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Genes & Diseases 2024年第2期11卷 874-889页

作者： Yancheng Lai Xiaole Lu Yankai Liao Pei Ouyang Hai Wang Xian Zhang Guanglong Huang Songtao Qi Yaomin Li Department of Neurosurgery Institute of Brain DiseaseNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Laboratory for Precision Neurosurgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Glioblastoma(GBM)is the most common intrinsic and aggressive primary brain tumor in adults,with a median survival of approximately 15 *** heterogeneity is considered responsible for the treatment resistance and unfavorable ***-mesenchymal transition(PMT)represents GBM malignant progression and recurrence,which might be a breakthrough to understand GBM heterogeneity and overcome treatment *** is a complicated process influenced by crosstalk between GBM and tumor microenvironment,depending on intricate ligand-receptor *** this review,we summarize the autocrine and paracrine pathways in the GBM microenvironment and related ligand-receptor interactions inducing *** also discuss the current therapies targeting the PMT-related autocrine and paracrine ***,this review offers a comprehensive understanding of the failure of GBM-targeted therapy and ideas for future tendencies of GBM treatment.

关键词： Autocrine Glioblastoma Ligand-receptor interaction Microenvironment Paracrine Proneural-mesenchymal transition

Effects of microenvironment and biological behavior on the paracrine function of stem cells

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Genes & Diseases 2024年第1期11卷 135-147页

作者： Zhixin Xue Yunjun Liao Ye Li The Department of Plastic and Cosmetic Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Mesenchymal stem cells(MSCs),the most well-studied cell type in the field of stem cell therapy,have multi-lineage differentiation and self-renewal ***-based thera-pies have been used to treat diverse diseases because of their ability to potently repair tissue and locally restore *** increasing body of evidence demonstrates that paracrine func-tion is central to the effects of MsC-based *** factors,cytokines,chemokines,extracellular matrix components,and extracellular vehicles all contribute to the beneficial ef-fects of MSCs on tissue regeneration and *** paracrine substances secreted by MSCs change depending on the tissue microenvironment and biological *** this review,we discuss the bioactive substances secreted by MsCs depending on the microenvironment and biological behavior and their regulatory mechanisms,which explain their potential to treat human diseases,to provide new ideas for further research and clinical cell-free therapy.

关键词： Bioactive behavior Mesenchymal stem cells Microenvironment Paracrine Secretome

Helicobacter pylori mediated niche environment aberrations promote the progression of gastric cancer

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Genes & Diseases 2024年第5期11卷 113-116页

作者： Teng Yan Hang Sun Yuhui Liao Jiajian Zhou nanfang hospital The First School of Clinical MedicineSouthern Medical UniversityGuangzhouGuangdong 510515China Dermatology hospital Southern Medical UniversityGuangzhouGuangdong 510091China

Intestinal metaplasia(IM)is a key stage in the tumorigenic Correa cascade from gastritis to final intestinal-type gastric cancer(GC).1 Helicobacter pylori(***)infection is the most common trigger of IM,and it promotes GC progression through induction of gastric epithelial transition.2 Currently,the mechanism by which *** infection promotes tumorigenesis in IM patients is poorly *** et *** a single-cell transcriptomic atlas on premalignant lesions and identified biomarkers of gastric early-malignant cells,providing an opportunity to explore the molecular mechanism of GC progression at the molecular level.

关键词： gastric pylori Helicobacter

Growth hormone promotes the reconstruction of injured axons in the hypothalamo-neurohypophyseal system

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Neural Regeneration Research 2024年第10期19卷 2249-2258页

作者： Kai Li Zhanpeng Feng Zhiwei Xiong Jun Pan Mingfeng Zhou Weizhao Li Yichao Ou Guangsen Wu Mengjie Che Haodong Gong Junjie Peng Xingqin Wang Songtao Qi Junxiang Peng Department of Neurosurgery Institute of Brain DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.

