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Cannabinoids and endocannabinoids as therapeutics for nervous system disorders:preclinical models and clinical studies

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Neural Regeneration Research 2024年第4期19卷 788-799页

作者： R.Scott Duncan Sean M.Riordan Matthew C.Gernon Peter Koulen Department of Ophthalmology School of MedicineUniversity of Missouri Department of Biomedical Sciences School of MedicineUniversity of Missouri

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human *** have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human *** of these include central nervous system(CNS)diseases and dysfunctions such as forms of epilepsy,multiple sclerosis,Parkinson’s disease,pain and neuropsychiatric *** addition,the endogenously produced cannabinoid lipids,endocannabinoids,are critical for normal CNS function,and if controlled or modified,may represent an additional therapeutic avenue for CNS *** review discusses in vitro cellular,ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS *** addition,the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS *** and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

关键词： anandamide cannabidiol cannabinoid endocannabinoid epilepsy multiple sclerosis neurodegeneration neuroprotection tetrahydrocannabinol

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam Department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

Effect of Chinese medicine in Patients with COVID-1.: A Multi-center Retrospective Cohort Study

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Chinese Journal of Integrative medicine 2024年第11期30卷 974-983页

作者： ZHAO Guo-zhen YAN Shi-yan LI Bo GUO Yu-hong SONG Shuang HU Ya-hui GUO Shi-qi HU Jing DU Yuan LU Hai-tian YE Hao-ran REN Zhi-ying ZHU Ling-fei XU Xiao-long SU Rui LIU Qing-quan Beijing Hospital of Traditional Chinese medicine Capital Medical University Beijing Institute of Traditional Chinese Medicine school of Clinical {1. Beijing University of Chinese Medicine school of Acupuncture-Moxibustion and Tuina Beijing University of Chinese Medicine College of Integrated Chinese medicine Tianjin University of Traditional Chinese Medicine

Objective: To evaluate the effectiveness and safety of Chinese medicine(CM) in the treatment of coronavirus disease 201.(COVID-1.) in China. Methods: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of 3 days during hospitalization as exposure. Data came from consecutive inpatients from December 1., 201. to May 1., 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting(IPTW), and the Cox proportional hazards regression model was used for statistical analysis. Results:A total of 2,272 COVID-1. patients were included. There were 1.684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio(HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval(CI): 0.41.to 0.64, P1.. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29(95% CI: 0.1. to 0.44, P1..Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. Conclusion: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-1.patients. This result can provide the new evidence to support the current treatment of COVID-1.. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions.(Registration No. ChiCTR220006291.)

关键词： Chinese medicine all-cause mortality cohort study coronavirus disease 201. deterioration rate

Commentary on“Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells”

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Research 2024年第3期6卷 621-623页

作者： Chen Li Craig N.Morrell Aab Cardiovascular Research Institute University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Pharmacology and Physiology University of Rochester School of Medicine and DentistryRochesterNYUSA Department of medicine University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Microbiology and Immunology University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Pathology and Laboratory medicine University of Rochester School of Medicine and DentistryRochesterNYUSA.

Platelets have long been studied for their roles in hemostasis and vascular injury repair. However, there is a continually evolving and deepening understanding that platelets initiate and regulate responses to tissue injury and pathogens, leading to platelets now being considered immune modulatory cells [1.. Platelets actively participate in host immune responses directly through pathogen engulfing and killing, or by regulating both innate and adaptive immune responses to infection or tissue injury [2]. Activated platelets promote inflammatory responses to tissue injury or infection by direct contact dependent interactions with immune cells and through indirect interactions via released soluble factors. However, mice that are deficient in platelets have skewed T helper cell differentiation [3] and increased vascular permeability [4], implying poorly defined roles for platelets in maintaining healthy immune homeostasis.

关键词： Platelet homeostasis Immune

Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

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World Journal of Emergency medicine 2024年第2期15卷 142-146页

作者： Yi Gu Xiandong Liu Tiancao Dong Qian Yang Xiaowei Bao Dongyang Zhao Lunxian Tang Department of Internal Emergency medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China school of {1. Tongji UniversityShanghai 200120China

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune *** was included on a list of the first batch of 1.1.rare diseases published by the Chinese National Health Commission on 1.^(th)May ***,patients with AE account for 1.%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1.In 201.,China reported the first case of a patient withanti-NMDARtype AE.

