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The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular Immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou Institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier Research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 298-306页

作者： Mohammad Hadi Zarei Sami Akbulut Maryam Zafari Elham Saghaei Zahra Lorigooini Hossein AminiKhoei Somaye Khosravi Elham Bijad medical Plants Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran department of Liver Transplant Institute and Biostatistics Inonu University Faculty of Medicine44280MalatyaTurkey Student Research Committee Shahrekord University of Medical SciencesShahrekordIran Physiology and Pharmacology department School of MedicineShahrekord University of Medical SciencesShahrekordIran department of Anatomical sciences School of MedicineShahrekord University of Medical SciencesShahrekordIran

Objective:To explore the effect of black radish(Raphanus sativus *** niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced ***:Thirty-two mice were divided into four groups:the control group received drinking water by gavage,the second group was administered with 100 mg/kg of sodium valproate,the third group received 300 mg/kg of black radish root extract,and the fourth group was given both sodium valproate(100 mg/kg)and black radish root extract(300 mg/kg).After 28 days,the mice were euthanized,and serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP),along with liver malondialdehyde(MDA),reactive oxygen species(ROS),mitochondrial parameters,tumor necrosis factor-alpha(TNF-α)gene expression,and histopathological changes were ***:Sodium valproate caused hepatic damage in mice,characterized by elevated serum levels of liver enzymes,increased MDA and ROS levels and TNF-αgene expression,as well as histopathological *** black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST,MDA,ROS,TNF-αgene expression,as well as mitochondrial impairment,but did not have a significant effect on sodium valproate-induced histopathological ***:The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury,possibly through mitigating oxidative stress,mitochondrial impairment,and inflammatory mediator expression.

关键词： Black radish Raphanus sativus Sodium valproate Hepatotoxicity Oxidative stress Anti-inflammation

Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1726-1741页

作者： Yanjiang Xing Yangfeng Hou Tianfei Fan Ran Gao Xiaohang Feng Bolun Li Junling Pang Wenjun Guo Ting Shu Jinqiu Li Jie Yang Qilong Mao Ya Luo Xianmei Qi Peiran Yang Chaoyang Liang Hongmei Zhao Wenhui Chen Jing Wang Chen Wang State Key Laboratory of Respiratory Health and Multimorbidity Institute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005China department of Lung Transplantation National Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina–Japan Friendship HospitalInstitute of Respiratory MedicineChinese Academy of Medical SciencesBeijing 100029China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300051China The State Key Laboratory of Complex Severeand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100005China department of Pharmacy West China HospitalSichuan UniversityChengdu 610044China

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

关键词： Phosphodiesterase 4B Pulmonary hypertension Endothelial-to-mesenchymal transition

Enhancing the Decomposition of Paper Cups Using Galleria Mellonella and Eisenia Fetida

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Journal of Renewable Materials 2024年第2期12卷 349-367页

作者： Shadi Moqbel Habib Al-Ghoul Abd Al-Majeed Al-Ghzawi Rami Mukbel Civil Engineering department The University of JordanAmman11942Jordan department of Chemistry Technical University of MunichMunichGermany Plant Production Jordan University of Science and TechnologyIrbid22110Jordan basic medical veterinary sciences Jordan University of Science and TechnologyIrbid22110Jordan

The composition of paper cups creates a challenge for the recycling industry,as the paperboard–plastic film composite is hard to ***,paper cups are sent to landfills or waste *** study explores the combined use of red worms(Eisenia fetida)and Greater wax moth(Galleria mellonella)in the biodegradation of paper *** study investigates the conditions and combinations that promote using Eisenia fetida and Galleria mellonella for degrading paper *** study considered the influence of environmental temperature,the presence of food waste,varying the number of Eisenia fetida worms,and the presence of a Galleria mellonella growth-slowing agent on the degradation *** achieve the study objectives,the study followed a quantitative *** study monitored the degradation of paper cup cuts that were placed in jars containing different combinations of Eisenia fetida worms,Galleria mellonella larvae,food waste,bedding material,and Galleria mellonella growth-slowing *** study found that the best operating temperature is *** study found that using food waste improves the performance of Eisenia fetida worms and Galleria mellonella larvae *** study found that adding a Galleria mellonella growth-slowing agent slightly enhances the degradation of the paper ***,a numerical model was obtained to simulate the paper cup degradation efficiency.