关键词： arginine vasopressin growth hormone hypothalamo-neurohypophyseal system hypothalamus injury insulin-like growth factor 1 oxytocin regeneration

Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

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Zoological Research 2024年第1期45卷 108-124页

作者： Huanpeng Lu Jinwei Chai Zijian Xu Jiena Wu Songzhe He Hang Liao Peng Huang Xiaowen Huang Xi Chen Haishan Jiang Shaogang Qu Xueqing Xu Department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence GuangzhouGuangdong 510515China Key Laboratory of Mental Health of the Ministry of Education Southern Medical UniversityGuangzhouGuangdong 510515China Department of Dermatology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Neurology Ganzhou Hospital-Nanfang HospitalSouthern Medical UniversityGanzhouJiangxi 341001China

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its *** peptides may thus present therapeutic potential for *** this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for *** vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant *** the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway *** focal adhesion kinase(FAK)and p38 were also identified as regulatory *** the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated *** the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative *** findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

关键词： Cath-KP Peptide Parkinson’s disease Oxidative stress Neuroprotection

Giant accessory hepatic lobe accompanied by inflammatory pseudotumor

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 194-195页

作者： Hong Yang Binglin Lai Department of medical Imaging Ganzhou People’s HospitalGanzhou Hospital-Nanfang HospitalSouthern Medical UniversityGanzhouChina

A 25-year-old female was admitted to the hospital 6 months after the discovery of a liver mass during a physical *** has no abdominal pain or abdominal wall *** function and alpha-fetoprotein(AFP)levels are *** tomogr... 详细信息

关键词： admitted Liver hepatic

Neurosyphilis complicated by anti-γ-aminobutyric acid-B receptor encephalitis: A case report

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World Journal of Clinical Cases 2024年第11期12卷 1960-1966页

作者： Ya-Xiu Fang Xiao-Ming Zhou Dong Zheng Guang-Hui Liu Peng-Bo Gao Xiao-Zhen Huang Zhi-Cheng Chen Hui Zhang Lin Chen Ya-Fang Hu Department of Neurology The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina Department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system,causing *** cases of anti-N-methyl-Daspartate receptor autoimmune encephalitis(AE)secondary to neurosyphilis have been *** report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor(GABABR)*** SUMMARY A young man in his 30s who presented with acute epileptic status was admitted to a local *** was diagnosed with neurosyphilis,according to serum and cerebrospinal fluid(CSF)tests for *** 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin,epilepsy was controlled but serious cognitive impairment,behavioral,and serious psychiatric symptoms were *** was then transferred to our *** Mini-Mental State Examination(MMSE)crude test results showed only 2 *** magnetic resonance imaging revealed significant cerebral atrophy and multiple fluidattenuated inversion recovery high signals in the white matter surrounding both lateral ventricles,left amygdala and bilateral ***-GABABR antibodies were discovered in CSF(1:3.2)and serum(1:100).The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE,and received methylprednisolone and *** treatment,his mental symptoms were *** impairment was significantly improved,with a MMSE of 8 *** anti-GABABR antibody titer decreased to 1:*** patient received methylprednisolone and penicillin after *** months later,the patient’s condition was stable,but the serum anti-GABABR antibody titer was 1:*** This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.

关键词： Anti-γ-aminobutyric acid-B receptor GABABR Neurosyphilis Tissue-based assay Magnetic resonance imaging Mini-mental state examination Case report

COX-2 blocking therapy in cisplatin chemosensitization of ovarian cancer:An allicin-based nanomedicine approach

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Chinese Chemical Letters 2024年第8期35卷 449-454页

作者： Huijiao Fu Peiqin Liang Qianwen Chen Yan Wang Guang Li Xuzi Cai Shengtao Wang Kun Chen Shengying Shi Zhiqiang Yu Xuefeng Wang Department of Obstetrics and Gynecology The Third Affiliated Hospital of Southern Medical UniversityGuangzhou 510630China Department of Obstetrics and Gynecology Huizhou Central People’s HospitalHuizhou 516001China Affiliated Foshan Maternity&Child Healthcare hospital Southern Medical University(Foshan Maternity&Child Healthcare Hospital)Foshan 528000China Guangdong Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Nursing Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Laboratory Medicine Dongguan Institute of Clinical Cancer ResearchThe Tenth Affiliated Hospital of Southern Medical University(Dongguan People’s Hospital)Dongguan 523018China

Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably ***,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting ***,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive *** one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP ***,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA *** essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.

