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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

T-tube bridging fistula jejunal anastomosis for treatment of pancreatic lumbar dorsal fistula after necrotizing pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 428-430页

作者： Su-Lai Liu Guo-Guang Li Wei Cheng Chuang Peng Ying-Hui Song Department of Hepatobiliary Surgery Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal UniversityChangsha 410000China

Infectious pancreatic necrosis causes external pancreatic fistula in some patients.Generally,external pancreatic fistula requires fistula-gastric and/or intestinal anastomosis,and digestive endoscopic interventional treatment[1–3].It is especially difficult to treat external pancreatic fistulas with small fistulas where the external fistula is located in the lower back.The common treatment is to remove the body and tail of the pancreas and the spleen.This operation is very traumatic.A new pancreatic fistula may still occur at the pancreatic stump.The above operations may lead to unnecessary resection of the spleen,colon injury and other complications.In order to solve this problem,we innovatively used T-tube bridging fistula jejunal anastomosis plus continuous negative pressure suction to treat three cases of external pancreatic fistulas in the lower back,and all of them achieved good results.

关键词： fistula anastomosis spleen

Systemic lupus erythematosus in a 15-year-old female with multiple splenic nodules:A case report

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World Journal of Clinical Cases 2024年第12期12卷 2128-2133页

作者： Mi Il Kang Hyeok Chan Kwon Division of Rheumatology Department of Internal MedicineDankook University College of MedicineCheonan-si 31116South Korea Division of Rheumatology Department of Internal MedicineDankook University HospitalDankook University College of MedicineCheonan-si 31116South Korea

BACKGROUND Systemic lupus erythematosus(SLE)is a chronic inflammatory disease primarily affecting young females.SLE can invade any organ,and various forms of splenic invasion have been reported.Manifestations include splenomegaly and splenic infarction,rupture,and calcification.The study encountered a rare case of splenic involvement,with nodules of various sizes without calcifications or ruptures.CASE SUMMARY A 15-year-old girl presented with arthralgia,weight loss,fever,increased levels of inflammatory markers,and positive antinuclear antibody test results.The patient was diagnosed with SLE.She was asymptomatic while taking steroids and hydroxychloroquine.Ten months after discharge,the patient developed a fever and abdominal pain.Lupus enteritis was suspected,and abdominopelvic computed tomography(AP-CT)was performed.There were no specific findings in the gastrointestinal tract,but multiple splenic nodules were observed.Infection or hemangioma was considered;however,no specific radiological findings were observed.A biopsy of the spleen was performed to determine the possibility of malignancy.The histological findings of the spleen included extensive periarteriolar necrosis with hematoxylin bodies and numerous karyorrhectic debris.Based on the biopsy results,the patient was diagnosed with an SLE flare-up and was maintained on high-dose steroids and immunosuppressants.CONCLUSION As disease activity increased,multiple nodules in the spleen that were previously unseen were observed using AP-CT and histologically confirmed.spleen invasion by SLE can appear in multiple nodular forms and patterns.Therefore,physicians should consider these findings when differentiating these nodules from infections and malignancies.

关键词： Multiple nodules spleen Splenectomy Systemic lupus erythematosus Differential diagnosis Case report

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： Jun Zhou Jiaqi Liu Bingjing Wang Nan Li Juan Liu Yanmei Han Xuetao Cao Institute of Immunology Zhejiang University School of MedicineHangzhou 310058China National Key Laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China Institute of Immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against infection.The cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains elusive.Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense.Here we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell apoptosis.Eosinophil-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)infection.Mechanistically,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon L.m.infection in vitro.Furthermore,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of L.m.infection in vivo.Adoptive transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory responses.Together,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against L.m.infection.Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen

Percutaneous ultrasound-guided coaxial core needle biopsy for the diagnosis of multiple splenic lesions: A case report

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 616-621页

作者： Sha-Hong Pu Wu-Yong-Ga Bao Zhen-Peng Jiang Rui Yang Qiang Lu Department of Medical Ultrasound West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND The overlap of imaging manifestations among distinct splenic lesions gives rise to a diagnostic dilemma.Consequently,a definitive diagnosis primarily relies on his-tological results.The ultrasound(US)-guided coaxial core needle biopsy(CNB)not only procures sufficient tissue to help clarify the diagnosis,but reduces the incidence of puncture-related complications.CASE SUMMARY A 41-year-old female,with a history of pulmonary tuberculosis,was admitted to our hospital with multiple indeterminate splenic lesions.Gray-scale ultrasono-graphy demonstrated splenomegaly with numerous well-defined hypoechoic ma-sses.Abdominal contrast-enhanced computed tomography(CT)showed an en-larged spleen with multiple irregular-shaped,peripherally enhancing,hypodense lesions.Positron emission CT revealed numerous abnormal hyperglycemia foci.These imaging findings strongly indicated the possibility of infectious disease as the primary concern,with neoplastic lesions requiring exclusion.To obtain the precise pathological diagnosis,the US-guided coaxial CNB of the spleen was ca-rried out.The patient did not express any discomfort during the procedure.CONCLUSION Percutaneous US-guided coaxial CNB is an excellent and safe option for obtaining precise splenic tissue samples,as it significantly enhances sample yield for exact pathological analysis with minimum trauma to the spleen parenchyma and sur-rounding tissue.

