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Neural Regeneration Research 2025年第6期20卷 1705-1706页

作者： Kazuki Watanabe Atsuhiko Hattori department of immunobiology Institute of Development Aging and CancerTohoku UniversitySendaiMiyagiJapan department of Sport and Wellness College of Sport and WellnessRikkyo UniversityNiizaSaitamaJapan

Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian *** hormone is primarily synthesized by the vertebrate pineal gland,but is ubiquitous among invertebrates,unicellular organisms,plants,and even cyanobacteria(Hattori and Suzuki,2024).Melatonin is well-conserved evolutionarily and possesses several physiological functions,such as immune response,bone and glucose metabolism,and memory formation besides regulating the circadian rhythm.

关键词： metabolism primarily agent

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

Infection,Pain,and Itch

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Neuroscience Bulletin 2018年第1期34卷 109-119页

作者： Isaac M.Chiu department of Microbiology and immunobiology Division of Immunology Harvard Medical School

Pain and itch are unpleasant sensations that often accompany infections caused by viral, bacterial, parasitic, and fungal pathogens. Recent studies show that sensory neurons are able to directly detect pathogens to mediate pain and itch. Nociceptor and pruriceptor neurons respond to pathogen-associated molecular patterns, including Toll-like receptor ligands, N-formyl peptides, and bacterial toxins. Other pathogens are able to silence neuronal activity to produce analgesia during infection. Pain and itch could lead to neuronal modulation of the immune system or behavioral avoidance of future patho- gen exposure. Conversely, pathogens could modulate neuronal signaling to potentiate their pathogenesis and facilitate their spread to other hosts. Defining how pathogens modulate pain and itch has critical implications for sensory neurobiology and our understanding of host- microbe interactions.

关键词： Pain Itch Bacteria Pathogens Infection Inflammation Viruses

Phylogenetic status of Pneumocystis from corticosteroid-treated gerbils

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Science China(Life Sciences) 2010年第10期53卷 1239-1246页

作者： RODNEY D Adam department of Medicine and immunobiology University of Arizona College of Medicine

Pneumocystis spp. infect the lungs of multiple mammalian species and cause disease in immunosuppressed individuals. The Pneumocystis isolates that have been studied to date fall into two major clades, those from primates and those from rodents. Within each of these clades, different species have been described on the basis of host specificity and differences in sequence and morphology. Here, we demonstrate that dexamethasone immunosuppression consistently results in histologically apparent lung infection in gerbils (28/35 animals). Sequence analysis of the 18S, 5.8S and internal transcribed spacer regions of the rDNA and a portion of the mitochondrial large subunit rDNA demonstrated that this gerbil Pneumocystis is grouped with other rodent Pneumocystis spp., but is distinct from them. Our results suggest that gerbil Pneumocystis differs sufficiently from Pneumocystis species found in other rodents to be considered a separate species.

关键词： 5.8S rRNA gene gerbil internal transcribed spacers (ITS) mitochondrial large subunit (mtLS) rRNA gene 18S rRNA gene Pneumocystis

Olfactory immune response to SARS-CoV-2

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Cellular & Molecular Immunology 2024年第2期21卷 134-143页

作者： Sebastian A.Wellford E.Ashley Moseman department of Integrative immunobiology Duke University School of MedicineDurhamNCUSA

Numerous pathogens can infect the olfactory tract,yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune *** in the nasal passages,the olfactory mucosa is directly exposed to the environment to sense airborne odorants;however,this also means it can serve as a direct route of entry from the outside world into the *** a result,olfactotropic infections can have serious consequences,including dysfunction of the olfactory system,CNS invasion,dissemination to the lower respiratory tract,and transmission between *** research has shown that a distinctive immune response is needed to protect this neuronal and mucosal tissue.A better understanding of innate,adaptive,and structural immune barriers in the olfactory mucosa is needed to develop effective therapeutics and vaccines against olfactotropic microbes such as ***,we summarize the ramifications of SARS-CoV-2 infection of the olfactory mucosa,review the subsequent immune response,and discuss important areas of future research for olfactory immunity to infectious disease.

