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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

Natural evidence of coronaviral 2′-O-methyltransferase activity affecting viral pathogenesis via improved substrate RNA binding

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2819-2834页

作者： Jikai Deng Shimin Yang Yingjian Li Xue Tan Jiejie Liu Yanying Yu Qiang Ding Chengpeng Fan Hongyun Wang Xianyin Chen Qianyun Liu Xiao Guo Feiyu Gong Li Zhou Yu Chen State Key Laboratory of Virology RNA InstituteCollege of Life Sciences and Frontier Science Center for Immunology and MetabolismWuhan UniversityWuhanChina school of medicine Tsinghua UniversityBeijingChina school of Basic Medical Sciences Wuhan UniversityWuhanChina Animal Bio-Safety Level Ⅲ Laboratory/Institute for Vaccine Research Wuhan University School of MedicineWuhanChina

Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune ***,the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses,including flaviviruses,vaccinia viruses,coronaviruses,and extends even to ***,we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV,despite the presence of a consistently active catalytic *** further identified critical residues(Leu-36,Asn-138 and Ile-153)which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and *** residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA *** interest,a triple substitution(Leu^(36)→Ile^(36),Asn^(138)→His^(138),Ile^(153)→Leu^(153),from SARS-CoV-2 to SARS-CoV)within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral ***,it led to a significant upregulation of type I interferon(IFN-I)and proinflammatory cytokines both in vitro and vivo,relying on the cooperative sensing of melanoma differentiation-associated protein 5(MDA5)and laboratory of genetics and physiology 2(LGP2).In conclusion,our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence *** changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.

关键词： pathogenesis impaired alterations

Targeting carnitine palmitoyl transferase 1A(CPT1A)induces ferroptosis and synergizes with immunotherapy in lung cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1675-1689页

作者： Lei Ma Chong Chen Chunxing Zhao Tong Li Lingyu Ma Jiayu Jiang Zhaojun Duan Qin Si Tsung-Hsien Chuang Rong Xiang Yunping Luo Department of immunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Collaborative Innovation Center for Biotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Department of Lung Cancer Surgery Tianjin Medical University General HospitalTianjin 300052China immunology Research Center National Health Research InstitutesZhunanMiaoliTaiwanROC Department of immunology Nankai UniversityTianjin 300071China

Despite the successful application of immune checkpoint therapy,no response or recurrence is typical in lung *** stem cells(CSCs)have been identified as a crucial player in immunotherapy-related ***,a form of cell death driven by iron-dependent lipid peroxidation,is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with *** adaption of CsCs drives tumor resistance,yet the mechanisms of their ferroptosis defense in tumor immune evasion remain ***,through metabolomics,transcriptomics,a lung epithelialspecific Cptla-knockout mouse model,and clinical analysis,we demonstrate that CPT1A,a key rate-limiting enzyme of fatty acid oxidation,acts with L-carnitine,derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8^(+)T cells inactivation in lung ***,CPT1A restrains ubiquitination and degradation of c-Myc,while c-Myc transcriptionally activates CPT1A *** CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating,thereby suppressing ferroptosis in ***,targeting CPT1A enhances immune checkpoint blockadeinduced anti-tumor immunity and tumoral ferroptosis in tumor-bearing *** results illustrate the potential of a mechanismguided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CsCs to improve the efficacy of lung cancer immunotherapy.

关键词： immunotherapy metabolism peroxidation

Harnessing SARS-CoV-2-specific CD8^(+)T cells to kill target tumor cells for cancer immunotherapy

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Cancer Communications 2024年第1期44卷 173-177页

作者： Keunok Jung Deok-Han Ko Jeong-Yun Jang Young Rong Kim Jung Yeon Heo Yong-Sung Kim Department of Allergy and Clinical immunology Ajou University School of MedicineSuwonRepublic of Korea Department of Molecular Science and Technology Ajou UniversitySuwonRepublic of Korea Department of Infectious Diseases Ajou University School of MedicineSuwonRepublic of Korea

Dear Editor,During the coronavirus disease 2019(COVID-19)pan-demic era,many individuals were naturally infected with or vaccinated against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),resulting in the p... 详细信息

关键词： acute respiratory immunotherapy

Caspase-11 mediated inflammasome activation in macrophages by systemic infection of *** exacerbates arthritis

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International Journal of Oral Science 2024年第3期16卷 499-514页

作者： Tokuju Okano Hiroshi Ashida Noriko Komatsu Masayuki Tsukasaki Tamako Iida Marie Iwasawa Yuto Takahashi Yasuo Takeuchi Takanori Iwata Miwa Sasai Masahiro Yamamoto Hiroshi Takayanagi Toshihiko Suzuki Department of Bacterial Pathogenesis Infection and Host ResponseGraduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Lifetime Oral Health Care Science Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Periodontology Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Immunoparasitology Research Institute for Microbial DiseasesOsaka UniversityOsakaJapan

Clinical studies have shown that Aggregatibacter actinomycetemcomitans(***)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly ***,we show that systemic infection with *** triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in *** administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in *** data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with *** work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with ***.

