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Higgs-like(pseudo)scalars in AdS_(4),marginal and irrelevant deformations in CFT_(3),and instantons on S^(3)

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Chinese Physics C 2024年第4期48卷 68-81页

作者： M.Naghdi department of Physics Faculty of Basic SciencesUniversity of IlamIlamIran

Employing a 4-form ansatz of 11-dimensional supergravity over a non-dynamical AdS_(4)×S^(7)/Z_(k)background and setting the internal space as an S1 Hopf fibration on CP3,we obtain a consistent ***(pseudo)scalars,in the resulting scalar equations in Euclidean AdS_(4)space,may be considered to arise from(anti)M-branes wrapping around the internal directions in the(Wick-rotated)skew-whiffed M2-brane background(as the resulting theory is for anti-M2-branes),thus realizing the modes after swapping the three fundamental representations 8_(s),8_(c),and 8_(v) of SO(8).Taking the backreaction on the external and internal spaces,we obtain the massless and massive modes,corresponding to exactly marginal and marginally irrelevant deformations on the boundary CFT3,***,we obtain a closed solution for the bulk equation and compute its correction with respect to the background ***,considering the Higgs-like(breathing)mode m^(2)=18,having all supersymmetries as well as parity and scale-invariance broken,solving the associated bulk equation with mathematical methods,specifically the Adomian decomposition method,and analyzing the behavior near the boundary of the solutions,we realize the boundary duals in the SU(4)×U(1)-singlet sectors of the ABJM ***,introducing the new dual deformationΔ_(+)=3,6 operators made of bi-fundamental scalars,fermions,and U(1)gauge fields,we obtain the SO(4)-invariant solutions as small instantons on a three-sphere with the radius at infinity,which correspond to collapsing bulk bubbles leading to big-crunch singularities.

关键词： AdS_(4)/CFT_(3)correspondence scalar equations in AdS_(4) instantons marginal and irrelevant operators (anti)M-branes

The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

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Oncology Research 2024年第7期32卷 1231-1237页

作者： MOHAMMAD-TAGHI MORADI DHIYA ALTEMEMY MAJID ASADI-SAMANI PEGAH KHOSRAVIAN MARZIYEH SOLTANI LEILA HASHEMI AZADEH SAMIEI-SEFAT Medical Plants Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran department of Pharmaceutics College of PharmacyAl-Zahraa University for WomenKarbalaIraq Cellular and Molecular Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran

Background:Despite the availability of chemotherapy drugs such as 5-ﬂuorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side *** study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their *** proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)*** synergistic effect of 5-FU and celastrol was studied using Compusyn *** DNA content at different phases of the cell cycle and apoptosis rate was measured usingﬂow ***:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU signiﬁcantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,*** mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,*** addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis ***:Although celastrol could decrease the concentration of 5-ﬂuorouracil that sufﬁced to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

关键词： Gastric cancer Celastrol Terpenoid Cell cycle regulation Apoptosis Synergism

Targeting carnitine palmitoyl transferase 1A(CPT1A)induces ferroptosis and synergizes with immunotherapy in lung cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1675-1689页

作者： Lei Ma Chong Chen Chunxing Zhao Tong Li Lingyu Ma Jiayu Jiang Zhaojun Duan Qin Si Tsung-Hsien Chuang Rong Xiang Yunping Luo department of Immunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Collaborative Innovation Center for Biotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China department of Lung Cancer Surgery Tianjin Medical University General HospitalTianjin 300052China Immunology Research Center National Health Research InstitutesZhunanMiaoliTaiwanROC department of Immunology Nankai UniversityTianjin 300071China

Despite the successful application of immune checkpoint therapy,no response or recurrence is typical in lung *** stem cells(CSCs)have been identified as a crucial player in immunotherapy-related ***,a form of cell death driven by iron-dependent lipid peroxidation,is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with *** adaption of CsCs drives tumor resistance,yet the mechanisms of their ferroptosis defense in tumor immune evasion remain ***,through metabolomics,transcriptomics,a lung epithelialspecific Cptla-knockout mouse model,and clinical analysis,we demonstrate that CPT1A,a key rate-limiting enzyme of fatty acid oxidation,acts with L-carnitine,derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8^(+)T cells inactivation in lung ***,CPT1A restrains ubiquitination and degradation of c-Myc,while c-Myc transcriptionally activates CPT1A *** CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating,thereby suppressing ferroptosis in ***,targeting CPT1A enhances immune checkpoint blockadeinduced anti-tumor immunity and tumoral ferroptosis in tumor-bearing *** results illustrate the potential of a mechanismguided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CsCs to improve the efficacy of lung cancer immunotherapy.

