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BACKGROUND: The senescence marker protein 30 (SMP30) is a calcium-binding protein whose expression decreases with age, and is closely associated with hepatocellular carcinoma (HCC) development. The primary goal of this study was to examine the mechanistic effect of SMP30 on HCC migration and invasion. METHODS: Bioinformatic and immunohistochemical approaches were used to examine the expression of SMP30 in HCC tissues and its relationship to patient survival. We investigated the effects of SMP30 expression on HCC cell proliferation, migration, invasion, and cell cycle dynamics. cDNA microarray technology was used to determine the gene expression profile of SK-Hep-1 cells following recombinant SMP30 overexpression to identify genes downstream of SMP30 that regulate HCC cell migration and invasion. We identified SMP30 interacting proteins by affinity purification-mass spectrometry (AP-MS) and co-immunoprecipitation/western blotting (COIP-WB). RESULTS: SMP30 expression was lower in HCC tissues compared with normal liver tissues, and its expression positively correlated with overall survival in HCC patients. Additionally, SMP30 overexpression effectively blocked the migratory and invasive properties of SK-Hep-1 cells, but did not affect either proliferation rates or cell cycle. cDNA microarray results confirmed that many of the differentially expressed genes identified are involved in the process of epithelial-mesenchymal transition (EMT). AP-MS and COIP-WB experiments confirmed that Rho-associated protein kinase 1 (ROCK1) interacts with SMP30 in SK-Hep-1 cells, and ROCK1 is known to intimately regulate the EMT process. CONCLUSION: SMP30 inhibits HCC metastasis by influencing the expression of EMT-related proteins after interacting with ROCK1.
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Proteínas de Ligação ao Cálcio , Carcinoma Hepatocelular , Movimento Celular , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , Invasividade Neoplásica , Quinases Associadas a rho , Humanos , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/genética , Transição Epitelial-Mesenquimal/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Feminino , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: The role of novel circular RNAs (circRNAs) in colorectal cancer (CRC) remains to be determined. This study aimed to identify a novel circRNA involved in CRC pathogenesis, assess its diagnostic value, and construct a regulatory network. METHODS: Differential expression analysis was conducted using circRNA datasets to screen for differentially expressed circRNAs. The expression of selected circRNAs was validated in external datasets and clinical samples. Diagnostic value of plasma circRNA levels in CRC was assessed. A competing endogenous RNA (ceRNA) network was constructed for the circRNA using TCGA dataset. RESULTS: Analysis of datasets revealed that hsa_circ_101303 was significantly overexpressed in CRC tissues compared to normal tissues. The upregulation of hsa_circ_101303 in CRC tissues was further confirmed through the GSE138589 dataset and clinical samples. High expression of hsa_circ_101303 was associated with advanced N stage, M stage, and tumor stage in CRC. Plasma levels of hsa_circ_101303 were markedly elevated in CRC patients and exhibited moderate diagnostic ability for CRC (AUC = 0.738). The host gene of hsa_circ_101303 was also found to be related to the TNM stage of CRC. Nine miRNAs were identified as target miRNAs for hsa_circ_101303, and 27 genes were identified as targets of these miRNAs. Subsequently, a ceRNA network for hsa_circ_101303 was constructed to illustrate the interactions between the nine miRNAs and 27 genes. CONCLUSIONS: The study identifies hsa_circ_101303 as a highly expressed circRNA in CRC, which is associated with the progression of the disease. Plasma levels of hsa_circ_101303 show promising diagnostic potential for CRC. The ceRNA network for hsa_circ_101303 provides valuable insights into the regulatory mechanisms underlying CRC.
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Biomarcadores Tumorais , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs , RNA Circular , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , RNA Circular/genética , RNA Circular/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Masculino , Feminino , MicroRNAs/genética , MicroRNAs/sangue , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Estadiamento de NeoplasiasRESUMO
Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and progressively worsening lung disease that poses a significant threat to patient prognosis, with a mortality rate exceeding that of some common malignancies. Effective methods for early diagnosis and treatment remain for this condition are elusive. In our study, we used the GEO database to access second-generation sequencing data and associated clinical information from IPF patients. By utilizing bioinformatics techniques, we identified crucial disease-related genes and their biological functions, and characterized their expression patterns. Furthermore, we mapped out the immune landscape of IPF, which revealed potential roles for novel kinase 1 and CD8+T cells in disease progression and outcome. These findings can aid the development of new strategies for the clinical diagnosis and treatment of IPF.
