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Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China department of Clinical Pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1

Defined hydrogels for spinal cord organoids:challenges and potential applications

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Neural Regeneration Research 2024年第11期19卷 2329-2330页

作者： Wai Hon Chooi Yuewen Wu Shi-Yan Ng Institute of Molecular and Cell Biology(IMCB) Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore department of physiology Yong Loo Lin School of MedicineNational University of Singapore(NUS)SingaporeSingapore

Organoids of the central nervous system,primarily derived from pluripotent stem cells or neural stem cells,are three-dimensional tissue cultures with self-organizing *** exposed to the right combinations of signals,they differentiate into a 3D tissue consisting of complex cytoarchitecture and native cell types,including various neuron subtypes and glial *** features closely mimic native tissues,making them invaluable for developmental studies and disease *** recent years,spinal cord organoids(SCOs)have been developed to investigate spinal cord development,injuries,and various neurological *** an integral part of the central nervous system,SCOs play a vital role and serve as a site for studying both neurodevelopment and neurodegenerative diseases.

关键词： properties injuries primarily

Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression

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Neural Regeneration Research 2024年第9期19卷 1890-1898页

作者： Qiuqin Han Wenhui Li Peiqing Chen Lijuan Wang Xiwen Bao Renyan Huang Guobin Liu Xiaorong Chen department of Scientific Research Shanghai University of Medicine&Health Sciences Affiliated Zhoupu HospitalShanghaiChina department of Traditional Chinese Vascular Surgery Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina department of physiology Laboratory of Neurodegenerative DiseasesChangzhi Medical CollegeChangzhiShanxi ProvinceChina

Previous studies have demonstrated a bidirectional relationship between inflammation and *** of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containing 3(NLRP3)inflammasomes is closely related to the pathogenesis of various neurological *** patients with major depressive disorder,NLRP3 inflammasome levels are significantly *** the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic *** this review,we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 ***,we outlined various therapeutic strategies that target the NLRP3 inflammasome,including NLRP3 inflammatory pathway inhibitors,natural compounds,and other therapeutic compounds that have been shown to be effective in treating ***,we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to ***,there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression *** modulation of NLRP3 inflammasomes in microglia holds promise for the management of *** investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

关键词： depression microglia neuroinflammation NLRP3 inflammasome

Garcinia Kola and Kolaviron Attenuates Bisphenol A-Induced Memory Impairment and Hippocampal Neuroinflammation in Male Wistar Rats

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Journal of Biosciences and Medicines 2024年第2期12卷 111-130页

作者： Nazizi Adamu Kayinu Bernard Omokheshi Adele Abayomi Oluwatosin Ige Applied and Environmental physiology Unit Department of Physiology University of Ibadan Ibadan Nigeria department of Physical and Health Education College of Education Akwanga Nigeria

Bisphenol A (BPA), a toxicant which can leach into food from plastic containers, is reported to induce neurotoxicity among others via oxidative mechanisms. However, antioxidant compounds have been suggested to mitigate BPA-induced toxicities. Garcinia kola (GK) and its bioactive compound, kolaviron, are well-established natural antioxidants, which can exert protective effects against BPA-induced toxicities. This study was designed to investigate the likely mitigating effect of GK and kolaviron on BPA-induced memory impairment and hippocampal neuroinflammation in male Wistar rats. Thirty-five rats were equally grouped and treated as follows: I and II received distilled water and corn oil, respectively at 0.2 mL, while III - VII received BPA (50 mg/kg), BPA + GK (200 mg/kg), BPA + kolaviron (200 mg/kg), GK and kolaviron, respectively for 28 days p.o. Thereafter, behavioral studies were done using the Novel Object Recognition and Y maze tests. Subsequently under anaesthesia, the hippocampus in each animal was dissected out, homogenized and analysed for malondialdehyde, superoxide dismutase, catalase, reduced glutathione, glutathione transferase, nitrites, interleukin-6, tumour necrosis factor-α, acetylcholinesterase, glutamate acid decarboxylase, and arginase activity. Data were analyzed by ANOVA and Tukey Post-hoc test at p p Garcinia kola and Kolaviron mitigate bisphenol A-induced memory impairment and neuroinflammation via antioxidant potentiation and neurotransmitter balance.

