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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner Department of molecular Biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

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Regulation of RIG-I-like receptor-mediated signaling:interaction between host and viral factors

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Cellular & molecular immunology 2021年第3期18卷 539-555页

作者： Koji Onomoto Kazuhide Onoguchi Mitsutoshi Yoneyama division of molecular immunology Medical Mycology Research CenterChiba University1-8-1InohanaChuo-kuChiba 260-8673Japan

Retinoic acid-inducible gene I(RIG-l)-like receptors(RLRs)are RNA sensor molecules that play essential roles in innate antiviral *** the three RLRs encoded by the human genome,RIG-1 and melanoma differentiation-associated gene 5,which contain N-terminal caspase recruitment domains,are activated upon the detection of viral RNAs in the cytoplasm of virus-infected *** RLRs induce downstream signaling via their interactions with mitochondrial antiviral signaling proteins and activate the production of type Ⅰ and Ⅲ interferons and inflammatory *** studies have shown that RLR-mediated signaling is regulated by interactions with endogenous RNAs and host proteins,such as those involved in stress responses and posttranslational *** RLR-mediated cytokine production is also involved in the regulation of acquired immunity,the deregulation of RLR-mediated signaling is associated with autoimmune and autoinflammatory ***,RLRmediated signaling might be involved in the aberrant cytokine production observed in coronavirus disease *** the discovery of RLRs in 2004,significant progress has been made in understanding the mechanisms underlying the activation and regulation of RLR-mediated signaling ***,we review the recent advances in the understanding of regulated RNA recognition and signal activation by RLRs,focusing on the interactions between various host and viral factors.

关键词： RIG-I-like receptors Viral infection Innate immunity Stress response

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Hepatitis C virus genotype 3a infection and hepatocellular carcinoma: Pakistan experience

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World Journal of Gastroenterology 2009年第40期15卷 5080-5085页

作者： Muhammad Idrees Shazia Rafi que Irshad-ur Rehman Haji Akbar Muhammad Zubair Yousaf Sadia Butt Zunaira Awan Sobia Manzoor Madiha Akram Mahwish Aftab Bushra Khubaib Sheikh Riazuddin division of molecular Virology & molecular Diagnostics National Centre of Excellence in Molecular BiologyUniversity of the Punjab Lahore National Centre of Excellence in molecular biology University of the Punjab Lahore

AIM: To assess the association between chronic hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) in Pakistan, and the genotype distribution among these HCC ***: One hundred and sixty-one subjects with HCC were included in this study. Liver biopsy was performed on 145 of the patients; sixteen were excluded because they failed to fulfill the inclusion criteria. Qualitative polymerase chain reaction (PCR) was performed for hepatitis B virus and HCV. Samples positive for HCV RNA were genotyped using genotype-specif ic PCR and conf irmed by HCV 5' noncoding region sequencing analysis. RESULTS: Chronic HCV infection was identified a major risk factor (63.44% of tested HCC patients) forthe development of HCC. The time from HCV infection to appearance of cancer was 10-50 years. In the HCC patient population, broader distributions of genotypes were present with genotype 3a as the predominant genotype. Using the type-specific genotyping method, we found HCV genotype 3a in 40.96%, 3b in 15.66%, 1a in 9.63%, and 1b in 2.40% of HCC tissue samples. About 28% of cases were found with mixed genotypes. Two cases were unable to be genotyped because of low viral load. Sixty-six percent of treated patients with cirrhosis had an end of treatment response, but unfortunately they relapsed quickly when the treatment was discontin-ued, and HCC developed during a median 3.8 years. CONCLUSION: There was a strong association between chronic HCV infection and HCC in Pakistan, and between HCV genotype 3a and HCC.

关键词： Hepatocellular carcinoma Hepatitis C Genotyping Etiology Prevalence

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Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

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Neural Regeneration Research 2025年第10期20卷 2895-2897页

作者： Nicolas Hugues Yu Luo Department of molecular and Cellular Biosciences University of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program University of CincinnatiCincinnatiOHUSA division of Immunobiology Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the *** the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

关键词： Figure signature critical

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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

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Bacterial inclusion bodies function as vehicles for dendritic cell-mediated T cell responses

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Cellular & molecular immunology 2020年第4期17卷 415-417页

作者： Sjoerd T.T.Schetters Wouter S.P.Jong Laura J.W.Kruijssen H.B.van den Berg van Saparoea Steef Engels Wendy W.J.Unger Diane Houben Joke M.M.den Haan Joen Luirink Yvette van Kooyk Department of molecular Cell biology and immunology Amsterdam UMCLocation VUmcAmsterdamThe Netherlands Abera Bioscience AB SolnaSweden Laboratory of Pediatrics Division of Pediatric Infectious Diseases and ImmunologyErasmus MC-Sophia Children’s HospitalRotterdamThe Netherlands Department of molecular Cell biology Section Molecular MicrobiologyFaculty of ScienceVU UniversityAmsterdamThe Netherlands

Immunogenic antigens for vaccination are often created through the production of recombinant proteins using Escherichia coli.1 As a side product,aggregates called inclusion bodies(IBs)are formed,containing largely misfolded forms of the overexpressed recombinant protein.2 The effect of IBs on the immune system and whether they can be used as effective vaccine products remain *** non-native conformation of proteins upon accumulation in IBs abrogates their use as vaccines aimed at generating high-affinity antibodies.3 However,IBs exhibit unique properties,including mechanical and thermal stability due to their intrinsic particulate nature,biocompatibility,high antigenic content,low toxicity and relative resistance to *** characteristics make IBs attractive as an antigenic vaccine formulation for T cell responses to linear *** IBs can trigger adaptive cellular responses initiated via uptake by dendritic cells for presentation to T cells is unknown.