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Linfócitos T CD8-Positivos , Fibrose Pulmonar Idiopática , Humanos , Linfócitos T CD8-Positivos/imunologia , Biologia Computacional , Progressão da Doença , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/patologia , PrognósticoRESUMO
OBJECTIVE: The aim of this study is to explore the efficacy and safety of chemotherapy (CT) as a monotherapy in patients with recurrent intermediate/high-risk factors following radical hysterectomy for stage IB-IIA cervical cancer. METHODS: A retrospective analysis was conducted on the medical records of patients diagnosed with stage IB-IIA cervical cancer who underwent radical hysterectomy at the People's Hospital of Suzhou High-tech District between 2010 and 2020. A total of 66 patients with intermediate or high-risk factors for recurrence were treated exclusively with CT. This cohort included 42 patients in the intermediate-risk group and 24 in the high-risk group. Treatment protocols consisted of 4-6 cycles of paclitaxel and cisplatin drugs for the intermediate-risk group, and 6 cycles for the high-risk group. The relapse-free survival (RFS), recurrence rates, and common CT-related adverse reactions, including bone marrow suppression, nausea and vomiting, and diarrhea, were assessed for both groups. RESULTS: (1) The cumulative 3-year RFS rates for the intermediate-risk and high-risk groups were 97.3% (36/37) and 82.4% (14/17), respectively, with cumulative 5-year RFS rates of 97.1% (34/35) and 82.4% (14/17), respectively. The Log rank test revealed no significant difference between the two groups (P > 0.05), (χ² = 2.718, P = 0.099). The 5-year recurrence rates in the intermediate-risk and high-risk groups were 2.38% (1/42) and 12.50% (3/24), respectively. (2) The incidence of grade III bone marrow suppression in the intermediate-risk and high-risk groups was 21.19% (11/42) and 25.00% (6/24), respectively, while the incidence of grade IV bone marrow suppression was 11.90% (5/42) and 8.33% (2/24), respectively. There was no statistically significant difference in bone marrow suppression grades between the two groups (P > 0.05). CONCLUSION: CT with paclitaxel and cisplatin, administered as monotherapy post-radical hysterectomy for stage IB-IIA cervical cancer, demonstrates satisfactory survival benefits with an acceptable safety profile. Moreover, no significant differences were observed in prognosis or adverse reactions between the different risk groups treated solely with CT.
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Cisplatino , Histerectomia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Paclitaxel , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Histerectomia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Adulto , Paclitaxel/uso terapêutico , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Fatores de Risco , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Antineoplásicos/uso terapêuticoRESUMO
In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future.
MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone.
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Carcinoma de Células Escamosas , Proliferação de Células , Integrina alfa2 , Integrina alfa3 , Mucina-1 , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Feminino , Integrina alfa2/metabolismo , Integrina alfa2/genética , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Mucina-1/metabolismo , Mucina-1/genética , Camundongos , Fosforilação , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto , Sistema de Sinalização das MAP Quinases , Camundongos Nus , MAP Quinases Reguladas por Sinal Extracelular/metabolismoRESUMO
BACKGROUND: Few studies are focusing on the mechanism of erastin acts on prostate cancer (PCa) cells, and essential ferroptosis-related genes (FRGs) that can be PCa therapeutic targets are rarely known. METHODS: In this study, in vitro assays were performed and RNA-sequencing was used to measure the expression of differentially expressed genes (DEGs) in erastin-induced PCa cells. A series of bioinformatic analyses were applied to analyze the pathways and DEGs. RESULTS: Erastin inhibited the expression of SLC7A11 and cell survivability in LNCaP and PC3 cells. After treatment with erastin, the concentrations of malondialdehyde (MDA) and Fe2+ significantly increased, whereas the glutathione (GSH) and the oxidized glutathione (GSSG) significantly decreased in both cells. A total of 295 overlapping DEGs were identified under erastin exposure and significantly enriched in several pathways, including DNA replication and cell cycle. The percentage of LNCaP and PC3 cells in G1 phase was markedly increased in response to erastin treatment. For four hub FRGs, TMEFF2 was higher in PCa tissue and the expression levels of NRXN3, CLU, and UNC5B were lower in PCa tissue. The expression levels of SLC7A11 and cell survivability were inhibited after the knockdown of TMEFF2 in androgen-dependent cell lines (LNCaP and VCaP) but not in androgen-independent cell lines (PC3 and C4-2). The concentration of Fe2+ only significantly increased in TMEFF2 downregulated LNCaP and VCaP cells. CONCLUSION: TMEFF2 might be likely to develop into a potential ferroptosis target in PCa and this study extends our understanding of the molecular mechanism involved in erastin-affected PCa cells.