关键词： COX-2 blocking therapy CDDP Chemosensitization Allicin Ovarian cancer

Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy

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Chinese Chemical Letters 2024年第4期35卷 268-274页

作者： Xinyue Lan Junguang Liang Churan Wen Xiaolong Quan Huimin Lin Qinqin Xu Peixian Chen Guangyu Yao Dan Zhou Meng Yu Breast Center Department of General SurgeryNanfang HospitalSouthern Medical UniversityGuangzhou 510515China NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Breast Surgery The First People's Hospital of FoshanFoshan 528100China Zhujiang hospital Southern Medical UniversityGuangzhou 510282China

Despite the synergy of immune checkpoint blockade(ICB) therapy and photodynamic therapy(PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6(Ce6) and programmed death-ligand 1 antibody(αPD-L1) for flexible local photoimmunotherapy with merely singledosed administration. The presence of polyunsaturated fatty acid(docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species(ROS)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. The immunogenic cell death(ICD) effect of PDT evoked “cold” breast tumor to “hot” one, and then assisted the cascade releasedαPD-L1 to synergistically boost the immunotherapy. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform,showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.

关键词： Photodynamic therapy Immunotherapy Responsive release Immunogenic cell death Liposomal hydrogel

Gut commensal metabolite rhamnose promotes macrophages phagocytosis by activating SLC12A4 and protects against sepsis in mice

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3068-3085页

作者： Dongping Li Rongjuan Wei Xianglong Zhang Shenhai Gong Meijuan Wan Fangzhao Wang Jiaxin Li Meiling Chen Ruofan Liu Yantong Wan Yinghao Hong Zhenhua Zeng Peng Gu Zhang Wang Kutty Selva Nandakumar Yong Jiang Hongwei Zhou Peng Chen Department of Pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510000China Department of Critical Care Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhen 518000China Institute of Ecological Sciences School of Life SciencesSouth China Normal UniversityGuangzhou 510000China Department of Environmental and Biosciences School of BusinessInnovation and SustainabilityKristian IV’s vag 3Halmstad UniversityHalmstad 30004Sweden Microbiome Medicine Center Zhujiang HospitalSouthern Medical UniversityGuangzhou 510000China

Sepsis progression is significantly associated with the disruption of gut ***,the modulatory mechanisms of gut microbiota operating during sepsis are still ***,we investigated how gut commensals impact sepsis development in a pre-clinical *** ligation and puncture(CLP)surgery was used to establish polymicrobial sepsis in *** depleted of gut microbiota by an antibiotic cocktail(ABX)exhibited a significantly higher level of mortality than *** determined by metabolomics analysis,ABX treatment has depleted many metabolites,and subsequent supplementation with L-rhamnose(rhamnose,Rha),a bacterial carbohydrate metabolite,exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis,which in turn improved organ damage and ***,rhamnose binds directly to and activates the solute carrier family 12(potassium-chloride symporter),member 4(SLC12A4)in macrophages and promotes phagocytosis by activating the small G-proteins,Ras-related C3 botulinum toxin substrate1(Rac1)and cell division control protein 42 homolog(Cdc42).Interestingly,rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis *** conclusion,by identifying SLC12A4 as the host interacting protein,we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

关键词： Gut microbiota Sepsis Rhamnose SLC12A4 GTP-Rac1 GTP-Cdc42 Macrophage Phagocytosis