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This study aimed to investigate the potential of mesenchymal stem cells (MSCs) in alleviating diabetic lung injury by decreasing inflammation, fibrosis and recovering tissue macrophage homeostasis. To induce pulmonary injuries in an in vivo murine model, we utilized a streptozotocin (STZ), and high-fat diet (HFD) induced diabetic C57 mouse model. Subsequently, human umbilical cord-derived MSCs (hUC-MSCs) were administered through the tail vein on a weekly basis for a duration of 4 weeks. In addition, in vitro experiments involved co-culturing of isolated primary abdominal macrophages from diabetic mice and high glucose-stimulated MLE-12 cells with hUC-MSCs. The objective was to evaluate if hUC-MSCs co-culturing could effectively mitigate cell inflammation and fibrosis. Following hUC-MSCs injection, diabetic mice displayed enhanced pulmonary functional parameters, reduced pulmonary fibrosis, and diminished inflammation. Notably, the dynamic equilibrium of lung macrophages shifted from the M1 phenotype to the M2 phenotype, accompanied by a notable reduction in various indicators associated with inflammation and fibrosis. Results from cell co-culturing experiments further supported this trend, demonstrating a reduction in inflammatory and fibrotic indicators. In conclusion, our findings suggest that hUC-MSCs treatment holds promise in mitigating diabetic pulmonary injury by significantly reducing inflammation, fibrosis and maintain tissue macrophage homeostasis within the lungs. This study sheds light on the therapeutic potential of hUC-MSCs in managing diabetic complications affecting the pulmonary system.
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In the present work, Fe88Zr8-xSmxB4 (x = 2, 4) amorphous alloys (AAs) were successfully synthesized into the shape of 40-micrometer-thick ribbons and their magnetic properties were measured. The Fe88Zr8-xSmxB4 (x = 2, 4) AAs exhibited a rather high maximum magnetic entropy change (-ΔSmpeak): ~3.53 J/(K × kg) near 317 K for x = 2 and ~3.79 J/(K × kg) near 348 K for x = 4 under 5 T. The effects of a Sm substitution for Zr on the Curie temperature (Tc) and -ΔSmpeak were studied and compared to those of Nd and Pr substitutions, for the purpose of revealing the mechanism involved in more detail.
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This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5 A, both FACS panels are identical and in Fig 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors' unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper.
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Cancer cells are typically characterized by abnormal quality control of mitochondria, production of reactive oxygen species (ROS), dysregulation of the cell redox state, and the Warburg effect. Mutation or depletion of PTEN-induced kinase 1 (PINK1) or Parkin leads to mitophagy defects and accumulation of malfunctioning mitochondria, and is often detected in a variety of tumors. However, PINK1's role in the progression of gastric cancer (GC) remains unclear, with its main effect being on mitochondrial turnover, metabolic reprogramming, and tumor microenvironment (TME) alteration. To address these issues, we first assessed the expression levels of PINK1, mitophagy-associated molecules, ROS, HIF-1α, glycolysis-associated genes, and macrophage signatures in GC tissues and matched tumor-adjacent normal samples. In addition, GC cell lines (AGS and MKN-45) and xenograft mouse models were used to determine the mechanism by which PINK1 regulates mitophagy, metabolic reprogramming, tumor-associated macrophage (TAM) polarization, and GC progression. We found that PINK1 loss correlated with advanced stage GC and poorer overall survival. GC tissues with lower PINK1 levels showed compromised mitophagy signaling and enhanced glycolytic enzyme expression. In vitro experiments demonstrated that PINK1 deficiency promoted GC cell proliferation and migration through the inhibition of mitophagy, production of mitochondrial ROS, stabilization of HIF-1α, and facilitation of the Warburg effect under both normoxic and hypoxic conditions. Moreover, PINK1 deficiency in GC cells promoted TAM polarization toward the M2-like phenotype. Reintroduction of PINK1 or inhibition of HIF-1α effectively repressed PINK1 deficiency-mediated effects on GC cell growth, metabolic shift, and TAM polarization. Thus, mitophagy defects caused by PINK1 loss conferred a metabolic switch through accumulation of mtROS and stabilization of HIF-1α, thereby facilitating the M2 polarization of TAM to remodel an immunosuppressive microenvironment in GC. Our results clarify the mechanism between PINK1 and GC progression and may provide a novel strategy for the treatment of GC.
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Mitofagia/genética , Proteínas Quinases/deficiência , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Efeito Warburg em Oncologia , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Expressão Gênica , Técnicas de Silenciamento de Genes , Glicólise , Xenoenxertos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imunofenotipagem , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Camundongos , Mitocôndrias/metabolismo , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Microambiente TumoralRESUMO
The long noncoding RNA (lncRNA) DLGAP1-AS2 has recently been characterized as an oncogenic lncRNA in several cancers. However, its biological roles and clinical significance in gastric cancer (GC) remains barely understood. In this study, we performed a systematic analysis of DLGAP1-AS2 expression with data from the TCGA and GEO database as well as our clinic GC samples. In agreement with previous studies, our findings demonstrated that DLGAP1-AS2 was significantly up-regulated in GC and its high expression was associated with poor prognosis, suggesting that DLGAP1-AS2 might be a putative oncogenic lncRNA of GC. Loss of DLGAP1-AS2 restricted cell proliferation, migration, and invasion in GC cell lines. Mechanically, Wnt1 was identified as the downstream target of DLGAP1-AS2 by using bioinformatics analysis coupled with qPCR and Western blot assays. Furthermore, DLGAP1-AS2 was found to directly interact with the transcriptional repressor Six3, and this interaction hampered Six3 binding to the promoter regions of the Wnt1 gene, thereby leading to transcriptional activation of Wnt1. Consequently, GC cells lacking DLGAP1-AS2 showed a decreased Wnt1 expression and weakened Wnt/ß-catenin signaling. Further, Six3 silencing could reverse the above effects, highlighting a pivotal role of Six3 in the DLGAP1-AS2-mediated activation of Wnt/ß-catenin signaling. Either genetic (Wnt1 knockdown) or pharmacological (LF3) inhibition of Wnt/ß-catenin signaling could effectively abolish the activation of Wnt/ß-catenin signaling by Six3 depletion, thereby preventing GC cell malignant transformation. Taken together, our results suggest that DLGAP1-AS2 functions as an oncogenic factor by directly interacting with Six3 to relieve its suppression on Wnt1 expression, thereby driving the malignancy of GC. DLGAP1-AS2/Six3/Wnt1/ß-catenin signaling axis might serve as a promising diagnostic and therapeutic target for GC.