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Ferroptose , Piperazinas , Neoplasias da Próstata , Masculino , Humanos , Androgênios , Ferroptose/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Próstata/metabolismo , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Receptores de NetrinaRESUMO
This study aims to investigate the regulatory effects of Shenling Baizhu Powder(SBP) on cellular autophagy in alcoholic liver disease(ALD) and its intervention effect through the TLR4/NLRP3 pathway. A rat model of chronic ALD was established by gavage of spirits. An ALD cell model was established by stimulating BRL3A cells with alcohol. High-performance liquid chromatography(HPLC) was utilized for the compositional analysis of SBP. Liver tissue from ALD rats underwent hematoxylin-eosin(HE) and oil red O staining for pathological evaluation. Enzyme-linked immunosorbent assay(ELISA) was applied to quantify lipopolysaccharides(LPS), tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1ß), and interleukin-18(IL-18) levels. Quantitative reverse transcription polymerase chain reaction(qRT-PCR) was conducted to evaluate the mRNA expression of myeloid differentiation factor 88(MyD88) and Toll-like receptor 4(TLR4). The effect of different drugs on BRL3A cell proliferation activity was assessed through CCK-8 analysis. Western blot analysis was performed to examine the protein expression of NOD-like receptor pyrin domain-containing 3(NLRP3), nuclear factor-kappa B P65(NF-κB P65), phosphorylated nuclear factor-kappa B P65(p-P65), caspase-1, P62, Beclin1, and microtubule-associated protein 1 light chain 3(LC3â ¡). The results showed that SBP effectively ameliorated hepatic lipid accumulation, reduced liver function, mitigated hepatic tissue inflammation, and reduced levels of LPS, TNF-α, IL-1ß, and IL-18. Moreover, SBP exhibited the capacity to modulate hepatic autophagy induced by prolonged alcohol intake through the TLR4/NLRP3 signaling pathway. This modulation resulted in decreased expression of LC3â ¡ and Beclin1, an elevation in P62 expression, and the promotion of autolysosome formation. These research findings imply that SBP can substantially enhance liver function and mitigate lipid irregularities in the context of chronic ALD. It achieves this by regulating excessive autophagic responses caused by prolonged spirit consumption, primarily through the inhibition of the TLR4/NLRP3 pathway.
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Medicamentos de Ervas Chinesas , Hepatopatias Alcoólicas , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Pós , Lipopolissacarídeos , Fator de Necrose Tumoral alfa , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteína Beclina-1 , NF-kappa B/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genéticaRESUMO
Background: Hepatocellular carcinoma (HCC) is one of the common primary cancers of the liver worldwide and leading cause of mortality. Gasdermins (GSDMs) family genes play an important role in the regulation of the normal physiological processes and have been implicated in multiple diseases. However, little is known about the relationship between different GSDMs proteins and HCC. The aim of this study was to explore the potential relationship between the expression, prognosis, genetic variation and immune infiltration of GSDMs family genes and HCC. Methods: We used different bioinformatics common public databases such as GSCA, GEPIA, UALCAN, HPA, Kaplan-Meier Plotter, LinkedOmics, GeneMANIA, STRING, cBioPortal, TIMER and TISIDB to analyze the differential expression of the different GSDMs, prognostic value, genetic alterations, immune cell infiltration and their functional networks in HCC patients. Results: All the members of the GSDMs family exhibited elevated mRNA expression levels in LIHC compared to the normal tissues, while only GSDMB, GSDMD and GSDME showed enhanced protein expression. The mRNA expression of most GSDMs members was found to be elevated in HCC patients at stages I-III (clinical stage) compared to the normal subjects. The expression of GSDMD was correlated with OS and DSS of patients, whereas GSDME was correlated with OS, DSS and RFS of patients. Gene amplification was observed to be main mode of variation in members of the GSDMs family. KEGG pathway analysis showed that genes associated with different members of the GSDMs family were enriched in the pathways of S. aureus infection, intestinal immunity, ribosome and protein assembly, oxidative phosphorylation, osteoclast differentiation and Fc gamma (γ) R-mediated phagocytosis. In addition, expression of both GSDMA and GSDME were found to be correlated most significantly with infiltration of immune cells, while GSDMA and GSDME somatic cell copy number alteration (CAN) were correlated significantly with the infiltration of immune cells. All GSDMs were noted to be associated with distinct subtypes of immune cells, except GSDMC. Conclusions: Our findings have provided useful insights to better understand the roles and functions of GSDMs in HCC that can provide novel direction for developing therapeutic modalities for HCC, including immunotherapy.
