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Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

Cancer Communications 2024年第1期44卷 101-126页

作者： Monika Raab Izabela Kostova Samuel Peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt department of Gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational Genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany German Cancer Consortium(DKTK) EssenGermany German Cancer Research Center(DKFZ) HeidelbergGermany Histology and embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany German Cancer Consortium(DKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human *** various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of *** intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 *** this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in ***:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector ***,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal *** alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way *** vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse ***:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based *** introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell *** analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA *** p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baselin

关键词： apoptosis cell cycle chromosomal instability HGSOC metastatic intraperitoneal mouse model HGSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

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Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice

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Chinese Journal of Natural Medicines 2024年第2期22卷 137-145页

作者： LIU Mingming GUO Jiatian ZHAO Jing LI Hongye FENG Xiaoxiao LIU Haojun ZHANG Hao JIA Xuejun WEI Rushuai LI Fang CHEN Chong HOU Mingzhuang LV Nanning XU Haiyan department of human anatomy Xuzhou Medical UniversityXuzhou 221004China department of Orthopedic Surgery The Affiliated Lianyungang Clinical College of Xuzhou Medical University(The Second People’s Hospital of Lianyungang)Lianyungang 222003China department of Orthopaedics The First Afliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Institute of Hematology Xuzhou Medical UniversityXuzhou 221004China

Excessive oxidative stress impairs cartilage matrix metabolism balance,significantly contributing to osteoarthritis(OA)***(CSL),a drug derived from Tripterygium wilfordii,has recognized applications in the treatment of cancer and immune system disorders,yet its antioxidative stress mechanisms in OA remain *** study aimed to substantiate CSL’s chondroprotective effects and unravel its underlying *** investigated CSL’s impact on chondrocytes under both normal and inflammatory *** vitro,CSL mitigated interleukin(IL)-1β-induced activation of proteinases and promoted cartilage extracellular matrix(ECM)*** vivo,intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA ***,it was found that inhibiting nuclear factor erythroid 2-related factor 2(NRF2)abrogated CSL-mediated antioxidative functions and exacerbated the progression of *** study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2,offering a novel therapeutic avenue for arthritis therapy.

关键词： Osteoarthritis Celastrol Articular cartilage Extracellular matrix NRF2

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Hepatic grooves:An observational study at laparoscopic surgery

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World Journal of Experimental Medicine 2024年第2期14卷 97-102页

作者： Shamir O Cawich Dexter A Thomas Fawwaz Mohammed Michael T Gardner Marlene Craigie Shaneeta Johnson Ramnanand S Kedambady department of Surgery University of the West IndiesSt Augustine 000000Trinidad and Tobago department of Surgery Port of Spain General HospitalPort of Spain 000000Trinidad and Tobago Section of anatomy Basic Medical SciencesUniversity of the West IndiesKingston 000000Jamaica department of Radiology University of the West IndiesKingston 000000Jamaica department of Surgery Morehouse School of MedicineAtlantaGA 30310United States Section of anatomy Department of Basic Medical SciencesUniversity of the West IndiesKingston KIN7Jamaica

BACKGROUND In traditional descriptions,the upper surface of the liver is smooth and convex,but deep depressions are variants that are present in 5%-40%of *** sought to determine the relationship between surface depressions and the *** To use exploratory laparoscopy to determine the relationship between surface depressions and the *** An observational study was performed in all patients undergoing laparoscopic upper gastro-intestinal operations between January 1,2023 and January 20,2024.A thirty-degree laparoscope was used to inspect the liver and *** surface depressions were present,we recorded patient demographics,presence of diaphragmatic bands,rib protrusions and/or any other source of compression during *** Of 394 patients,343 had normal surface anatomy,and 51(12.9%)had prominent surface depressions on the *** was no significant relationship between the presence of surface depressions and gender nor the presence of rib ***,there was significant association between the presence of surface depressions and diaphragmatic muscular bands(P<0.001).CONCLUSION With these data,the diaphragmatic-band theory has gained increased importance over other theories for surface *** studies are warranted using cross sectional imaging to confirm relationships with intersectional planes as well as beta-catenin assays in the affected liver parenchyma.

