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Quercetin regulates depression-like behavior in CUMS rat models via TLR4/NF-κB signaling

BIOCELL 2024年第5期48卷 731-744页

作者： YUANYUAN LI BITAO ZHANG ZILONG CUI PEIJIAN FAN SHAOXIAN WANG College of Basic medicine Hebei University of Chinese MedicineShijiazhuang050200China Hebei Key Laboratory of Integrated Chinese and Western medicine for Lung Disease Research Shijiazhuang050091China

Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA

关键词： Quercetin Chronic unpredictable mild stress Depression Microglia TLR4/NF-κB inflammatory pathway

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Amplifying protection against acute lung injury: Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

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Chinese Herbal medicines 2024年第3期16卷 422-434页

作者： Junjie Li Ming Dong Qing Yao Xu Dong Yuanyuan Chen Jincai Wen Yingjie Xu Zhixin Wu Xiaomei Zhao Ye Xiu Xiaoyan Zhan Zhaofang Bai Xiaohe Xiao Chengde Medical University Department of Hepatology The Fifth Medical Center of PLA General Hospital China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General Hospital National Key Laboratory of Kidney Diseases The Fifth Medical Center of PLA General Hospital School of Stomatology Heilongjiang Key Lab of Oral Biomedicine Materials and Clinical Application & Experimental Center for Stomatology EngineeringJiamusi University Southern Medical University

Objective:Acute lung injury(ALI) is characterized by inflammation and currently lacks an efficacious pharmacological intervention.The medicine combination of Lonicerae Japonicae Flos(LJF) and Forsythiae Fructus(FF) demonstrates combined properties in its anti-infective,anti-inflammatory,and therapeutic effects,particularly in alleviating respiratory symptoms.In previous studies,Chinese medicine has shown promising efficacy in lipopolysaccharides(LPS)-induced ALI.However,there have been no reports of LJF and FF pairing for lung injury.The aim of this study is to compare the efficacy of herb pair Lonicerae Japonicae Flos-Forsythiae Fructus(LF) with LJF or FF alone in the treatment of ALI,and to explore whether LJF and FF have a combined effect in the treatment of lung injury,along with the underlying mechanism involved.Methods:A total of 36 mice were divided into six groups(control,model,LJF,FF,LF,dexamethasone)based on the treatments they received after undergoing sham-operation/LPS tracheal instillation.H&E staining and pulmonary edema indexes were used to evaluate lung injury severity.Alveolar exudate cells(AECs) were counted based on cell count in bronchoalveolar lavage fluid(BALF),and neutrophil percentage in BALF was measured using flow cytometry.Myeloperoxidase(MPO) activity in BALF was measured using enzyme-linked immunosorbent assay(ELISA),while the production of IL-1β,TNF-α,and IL-6 in the lung and secretion level of them in BALF were detected by quantitative polymerase chain reaction(qPCR)and ELISA.The effect of LJF,FF,and LF on the expression of Caspase-1 and IL-1β proteins in bone marrow derived macrophages(BMDMs) supernatant was assessed using Western blot method under various inflammasome activation conditions.In addition,the concentration of IL-1β and changes in lactatedehydrogenase(LDH) release levels in BMDMs supernatant after LJF,FF,and LF administration,respectively,were measured using ELISA.Furthermore,the effects of LJF,FF and LF on STING and IRF3 phosphorylation in BMDMs were detected by West

关键词： acute lung injury BMDMs inflammasomes Lonicerae Japonicae Flos - Forsythia Fructus drug pair STING

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A strategy for mechanically integrating robust hydrogeltissue hybrid to promote the anti-calcification and endothelialization of bioprosthetic heart valve

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Regenerative Biomaterials 2024年第2期3卷 123-136页

作者： Haoshuang Wu Nuoya Chen Tiantian Zheng Li Li Mengyue Hu Yumei Qin Gaoyang Guo Li Yang Yunbing Wang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China Institute of clinical Pathology West China Hospital of Sichuan UniversityChengdu 610041China College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China

Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over decades.Most clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed endothelializa-tion.Here,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs.In particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond interactions.Then,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates.In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification properties.Therefore,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

关键词： bioprosthetic heart valves recombinant humanized collagen typeⅢ endothelialization anti-calcification anti-coagulation

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Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection

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Journal of Intensive medicine 2024年第1期4卷 81-93页

