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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou michael g.Fehlings Division of genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of Medical Science University of TorontoTorontoONCanada Division of Neurosurgery and Spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

Multiple sclerosis drug repurposing for neuroregeneration

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Neural Regeneration Research 2024年第3期19卷 507-508页

作者： Peter göttle michael Dietrich Patrick Küry Department of Neurology Medical FacultyHeinrich-Heine UniversityDüsseldorfGermany

Multiple sclerosis(MS)is an autoimmune disorder of the central nervous system(CNS)and is primarily characterized by immune cell infiltration leading to relapses followed by remission phases and a disease course turning progressive over time with neurodegenerative processes taking over(Amin and Hersh,2023).Of note,beyond relapse-associated worsening early in disease progression independent of relapse activity may arise independently of relapse activity and can occur in all phenotypes.Autoimmune-mediated damage of myelin sheaths and the subsequent loss of mature oligodendrocytes are resulting in impaired axonal integrity,neurodegeneration and accounts for irreversible neuronal damage(Kuhlmann et al.,2023).The current landscape of available disease-modifying therapies comprises mainly immunomodulatory drugs that effectively diminish relapses and slow down progression at the onset form of the disease,namely relapsing MS(RMS).In this regard,a number of drugs have been approved as disease-modifying therapies for MS by US Food and Drug Administration and European Medicines Agencies(Box 1).

关键词： drugs impaired irreversible

Use of an immunocapture device to detect cytokine release in discrete brain regions

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Neural Regeneration Research 2024年第4期19卷 703-704页

作者： Matthew g.Frank michael V.Baratta Department of Integrative Physiology University of Colorado BoulderBoulderCOUSA(Frank MG)Department of Psychology and NeuroscienceUniversity of Colorado BoulderBoulderCOUSA(Baratta MV)

Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).

关键词： system release innate

A randomized,controlled,open label non-inferiority trial of intravenous ferric carboxymaltose versus iron sucrose in patients with iron deficiency anemia in China

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Frontiers of Medicine 2024年第1期18卷 98-108页

作者： Jie Jin Zhihua Ran Emanuele Noseda Bernard Roubert Matthieu Marty Anna Mezzacasa Udo michael göring The First Affiliated Hospital Zhejiang University College of MedicineHangzhou310058China Renji Hospital Shanghai Jiao Tong University School of MedicineShanghai200025China Vifor Pharma Glattbrugg8152Switzerland

Iron deficiency(ID)and ID anemia(IDA)pose significant public health concerns in China.Although iron sucrose(IS)treatment is well-established in the country,ferric carboxymaltose(FCM)offers the advantage of higher doses and fewer infusions.This open label,randomized,controlled,non-inferiority trial was conducted at multiple sites in China to compare the outcomes of FCM(maximum of 2 doses,500 or 1000 mg iron)and IS(up to 11 infusions,200 mg iron)treatments in subjects with IDA.The primary endpoint was the achievement of hemoglobin(Hb)response(an increase of⩾2 g/dL from baseline)within 8 weeks,whereas secondary endpoints included changes in Hb,transferrin saturation,and serum ferritin levels.Among the 371 randomized subjects,a similar percentage of subjects treated with FCM and IS achieved Hb-response(FCM 99.4%,IS 98.3%),thereby confirming the non-inferiority of FCM compared with IS(difference 1.12(−2.15,4.71;95%confidence interval(CI))).Furthermore,a significantly higher proportion of FCM-treated subjects achieved early Hb-response at Week 2(FCM 85.2%,IS 73.2%;difference 12.1(3.31,20.65;95%CI)).Additionally,the increase in TSAT and serum ferritin levels from baseline was significantly greater at all time points for FCM-treated subjects.The safety profiles of FCM and IS were comparable,with the exception of transient hypophosphatemia and pyrexia,which are consistent with FCM’s known safety profile.In conclusion,FCM proves to be an efficacious treatment for IDA,providing faster Hb-response and correction of ID with fewer administrations than IS.