关键词： CD11b inflam infection

DNA methylation profiles in cancer:functions,therapy,and beyond

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Cancer Biology & medicine 2024年第2期21卷 111-116页

作者： Jinrong Zhu Yongjie Yang Li Li Jiuren Tang Rongxin Zhang Laboratory of immunology and Inflammation School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China

DNA methylation in cancer DNA methylation,a reversible post-replication modification,defines gene expression and function in different physiologic *** is quite common among global DNA modifications,while promoter hypermethylation often occurs in local regions during cancer,as in CpG island formation,thereby perpetuating the inactivation of tumor suppressor genes.

关键词： cancer suppressor thereby

Cortical Organoid-on-a-Chip with Physiological Hypoxia for Investigating Tanshinone IIA-Induced Neural Differentiation

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Research 2024年第3期2023卷 457-468页

作者： Yue Zhi Yujuan Zhu Jinglin Wang Junqi Zhao Yuanjin Zhao Department of Rheumatology and immunology Nanjing Drum Tower HospitalClinical Medical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210023China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Shenzhen Research Institute Southeast UniversityShenzhen518038China

Cortical organoids represent cutting-edge models for mimic human brain development during the early and even middle stage of pregnancy, while they often fail to recreate the complex microenvironmental factors, such as physiological hypoxia. Herein, to recapitulate fetal brain development, we propose a novel cortical organoid-on-a-chip with physiological hypoxia and further explore the effects of tanshinone IIA (Tan IIA) in neural differentiation. The microfluidic chip was designed with a micropillar array for the controlled and efficient generation of cortical organoids. With low oxygen, the generated cortical organoids could recapitulate key aspects of early-gestational human brain development. Compared to organoids in normoxic culturing condition, the promoted neurogenesis, synaptogenesis and neuronal maturation were observed in the present microsystem, suggesting the significance of physiological hypoxia in cortical development. Based on this model, we have found that Chinese herbal drug Tan IIA could promote neural differentiation and maturation, indicating its potential therapeutic effects on neurodevelopmental disorders as well as congenital neuropsychiatric diseases. These results indicate that the proposed biomimetic cortical organoid-on-a-chip model with physiological hypoxia can offer a promising platform to simulate prenatal environment, explore brain development, and screen natural neuroactive components.

关键词： promoted herbal cutting

Effect of Chinese medicine in Patients with COVID-19: 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 medicine 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 2019(COVID-19) 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 19, 2019 to May 16, 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-19 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, P<0.001]. 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: 0.19 to 0.44, P<0.001).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-19patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions.(Registration No. ChiCTR2200062917)

关键词： Chinese medicine all-cause mortality cohort study coronavirus disease 2019 deterioration rate

Tryptophan-specific peptide modification through metal-free photoinduced N-H alkylation employing N-aryl glycines

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Chinese Chemical Letters 2024年第6期35卷 316-319页

作者： Jianhui Yin Wenjing Huang Changyong Guo Chao Liu Fei Gao Honggang Hu school of medicine or Institute of Translation medicine Shanghai UniversityShanghai 200444China

Tryptophan(Trp)carries a unique heteroaromatic indole side chain and plays a critical role in peptide or protein ***,we have reported a metal-free photoinduced N-H alkylation strategy using N-aryl glycines for specific modification of tryptophan-containing *** robustness of our approach is demonstrated by its wide substrate scope,excellent isolated yields,as well as almost unobservable side *** this highly efficiently metal-free condition,alkylated Trp-containing peptides can be smoothly *** study provides a reliable and practical tool for the chemo-selective modification of various tryptophan containing oligopeptides.

关键词： Tryptophan Peptide Modification Glycine Photoinduced

Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern Chinese medicine Resources Chengdu University of Traditional Chinese Medicine school of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina school Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the ***,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this *** a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous ***,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention *** treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention *** the most vital component of the limbs,skeletal muscles have become potential points of *** this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal *** current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke *** addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin