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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria department of anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges

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World Journal of Diabetes 2024年第5期15卷 853-866页

作者： Md Abdul Alim Al-Bari Nicholas Peake Nabil Eid department of Pharmacy University of RajshahiRajshahi 6205Bangladesh Biosciences and Chemistry and Biomolecular Research Centre Sheffield Hallam UniversitySheffield S11WBUnited Kingdom department of anatomy Division of Human BiologySchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia

Tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor *** infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of chronic illnesses such as diabetes mellitus(DM)greatly aggravate TB morbidity and ***[particularly type 2 DM(T2DM)]and TB have converged making their control even more *** contemporary global epidemics,TB-DM behaves like a syndemic,a synergistic confluence of two highly prevalent diseases.T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive *** a bidirectional relationship exists between TB and DM,it is necessary to concurrently treat both,and promote recommendations for the joint management of both *** are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure,and *** addition,autophagy may play a role in these ***,the TB-DM comorbidities present several health challenges,requiring a focus on multidisciplinary collaboration and integrated strategies,to effectively deal with this double *** effectively manage the comorbidity,further screening in affected countries,more suitable drugs,and better treatment strategies are required.

关键词： Diabetes mellitus Tuberculosis Coinfections Comorbidity Drug-drug interactions Autophagy Treatment challenges

Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model

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Neuroscience Bulletin 2024年第8期40卷 1037-1052页

作者： Chenrui Yin Kefei Luo Xinyue Zhu Ronghang Zheng Yu Wang Guangdan Yu Xiaorui Wang Fei She Xiaoying Chen Tao Li Jingfei Chen Baduojie Bian Yixun Su Jianqin Niu Yuxin Wang department of Histology and embryology Third Military Medical UniversityChongqing 400038China department of Respiratory Diseases Central Medical Branch of PLA General HospitalBeijing 100853China China Astronaut Research and Training Center Beijing 100094China department of Emergency the Fourth Medical Center of the Chinese PLA General HospitalBeijing 100142China Army 953 Hospital Shigatse Branch of Xinqiao HospitalThird Military Medical University(Army Medical University)Shigatse 857000China Research Centre Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen 518107China

Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience *** current first-line treatments are linked with clinically important symptom reduction,a large proportion of patients retained to experience considerable residual symptoms,indicating pathogenic mechanism should be illustrated *** studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory ***,its role in PTSD remains to be *** this study,we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and ***,but not risperidone or sertraline,has a more profound rescue effect on neuropsychological behaviors and myelin *** mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt *** data demonstrated the correlation between PTSD and abnormal myelination,suggesting that the oligodendroglial lineage could be a target for PTSD treatment.

关键词： PTSD Fear memory Myelination Oligodendroglial differentiation Fluoxetine Wnt signaling

Modulation of p75 neurotrophin receptor mitigates brain damage following ischemic stroke in mice

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Neural Regeneration Research 2024年第10期19卷 2093-2094页

作者： Golnoush Mirzahosseini Tauheed Ishrat department of anatomy and Neurobiology College of MedicineThe University of Tennessee Health Science CenterMemphisTNUSA Pharmaceutical Sciences College of PharmacyThe University of Tennessee Health Science CenterMemphisTNUSA Neuroscience Institute The University of Tennessee Health Science CenterMemphisTNUSA

Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic ***,tPA has been an integral part of managing acute ischemic stro ke.

关键词： damage arterial death p75

Intense pulsed light‑based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops

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Eye and Vision 2024年第2期10卷 12-21页

作者： Jose Maria Martinez‑de‑la‑Casa Carlos Oribio‑Quinto Almudena Milans‑del‑Bosch Pilar Perez‑Garcia Laura Morales‑Fernandez Javier Garcia‑Bella Jose Manuel Benitez‑del‑Castillo Julian Garcia‑Feijoo David P.Pinero Ophthalmology Unit Department of Ophthalmology and ORLFaculty of MedicineHospital Clinico San-CarlosUniversidad Complutense de MadridInstituto de Investigacion Sanitaria del Hospital Clinico San-Carlos(IdISSC)28040 MadridSpain department of Immunology Ophthalmology and ORLSchool of MedicineInstituto de Investigaciones Oftalmologicas Ramon CastroviejoUniversidad Complutense de MadridMadridSpain department of Optics Pharmacology and AnatomyUniversity of AlicanteAlicanteSpain

Background:Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40%to 59%of these patients *** current study was aimed at evaluating the potential clinical benefit of an intense pulsed light(IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop *** our knowledge,this is the first series analyzing the therapeutic effect of this treatment option in this type of ***:This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye *** patients received four sessions of IPL treatment using the Optima IPL system(Lumenis,Yokneam,Israel)adjusted to the official optimized Lumenis *** in symptomatology,corneal staining,conjunctival hyperemia,non-invasive break-up time(NIBUT),tear osmolarity,tear meniscus height(TMH),meiboscore and meibomian gland expressibility was analyzed after ***:Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires[ocular surface disease index(OSDI),standard patient evaluation of eye dryness(SPEED)and symptom assessment questionnaire in dry eye(SANDE)]as well as with the visual analogue scale(P<0.001).Mean change in OSDI was−15.0±11.3.A significant reduction was found after treatment in the corneal staining score(P<0.001).A significant reduction was found in tear film meniscus height(P=0.012),as well as in tear film osmolarity(P=0.001).A significant reduction was also found in meibomian gland expressibility(P=0.003),changing the percentage of grade 3 eyes from 44.4%before IPL to 17.2%after ***:IPL therapy combined with meibomian gland expression(MGX)seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface diseas

关键词： Glaucoma Intense pulsed light Dry eye Meibomian glands

YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

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Research 2024年第2期6卷 401-415页

作者： Jiadi Lv Xiaohan Liu Yabo Zhou Feiran Cheng Haoran Chen Shunshun Li Dianheng Wang Li Zhou Zhenfeng Wang Nannan Zhou Jie Chen Bo Huang department of Immunology&State Key Laboratory of Common Mechanism Research for Major Diseases Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical College(PUMC)Beijing100005China department of Histology and embryology Basic Medical CllegeChina Medical UniversityShenyangLiaoning 11122China department of Immunology Basic Medical Cllege China Medical UniversityShenyangLiaoning 110122China department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China

Solid tumor cells live in a highly dynamic mechanical *** the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an ***,we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like ***,integrin?was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein(YAP).YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G(MAFG),allowing MAFG to transactivate the stemness genes NANOG,SOX2,and *** also restoredβ8 expression,thereby forming a closed mechanical ***,MAFG expression is correlated with worse *** findings provide mechanical insights into the regulation of tumor cell dedifferentiation,which has therapeutic implications for exploring innovative strategies to attack malignancies.

关键词： activation thereby MAF

Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

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Neural Regeneration Research 2024年第12期19卷 2708-2722页

作者： He Fang Mengjie Li Jingchen Yang Shunping Ma Li Zhang Hongqi Yang Qiongyan Tang Jing Cao Weimin Yang department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina department of Nutrition The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Neurology Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina department of Human anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Neuroscience Research Institute Zhengzhou University Academy of Medical SciencesZhengzhouHenan ProvinceChina

Thalamic hemorrhage can lead to the development of central post-stroke *** in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic ***,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea ***,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus *** this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central ***,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain ***,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain *** results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

关键词： central post-stroke pain hemorrhagic stroke histone deacetylase iron overload voltage-gated potassium ion channel 1.2

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

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World Journal of Gastroenterology 2024年第11期30卷 1524-1532页

作者： Yi-Fan Chang Jia-Jing Li Tao Liu Chong-Qing Wei Li-Wei Ma Vladimir N Nikolenko Wei-Long Chang department of Gastrointestinal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Clinical Laboratory The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Human anatomy and Histology I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia

Autophagy is a cellular catabolic process characterized by the formation of double-membrane *** electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation.A large number of studies have shown that autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal(GI)***,the role of autophagy in GI diseases remains *** article focuses on the morphological and biochemical characteristics of autophagy in GI diseases,in order to provide new ideas for their diagnosis and treatment.

关键词： Autophagy Morphological study Biochemical characteristics Subcellular structure Transmission electron microscopy Gastrointestinal diseases

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 89-101页

作者： Yunhan Zhang Zhulin Zou Shuang Liu Fangfang Chen Minglu Li Haoyang Zou Haiyan Liu Jianxun Ding Key Laboratory of Pathobiology Ministry of Education Department of AnatomyCollege of Basic Medical SciencesJilin UniversityChangchun 130061China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China department of Gastrointestinal Colorectaland Anal SurgeryChina-Japan Union Hospital of Jilin UniversityChangchun 130033China

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

关键词： Poly(amino acid)nanogel Controlled drug delivery Inhibition of ferroptosis Neuroprotection Cerebral ischenia injury therapy