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Here, using viral metagenomics combined with conventional PCR, the complete genome sequence of a novel anellovirus (named anel-ch-zj and GenBank no. MT157223) from nasopharynx secretion specimens from hospitalized neonates was determined, and the deduced amino acid sequence of its ODF1 protein was found to be only 33.19%-39.33% identical to those of related anelloviruses with sequences available in the GenBank database, suggesting that it represents a putative new genus within the family Anelloviridae. PCR screening of 135 samples (including 45 nasopharynx secretion, 45 blood, and 45 fecal specimens collected from 45 individual hospitalized neonates) indicated that two nasopharynx secretion, two blood, and four fecal samples were positive for anel-ch-zj. Further PCR screening of 50 blood samples, 115 fecal samples, and 396 nasopharynx secretions collected from hospitalized children 1-5 years old did not yield any positive results. Whether this novel anellovirus detected in neonates is associated with specific diseases needs future investigation.
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Anelloviridae/classificação , Anelloviridae/isolamento & purificação , Criança Hospitalizada , Filogenia , Anelloviridae/genética , DNA Viral/genética , Fezes/virologia , Humanos , Recém-Nascido , Metagenômica , Nasofaringe/virologia , Reação em Cadeia da Polimerase , Sequenciamento Completo do GenomaRESUMO
In this study, using a viral metagenomic method, we investigated the composition of virome in blood and cancer tissue samples that were collected from 25 patients with lung adenocarcinoma. Results indicated that virus sequences showing similarity to human pegivirus (HPgV), anellovirus, human endogenous retrovirus (HERV), and polyomavirus were recovered from this cohort. Three different complete genomes of HPgV were acquired from the blood samples and one complete genome of polyomavirus was determined from the cancer tissue sample. Phylogenetic analysis indicated that the three HPgV strains belonged to genotype 3 and the polyomavirus showed the highest sequence identity (99.73%) to trichodysplasia spinulosa-associated polyomavirus. PCR screening results indicated that the three HPgVs were present in 5 out of the 25 blood samples and the polyomavirus only existed in a cancer tissue sample pool. Whether infections with viruses have an association with lung cancer needs further study with a larger size of sampling.
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Adenocarcinoma de Pulmão/virologia , Neoplasias Pulmonares/virologia , Viroma/genética , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/patologia , Genoma Viral/genética , Genótipo , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Metagenômica , Pegivirus/classificação , Pegivirus/genética , Pegivirus/isolamento & purificação , Filogenia , Polyomavirus/classificação , Polyomavirus/genética , Polyomavirus/isolamento & purificaçãoRESUMO
BACKGROUND: Although some studies have investigated the bacterial community in vaginal tract of pregnant women, there are few reports about the viral community (virome) in this type of microenvironment. METHODS: To investigate the composition of virome in vaginal secretion samples, 40 vaginal secretion samples from pregnant women with vaginitis and 20 vaginal secretion samples from pregnant women without vaginitis, pooled into 4 and 2 sample pools, respectively, were subjected to viral metagenomic analysis. RESULTS: Results indicated virus sequences showing similarity to human papillomavirus (HPV), anellovirus, and norovirus were recovered from this cohort of pregnant women. Further analysis indicated that 15 different defined types and one unclassified type of HPV were detected from pregnant women with vaginitis while only 3 defined types of HPV were detected in pregnant women without vaginitis. Five different groups of viruses from the family Anelloviridae were present in pregnant women with but none of them were detected in pregnant women without vaginitis. Norovirus was detected in 3 out of the 4 sample pools from pregnant women with vaginitis but none in the pregnant women without vaginitis. Twelve complete genomes belonging to 10 different types of HPV, and 5 novel anllovirus genomes belonging 2 different genera in Anelloviridae were acquired from these libraries, based on which phylogenetical analysis and pairwise sequence comparison were performed. Phageome in these samples was also briefly characterized and compared between two groups. CONCLUSION: Our data suggested that virome might play an important role in the progression of vaginitis in pregnant women.
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Gestantes , Vaginite/virologia , Viroma , Adulto , Feminino , Genoma Viral/genética , Humanos , Metagenômica , Filogenia , Gravidez , Vagina/virologia , Viroma/genética , Vírus/classificação , Vírus/genética , Vírus/isolamento & purificaçãoRESUMO
Pangolin metagenomic data obtained from public databases were used to assemble partial or complete viral genomes showing genetic relationship to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Sendai virus, flavivirus, picornavirus, parvovirus, and genomovirus, respectively. Most of these virus genomes showed genomic recombination signals. Phylogeny based on the SARS-CoV-2-related virus sequences assembled in this study and those recently published indicated that pangolin SARS-CoV-2-related viruses were clustered into two sub-lineages according to geographic sampling sites. These findings suggest the need for further pangolin samples, from different countries, to be collected and analyzed for coronavirus to elucidate whether pangolins are intermittent hosts for SARS-CoV-2.