关键词： Bisphenol A Memory Impairment Neuroinflammation Neuroprotection Garcinia Kola Kolaviron Antioxidant

Adult neurogenesis:a real hope or a delusion?

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Neural Regeneration Research 2024年第1期19卷 6-15页

作者： Ghulam Hussain Rabia Akram Haseeb Anwar Faiqa Sajid Tehreem Iman Hyung Soo Han Chand Raza Jose-Luis Gonzalez De Aguilar Neurochemicalbiology and Genetics Laboratory(NGL) Department of PhysiologyFaculty of Life SciencesGovernment College UniversityFaisalabadPunjabPakistan department of physiology School of MedicineClinical Omics InstituteKyungpook National UniversityDaeguKorea department of Zoology Faculty of Chemistry and Life SciencesGovernment College UniversityLahorePakistan INSERM U1118Mécanismes Centraux et Péripheriques de la NeurodégénérescenceStrasbourgFranceUniversitéde StrasbourgStrasbourgFrance

Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem *** process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory *** has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem ***,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult ***,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem *** this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife *** on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature ***,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.

关键词： adult neurogenesis aging brain-derived neurotrophic factor dentate gyrus hippocampus neural stem cells neurotrophic factors Notch oxidative stress stem cells subgranular zone

Aerobic interval training preconditioning protocols inhibit isoproterenol-induced pathological cardiac remodeling in rats:Implications on oxidative balance,autophagy,and apoptosis

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Sports Medicine and Health Science 2024年第4期6卷 344-357页

作者： Hakimeh Shahsavarnajand Bonab Javad Tolouei Azar Hamid Soraya Akbar Nouri Habashi department of Exercise physiology and Corrective Exercises Faculty of Sport SciencesUrmia UniversityUrmiaIran department of Pharmacology and Toxicology School of PharmacyUrmia University of Medical SciencesUrmiaIran

This study aimed to investigate the potential cardioprotective effects of moderate and high-intensity aerobic interval training(MIIT and HIIT)*** focus was on histological changes,pro-oxidant-antioxidant balance,autophagy initiation,and apoptosis in myocardial tissue incited by isoproterenol-induced pathological cardiac remodeling(ISO-induced PCR).Male Wistar rats were randomly divided into control(n=6),ISO(n=8),MIIT(n=4),HIIT(n=4),MIIT+ISO(n=8),and HIIT+ISO(n=8)*** MIIT and HIIT protocols were administered for 10 weeks,followed by the induction of cardiac remodeling using subcutaneous injection of ISO(100 mg/kg for two consecutive days).Alterations in heart rate(HR),mean arterial pressure(MAP),rate pressure product(RPP),myocardial oxygen consumption(MVO_(2)),cardiac hypertrophy,histopathological changes,prooxidant-antioxidant balance,autophagy biomarkers(Beclin-1,Atg7,p62,LC3Ⅰ/Ⅱ),and apoptotic cell distribution were *** findings revealed that the MIIT+ISO and HIIT+ISO groups demonstrated diminished myocardial damage,hemorrhage,immune cell infiltration,edema,necrosis,and apoptosis compared to ISO induced *** and HIIT preconditioning mitigated HR,enhanced MAP,and preserved MVO_(2)and *** pro-oxidant-antioxidant balance was sustained in both MIIT+ISO and HIIT+ISO groups,with MIIT primarily inhibiting pro-apoptotic autophagy progression through maintaining pro-oxidant-antioxidant balance,and HIIT promoting pro-survival *** results demonstrated the beneficial effects of both MIIT and HIIT as AITs preconditioning in ameliorating ISO-induced PCR by improving exercise capacity,hemodynamic parameters,and histopathological *** of these protective effects can be attributed to the modulation of cardiac apoptosis,autophagy,and oxidative stress.