关键词： Liver Variant Vein Hepatic Surgery

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Liver surface depressions in the presence of diaphragmatic muscular bands on trans-illumination

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World Journal of Experimental Medicine 2024年第2期14卷 5-10页

作者： Shamir O Cawich Michael T Gardner Ramanand Shetty Jean Pierre Louboutin Zenica Dabichan Shaneeta Johnson department of Surgery University of the West IndiesSt AugustineTrinidad and Tobago Section of anatomy Department of Basic Medical SciencesUniversity of the West IndiesKingston KIN7Jamaica department of Surgery Morehouse School of MedicineAtlantaGA 30310United States

Traditional descriptions of liver anatomy refer to a smooth,convex surface contacting the *** depressions are recognized anatomic *** are many theories to explain the cause of the *** discuss the theory that these are... 详细信息

关键词： Liver anatomy Depressions Fissure Groove Sulcus Variant

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The immune system: uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares Mar Cuadrado-Tejedor Ana García-Osta Juan José Lasarte Immunology and Immunotherapy Program Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Pathology Anatomy and Physiology Department School of Medicine University of NavarraIDISNA

Humans and animals use the classic five senses-sight, hearing, touch, smell, and taste-to detect and monitor their environment, with the sense of position and movement often referred to as the sixth sense. The perception of external signals through the senses is essential to an organism’s survival, transmitting signals to the central nervous system(CNS) and prompting physiological changes in other biological systems. In addition to the direct effects of sense-induced mediators in the brain,

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Multiple pretreatments can effectively improve the functionality of mesenchymal stem cells

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World Journal of Stem Cells 2024年第2期16卷 58-63页

作者： Xin-Xing Wan Xi-Min Hu Kun Xiong department of Endocrinology Third Xiangya HospitalCentral South UniversityChangsha 410013Hunan ProvinceChina department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008Hunan ProvinceChina department of anatomy and Neurobiology School of Basic Medical ScienceCentral South UniversityChangsha 410013Hunan ProvinceChina

In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cells”,recently published in World Journal of Stem *** over three decades of research on the clinical application of mesenchymal stem cells(MSCs),only a few therapeutic products have made it to clinical use,due to multiple preclinical and clinical challenges yet to be *** study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics,which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of *** we delve deeper into the intricacies of pretreat-ment methodologies,we anticipate a transformative shift in the landscape of MSC-based therapies,ultimately contributing to improved patient outcomes and advancing the field as a whole.

关键词： Mesenchymal stem cells Inflammatory factor Hypoxia Pretreatment

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Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： Ana Milena Silva Olaya Fernanda Martins Almeida Ana Maria Blanco Martinez Suelen Adriani Marques PhD Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

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Paclitaxel induces human KOSC3 oral cancer cell apoptosis through caspase pathways

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BIOCELL 2024年第7期48卷 1047-1054页

作者： YU-YAN LAN TSUN-CHIH CHENG YI-PING LEE CHIA-YIH WANG BU-MIIN HUANG School of Medicine College of MedicineI-Shou UniversityKaohsiung82445Taiwan department of Otolaryngology An Nan HospitalChina Medical UniversityTainan70965Taiwan department of Cell Biology and anatomy College of MedicineNational Cheng Kung UniversityTainan70101Taiwan department of Medical Research China Medical University HospitalChina Medical UniversityTaichung40402Taiwan

Background:Paclitaxel is a compound derived from Paciﬁc yew bark that induces various cancer cell ***,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is ***:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,ﬂow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,***:Ourﬁndings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 ***,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 *** addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell ***,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 ***:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.

关键词： Paclitaxel Oral cancer KOSC3 cells Apoptosis Caspase pathways

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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

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Roles of combined femoral and acetabular anteversion in pathological changes of hip dysplasia and hip reconstructive surgery

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World Journal of Orthopedics 2024年第5期15卷 390-399页

作者： Can Liu Zheng Xu Jian-Fa Zeng Zhen-Qi Song Yu-Yin Xie Zhong-Wen Tang Jie Wen Sheng Xiao department of anatomy Hunan Normal University School of MedicineChangsha 410003Hunan ProvinceChina department of Pediatric Orthopedics Hunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 410013Hunan ProvinceChina

Combined femoral and acetabular anteversion is the sum of femoral and acetabular anteversion,representing their morphological relationship in the axial *** with the increasing understanding of hip dysplasia in recent years,numerous scholars have confirmed the role of combined femoral and acetabular anteversion in the pathological changes of hip *** present,the reconstructive surgery for hip dysplasia includes total hip replacement and redirectional hip preservation *** an important surgery index,combined femoral and acetabular anteversion have a crucial role in these ***,we discuss the role of combined femoral and acetabular anteversion in pathological changes of hip dysplasia,total hip replacement,and redirectional hip preservation surgery.

关键词： Combined anteversion Femoral anteversion Acetabular anteversion Hip dysplasia Hip preservation surgery Total hip replacement

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