关键词： Mucosal immunology Neuroimmunology Infectious Disease Sars-CoV-2

Differences in the immunogenicity of engineered circular RNAs

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Journal of Molecular Cell Biology 2023年第1期15卷 1-6页

作者： Justin Tai Y.Grace Chen department of immunobiology Yale University School of MedicineNew HavenCTUSA

Circular RNAs(circRNAs)are single-stranded RNAs that are covalently closed and lack free *** current understanding of the functions and regulation of circRNAs in immune systems is still in the nascent stages,but several groups have recently investigated the immunogenicity of engineered ***,which factors determine engineered circRNA immunogenicity still remains ***,we review and compare these investigations on engineered circRNA *** discuss the possible factors that may alter the immunogenic potential of a circRNA,such as its generation,purification,primary sequence,secondary structure,and RNA *** also suggest approaches for designing a circRNA with immunostimulatory or immune-evasive properties and recommend future areas for the field to *** the factors underlying engineered circRNA immunogenicity is an important step towards understanding endogenous circRNA immunity and increasing the therapeutic potential of circRNAs.

关键词： immunity immunogenicity endogenous

mmunomodulatory properties of silver nanoparticles ontribute to anticancer strategy for murine fibrosarcoma

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Cellular & Molecular Immunology 2016年第2期13卷 191-205页

作者： Biswajit Chakraborty Ramkrishna Pal Mohammed Ali Leichombam Mohindro Singh Dewan Shahidur Rahman Sujit Kumar Ghosh Mahuya Sengupta immunobiology Laboratory Department of Biotechnology Assam University Silchar India department of Chemistry Assam University Silchar India

The use of nanotechnology in nanoparticle-based cancer therapeutics is gaining impetus due to the unique biophysical properties of nanoparticles at the quantum level. Silver nanoparticles （AgNPs） have been reported as one type of potent therapeutic nanoparticles. The present study is aimed to determine the effect of AgNPs in arresting the growth of a murine fibrosarcoma by a reductive mechanism. Initially, a bioavailability study showed that mouse serum albumin （MSA）-coated AgNPs have enhanced uptake; therefore, toxicity studies of AgNP-MSA at 10 different doses （1-10 mg/kg b.w.） were performed in LACA mice by measuring the complete blood count, lipid profile and histological parameters. The complete blood count, lipid profile and histological parameter results showed that the doses from 2 to 8 mg （IC50： 6.15 mg/kg b.w.） sequentially increased the count of leukocytes, lymphocytes and granulocytes, whereas the 9- and 10-mg doses showed conclusive toxicity. In an antitumor study, the incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA. Transmission electron micrographs showed that considerable uptake of AgNP-MSA by the sentinel immune cells associated with tumor tissue and a morphologically buckled structure of the immune cells containing AgNP-MSA. Because the toxicity studies revealed a relationship between AgNPs and immune function, the protumorigenic cytokines TNF-α, IL-6 and IL-1β were also assayed in AgNP-MSA-treated and non-treated fibrosarcoma groups, and these cytokines were found to be downregulated after treatment with AgNP-MSA.

关键词： AgNP-MSA fibrosarcoma IL-1β IL-6 immunomodulation nanoparticles TNF-α

Perspectives on the role of mTORC2 in B lymphocyte development,immunity and tumorigenesis

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Protein & Cell 2011年第7期2卷 523-530页

作者： Adam S.Lazorchak Bing Su department of immunobiology and the Vascular Biology and Therapeutic Program Yale School of MedicineNew HavenCT 06519USA