关键词： spleen Splenic disease Ultrasound Biopsy Ultrasound-guided coaxial core needle biopsy Case report

Bleeding control during complex laparoscopic surgeries of the spleen:current status and challenges

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Chinese Medical Journal 2022年第24期135卷 2938-2940页

作者： Nan You Jing Li Lu Zheng Department of Hepatobiliary Surgery The Second Affiliated HospitalThird Military Medical University(Army Medical University)Chongqing 400037China

Severe intra-operative bleeding has limited the application of complex laparoscopic splenectomy(LS),including laparoscopic total splenectomy(LTS)and laparoscopic partial splenectomy(LPS).Therefore,reducing bleeding ri... 详细信息

关键词： laparoscopic spleen bleeding

Establishment,Characterization and Expression Pattern of a spleen Cell Line,SMSP,Derived from Turbot(Scophthalmus maximus)

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中国海洋大学学报:英文版 2023年第5期22卷 1403-1411页

作者： XUE Ting LIU Yiping GE Xuefeng LI Chao School of Marine Science and Engineering Qingdao Agricultural UniversityQingdao 266109China

A turbot(Scophthalmus maximus)cell line named SMSP was obtained from the spleen.The origin of the cells was identified by morphology,chromosome number and COI gene.The optimal basic medium,serum concentration and growth temperature of the cells were detected.SMSP cell line is mainly composed of fibroblast-like cells.Most of the SMSP cells contained 44 chromosomes,and the sequence of COI gene confirmed that the cells were originated from turbot.The optimal culture conditions were 24℃,DMEM+10%FBS.The cell line had high transfection efficiency for siRNA and plasmid.After stimulation with lipopolysaccharide(LPS)or poly(I:C),the expressions of immune-related genes such as TNF-β,IL-12s,IL-10 and IL-1βwere up-regulated significantly in the early stage(P<0.05).This study will provide a model for exploring immune mechanism of turbot against pathogen in vitro.

关键词： Scophthalmus maximus cell line spleen pathogen-associated molecular patterns immunity

Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation

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Signal Transduction and Targeted Therapy 2022年第8期7卷 3021-3031页

作者： Qilong Li Quan Yuan Ning Jiang Yiwei Zhang Ziwei Su Lei Lv Xiaoyu Sang Ran Chen Ying Feng Qijun Chen Key Laboratory of Livestock Infectious Diseases Ministry of EducationKey Laboratory of ZoonosisCollege of Animal Science and Veterinary MedicineShenyang Agricultural University120 Dongling Road110866 ShenyangChina Research Unit for Pathogenic Mechanisms of Zoonotic Parasites Chinese Academy of Medical Sciences120 Dongling Road110866 ShenyangChina

Artemisinin(ART)and dihydroartemisinin(DHA),apart from their profound anti-malaria effect,can also beneficially modulate the host immune system;however,the underlying molecular mechanisms remain unclear.Here,we report that DHA selectively induced T-cell activation,with an increased proportion of Ki67^(+)CD4^(+)T cells,CD25^(+)CD4^(+)T cells,interferon(IFN)-γ-producing CD8^(+)T cells,Brdu^(+)CD8^(+)T cells and neutrophils,which was found to enhance cellular immunity to experimental malaria and overcome immunosuppression in mice.We further revealed that DHA upregulated the expression of cell proliferation-associated proteins by promoting the phosphorylation of mitogen-activated protein kinase(MAPK),cyclin-dependent kinases(CDKs),and activator protein 1 in the spleen.This study is the first to provide robust evidence that DHA selectively induced the expansion of subsets of splenic T cells through phosphorylated CDKs and MAPK to enhance cellular immune responses under non-pathological or pathological conditions.The data significantly deepened our knowledge in the mechanism underlying DHA-mediated immunomodulation.

关键词： immunity spleen malaria

spleen-preserving distal pancreatectomy with conservation of the spleen vessels

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Chinese Medical Journal 2011年第8期124卷 1217-1220页

作者： MA Jin-ping CHEN Chuang-qi PENG Lin ZHAO Gang CAI Shi-rong HU Shi-xiong HE Yu-long ZHAN Wen-hua Department of Gastrointestinal and Pancreatic Surgery the FirstAffiliated Hospital Sun Yat-sen University GuangzhouGuangdong 510080 China Department of General Surgery Guangdong General HospitalGuangzhou Guangdong 510080 China

Background Distal pancreatectomy traditionally included splenectomy; the spleen, however, is an important organ in the immunologic defense of the host and is worthy of preservation. The aim of this research was to study the feasibility,safety and clinical effects of spleen and splenic vessel-preserving distal pancreatectomy.Methods A retrospective review was performed for 26 patients undergoing distal pancreatectomy for benign or low grade malignant disease with splenectomy （n=13） or splenic preservation （n=13） at the First Hospital of Sun Yat-sen University and Guangdong General Hospital in Southern China from May 2002 to April 2009.Results All 26 pancreatectomies with splenectomy or splenic preservation were performed successfully. There was no statistically significant difference between two groups in mean operative time （（172±47） minutes vs. （157±52） minutes, P ＞0.05）, intraoperative estimated blood loss （（183±68） ml vs. （160±51） ml, P ＞0.05）, incidence of noninfectious and infection complication and mean length of postoperative hospital stay （（10.1±2.2） days vs. （12.1 ±4.6） days, P ＞0.05）. The platelet counts examined one week after operation were significantly higher in the distal pancreatectomy with splenectomy group than the other group （（37.3±12.8）×109/L vs. （54.7±13.2）×109/L, P ＜0.05）.Conclusions spleen-preserving distal pancreatectomy appears to be a feasible and safe procedure. In selected cases of benign or low-grade malignant disease, spleen-preserving distal pancreatectomy is recommended.

关键词： distal pancreatectomy spleen spleen-preserving distal pancreatectomy