关键词： iron deficiency anemia intravenous iron ferric carboxymaltose iron sucrose Hb response early response

Neuronal trafficking as a key to functional recovery in immune-mediated neuropathies

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Neural Regeneration Research 2024年第11期19卷 2331-2332页

作者： Felix Kohle michael Schroeter Department of Neurology University of Cologne and University Hospital CologneCologneGermany

Immune-mediated neuropathies are rare diseases of the peripheral nervous system(PNS),substantially affecting patients’functionality and quality of life.They are amenable to immunomodulatory treatments,which in many cases stabilize disease progression,but long-term deficits persist in many patients.Such long-term deficits are particularly observed in monophasic autoimmune neuropathies like guillain-Barrésyndrome and also in chronic variants,e.g.,chronic inflammatory demyelinating neuropathy(Fadia et al.,2019).

关键词： diseases autoimmune

Basis for the diversity and extent in loss of digestible nutrients created by dietary phytin: Emphasis on fowl and swine

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Animal Nutrition 2024年第1期16卷 422-428页

作者： Edwin T.Moran michael R.Bedford Poultry Science Department Auburn University AB Vista Woodstock Court Blenheim Road

Phytin is the Ca2+-Mg2+-K+salt of phytic acid that is created and deposited in the aleurone layer and/or germ of grains and legumes. Its high presence in feedstuffs for fowl and swine diets results in it being a universal and significant impediment to optimum performance. Phytin impairs gastrointestinal recovery of a wide array of nutrients, the effect varying with the nutrient concerned. On exposure to low pH during gastric digestion, phytin dissociates into phytic acid and solubilized Ca2+. Even at low gastric pH,phytic acid is negatively charged which forms the basis of its anti-nutritive behavior. Pepsinogen has extensive basic amino acids on its activation peptide that are presented as cations at low pH which are targeted by pepsin for activation. Partially crystalized Ca2+near the enzyme?s active site further stabilizes its newly formed structure. Thus, phytic acid appears to interfere with gastric digestion by several mechanisms; interfering with pepsinogen activation by binding to the polypeptide?s basic amino acids;coordinating free Ca2+, destabilizing pepsin; binding some dietary proteins directly, further compromising gastric proteolysis. Upon digesta attaining neutrality in the duodenum, Ca2+and other cations rebind with accessible anions, phytic acid being a significant contender. Phytate not only binds free cations but can also strip them from enzymes(e.g. Ca2+, Zn2+) which reduces their structural resistance to autolysis and ability as co-factors(e.g. Zn2+) to increase enzyme activity. goblet cells initially employ Ca2+as an electronic shield between mucin layers enabling granule formation and cell storage. After mucin granule release, Ca2+is progressively displaced by Na+to free the viscous mucins enabling its translocation. Mucin entangles with the glycocalyx of adjacent enterocytes thereby constructing the unstirred water layer（USWL）. Excessive removal of Ca2+from mucin by phytic acid increases its fluidity facilitating its loss from the USWL with its associated Na+. This partly explains increas

关键词： Digestive enzyme Calcium Endogenous protein Mucin Phytin

Implementation and validation of a bonded particle model to predict rheological properties of viscoelastic materials

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Particuology 2024年第6期89卷 198-210页

作者： michael Mascara Arno Mayrhofer Stefan Radl Christoph Kloss Institute of Process and Particle Engineering Graz University of TechnologyInffeldgasse 13Graz8010Austria DCS Computing gmbH Industriezeile 35Linz4020Austria