关键词： encephalitis autoimmune aspartate

One-pot and One-step Cu(0)-mediated Reversible-Deactivation Radical Polymerization of N-Isopropylacrylamide(NIPAM) in Water

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Chinese Journal of Polymer Science 2024年第1期42卷 1-6,I0004页

作者： Zi-Shan Li Jing Lyu Bei Qiu Ying-Hao Li Ruth Foley Ri-Jian Song Melissa Johnson Qiang Geng Wen-Xin Wang Institute of Precision medicine(AUST-IPM) Anhui University of Science and TechnologyHuainan 232001China Charles Institute of Dermatology School of MedicineUniversity College DublinDublin D04 V1W8Ireland

Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.

关键词： Cu(0)-mediated RDRP N-isopropylacrylamide Propagation Deactivation Reaction parameters

Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

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Journal of Pharmaceutical Analysis 2024年第6期14卷 889-901页

作者： Shaowei Huang Xueqian Xie Bo Xu Zengfeng Pan Junjie Liang Meiling Zhang Simin Pan Xiaojing Wang Meng Zhao Qing Wang Jinyan Chen Yanyang Li Lian Zhou Xia Luo school of Pharmaceutical Sciences Guangzhou University of Chinese Medicine510006China school of Basic {1. Guangzhou University of Chinese Medicine510006China First Clinical Medical College Guangzhou University of Chinese Medicine510000China

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains *** this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 1.0 mg/kg),the anti-tumor necrosis factor-like ligand 1.(anti-TL1.)antibody group,and the IgG *** detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,***,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1.(-/-)mice were used for *** results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal ***,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-1.A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune *** additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via *** conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

关键词： Paeoniflorin Ulcerative colitis Intestinal mucosal barrier DR3 signaling pathway Group 3 innate lymphoid cells

Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A1./GPX4 Signaling Pathway

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Chinese Journal of Integrative medicine 2024年第11期30卷 1001-1006页

作者： HE Dan TAN Xiao-ning LI Lin-pei GAO Wen-hui TIAN Xue-fei ZENG Pu-hua Hunan Academy of Chinese medicine school of Integrated Chinese and Western {1. Hunan University of Chinese Medicine Scientific Research Department The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine Oncology Department The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine school of Traditional Chinese {1. Hunan University of Chinese Medicine

Objective:To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer ***:Breast cancer 4T1.cells were divided into 6 groups:control,brazilin 1.2 half maximal inhibitory concentration(IC50),IC50,2×IC50,erastin（1. μg/mL） and capecitabine（1. μg/mL） *** effect of brazilin on the proliferation of 4T1.cells was detected by cell counting kit-8 assay,and the treatment dose of brazilin was *** effect of brazilin on the mitochondrial morphology of 4T1.cells,and the mitochondrial damage was evaluated under electron *** levels of Fe2+,reactive oxygen species（ROS）,malondialdehyde（MDA）,glutathione（GSH） and glutathione peroxidase 4（GPX4） were estimated using various detection *** invasion and migration abilities of 4T1.cells were detected by scratch assay and transwell *** expressions levels of tumor protein p53, solute carrier family 7 member 1.（SLC7A1.）,GPX4 and acyl-CoA synthetase long-chain family member 4（ACSL4） proteins were quantified by Western blot ***:Compared to the control group,the 1.(1.2 IC50),20(IC50) and 40(2×IC50) μg/mL brazilin,erastin,and capecitabine groups showed a significant decrease in the cell survival rate,invasion and migration abilities,GSH,SLC7A1. and GPX4 protein expression levels,and mitochondrial volume and ridge（P1./GPX4 signaling pathway.

关键词： Chinese medicine brazilin breast cancer ferroptosis p53/SLC7A1./GPX4 axis

Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units

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Neural Regeneration Research 2024年第4期19卷 887-894页

作者： Yifang Wu Jun Sun Qi Lin Dapeng Wang Jian Hai Department of Neurosurgery Tongji HospitalSchool of MedicineTongji University Department of Pharmacy Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective ***,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently *** this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning *** found that a membrane containing 1. layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1.*** 1.-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose ***,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved ***,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

关键词： brain ischemia brain microvascular endothelial cell nanofiber membrane neurovascular unit