المؤلفون: De-Cong Zhu, Zhiqi Hu, Jin Wang, Yuan Gao, Yong Miao

المصدر: Molecular Immunology. 134:25-33

مصطلحات موضوعية: 0301 basic medicine, Immunology, Cell, Biology, 03 medical and health sciences, 0302 clinical medicine, Lineage tracing, medicine, Animals, Humans, Regeneration, Macrophage, Molecular Biology, Skin, integumentary system, Macrophages, Regeneration (biology), Structural integrity, Hair follicle, medicine.disease, Phenotype, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Hair loss, Hair Follicle, 030215 immunology

الوصف: Hair follicle (HF) is an excellent mini-model to study adult tissue regeneration, since it can regenerate itself under appropriate stress settings via interaction with niche components. Dermal macrophages, a group of heterogeneous cell populations, serve as key regulators in this microenvironment. Recent advances in phenotype identification and lineage tracing have unveiled various dermal macrophage subsets involved in stress-induced hair regeneration through different mechanisms, where HF structural integrity is impaired to varying degrees. This review summarized current knowledge regarding the distribution, sources, phenotypes of dermal macrophages in association with HF, as well as the mechanisms underlying macrophage-mediated hair regeneration in response to different internal-stress settings. Further investigation on macrophage dynamics will provide novel cell-targeting therapies for HF engineering and hair loss.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f00acb91094bb060a16f051456f3e9a7Test
https://doi.org/10.1016/j.molimm.2021.02.021Test

المؤلفون: Yenarae Lee, Xiaoping Yang, Lisa Brenan, Priya Pancholi, Utthara Nayar, M. Do Carmo, David E. Root, Sasha Pantel, Desiree Hernandez, J. Cordova, Cory M. Johannessen, Federica Piccioni, Tarjei S. Mikkelsen, Amanda J. Walker, Shunsuke Kitajima, Ofir Cohen, Rizwan Haq, P. Ram, Murugappan Sathappa, T. K. Hayes, Nicole S. Persky, Cong Zhu, David A. Barbie

المصدر: Nature Structural & Molecular Biology. 27:92-104

مصطلحات موضوعية: Models, Molecular, Proteomics, Mutant, Drug Resistance, Drug resistance, Computational biology, 03 medical and health sciences, Adenosine Triphosphate, 0302 clinical medicine, Structural Biology, Neoplasms, Drug Discovery, Animals, Humans, Point Mutation, Kinome, Amino Acid Sequence, Kinase activity, Protein Kinase Inhibitors, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, Kinase, Drug discovery, Drug Resistance, Neoplasm, biology.protein, Cyclin-dependent kinase 6, Protein Kinases, 030217 neurology & neurosurgery

الوصف: Kinases are involved in disease development and modulation of their activity can be therapeutically beneficial. Drug-resistant mutant kinases are valuable tools in drug discovery efforts, but the prediction of mutants across the kinome is challenging. Here, we generate deep mutational scanning data to identify mutant mammalian kinases that drive resistance to clinically relevant inhibitors. We aggregate these data with subsaturation mutagenesis data and use it to develop, test and validate a framework to prospectively identify residues that mediate kinase activity and drug resistance across the kinome. We validate predicted resistance mutations in CDK4, CDK6, ERK2, EGFR and HER2. Capitalizing on a highly predictable residue, we generate resistance mutations in TBK1, CSNK2A1 and BRAF. Unexpectedly, we uncover a potentially generalizable activation site that mediates drug resistance and confirm its impact in BRAF, EGFR, HER2 and MEK1. We anticipate that the identification of these residues will enable the broad interrogation of the kinome and its inhibitors.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f01c579a92a7d64907e816ad433a6adTest
https://doi.org/10.1038/s41594-019-0358-zTest

المؤلفون: Nanyan Lu, Cong Zhu, Susan J. Brown, Vaughn Hamill, Jianfa Bai, Elizabeth Porter, Rachel Palinski, Lance W. Noll, Yin Wang

المصدر: The Journal of general virology. 102(5)