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The active ingredient in Poria cocos, a parasitic plant belonging to the family Polyporaceae, is Poria cocos polysaccharide (PCP). PCP exhibits liver protection and anti-inflammatory effects, although its effect on alcoholic liver disease (ALD) remains unstudied. This study investigated the mechanism of PCP in improving ALD by regulating the Nrf2 signaling pathway. After daily intragastric administration of high-grade liquor for 4 hours, each drug group received PCPs or the ferroptosis inhibitor ferrostatin-1. The Nrf2 inhibitor ML385 (100 mg/kg/day) group was intraperitoneally injected, after which PCP (100 mg/kg/day) was administered by gavage. Samples were collected after 6 weeks for liver function and blood lipid analysis using an automatic biochemical analyzer. In the alcoholic liver injury cell model established with 150 mM alcohol, the drug group was pretreated with PCP, Fer-1, and ML385, and subsequent results were analyzed. The results revealed that PCP intervention significantly reduced liver function and blood lipid levels in alcohol-fed rats, along with decreased lipid deposition. PCP notably enhanced Nrf2 signaling expression, regulated oxidative stress levels, inhibited NF-κß, and its downstream inflammatory signaling pathways. Furthermore, PCP upregulated FTH1 protein expression and reduced intracellular Fe2+, suggesting an improvement in ferroptosis. In vitro studies yielded similar results, indicating that PCP can reduce intracellular ferroptosis by regulating oxidative stress and improve alcoholic liver injury by inhibiting the production of inflammatory factors.
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Ferroptose , Hepatopatias Alcoólicas , Fator 2 Relacionado a NF-E2 , Polissacarídeos , Animais , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Polissacarídeos/farmacologia , Ratos , Masculino , Transdução de Sinais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Humanos , Ratos Sprague-Dawley , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Wolfiporia/química , Modelos Animais de DoençasRESUMO
Mitochondrial metabolism has been shown to play a key role in immune cell survival and function, but mitochondrial creatine kinase 2 (CKMT2) has been relatively little studied about tumor immunity. We aimed to explore the prognostic value of CKMT2 in 33 cancer types and investigate its potential immune function. We used a range of bioinformatics approaches to explore the potential carcinogenic role of CKMT2 in multiple cancers. CKMT2 was lowly expressed in 14 tumor tissues and highly expressed in 4 tumor tissues. Immunohistochemical assays showed overexpression of CKMT2 in colon cancer and rectal cancer. CKMT2 overexpression was positively correlated with the prognosis of lung adenocarcinoma and prostate cancer. CKMT2 overexpression is mainly enriched in the adaptive immune system and immune regulatory pathways of immunoglobulins. Seven cancers were positively correlated with low CKMT2 expression in tumor microenvironment analysis. Among the five cancers, low expression of CKMT2 resulted in better immunotherapy treatment outcomes. There was a strong correlation between CKMT2 and most immune-related genes in specific cancer types. CKMT2 plays an important role in tumorigenesis and cancer immunity and can be used as a prognostic biomarker and potential target for cancer immunotherapy.