作者： Marie Dejonckheere Massimo Antonelli Kostoula Arvaniti Koen Blot Ben CreaghBrown Dylan Wde Lange Jan De Waele Mieke Deschepper Yalim Dikmen George Dimopoulos Christian Eckmann Guy Francois Massimo Girardis Despoina Koulenti Sonia Labeau Jeffrey Lipman Fernando Lipovestky Emilio Maseda Philippe Montravers Adam Mikstacki JoseArtur Paiva Cecilia Pereyra Jordi Rello JeanFrancois Timsit Dirk Vogelaers Stijn Blot the Abdominal Sepsis Study(AbSeS)group on behalf of the Trials Group of the European Society of Intensive Care medicine Department of Internal medicine and Pediatrics Faculty of Medicine and Health SciencesGhent UniversityGhentBelgium Department of Anesthesiology Intensive Care and Emergency MedicineFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly UniversitàCattolica del Sacro Cuore RomeItaly Intensive Care Unit Papageorgiou University Affiliated HospitalThessaloníkiGreece Department of Epidemiology and Public Health SciensanoIxellesBelgium Surrey Perioperative Anaesthetic Critical Care Collaborative Research Group(SPACeR) Royal Surrey County HospitalGuildfordUK Department of clinical and experimental medicine University of SurreyGuildfordUK Department of Intensive Care medicine University Medical Center UtrechtUniversity UtrechtUtrechtthe Netherlands Department of Intensive Care medicine Ghent University HospitalGhentBelgium Data Science Institute Ghent University HospitalGhentBelgium Department of Anesthesiology and Reanimation Cerrahpasa School of MedicineIstanbul University-CerrahpasaIstanbulTurkey rd Department of Critical Care “EVGENIDIO”HospitalNational and Kapodistrian University of AthensAthensGreece Department of General Visceral and Thoracic SurgeryKlinikum Hannoversch-MuendenGoettingen UniversityGöttingenGermany Division of Scientific Affairs-Research European Society of Intensive Care MedicineBrusselsBelgium Anesthesia and Intensive Care Department University Hospital of ModenaModenaItaly UQ Centre for clinical Research Faculty of MedicineThe University of QueenslandBrisbaneQLDAustralia nd Critical Care Department Attikon University HospitalAthensGreece Department of Nursing Faculty of EducationHealth and Social WorkUniversity College GhentGhentBelgium Jamieson Trauma Institute The University of QueenslandBrisbaneQLDAustralia Nimes University Hospital University of MontpellierNimesFrance Critical Care Department Hospital of the Interamerican Open University(UAI)Buenos AiresArgentina Surgical Critical Care Department of AnesthesiaHospital Universitario

Background:The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the(1)setting of infection onset(community-acquired,early onset,or late-onset hospital-acquired),(2)presence or absence of either localized or diffuse peritonitis,and(3)severity of disease expression(infection,sepsis,or septic shock).This classification system demonstrated reliable risk stratification in intensive care unit(ICU)patients with intra-abdominal infection.This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality.Methods:This was a secondary analysis of an international observational study(“AbSeS”)investigating ICU patients with intra-abdominal infection.Only patients with pancreatic infection were included in this analysis(n=165).Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU.Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio(OR)and 95%confidence interval(CI).Results:The overall mortality was 35.2%(n=58).The independent risk factors for mortality included older age(OR=1.03,95%CI:1.0 to 1.1 P=0.023),localized peritonitis(OR=4.4,95%CI:1.4 to 13.9 P=0.011),and persistent signs of inflammation at day 7(OR=9.5,95%CI:3.8 to 23.9,Pclinically relevant differences in microbial etiology between survivors and non-survivors.Conclusions:In pancreatic infection,a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome.In this limited series,essentials of the AbSeS-classification,such as the setting of infection onset,diffuse peritonitis,and severity of disease expression,

关键词： Pancreatic infection Intensive care unit Mortality Intra-abdominal infection Sepsis

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Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

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Food Science and Human Wellness 2024年第2期13卷 568-596页

作者： Sijia Wu Siyuan Zhang Bo Peng Dechao Tan Mingyue Wu Jinchao Wei Yitao Wang Hua Luo Macao Centre for Research and Development in Chinese medicine State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China College of Pharmacy Guangxi Medical UniversityNanning 530021China Guangxi University of Chinese medicine Nanning 530001China

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.