关键词： Pathological cardiac remodeling Aerobic interval training preconditioning Oxidative stress Autophagy Apoptosis

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong department of Neurology of the Second Afliated Hospital and department of Human Anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China department of physiology and department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of Human Reproduction and Developmental Genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral *** a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into *** and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent *** review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and *** on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also *** lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

EventLFM:event camera integrated Fourier light field microscopy for ultrafast 3D imaging

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Light(Science & Applications) 2024年第7期13卷 1401-1415页

作者： Ruipeng Guo Qianwan Yang Andrew S.Chang Guorong Hu Joseph Greene Christopher V.Gabel Sixian You Lei Tian department of Electrical and Computer Engineering Boston UniversityBostonMA 02215USA department of physiology and Biophysics Boston UniversityBostonMA 02215USA. Neurophotonics Center Boston UniversityBostonMA 02215USA. Research Laboratory of Electronics(RLE)in the department of Electrical Science and Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA. department of Biomedical Engineering Boston UniversityBostonMA 02215USA

Ultrafast 3D imaging is indispensable for visualizing complex and dynamic biological *** scanning-based techniques necessitate an inherent trade-off between acquisition speed and space-bandwidth product(SBP).Emerging single-shot 3D wide-field techniques offer a promising alternative but are bottlenecked by the synchronous readout constraints of conventional CMOS systems,thus restricting data throughput to maintain high SBP at limited frame *** address this,we introduce EventLFM,a straightforward and cost-effective system that overcomes these challenges by integrating an event camera with Fourier light field microscopy(LFM),a state-of-theart single-shot 3D wide-field imaging *** event camera operates on a novel asynchronous readout architecture,thereby bypassing the frame rate limitations inherent to conventional CMOS *** further develop a simple and robust event-driven LFM reconstruction algorithm that can reliably reconstruct 3D dynamics from the unique spatiotemporal measurements captured by *** results demonstrate that EventLFM can robustly reconstruct fast-moving and rapidly blinking 3D fluorescent samples at kHz frame ***,we highlight EventLFM’s capability for imaging of blinking neuronal signals in scattering mouse brain tissues and 3D tracking of GFP-labeled neurons in freely moving *** believe that the combined ultrafast speed and large 3D SBP offered by EventLFM may open up new possibilities across many biomedical applications.

关键词： field linking overcome

Intestinal glucagon-like peptide-1:A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice

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World Journal of Diabetes 2024年第8期15卷 1764-1777页

作者： Fang-Xin Jin Yan Wang Min-Ne Li Ru-Jiang Li Jun-Tang Guo department of Histology and Embryology Key Laboratory of Universities in Shandong ProvinceShandong Second Medical UniversityWeifang 261053Shandong ProvinceChina department of Pathological physiology Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina

BACKGROUND Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic ***,the pathogenesis of hypoglycaemic counterregulation is still ***-like peptide-1(GLP-1)and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus(T1DM).The role of GLP-1 in counterregulatory dysfunction during hypoglycaemia in patients with T1DM has not been *** To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic *** T1DM was induced in C57BL/6J mice using streptozotocin,followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia(DH5).Immunofluorescence,Western blot,and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon(GCG)*** GLP-1 receptor agonist GLP-1(7-36)or the antagonist exendin(9-39)were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model *** The expression levels of intestinal GLP-1 and its receptor(GLP-1R)were significantly increased in DH5 *** instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex,leading to dysfunction of adrenal counterregulation during ***5 mice showed increased pancreaticδ-cell mass,cAMP levels inδcells,and plasma somatostatin concentrations,while cAMP levels in pancreaticαcells and plasma GCG levels ***,GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 *** experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstra

关键词： Glucagon-like peptide-1 Impaired hypoglycaemic counterregulation Type 1 diabetes Intestine Pancreas