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Adenocarcinoma de Pulmão , Neoplasias do Colo , Neoplasias Pulmonares , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Carcinogênese , Microambiente Tumoral/genética , Creatina Quinase MitocondrialRESUMO
BACKGROUND: To evaluate through meta-analysis whether long-term use of proton pump inhibitor (PPI) increases the risk of precancerous lesions in the stomach. METHODS: Randomized controlled trials that compared the occurrence and progression of precancerous lesions in patients receiving PPI treatment versus non-PPI treatment were retrieved from CNKI, VIP, Wanfang, CBM, Pubmed, Embase, Web of Science, and Cochrane Library databases (from database inception to May 1, 2023). The Revman 5.3 and STATA 17.0 software were used for analysis, and subgroup analysis was conducted based on follow-up time (≤12 months and > 12 months) and lesion type (atrophic gastritis, intestinal metaplasia, and epithelial dysplasia). RESULTS: Six randomized controlled trials with a total of 1623 cases were included, including 1015 cases in the experimental group and 608 cases in the control group. The meta-analysis results showed that the overall abnormal lesion rate combined with statistical relative risk (RR) = 1.31 (0.85-2.02), P = .23. Subgroup analysis showed that the follow-up time > 12 months combined result was RR = 2.21 (1.47-3.33), P = .0001, the intestinal metaplasia group combined result was RR = 1.96 (0.91-2.47), P = .04. CONCLUSION SUBSECTIONS: During long-term follow-up, patients using PPI exhibited a significantly higher incidence of overall abnormal lesions compared to the control group, particularly with a higher risk observed for intestinal metaplasia. However, there were no statistically significant differences between the 2 groups in terms of short-term follow-up and other types of lesions. It is important to exercise caution when interpreting these findings due to the limited number of nominated investigations included in the meta-analysis.
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Carcinoma in Situ , Lesões Pré-Cancerosas , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estômago , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/epidemiologiaRESUMO
To investigate the potential of H2-calponin (CNN2) as a serum biomarker for hepatocellular carcinoma (HCC), this study employed the serological analysis of recombinantly expressed cDNA clone (SEREX) technique to identify the presence of CNN2 antibody in the serum of patients with HCC and other tumors. The CNN2 protein was produced through genetic engineering and used as an antigen to determine the positive rate of serum CNN2 autoantibodies via indirect enzyme-linked immunosorbent assay (ELISA). In addition, the mRNA and protein expressions of CNN2 in cells and tissues were evaluated using RT-PCR, in situ RT-PCR, and immunohistochemistry methods. The HCC group exhibited a significantly higher positive rate of anti-CNN2 antibody (54.8%) compared to gastric cancer (6.5%), lung cancer (3.2%), rectal cancer (9.7%), hepatitis (3.2%), liver cirrhosis (3.2%), and normal tissues (3.1%). The positive rates of CNN2 mRNA in HCC with metastasis, non-metastatic HCC, lung cancer, gastric cancer, nasopharyngeal cancer, liver cirrhosis, and hepatitis were 56.67%, 41.67%, 17.5%, 10.0%, 20.0%, 53.13%, and 41.67%, respectively. Meanwhile, the positive rates of CNN2 protein were 63.33%, 37.5%, 17.5%, 27.5%, 45%, 31.25%, and 20.83%, respectively. The down-regulation of CNN2 could inhibit the migration and invasion of liver cancer cells. CNN2 is a newly identified HCC-associated antigen that is implicated in the migration and invasion of liver cancer cells, making it a promising target for liver cancer therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Nasofaríngeas , Humanos , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/metabolismo , Autoanticorpos , Cirrose Hepática , RNA Mensageiro , Biomarcadores Tumorais/genética , CalponinasRESUMO
Here, we describe a novel method for the on-DNA synthesis of cyclic imides, an important class of molecules that includes several well-known medications. Significantly, the new method enabled on-DNA synthesis under mild conditions with high conversions and a broad functional group tolerance, utilizing ubiquitous bifunctional amines and bis-carboxylic acid, or alkyl halides, and therefore served as the linchpin for DNA encoded library (DEL) synthesis. The mechanism study of off-DNA and on-DNA chemical transformations revealed unique insights in contrast to conventional chemical transformation.