مصطلحات موضوعية: Diarrhea, Rotavirus, Genes, Viral, Genotype, Swine, viruses, Reassortment, Genome, Viral, Biology, Viral Nonstructural Proteins, Rotavirus Infections, Evolution, Molecular, Virology, Animals, Genotyping, Phylogeny, Genetics, Swine Diseases, Viral Structural Proteins, Genetic diversity, Phylogenetic tree, Whole Genome Sequencing, Strain (biology), virus diseases, Genetic Variation, United States, Genetic distance, GenBank, Databases, Nucleic Acid

الوصف: Rotavirus C (RVC) is associated with acute diarrhoea in both children and young animals. Because of its frequent occurrence, additional sequences have recently been generated. In this study, we sequenced 21 complete genomes from porcine diarrhoea samples and analysed them together with all available reference sequences collected from the GenBank database [National Center for Biotechnology Information (NCBI)]. Based on phylogenetic analysis and genetic distance calculation, the number of each segment was identified as 31G, 26P, 13I, 5R, 5C, 5M, 12A, 10 N, 9T, 8E and 4 H for genotypes encoding VP7, VP4, VP6, VP1, VP2, VP3 and NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. From the analysis, genotypes G19–G31, P[22]–P[26], R5, A9–A12, N9–N10, T7–T9 and E6–E8 were defined as newly identified genotypes, and genotype C6 was combined with C5, and M6 was combined with M1, due to their closely related nature. Estimated with the identity frequency ratio between the intergenotype and intragenotype, the nucleotide identity cutoff values for different genotypes were determined as 85, 85, 86, 84, 83, 84, 82, 87, 84, 81 and 79 % for VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Genotyping of the 49 US strains indicated possible segment reassortment in 9 of the 11 segments, with the exceptions being VP1 and NSP5, and the most prevalent genotypes for each segment genes in the USA were G6/G5/G21/G9-P5/P4-I6/I5-R1-C5-M1-A8-N1/N10-T1-E1-H1. Our study updated the genotypes of RVC strains and provided more evidence of RVC strain diversity that may be relevant to better understand genetic diversity, and the distribution and evolution of RVC strains.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9b28da99fa6990376485482684ae979Test
https://pubmed.ncbi.nlm.nih.gov/33950806Test

المؤلفون: Jia Huo, Ronghua Yang, Caixia Huang, Wenlong Tan, Jing Zheng, Cong Zhu

المصدر: ACS Applied Materials & Interfaces. 11:25740-25749

مصطلحات موضوعية: Small interfering RNA, Materials science, Oligonucleotides, Cancer therapy, Mice, Nude, 02 engineering and technology, Drug resistance, 010402 general chemistry, 01 natural sciences, Mice, Downregulation and upregulation, medicine, Animals, Humans, NADH, NADPH Oxidoreductases, General Materials Science, Drug Carriers, Mice, Inbred BALB C, Neoplasms, Experimental, Nitroreductases, Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, 021001 nanoscience & nanotechnology, Xenograft Model Antitumor Assays, Cell Hypoxia, Nanostructures, Neoplasm Proteins, 0104 chemical sciences, Drug Resistance, Neoplasm, Delayed-Action Preparations, Drug delivery, Cancer cell, MCF-7 Cells, Cancer research, Female, Efflux, medicine.symptom, 0210 nano-technology

الوصف: The insufficient oxygen supply may cause hypoxia in a solid tumor, which can lead to drug resistance and unsatisfactory chemotherapy effect. To address this issue, a new nanodrug has been developed with azoreductase-responsive functional metal-organic frameworks (AMOFs), where chemotherapeutic drugs were encapsulated in the AMOFs and small interfering RNAs (siRNAs) were absorbed on the surface of AMOFs. The siRNA was designed to contain hypoxia-inducible factor (HIF)-1α against RX-0047, which can induce significant downregulation of HIF-1α protein. The azobenzene units within the frameworks of AMOFs could be reduced to amines by the highly expressed azoreductase under the oxygen-deficient environment, which results in azoreductase-responsive release of the encapsulated drugs and siRNAs under the hypoxic condition. Therefore, once the drug-loaded AMOF entered the hypoxic cancer cells, the azoreductase-responsive release of siRNA could decrease the efflux of chemotherapeutic drugs via inhibiting the expressions of HIF-1α, multidrug resistance gene 1, and P-glycoprotein. This nanodrug can thus efficiently break hypoxia-induced chemoresistance and result in high-efficient cancer therapy in hypoxic tumors. As far as we know, this is the first attempt to construct an AMOF-based nanodrug with hypoxic harvesting behaviors. This proof-of-concept research provides a simple strategy for the construction of hypoxic-responsive AMOFs and also offers a unique on-command drug delivery platform, which can effectively break hypoxia-induced chemoresistance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::38a252ae53cf0ad1bab7a3387cef3bb4Test
https://doi.org/10.1021/acsami.9b08115Test

