blood-Brain Barrier/immunology ; Blood-Brain Barrier/pathology ; Cytokines/metabolism ; Disease Models, Animal ; Endothelial Cells/immunology ; Endothelial Cells/metabolism ; Humans ; Inflammation Mediators/metabolism ; Ischemic Stroke/immunology ; Ischemic Stroke/pathology ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Microglia/immunology ; Microglia/metabolism ; Neovascularization, Physiologic/immunology ; Neural Stem Cells/immunology ; Neural Stem Cells/metabolism ; Neuroinflammatory Diseases/immunology ; Neuroinflammatory Diseases/pathology ; Neuronal Plasticity/immunology ; Recovery of Function/immunology
Chemical Substances	Cytokines ; Inflammation Mediators
Language	English
Publishing date	2021-12-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.784098
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Article ; Online: Spatiotemporal lipidomics reveals key features of brain lipid dynamic changes after cerebral ischemia and reperfusion therapy.

Ma, Yinzhong / Chen, Zhiyu / He, Qianyan / Guo, Zhen-Ni / Yang, Yi / Liu, Fulin / Li, Fang / Luo, Qian / Chang, Junlei

Pharmacological research

2022 Volume 185, Page(s) 106482

Abstract: Reperfusion therapy with recombinant tissue plasminogen activator (rtPA) or mechanical thrombectomy is the most effective treatment for ischemic stroke. However, a large proportion of stroke patients remain severely disabled even after receiving timely ... ...

Abstract	Reperfusion therapy with recombinant tissue plasminogen activator (rtPA) or mechanical thrombectomy is the most effective treatment for ischemic stroke. However, a large proportion of stroke patients remain severely disabled even after receiving timely reperfusion therapy. It remains unclear how reperfusion therapy results in secondary injury to the brain tissue and whether different reperfusion therapies induce differential effects. Here, we comprehensively determined the spatiotemporal dynamic changes in brain lipids during the acute phase after reperfusion in a mouse model of transient middle cerebral artery occlusion, with or without rtPA administration, using desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI). Several phospholipids, sphingolipids, and neutral lipids were significantly altered both spatially and temporally at multiple timepoints after reperfusion, many of which were closely associated with expansion of the brain infarction territory and neurological function impairment. Furthermore, rtPA treatment significantly increased brain infarction, cerebral edema, and neurological deficits. Consistently, rtPA treatment caused extensive brain lipid alterations by facilitating brain-wide changes in lipid metabolism and inducing ischemic region-specific lipid changes. Overall, these results provide novel insights into how reperfusion therapy affects brain tissue and the outcome of stroke patients, and thus may facilitate the optimization of the treatment of ischemic stroke.
MeSH term(s)	Animals ; Mice ; Tissue Plasminogen Activator ; Lipidomics ; Brain Ischemia/drug therapy ; Reperfusion/methods ; Stroke/drug therapy ; Infarction, Middle Cerebral Artery/drug therapy ; Brain/metabolism ; Ischemic Stroke ; Lipid Metabolism ; Lipids ; Fibrinolytic Agents/therapeutic use
Chemical Substances	Tissue Plasminogen Activator (EC 3.4.21.68) ; Lipids ; Fibrinolytic Agents
Language	English
Publishing date	2022-10-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2022.106482
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Zs.A 721: Show issues

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Article: Thalidomide for Recurrence of Symptoms following HIV-Associated Cryptococcal Meningitis.

Qi, Tangkai / Chen, Fang / Ma, Siyue / Zhang, Renfang / Liu, Li / Wang, Zhenyan / Tang, Yang / Song, Wei / Sun, Jianjun / Yang, Junyang / Xu, Shuibao / Zhao, Bihe / Shen, Yinzhong / Chen, Jun

Infectious diseases and therapy

2023 Volume 12, Issue 6, Page(s) 1667–1675

Abstract: Introduction: Cryptococcal meningitis (CM) is a serious and fatal fungal infection that affects individuals infected with human immunodeficiency virus (HIV). Despite treatment, recurrence of symptoms is common and could lead to poor outcomes. ... ...