关键词： Paper cups resource recovery recycling circular economy Galleria mellonella Eisenia fetida

Molecular Investigation of Theileria in Ixodid Ticks from Changzhi,Shanxi Province,China

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Biomedical and Environmental sciences 2024年第8期37卷 922-925页

作者： Jia Cui Hua Xiang Rao Yiping Liu Dongmei Li Juan Yu department of Microbiology of basic medical sciences Changzhi Medical CollegeChangzhi 046000ShanxiChina department of Epidemiology and Health Statistics of Public Health and Preventive Medicine Changzhi Medical CollegeChangzhi 046000ShanxiChina department of medical parasitology of basic medical sciences Changzhi Medical CollegeChangzhi 046000ShanxiChina department of Vector Biology and Control National Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Theileria is a tick-borne intracellular protozoan that typically parasitizes erythrocytes,lymphocytes,and macrophages and causes acute clinical symptoms in host animals,including high fever,anemia,jaundice,and swelling of superficial lymph nodes[1].Theileriosis can lead to high mortality rates,and its rising global prevalence has resulted in significant economic losses to livestock husbandry and the national economy[2].

关键词： husbandry swelling typically

Dietary long-chain fatty acid metabolism boosts antitumorimmune response

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Cancer Communications 2024年第5期44卷 580-583页

作者： Jiaming Wang Xuetao Cao department of Immunology Institute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingP.R.China Institute of Immunology College of Life SciencesNankai UniversityTianjinP.R.China

Overcoming resistance to immune checkpoint blockade(ICB)therapy will pave the way for effective ICB cancer immunotherapy since a large proportion of cancer patients are not responsive to ICB immunotherapy[1].The molecular mechanisms of ICB resistance are diverse,including tumor-intrinsic resistant factors(such as genetic and epigenetic disorders),immunosuppressive/disabled factors(such as T cell exhaustion),and environmental restrictive factors(such as neuroendocrine stress and metabolic reprogramming).

关键词： metabolism cancer immune

In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke

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Neural Regeneration Research 2024年第10期19卷 2240-2248页

作者： Meng Yuan Yao Tang Tianwen Huang Lining Ke En Huang Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province Fujian Medical UniversityFuzhouFujian ProvinceChina department of Human Anatomy School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Scientific Research Center School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina department of Neurology Fujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Key Laboratory of Vascular Aging Fujian Medical UniversityFuzhouFujian ProvinceChina

In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1(PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.e B-GFAP-sh PTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-sh PTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

关键词： astrocyte in situ direct reprogramming ischemic stroke miR-30 based shRNA neuron polypyrimidine tract-binding protein 1 transdifferentiation

Managing immune checkpoint inhibitor-associated gastritis: Insights and strategies

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World Journal of Gastroenterology 2024年第24期30卷 3120-3122页

作者： Li-Li Yu Zhi-Lin He Xin-Lai Qian department of Pathology The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiang Medical UniversityXinxiang 453003Henan ProvinceChina department of basic medical sciences Xinxiang Medical UniversityXinxiang 453003Henan ProvinceChina

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various ***-related adverse events(irAEs)are defined as adverse effects resulting from ICI *** irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the discontinuation of ICIs.

关键词： Immunotherapy Immune checkpoint inhibitor Immune checkpoint inhibitor-related gastritis Immune-related adverse events Autoimmune responses

Etomidate protects retinal ganglion cells from hydrogen peroxide-induced injury via Nrf2/HO-1 pathway

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International Journal of Ophthalmology(English edition) 2024年第9期17卷 1606-1613页

作者： Xuan Zhao De-Gang Fan Xin-Chao Zhang Si-Wei You Fang Kuang Ming-Mei Wu department of Histology and Embryology School of Basic Medical SciencesXi’an Medical UniversityXi’an 710021Shaanxi ProvinceChina department of Neurobiology the Basic Medical Science Academythe Fourth Military Medical UniversityXi’an 710032Shaanxi ProvinceChina department of Spinal Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina College of Life sciences Northwestern UniversityXi’an 710069Shaanxi ProvinceChina

AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(H_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect of ***:Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and *** injury model of H_(2)O_(2)-induced RGCs oxidative stress was established in *** were pretreated with different concentrations of ET(1,5,and 10μmol/L)for 4h,followed by further exposure to H_(2)O_(2)at 1000μmol/*** counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12,24,and 48h after H_(2)O_(2)*** levels of nitric oxide,malondialdehyde,and glutathione in culture media were measured at these time *** reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase(iNOS),nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12,24,and 48h after H_(2)O_(2)stimulation and in the retina at 12h after optic nerve transection(ONT).RESULTS:The applications of 5 and 10μmol/L of ET significantly increased the viability of *** from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ETpretreated RGCs at 12,24 and 48h after H_(2)O_(2)stimulation,as well as in ET-treated retinas at 12h after *** blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein,along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in ***:ET is a neuroprotective agent in primary cultured RGCs injured by H_(2)O_(2).The effect of ET is dosedependent with the

关键词： etomidate retinal ganglion cell neuroprotection hydrogen peroxide-induced injury nuclear factor erythroid 2-related factor 2 heme oxygenase 1