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DNA , Imidas , Imidas/química , DNA/química , Replicação do DNA , Biblioteca Gênica , Aminas/químicaRESUMO
Background: Immune microenvironment implicated in liver cancer development. Nevertheless, previous studies have not fully investigated the immune microenvironment in liver cancer. Methods: The open-access data used for analysis were obtained from The Cancer Genome Atlas (TCGA-LIHC) and the International Cancer Genome Consortium databases (ICGC-JP and ICGC-FR). R program was employed to analyze all the data statistically. Results: First, the TCGA-LIHC, ICGC-FR, and ICGC-JP cohorts were selected for our analysis, which were merged into a combined cohort. Then, we quantified 53 immune terms in this combined cohort with large populations using the ssGSEA algorithm. Next, a prognostic approach was established based on five immune principles (CORE.SERUM.RESPONSE.UP, angiogenesis, CD8.T.cells, Th2.cells, and B.cells) was established, which showed great prognostic prediction efficiency. Clinical correlation analysis demonstrated that high-risk patients could reveal higher progressive clinical features. Next, to examine the inherent biological variations in high- and low-risk patients, pathway enrichment tests were conducted. DNA repair, E2F targets, G2M checkpoints, HEDGEHOG signaling, mTORC1 signaling, and MYC target were positively correlated with the risk score. Examination of genomic instability revealed that high-risk patients may exhibit a higher tumor mutation burden score. Meanwhile, the risk score showed a strong positive correlation with the tumor stemness index. In addition, the Tumor Immune Dysfunction and Exclusion outcome indicated that high-risk patients could be higher responsive to immunotherapy, whereas low-risk patients may be higher responsive to Erlotinib. Finally, six characteristic genes DEPDC1, DEPDC1B, NGFR, CALCRL, PRR11, and TRIP13 were identified for risk group prediction. Conclusions: In summary, our study identified a signature as a useful tool to indicate prognosis and therapy options for liver cancer patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteínas Hedgehog , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Prognóstico , Imunoterapia , Microambiente Tumoral/genética , ATPases Associadas a Diversas Atividades Celulares , Proteínas de Ciclo Celular , Proteínas de Neoplasias , Proteínas Ativadoras de GTPaseRESUMO
It is widely accepted that kisspeptin plays an integral role in the regulation of reproduction. Genetic variations in the KISS1 gene have been frequently reported to be linked to reproductive diseases, but there is still a lack of data on the association between KISS1 variations and female reproductive disorders. The present study aimed to examine the association of three missense SNPs in the KISS1 gene including rs12998, rs35431622, and rs4889 in association with idiopathic recurrent pregnancy loss (iRPL). A total of 720 individuals were recruited in this study. The DNA from the blood sample was extracted and genotyped using the PCR method. Haplotype and linkage disequilibrium (LD) have also been analyzed. The results of this study suggested that rs12998 G > A and rs4889 C > G had a significant association with iRPL (p < 0.05); while rs35431622 A > G didn't indicate any association with iRPL. A significant association was also found for three haplotypes including C-A-A, G-G-G, and G-G-A in this population. The analysis also showed a significant LD between rs12998 and rs35431622 (P < 0.0005). The rs12998 G > A and rs4889 C > G variants of KISS1 are linked to unexplained recurrent pregnancy loss and may be risk factors for this disease.
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Aborto Habitual , Kisspeptinas , Gravidez , Humanos , Feminino , Kisspeptinas/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Genes Supressores de Tumor , Aborto Habitual/genéticaRESUMO
Vascular aging is an independent risk factor for cardiovascular diseases, but the regulatory mechanism is not clearly understood. In this study, we found that endothelial PKR activity is elevated in aging aorta tissues, which is accompanied with increased endothelial cell hyperactivation, IL-1ß and HMGB1 release and vascular smooth muscle cell (VSMC) phenotype transforming. Global knockout of PKR exhibits significantly delayed vascular aging compared to wild-type mice at the same age. In vitro, using PKR siRNA or the cell hyperactivation inhibitor glycine or disulfiram can effectively inhibit H2O2 or palmitic acid-induced endothelial cell hyperactivation, IL-1ß and HMGB1 release and co-cultured VSMC phenotype transforming. These results demonstrate that endothelial PKR activation induces GSDMD-mediated endothelial cell hyperactivation to release HMGB1 and IL-1ß, which promotes the phenotype transforming of VSMC and subsequent accelerates the process of vascular aging. These discoveries will help to explore the new drug target to inhibit vascular aging.