This work focuses on implementing a particle-based method able to characterize viscoelastic materials whose rheological properties,such as storage modulus g′and loss modulus g″,are known.It is based on the bonded particle model,with the elastic constitutive relation here substituted with a viscoelastic one to capture time-scale effects.The Burgers model,vastly used in literature to model viscoelastic systems,is discretized and implemented.The test case used for calibration comprises of a cubic lattice,sheared with a periodic motion,to mimic the effect of a shear rheometer.After appropriate filtering of the stress response,the rheological properties are obtained,highlighting the effect of the lattice geometry,as well as the particle size,on the accuracy of the model.Moreover,the Burgers parameters are calibrated by analytically fitting the experimental dataset,showing the limitation of the Burgers model.The micro-contact parameters are obtained from the macro parameters through appropriate scaling.After completing a frequency sweep,the simulated g′and g″show a relatively large error,around 25%for g’for example.For this reason,a more robust model,namely the generalized Maxwell model,has been implemented.The calibration procedure is performed in the same fashion as for the Burgers model.Moreover,the tangential micro-contact parameters are scaled w.***.t.the normal ones.This scaling parameter,calledα,is calibrated by minimizing the root mean square error between simulation and experimental data,giving errors below 10%in both g′and g″for a large dataset.Additionally,a full ring plate-plate rheometer setup is simulated,and the simulation is compared with the given experimental dataset,again finding a good agreement.

关键词： DEM Rheology Numerical modeling Viscoelasticity

Outcomes following minimally invasive dorsal cheilectomy for hallux rigidus:A systematic review

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World Journal of Orthopedics 2024年第6期15卷 585-592页

作者： Katherine Esser James J Butler Mackenzie Roof Nathaniel P Mercer michael C Harrington Alan P Samsonov Andrew J Rosenbaum John g Kennedy Department of Orthopaedic Surgery University of Toledo Medical Center University of Toledo College of Medicine and Life SciencesToledoOH 43614United States Department of Orthopedic Surgery NYU Langone HealthNew YorkNY 10002United States Department of Orthopedic Surgery Albany Medical CenterAlbanyNY 12208United States

BACKgROUND Cheilectomy of the 1^(st)metatarsophalangeal joint(MTPJ)is one of the most common procedures for the management of hallux rigidus.However,there is no consensus regarding outcomes following minimally invasive dorsal cheilectomy(MIDC)for the management of hallux rigidus.AIM To evaluate outcomes following MIDC for the management of hallux rigidus.METHODS During November 2023,the PubMed,EMBASE and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following MIDC for the management of hallux rigidus.RESULTS Six studies were included.In total,348 patients(370 feet)underwent MIDC for hallux rigidus at a weighted mean follow-up of 37.9±16.5 months.The distribution of patients by Coughlin and Shurna's classification was recorded in 4 studies as follows:Ⅰ(58 patients,27.1%),Ⅱ(112 patients,52.3%),Ⅲ(44 patients,20.6%).Three studies performed an additional 1^(st)MTPJ arthroscopy and debridement following MIDC.Retained intra-articular bone debris was observed in 100%of patients in 1 study.The weighted mean American orthopedic foot and ankle society score improved from a preoperative score of 68.9±3.2 to a postoperative score of 87.1.The complication rate was 8.4%,the most common of which was persistent joint pain and stiffness.Thirty-two failures(8.7%)were observed.Thirty-three secondary procedures(8.9%)were performed at a weighted mean time of 8.6±3.2 months following the index procedure.CONCLUSION This systematic review demonstrated improvements in subjective clinical outcomes together with a moderate complication rate following MIDC for the management of hallux rigidus at short-term follow-up.A moderate reoperation rate at short-term follow-up was recorded.The marked heterogeneity between included studies and paucity of high quality comparative studies limits the generation of any robust conclusions.

关键词： Minimally invasive dorsal cheilectomy Hallux rigidus The first metatarsophalangeal joint Cheilectomy Minimally invasive surgery

New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology Research 2024年第1期32卷 1-17页

作者： gERWIN HELLER THORSTEN FUEREDER ALEXANDER michael gRANDITS ROTRAUD WIESER Division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for Hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy gene expression Omics