المؤلفون: Weibin Lin, Cong Zhu, Mingming Gao, Benwen Wu, Jianbiao Lin, Huixiang Jiang, Zhenqi Ding, Guofeng Huang, Jianting Gao

المصدر: Cell and tissue researchReferences. 385(3)

مصطلحات موضوعية: 0301 basic medicine, Scaffold, Histology, Tissue Engineering, Chemistry, Mesenchymal stem cell, Cell Biology, Bone healing, Bone morphogenetic protein 2, Molecular medicine, Bone and Bones, Pathology and Forensic Medicine, Andrology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Tissue engineering, medicine, Animals, Bone marrow, Rabbits, Cancellous bone, 030217 neurology & neurosurgery

الوصف: In this study, effects of combining optimized tissue engineering bone (TEB) implantation with heel-strike like mechanical loading to repair segmental bone defect in New Zealand rabbits were investigated. Physiological characteristics of bone marrow mesenchymal stem cells (BMMSCs), compact bone cells (CBCs), and bone marrow and compact bone coculture cells (BMMSC-CBCs) were compared to select the optimal seed cells for optimized TEB construction. Rabbits with segmental bone defects were treated in different ways (cancellous bone scaffold for group A, cancellous bone scaffold and mechanical loading for group B, optimized TEB for group C, optimized TEB and mechanical loading for group D, n = 4), and the bone repair were compared. BMMSC-CBCs showed better proliferation capacity than CBCs (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99843802aefc9a49238dc88a5ed73a99Test
https://pubmed.ncbi.nlm.nih.gov/33966092Test

المؤلفون: Wenchang Li, Jianbiao Lin, Guofeng Huang, Zhenqi Ding, Cong Zhu, Mo Sha, Xiaoshan Chen, Weibin Lin, Huixiang Jiang

المصدر: Journal of Orthopaedic Surgery and Research
Journal of Orthopaedic Surgery and Research, Vol 14, Iss 1, Pp 1-11 (2019)

مصطلحات موضوعية: Male, lcsh:Diseases of the musculoskeletal system, Healing, Bone healing, Mesenchymal Stem Cell Transplantation, Bone tissue, Rats, Sprague-Dawley, Andrology, 03 medical and health sciences, 0302 clinical medicine, lcsh:Orthopedic surgery, Bone Marrow, Osteogenesis, Osteogenic differentiation, medicine, Animals, Orthopedics and Sports Medicine, Femur, Fracture Healing, 030203 arthritis & rheumatology, 030222 orthopedics, Osteoblasts, Tibia, business.industry, Mesenchymal stem cell, Mesenchymal Stem Cells, Osteoblast, Bone fracture, medicine.disease, Coculture Techniques, Rats, Staining, Tibial Fractures, Blot, lcsh:RD701-811, medicine.anatomical_structure, Surgery, Bone marrow, lcsh:RC925-935, Co-culture, business, Research Article