Mammalian target of rapamycin complex 2(mTORC2)is a key downstream mediator of phosphoinositol-3-kinase(PI3K)dependent growth factor *** lymphocytes,mTORC2 has emerged as an important regulator of cell development,homeostasis and immune ***,our current understanding of mTORC2 functions and the molecular mechanisms regulating mTORC2 signaling in B and T cells are still largely *** studies have begun to shed light on this important *** have previously reported that mTORC2 mediates growth factor dependent phosphorylation of Akt and facilitates Akt dependent phosphorylation and inactivation of transcription factors FoxO1 and *** have recently explored the functions of mTORC2 in B cells and show that mTORC2 plays a key role in regulating survival and immunoglobulin(Ig)gene recombination of bone marrow B cells through an Akt2-FoxO1 dependent *** recombination is suppressed in proliferating B cells to ensure that DNA double strand breaks are not generated in actively dividing *** results raise the possibility that genetic or pharmacologic inhibition of mTORC2 may promote B cell tumor development as a result of inefficient suppression of Ig recombination in dividing B *** also propose a novel strategy to treat cancers based on our recent discovery that mTORC2 regulates Akt protein stability.

关键词： mTOR lymphocyte B cell cancer mTORC2 FoxO Akt Sin1

Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease

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World Journal of Gastroenterology 2011年第37期17卷 4166-4173页

作者： Kara Bradford David Q Shih department of Medicine Cedars Sinai Medical Center Inflammatory Bowel and immunobiology Research Institute Cedars-Sinai Medical Center

The thiopurine drugs,6-mercaptopurine(6-MP) and azathioprine,are efficacious in the arsenal of inflammatory bowel disease(IBD) *** reports indicate that 6-thioguanine nucleotide(6-TGN) levels correlate with therapeutic efficacy,whereas high 6-methylmercaptopurine(6-MMP) levels are associated with hepatotoxicity and *** to their complex metabolism,there is wide individual variation in patient response therein,both in achieving therapeutic drug levels as well as in developing adverse *** strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to *** this report,we will review different approaches to administer the thiopurine medications,including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine;coadministration of thiopurine with allopurinol;co-administration of thiopurine with anti-tumor necrosis factor α;6-TGN administration;desensitization trials;and split dosing of 6-MP.

关键词： Azathioprine Drug levels Inflammatory bowel disease 6-Mercaptopurine Thiopurine

SOCS3 dictates the transition of divergent time-phased events in granulocyte TNF-a signaling

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Cellular & Molecular Immunology 2014年第1期11卷 105-116页

作者： Jasmeet Kaur Chhabra Brajadulal Chattopadhyay Bhola Nath Paul immunobiology Division CSlR-Indian Institute of Toxicology Research Lucknow India department of Physics Faculty of Science JadavpurUniversity Kolkata India

Tumor-necrosis factor-a （TNF-a）-driven nuclear factor-KB （NF-KB） activation and apoptosis are opposing pathways; the growing recognition of these conflicting roles of TNF-a is perplexing. Here, we show that inflammation and apoptosis are time-phased events following TNF-a signaling and that emergence of suppressor of cytokine signaling 3 （SOCS3） expression limits the ongoing NF-KB activation and promotes apoptosis; further, we suggest an altered view of how inflammatory diseases are initiated and sustained. In vitro, TNF-a （50 ng/ml） induced granulocyte SOCS3 protein, inhibited nuclear accumulation of the p65NF-KB subunit and enhanced apoptosis, as shown by DNA laddering, annexin V positivity, and overexpression of caspase-3 and Bax in the late phase, whereas the early phase was marked by NF-KB activation. Conversely, SOCS3 knockdown by small interfering RNA （siRNA） inhibited granulocyte apoptosis and enhanced nuclear accumulation of p65 and 5＇ lipooxygenase expression in the late phase of TNF-a signaling. As apoptosis is associated with SOCS3 abundance, we suggest that these divergent TNF-a-driven events are time-phased, interconnected, opposing control mechanisms and one of the central features through which the immune system resolves pulmonary inflammation. Dysregulation may initiate mucosal inflammation, thus changing the landscape of asthma theraov.

关键词： apoptosis granulocytes lung inflammation NF-kB TNF-a SOCS3