关键词： vaccine attractive initiated

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Sensing of physiological regulators by innate lymphoid cells

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Cellular & molecular immunology 2019年第5期16卷 442-451页

作者： Cyril Seillet Nicolas Jacquelot molecular immunology division Walter and Eliza Hall Institute of Medical ResearchMelbourneVIC 3052Australia Department of Medical biology University of MelbourneMelbourneVIC 3010Australia

Maintenance of homeostasis and immune protection rely on the coordinated action of different physiological *** communication between the immune system and physiological systems is required to sense and restore any disruption of *** transcriptomic analyses of innate lymphoid cells(ILCs)from different tissues have revealed that ILCs express a large array of receptors involved in the recognition of neuropeptides,hormones and metabolic *** rapidly secrete effector cytokines that are central in the development and activation of early immune responses,but they also constitutively secrete mediators that are important for tissue *** achieve these functions effectively,ILCs integrate intrinsic and extrinsic signals that modulate their constitutive and induced *** of the regulation of ILCs by physiological regulators leads to altered immune responses with harmful consequences for the *** understanding of these complex interactions between the immune system and physiological mediators is crucial to decipher the events leading to the protective versus pathological effects of these cells.

关键词： innate lymphoid cells immunity immune protection homeostasis

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CD38 expression on CD8+ cells—Its influence on development of tuberculosis in HIV positive individuals

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Open Journal of immunology 2012年第2期2卷 65-71页

作者： Ramaseri Sunder Sharada Hanumanth Surekha Rani Satya Sudheer Pydi Jonnalagada Subbanna Vijaya lakshmi Valluri 1immunology and molecular biology division LEPRA India-Blue Peter Public Health & Research Centre Hyderabad India Department of Genetics Osmania University Hyderabad India immunology and molecular biology division LEPRA India-Blue Peter Public Health & Research Centre Hyderabad India

CD38 expression on CD8+ cells seems to correlate well with HIV viral-loads, while the ex-pression levels are thought to be low in patients with tuberculosis. This study aimed at determining the levels of CD38 expression in HIV+ individuals who develop tuberculosis. Expression levels of CD8 and CD38 were analysed in peripheral blood collected from HIV (73), TB (32), HIV-TB (31) and healthy controls (20). The percentage of CD8+/CD38+ cells significantly increased during the first few years of seropositivity and decreased during 5 - 6 years. A decline in the expression of CD38, especially on CD8+ cells in a HIV+ individual within first 2 years of seropositivity, may be indicative of susceptibility to tuberculosis. This observation was reiterated when two patients developed TB during follow-up. CD38 on CD8 cells could perhaps be useful as an early biomarker for tuberculosis in HIV-positive individuals.

关键词： HIV-TB CD38 CD8 CD4 Viral Load

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Effect of Tb(Ⅲ) on activity and stability of nattokinase

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Journal of Rare Earths 2017年第5期35卷 510-517页

作者：牟小超杨仁佳张文龙杨斌盛 Institute of molecular Science Key Laboratory of Chemical Biology of Molecular Engineering of Education Ministry Shanxi University Blood division Shanxi Dayi Hospital

Nattokinase, is an effective fibrinolytic enzyme with the potential for fighting cardiovascular disease. The aim of study was to investigate the interaction of Tb（Ⅲ） with nattokinase and the impact of Tb（Ⅲ） on the enzyme activity and protein stability. The binding of Tb（Ⅲ） with nattokinase was studied by fluorescence spectrum in 100 mmol/L Tris-HCl（pH 8.0）. It could be seen that the protein bound one Tb（Ⅲ） with low affinity, and the binding constants K were 2.90×10~4 L/mol at 288 K. Although the activity of nattokinase determined by tetra-peptide substrate method at proper pH and temperature was not influenced for the binding of Tb（Ⅲ）, the transformation rate of substrate was increased to 113%. To better assess the stability of protease in the absence and presence of Tb（Ⅲ）, nattokinase was unfolded through continuous concentrations urea. Based on the model of structural element, the results showed that Tb（Ⅲ） could not change the average structural element free energy of nattokinase by the measurement of enzyme activity, but it could improve the stability of the global protein by the fluorescence spectral measurement.

关键词： constants protease tetra affinity cardiovascular fighting Effect of Tb aromatic absence tryptophan

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Msx homeobox gene family and craniofacial development

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Cell Research 2003年第6期13卷 429-442页

作者： SYLVIA ALAPPAT division of Developmental biology Department of Cell and molecular biology Tulane University New Orleans LA 70118 USA.

Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene. These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development. Inductive interactions mediated by the Msx genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice, as manifested by the pheno typic abnormalities shown in knockout mice and in humans. This review summarizes studies on the expression, regulation, and functional analysis of Msx genes that bear relevance to craniofacial development in humans and mice.

关键词： Msx genes craniofacial tooth cleft palate suture development transcription factor signaling molecule.

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