الوصف: Background Mesenchymal stem cells (MSCs) have great potential for the repair and regeneration of bone fracture, but their optimal origins remain controversial. Methods Bone marrow-MSCs (BM-MSCs) and bone-bone marrow-MSCs (B-BM-MSCs) were isolated from 12 SD rats, and the morphology, MSC-associated markers, and proliferative capacity of these cells were compared using an inverted microscope, flow cytometry, and CCK-8 assays, respectively. After 14 days of osteoblastic induction, osteoblast phenotypes were detected by ALP and calcium nodule staining, and the expression of BMP-2 and TGF-β1 was observed by western blotting. Then, the rat tibia fracture model was established with 3 groups (n = 6 per group), the control, BM-MSC, and B-BM-MSC groups. Computed tomography (CT) imaging was performed to evaluate fracture healing at weeks 2, 4, and 6. Finally, the fractured bones were removed at weeks 4 and 6, and HE staining was performed to evaluate fracture healing. Results Although the 2 types of MSCs shared the same cellular morphology and MSC-associated markers, B-BM-MSCs had a higher proliferative rate than BM-MSCs from day 9 to day 12 (p < 0.05), and the expression levels of ALP and calcium were obviously higher in B-BM-MSCs than in BM-MSCs after osteogenic induction (p < 0.01 and p < 0.001, respectively). Western blot results showed that the expression levels of BMP-2 and TGF-β1 in B-BM-MSCs were higher than in BM-MSCs before and after osteogenic induction (p < 0.01). In the animal experiments, CT imaging and gross observation showed that B-BM-MSCs had a greater capacity than BM-MSCs to promote fracture healing, as the Lane-Sandhu scores of B-BM-MSCs at weeks 4 and 6 after operation (3.00 ± 0.81 and 9.67 ± 0.94, respectively) were higher than those of BM-MSCs (1.33 ± 0.47 and 6.67 ± 1.25, respectively; both p < 0.05). The HE staining results further supported this conclusion. Conclusions Taken together, our study results proved that MSCs obtained by co-culturing the bone and bone marrow from SD rats had better proliferative, osteogenic differentiation, and fracture healing capacities than BM-MSCs, perhaps suggesting a novel way to obtain MSCs for bone tissue repair.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71a7df644a78b082a66d74265e8a690eTest
https://doi.org/10.1186/s13018-019-1346-zTest

المؤلفون: Satu Mustjoki, Ernest Fraenkel, Chris C. Mader, Yiguo Hu, Nicky A. Beelen, Jordan Bryan, Ifrah Tariq, Todd R. Golub, Samuel S. Freeman, Vasilis Syrgkanis, Michal Sheffer, Cong Zhu, Eugen Dhimolea, Govinda M. Kamath, Emily Lowry, Channing Yu, Jennifer Roth, Aviad Tsherniak, Marios Giannakis, Suha Naffar-Abu Amara, Lotte Wieten, Aedín C. Culhane, Olli Dufva, Constantine S. Mitsiades, Olga Dashevsky, Rizwan Romee, Sara Gandolfi, Ricardo De Matos Simoes, Minasri Borah, Samantha Bender, Li Wang

المساهمون: RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, Transplant. Immunology/Tissue Typing lab, MUMC+: DA TI Laboratorium (9)

المصدر: Nature Genetics, 53(8), 1196-+. Nature Publishing Group

مصطلحات موضوعية: Cytotoxicity, Immunologic, B7 Antigens, medicine.medical_treatment, Cell, Antigen presentation, INHIBITION, MELANOMA, Biology, Chromatin remodeling, Mice, Inbred NOD, Cell Line, Tumor, Genetics, medicine, Animals, Humans, PEMBROLIZUMAB, Immune Checkpoint Inhibitors, SARCOMA, Regulation of gene expression, Genome, Human, Melanoma, Allogeneic Cells, Histocompatibility Antigens Class I, Immunotherapy, EXPANSION, GAMMA, SARC028, medicine.disease, Chromatin Assembly and Disassembly, Cytotoxicity Tests, Immunologic, Xenograft Model Antitumor Assays, Cell biology, Gene expression profiling, Gene Expression Regulation, Neoplastic, Killer Cells, Natural, medicine.anatomical_structure, Cell culture, Drug Resistance, Neoplasm, T-CELLS, Female, LIGAND, RESISTANCE