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OBJECTIVES: The intestinal flora is closely related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study intends to systematically evaluate the efficacy and safety of probiotics in the treatment of NAFLD through a meta-analysis of published randomized controlled trials. METHODS: This study was conducted through a search of published randomized controlled trials using probiotic-related drugs for the treatment of nonalcoholic fatty liver disease (up to April 6, 2022). The JADAD evaluation table was used to evaluate the quality of the literatures included in the search, and the risk of bias was evaluated according to the Cochrane evaluation manual. Finally, RevMan5.4 software was used for meta-analysis. RESULTS: A total of 21 randomized clinical trials involving 1037 patients with NAFLD were included in this study. Meta-analysis results showed that after probiotic intervention, liver function, blood lipid level, blood glucose levels and insulin levels were significantly reduced, which had a good effect on improving hepatic steatosis. However, it did not significantly improve BMI, inflammatory factors, or homeostasis model assessment of insulin resistance. Through the subgroup analysis of the course of treatment, it was found that ALT, GGT, TG, and blood sugar improved better in the probiotic treatment course of greater than or equal to 12 weeks. CONCLUSION: This study shows that the use of probiotics therapy has a good regulating effect on liver function, steatosis, blood glucose level, insulin level and blood lipid level in NAFLD patients.
Assuntos
Insulinas , Hepatopatia Gordurosa não Alcoólica , Probióticos , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Glicemia/análise , Probióticos/uso terapêutico , Lipídeos , Fígado/patologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We performed a meta-analysis to evaluate the effect of wound protectors in reducing the incidence of surgical site wound infection in lower gastrointestinal surgery. A systematic literature search up to June 2022 was performed and 6026 subjects with lower gastrointestinal surgery at the baseline of the studies; 3090 of them were using the wound protector, and 2936 were using no wound protector. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of wound protectors in reducing the incidence of surgical site wound infection in lower gastrointestinal surgery using the dichotomous methods with a random or fixed-effect model. The surgical site wound infection was significantly lower with single-ring wound protectors (OR, 0.53; 95% CI, 0.39-0.83, P = .004), and dual-ring wound protectors (OR, 0.44; 95% CI, 0.35-0.56, P < .001) in subjects with lower gastrointestinal surgery compared with no wound protector. The surgical site wound infection was significantly lower with single-ring wound protectors, and dual-ring wound protectors in subjects with lower gastrointestinal surgery compared with no wound protector. The analysis of outcomes should be with caution because of the low sample size of 5 out of 28 studies in the meta-analysis and a low number of studies in certain comparisons.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Incidência , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/etiologia , Desenho de EquipamentoRESUMO
Sclerosing epithelioid fibrosarcoma (SEF) is a rare subtype of soft tissue tumors, and SEF originating from the side of the spine is even rarer. We report that a 28-year-old young woman suffered from chest pain and back pain for 3 years, and thereafter she went to see a doctor because her condition deteriorated. Enhanced CT showed that the right posterior upper chest wall mass invaded the adjacent bone, and the boundary between the lesion and the surrounding tissues was relatively clear. She then underwent posterior tumor removal surgery. The pathological examination confirmed the diagnosis of SEF. In histomorphology, the tumor displayed a typical epithelioid clear cell morphology, accompanied by extensive vitrification and fibrosis, which better helped to differentiate the tumor from low grade fibromyxoid sarcoma, solitary fibrous tumor and other entities. The immunohistochemical analysis showed a diffuse positive reaction to MUC4, a highly specific marker of SEF, which was detected by Immunohistochemistry (IHC), and fluorescence in-situ hybridization (FISH) confirmed that the EWSR1 gene was rearranged, while the FUS gene was not rearranged. This is the first time that we have encountered such this rare case and thus report this case with updated literature related to this tumor.
RESUMO
With the rapid development of wireless communication and edge computing, UAV-assisted networking technology has great significance in many application scenarios such as traffic forecasting, emergency rescue, military reconnaissance. However, due to dynamic topology changes of Flying Ad-hoc Networks (FANET), frequent identity authentication is easy to cause the instability of communications between UAV nodes, which makes FANET face serious identity security threats. Therefore, it is an inevitable trend to build a secure and reliable FANET. In this paper, we propose a lightweight mutual identity authentication scheme based on adaptive trust strategy for Flying Ad-hoc Networks (ATS-LIA), which selects the UAV with the highest trust value from the UAV swarm to authenticate with the ground control station (GCS). While ensuring the communication security, we reduce the energy consumption of UAV to the greatest extent, and reduce the frequent identity authentication between UAV and GCS. Through the security game verification under the random oracle model, it is proved that the proposed method can effectively resist some attacks, effectively reduce the computational overhead, and ensure the communication security of FANET. The results show that compared with the existing schemes, the proposed ATS-LIA scheme has lower computational overhead.