关键词： immunotherapy metabolism peroxidation

Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell *** review summarizes the existing scRNA-seq technologies together with their strengths and *** applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune ***-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

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Journal of Genetics and Genomics 2024年第5期51卷 531-542页

作者： Danhui Ruan Jiancheng Xu Yang Liu Juan Luo Xuyang Zhao Yuhua Li Guangxi Wang Jiawen Feng Hui Liang Yue Yin Jianyuan Luo Yuxin Yin Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesBeijing Key Laboratory of Tumor Systems BiologyPeking University International Cancer InstitutePeking-Tsinghua Center of Life SciencesPeking University Health Science CenterBeijing 100191China Institute of Precision Medicine Peking University Shenzhen HospitalShenzhenGuangdong 518036China department of Pharmacology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China department of Medical Genetics Center for Medical GeneticsSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Soochow University Cancer Institute SuzhouJiangsu 215127China

Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological *** RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or ***,PTEN-related circRNAs are largely ***,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy ***-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in *** down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate *** data demonstrate that circPTEN-MT is an important regulator of cellular energy *** study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.

关键词： Circular RNA LRPPRC Mitochondrial energy metabolism mtDNA post-transcriptional regulation

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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World Journal of Clinical Cases 2024年第3期12卷 474-478页

作者： Yusuf Tutar department of basic Pharmaceutical sciences Faculty of PharmacyDivision of BiochemistryUniversity of Health SciencesIstanbul 34668Turkey health sciences Faculty Recep Tayyip Erdogan UniversityRize 53350Turkey Molecular Oncology Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey Molecular Medicine Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):*** all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural *** methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized *** is a popular technique for collecting direct mea-surements of metabolic activity from many biological ***,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme *** annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called *** network uses an approach that emphasizes metabolite-gene consensus via biochemical *** metabolomics and genomics data is ***,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical *** The genome and metabolites of biological organisms are not fully characterized with current ***,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug *** network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical ***,clinical data may be integrated to gene expression–metabolite expression by system genetics appr

关键词： Network pharmacology Metabologenomics Genome Pathways Cancer

Therapeutic and regenerative potential of different sources of mesenchymal stem cells for cardiovascular diseases

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BIOCELL 2024年第4期48卷 559-569页

作者： YARA ALZGHOUL HALA J.BANI ISSA AHMAD K.SANAJLEH TAQWA ALABDUH FATIMAH RABABAH MAHA AL-SHDAIFAT EJLAL ABU-EL-RUB FATIMAH ALMAHASNEH RAMADA R.KHASAWNEH AYMAN ALZU’BI HUTHAIFA MAGABLEH department of basic Medical sciences Faculty of MedicineYarmouk UniversityIrbidJordan

Mesenchymalstemcells(MSCs)*** the internal cardiac microenvironment to facilitate their immunomodulatory and differentiation abilities,which are essential to restore heart *** can be easily isolated from different sources,including bone marrow,adipose tissues,umbilical cord,and dental *** from various sources differ in their regenerative and therapeutic abilities for cardiovascular *** this review,we will summarize the therapeutic potential of each MSC source for heart diseases and highlight the possible molecular mechanisms of each source to restore cardiac function.

关键词： Bone marrow mesenchymal stem cells Adipose tissue mesenchymal stem cells Dental pulp stem cells Umbilical cord mesenchymal stem cells Cardiomyocytes Regeneration Myocardial infarction Mesenchymal stem cells Differentiation Immunomodulation

Priming mesenchymal stem cells to develop “super stem cells”

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World Journal of Stem Cells 2024年第6期16卷 623-640页

作者： Khawaja Husnain Haider department of basic sciences Sulaiman AlRajhi UniversityAlQaseem 52736Saudi Arabia

The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment,genetic manipulation,and chemical and pharmacological treatment,each strategy having advantages and *** of these pre-treatment protocols are *** editorial is a continuum of Li et al’s published article and Wan et al’s editorial focusing on the significance of pre-treatment strategies to enhance their stemness,immunoregulatory,and immunosuppressive *** have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and *** a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells(MSCs),pre-treatment based on the mechanistic understanding is expected to develop“Super MSCs”,which will create a transformative shift in MSC-based therapies in clinical settings,potentially revolutionizing the *** optimized,the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop“super stem cells”with augmented stemness,functionality,and reparability for diverse clinical applications with better outcomes.

关键词： Cell survival Cell therapy Preconditioning Pre-treatment Stem cells Super stem cells

Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1344-1360页

作者： Chun-Yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-Wei Tang Qiu-Lu Zhang Ling-Fu Zhang Jian-Yuan Luo department of Pathology Institute of Systems BiomedicineSchool of Basic Medical Sciences Peking UniversityPeking University Third HospitalPeking University Health Science CenterBeijing 100191China department of General Surgery Peking University Third HospitalBeijing 100191China department of Medical Genetics Department of Biochemistry and BiophysicsSchool of Basic Medical Sciences Peking UniversityPeking University Health Science CenterBeijing 100191China

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin ***1 has been identified as a critical oncogene in the progression of ***,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still *** To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA *** Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic ***-quent validations were conducted through spatial transcriptomics and *** construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data *** CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased ***5AC-high cells were found to promote CCA progression through WNT ***5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral ***13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor ***16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with *** the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple *** samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer *** Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关键词： Mucin Cholangiocarcinoma Single-cell RNA sequencing Spatial transcriptomics Prognosis