الوصف: To systematically define molecular features in human tumor cells that determine their degree of sensitivity to human allogeneic natural killer (NK) cells, we quantified the NK cell responsiveness of hundreds of molecularly annotated ‘DNA-barcoded’ solid tumor cell lines in multiplexed format and applied genome-scale CRISPR-based gene-editing screens in several solid tumor cell lines, to functionally interrogate which genes in tumor cells regulate the response to NK cells. In these orthogonal studies, NK cell–sensitive tumor cells tend to exhibit ‘mesenchymal-like’ transcriptional programs; high transcriptional signature for chromatin remodeling complexes; high levels of B7-H6 (NCR3LG1); and low levels of HLA-E/antigen presentation genes. Importantly, transcriptional signatures of NK cell–sensitive tumor cells correlate with immune checkpoint inhibitor (ICI) resistance in clinical samples. This study provides a comprehensive map of mechanisms regulating tumor cell responses to NK cells, with implications for future biomarker-driven applications of NK cell immunotherapies. The use of natural killer (NK) cells in immunotherapy as an alternative to allogeneic T cells is gaining ground. Here, two genome-scale high-throughput platforms are used to identify genes that modulate the sensitivity of multiple solid tumor cell lines to NK-mediated killing.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53da45fbcbee64a206937aeeb815bf82Test
https://doi.org/10.1038/s41588-021-00889-wTest

المؤلفون: He Shan, Shuai Li, Zhou Rongyun, Yucheng Huang, Pengpeng Xia, Shuangjie Li, Mengxue Ye, Cong Zhu, Jianzhong Zhu, Nanhua Chen, Zhu Meiqin

المصدر: Virus Research. 242:90-95

مصطلحات موضوعية: 0301 basic medicine, China, Cancer Research, medicine.medical_specialty, Swine, Sequence Homology, Genome, Viral, Genome, Virus, law.invention, 03 medical and health sciences, law, Phylogenetics, Virology, Molecular genetics, medicine, Animals, Cluster Analysis, Phylogeny, Recombination, Genetic, Swine Diseases, Genetics, biology, Phylogenetic tree, Porcine epidemic diarrhea virus, Genetic Variation, Sequence Analysis, DNA, biology.organism_classification, Vaccination, 030104 developmental biology, Infectious Diseases, Recombinant DNA, Coronavirus Infections

الوصف: Porcine epidemic diarrhea virus (PEDV) causes devastating impact on global pig-breeding industry and current vaccines have become not effective against the circulating PEDV variants since 2011. During the up-to-date investigation of PEDV prevalence in Fujian China 2016, PEDV was identified in vaccinated pig farms suffering severe diarrhea while other common diarrhea-associated pathogens were not detected. Complete genomes of two PEDV representatives (XM1-2 and XM2-4) were determined. Genomic comparison showed that these two viruses share the highest nucleotide identities (99.10% and 98.79%) with the 2011 ZMDZY strain, but only 96.65% and 96.50% nucleotide identities with the attenuated CV777 strain. Amino acid alignment of spike (S) proteins indicated that they have the similar mutation, insertion and deletion pattern as other Chinese PEDV variants but also contain several unique substitutions. Phylogenetic analysis showed that 2016 PEDV variants belong to the cluster of recombination strains but form a new branch. Recombination detection suggested that both XM1-2 and XM2-4 are inter-subgroup recombinants with breakpoints within ORF1b. Remarkably, the natural recombinant HNQX-3 isolate serves as a parental virus for both natural recombinants identified in this study. This up-to-date investigation provides the direct evidence that natural recombinants may serve as parental viruses to generate recombined PEDV progenies that are probably associated with the vaccination failure.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b98302912d781499fafbc0d7a7312d61Test
https://doi.org/10.1016/j.virusres.2017.09.013Test

المؤلفون: Yan Huo, Zhi Lin, Xiaobing Zhou, Xue Wang, Zhe Qu, Cong Zhu, Bo Li, Jufeng Wang

المصدر: Regulatory Toxicology and Pharmacology. 78:78-84

مصطلحات موضوعية: Genetic Markers, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Time Factors, Biopsy, Urinary system, medicine.medical_treatment, Intraperitoneal injection, Urine, Urinalysis, Pharmacology, Kidney, Toxicology, Risk Assessment, Toxicogenetics, Nephrotoxicity, 03 medical and health sciences, chemistry.chemical_compound, Predictive Value of Tests, microRNA, medicine, Animals, Rats, Wistar, Creatinine, Dose-Response Relationship, Drug, business.industry, Gene Expression Profiling, Acute kidney injury, General Medicine, Acute Kidney Injury, medicine.disease, MicroRNAs, 030104 developmental biology, ROC Curve, chemistry, Area Under Curve, Gentamicin, Gentamicins, business, Injections, Intraperitoneal, medicine.drug