关键词： Ganoderma lucidum Phytochemistry Efficacy Safety clinical study

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Paeoniflorin,the Main Monomer Component of Paeonia lactiflora,Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation

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Chinese Journal of Integrative medicine 2024年第5期30卷 433-442页

作者： CHEN Pu ZHOU Jun RUAN An-min MA Yu-feng WANG Qing-fu Department of Orthopaedic Surgery Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China Department of Orthopaedic Surgery Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China Department of Orthopaedic Surgery Beijing Longfu HospitalBeijing 100010China

Objective:To explore the mechanism of paeoniflorin(PF)on osteoarthritis(OA)synovial inflammation from network pharmacology to experimental pharmacology.Methods:Targets of OA were constructed by detecting the database of network database platforms(Therapeutic Target database,Drug Bank and Gene Cards),and the targets of PF were constructed by Pub Chem and Herbal Ingredients'Targets database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of these co-targeted genes were conducted via Database for Annotation,Visualization,and Integrated Discovery(DAVID)database,and protein-protein interaction(PPI)networks were conducted via the search tool for the retrieval of interacting genes(STRING)database.Cell counting kit-8(CCK-8)assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes(FLS),quantitative real-time polymerase chain reaction(q PCR),enzyme-linked immunosorbent assay(ELISA)and Western blot were used to verify the potential mechanism of PF in synovial inflammation.Results:Twenty-six co-targeted genes were identified.GO enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm,and the biological processes mainly involved'cellular response to hypoxia''lipopolysaccharide(LPS)-mediated signaling pathway'and'positive regulation of gene expression'.KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with'hypoxia-inducible factor-1(HIF-1)signaling pathway'and'tumornecrosis factor(TNF)signaling pathway'.The PPI network showed that the top 3 hub genes were TP53,TNF,and CASP3.Molecular docking results showed that PF was well docking with TNF.CCK-8 showed no potential toxicity of 10,20 and 50μmol/L PF on human OA FLS.And PF significantly decreased the expression levels of interleukin-1β,interleukin-6,TNF-αmatrix metalloproteinase 13(MMP13),and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5)and TNF-αin LPS-induced OA FLS.Conclusion:PF exhibited

关键词： paeoniflorin osteoarthritis synovial inflammation tumor necrosis factor-α network pharmacology Paeonia lactiflora

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Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates inflammatory response ulcerative colitis through TLR4/NF-κB signaling pathway

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1149-1154页

作者： Li Han Kun Tang Xiao-Li Fang Jing-Xi Xu Xi-Yun Mao Ming Li Department of Anorectal Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Anhui HospitalHefei 230001Anhui ProvinceChina Anorectal Center The First Affiliated Hospital of Anhui University of Traditional Chinese MedicineHefei 230001Anhui ProvinceChina Department of Spleen and Stomach Diseases Department of GastroenterologyAffiliated Wuhu Hospital of Traditional Chinese Medicine of Anhui College of Traditional Chinese MedicineWuhu 241000Anhui ProvinceChina

BACKGROUND Ulcer colitis(UC)is a chronic,nonspecific,and noninfectious inflammatory bowel disease.Recently,Toll-like receptors(TLRs)have been found to be closely associated with clinical inflammatory diseases.Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging.Moreover,no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.AIM To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.METHODS This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021.The patients with UC were divided into two groups(control and experimental).The peripheral blood of the experimental and control groups were collected under aseptic conditions.The expression of TLR4 protein,NF-κB,IL-6,and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug.Linear co rrelation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17,and Pexperimental groups.The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group(Pexperimental group were significantly lower than those in the control group(Pexperimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17(r=0.823,P<0.05).CONCLUSION Kuicolong-yu enema

关键词： Ulcerative colitis TLR4 NF-κB signaling pathway Kuicolong-yu enema

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Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B

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Animal Models and experimental medicine 2024年第3期7卷 324-336页

作者： Bowen Niu Lingling Liu Qian Gao Meng-Min Zhu Lixiang Chen Xiu-Hua Peng Boying Qin Xiaohui Zhou Feng Li Department of Laboratory Animal Science Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Biology College of Life SciencesShanghai Normal UniversityShanghaiPeople's Republic of China

Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

关键词： bitter taste receptor CRISPR/Cas9 genetic mutation two-bottle preference test type 2 taste receptors(Tas2rs)

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Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

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Neural Regeneration Research 2024年第2期19卷 272-276页

作者： Marta Celorrio Kirill Shumilov Stuart H.Friess Department of Pediatrics Washington University in St.Louis School of MedicineSt.LouisMOUSA

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

关键词： gut microbiome gut microbiota gut-brain axis macrophage microglia monocyte neuroinflammation short-chain fatty acids T cell traumatic brain injury

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MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1453-1464页

作者： Mei-Zhu Shen Yong Zhang Fang Wu Mei-Zhen Shen Jun-Lin Liang Xiao-Long Zhang Xiao-Jian Liu Xin-Shu Li Ren-Sheng Wang Department of Radiotherapy The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Radiotherapy People’s Hospital of Guangxi Zhuang Autonomous RegionNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Colorectal Anal Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of clinical medicine Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.

关键词： MicroRNA-298 Human dual-specificity tyrosine(Y)-regulated kinase 1A Colorectal cancer Radio-resistance p53 binding protein 1

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