Abstract	Introduction: Cryptococcal meningitis (CM) is a serious and fatal fungal infection that affects individuals infected with human immunodeficiency virus (HIV). Despite treatment, recurrence of symptoms is common and could lead to poor outcomes. Corticosteroids are not always useful in treating symptom recurrence following HIV/CM; thus, alternative therapy is needed. Thalidomide has been reported to be effective in treating symptom recurrence in several patients with HIV/CM. This retrospective study aimed to investigate the efficacy and safety of thalidomide in the treatment of symptom recurrence following HIV/CM. Methods: Patients who were treated with thalidomide for symptom recurrence following HIV/CM were retrospectively included. Clinical outcomes and adverse events were recorded and analyzed. Results: Sixteen patients admitted between July 2018 and September 2020 were included in the analysis. During a median follow-up period of 295 (166, 419) days, all patients achieved clinical improvement in a median of 7 (4, 20) days. Among them, nine (56%) achieved complete resolution of symptoms at a median of 187 (131, 253) days, including 40% (2/5) of immune reconstitution inflammatory syndrome (IRIS), 50% (3/6) of patients with elevated ICP only, and 80% (4/5) of patients with symptoms only. Seven (43%) patients experienced nine episodes of adverse events, but no severe adverse event attributable to thalidomide was observed. None of the patients withdrew from thalidomide due to adverse events. Conclusion: Thalidomide appears to be effective and safe in treating different types of symptom recurrence in HIV/CM. This study provides preliminary evidence supporting future randomized clinical trials to further investigate the efficacy and safety of thalidomide in treating symptom recurrence in this population.
Language	English
Publishing date	2023-06-08
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2701611-0
ISSN	2193-6382 ; 2193-8229
ISSN (online)	2193-6382
ISSN	2193-8229
DOI	10.1007/s40121-023-00817-x
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Article ; Online: An MMP-9 exclusive neutralizing antibody attenuates blood-brain barrier breakdown in mice with stroke and reduces stroke patient-derived MMP-9 activity.

Ji, Yabin / Gao, Qiang / Ma, Yinzhong / Wang, Fang / Tan, Xixi / Song, Dengpan / Hoo, Ruby L C / Wang, Zening / Ge, Xin / Han, Hongjie / Guo, Fuyou / Chang, Junlei

Pharmacological research

2023 Volume 190, Page(s) 106720

Abstract: Rapid upregulation of matrix metalloproteinase 9 (MMP-9) leads to blood-brain barrier (BBB) breakdown following stroke, but no MMP-9 inhibitors have been approved in clinic largely due to their low specificities and side effects. Here, we explored the ... ...

Abstract	Rapid upregulation of matrix metalloproteinase 9 (MMP-9) leads to blood-brain barrier (BBB) breakdown following stroke, but no MMP-9 inhibitors have been approved in clinic largely due to their low specificities and side effects. Here, we explored the therapeutic potential of a human IgG monoclonal antibody (mAb), L13, which was recently developed with exclusive neutralizing specificity to MMP-9, nanomolar potency, and biological function, using mouse stroke models and stroke patient samples. We found that L13 treatment at the onset of reperfusion following cerebral ischemia or after intracranial hemorrhage (ICH) significantly reduced brain tissue injury and improved the neurological outcomes of mice. Compared to control IgG, L13 substantially attenuated BBB breakdown in both types of stroke model by inhibiting MMP-9 activity-mediated degradations of basement membrane and endothelial tight junction proteins. Importantly, these BBB-protective and neuroprotective effects of L13 in wild-type mice were comparable to Mmp9 genetic deletion and fully abolished in Mmp9 knockout mice, highlighting the in vivo target specificity of L13. Meanwhile, ex vivo co-incubation with L13 significantly neutralized the enzymatic activities of human MMP-9 in the sera of ischemic and hemorrhagic stroke patients, or in the peri-hematoma brain tissues from hemorrhagic stroke patients. Overall, we demonstrated that MMP-9 exclusive neutralizing mAbs constitute a potential feasible therapeutic approach for both ischemic and hemorrhagic stroke.
MeSH term(s)	Mice ; Humans ; Animals ; Matrix Metalloproteinase 9/metabolism ; Blood-Brain Barrier/metabolism ; Hemorrhagic Stroke/metabolism ; Stroke/drug therapy ; Stroke/metabolism ; Brain Ischemia/metabolism ; Mice, Knockout
Chemical Substances	Matrix Metalloproteinase 9 (EC 3.4.24.35)
Language	English
Publishing date	2023-03-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2023.106720
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