الوصف: MicroRNAs (miRNAs) have been recently recognized as promising non-invasive biomarkers for detecting the organ injuries. To further understand the sensibility and reliability of miRNA measurements in urine sample for predicting drug-induced early nephrotoxicity, a global urinary miRNA expression analysis was performed in the rodent models with gentamicin-induced acute kidney injury (AKI). Male Wistar rats were daily administrated with gentamicin (0, 60, and 120 mg/kg) for up to 10 days by intraperitoneal injection, and the miRNA profiling of animal urine samples were subsequently analyzed using TaqMan ® Array Rodent miRNA Cards. The results showed that four miRNAs (mmu-miR-138-5p, mmu-miR-1971, mmu-miR-218-1-3p, and rno-miR-489) were continuously increased in urine samples since day 4 after administration with gentamicin, which was not reflected by the standard markers such as serum creatinine (Cr) and urea nitrogen (BUN). Furthermore, other nine urinary miRNAs were increased in both 60 and 120 mg/kg groups on day 8. Receiver operator characteristics analysis demonstrated that the performance of these miRNAs with time- or dose-dependent increases were comparable to standard biomarkers (i.e. serum Cr and BUN), suggesting that the urinary miRNA panel can be used as potential biomarkers for the detection of gentamicin-induced AKI in rats. Moreover, the computer prediction analysis showed that these differentially expressed miRNAs were potentially targeted to many genes, which were mainly associated with the regulation of metabolic process and signaling. These data will improve the understanding and prediction of toxicology processes induced by nephrotoxicants.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::42594ea466770f738eb9a26e0abae8a3Test
https://doi.org/10.1016/j.yrtph.2016.04.001Test

المؤلفون: Mengling Xia, Cuicui Chen, Hui Xu, Sunshun Yan, Cong Zhu, Wangfeng Zhou, Wei Dai, Liqin Wu, Xiangting Ge, Yuanrong Dai

المصدر: The Journal of asthma : official journal of the Association for the Care of Asthma. 55(4)

مصطلحات موضوعية: 0301 basic medicine, Pulmonary and Respiratory Medicine, Neutrophils, Ovalbumin, Histone Deacetylase 2, 03 medical and health sciences, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Intervention (counseling), Smoke, Tobacco, medicine, Immunology and Allergy, Cigarette smoke, Asthmatic patient, Animals, Anti-Asthmatic Agents, Lung, Asthma, Mice, Inbred BALB C, Roxithromycin, Histone deacetylase 2, business.industry, Airway inflammation, Allergens, medicine.disease, Anti-Bacterial Agents, Eosinophils, Disease Models, Animal, 030104 developmental biology, 030228 respiratory system, Murine model, Pediatrics, Perinatology and Child Health, Immunology, Female, business, Bronchoalveolar Lavage Fluid, Proto-Oncogene Proteins c-akt, medicine.drug

الوصف: Cigarette smoke is well known to worsen asthma symptoms in asthmatic patients and to make them refractory to treatment, but the underling molecular mechanism is unclear. We hypothesized that cigarette smoke can reduce the expression of HDAC2 in asthma and the process was achieved by activating the PI3K-δ/Akt signaling pathway. We further hypothesized that roxithromycin (RXM) can alleviate the impacts by cigarette smoke.A murine model of asthma induced by ovalbumin (OVA) and cigarette smoke has been established. The infiltration of inflammatory cells and inflammatory factors was examined in this model. Finally, we evaluated the expression of HDAC2, Akt phosphorylation levels, and the effects of RXM treatment on the model described earlier.Cigarette smoke exposure reduced HDAC2 protein expression by enhancing the phosphorylation of Akt in PI3K-δ/Akt signaling pathway. Furthermore, RMX reduced the airway inflammation and improved the level of expression of HDAC2 in the cigarette smoke-exposed asthma mice.This study provides a novel insight into the mechanism of cigarette smoke exposure in asthma and the effects of RXM treatment on this condition. These results may be helpful for treating refractory asthma and emphasizing the need for a smoke-free environment for asthmatic patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1633b91a2707dae4faca196abde0891Test
https://pubmed.ncbi.nlm.nih.gov/28960099Test