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BACKGROUND: The COVID-19 pandemic has underscored the critical role of sequencing technology in disease control and outbreak response. However, resource limitations and challenging environments often impede such efforts in low and middle-income countries. This study aimed to investigate the spectrum of viral co-infections, particularly with human viral pathogens, in SARS-CoV-2 positive individuals in Sierra Leone using metagenomic sequencing, evaluating the feasibility of utilizing this technology for epidemiological and evolutionary surveillance of pathogens related to public health in low-income environments. METHODS: We retrospectively collected and analyzed 98 nasopharyngeal swab specimens from SARS-CoV-2 positive individuals in Sierra Leone. Samples were pre-processed locally and transferred to China via FTA cards for metagenomic sequencing, which was performed using the Novaseq platform. The study focused on the identification of nasopharyngeal viruses co-infecting with SARS-CoV-2, with a deeper analysis of significant human viral pathogens such as HPV. RESULTS: The study identified 22 viral taxa from 20 families, including 4 human viruses. Notably, 19.4% of samples showed HPV co-infection with 34 distinct types, predominantly beta and gamma HPVs. Multiple HPV types were found in individual samples, indicating a high complexity of viral co-infections. CONCLUSIONS: The identification of a wide range of co-infecting viruses, particularly multiple HPV genotypes, highlights the complexity of viral interactions and their potential implications for public health. These findings enhance our understanding of viral co-infections and provide valuable insights for public health interventions in Sierra Leone. Further research is needed to explore the clinical significance of these findings and their impact on disease outcomes.
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COVID-19 , Coinfecção , Infecções por Papillomavirus , SARS-CoV-2 , Humanos , Serra Leoa/epidemiologia , Estudos Retrospectivos , COVID-19/virologia , COVID-19/epidemiologia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/classificação , Coinfecção/virologia , Coinfecção/epidemiologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Nasofaringe/virologia , Adolescente , Metagenômica , Filogenia , Papillomaviridae/genética , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Idoso , CriançaRESUMO
The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4-gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low-risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c-Myc. Furthermore, co-immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c-Myc. Additionally, we confirmed that RGS5 regulates c-Myc through the ubiquitin-proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD-L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.
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Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-myc , Proteínas RGS , Neoplasias Gástricas , Humanos , Proteínas RGS/genética , Proteínas RGS/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Reparo de Erro de Pareamento de DNA , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/genéticaRESUMO
Hydrolyzable tannins (HTs), a class of polyphenolic compounds found in dicotyledonous plants, are widely used in food and pharmaceutical industries because of their beneficial effects on human health. Although the biosynthesis of simple HTs has been verified at the enzymatic level, relevant genes have not yet been identified. Here, based on the parent ion-fragment ion pairs in the feature fragment data obtained using UPLC-Q-TOF-/MS/MS, galloyl phenolic compounds in the leaves of Camellia sinensis and C. oleifera were analyzed qualitatively and quantitatively. Correlation analysis between the transcript abundance of serine carboxypeptidase-like acyltransferases (SCPL-ATs) and the peak area of galloyl products in Camellia species showed that SCPL3 expression was highly correlated with HT biosynthesis. Enzymatic verification of the recombinant protein showed that CoSCPL3 from C. oleifera catalyzed the four consecutive steps involved in the conversion of digalloylglucose to pentagalloylglucose. We also identified the residues affecting the enzymatic activity of CoSCPL3 and determined that SCPL-AT catalyzes the synthesis of galloyl glycosides. The findings of this study provide a target gene for germplasm innovation of important cash crops that are rich in HTs, such as C. oleifera, strawberry, and walnut.
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Aciltransferases , Camellia , Carboxipeptidases , Taninos Hidrolisáveis , Proteínas de Plantas , Camellia/genética , Camellia/enzimologia , Camellia/metabolismo , Carboxipeptidases/metabolismo , Carboxipeptidases/genética , Aciltransferases/genética , Aciltransferases/metabolismo , Taninos Hidrolisáveis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/enzimologia , Espectrometria de Massas em TandemRESUMO
Background: Colon cancer (CC) stem cells can self-renew as well as expand, thereby promoting tumor progression and conferring resistance to chemotherapeutic agents. The acetyltransferase NAT10 mediates N4-acetylcytidine (ac4C) modification, which in turn drives tumorigenesis, metastasis, stemness properties maintenance, and cell fate decisions. Nonetheless, the specific involvement of ac4C modification mediated by NAT10 in regulating stemness and chemosensitivity in CC remains undetermined. Methods: The levels of NAT10 in normal colon and chemoresistant CC tissues were determined utilizing quantitative real-time polymerase chain reaction alongside immunohistochemistry. Assessing cancer cell stemness and chemosensitivity was conducted by various methods including spheroid and colony formation, western blotting, and flow cytometry. RNA-Seq was used to identify target genes, and RNA immunoprecipitation analysis was used to explore the potential mechanisms. Results: We observed NAT10 overexpression and increased ac4C modification levels in chemoresistant CC tissues. The in vivo and in vitro analysis findings suggested that NAT10 promoted CC cell stemness while suppressing their chemosensitivity. Conversely, Remodelin, a NAT10-specific inhibitor, enhanced CC cell chemosensitivity. Mechanistically, NAT10 increased the level of NANOGP8 ac4C modification and promoted NANOGP8 mRNA stability. Conclusions: NAT10 promotes the maintenance of stemness and chemoresistance in CC cells by augmenting the mRNA stability of NANOGP8. The inhibition of NAT10 via Remodelin improves chemotherapeutic efficacy and impedes CC progression.
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BACKGROUND: Recent studies have identified empathy deficit as a core impairment and diagnostic criterion for people with autism spectrum disorders; however, the improvement of empathy focuses primarily on behavioural interventions without the target regulation. We sought to compare brain regions associated with empathy-like behaviours of fear and pain, and to explore the role of the oxytocin-oxytocin receptor system in fear empathy. METHODS: We used C57BL mice to establish 2 models of fear empathy and pain empathy. We employed immunofluorescence histochemical techniques to observe the expression of c-Fos throughout the entire brain and subsequently quantified the number of c-Fos-positive cells in different brain regions. Furthermore, we employed chemogenetic technology to selectively manipulate these neurons in Oxt-Cre-/+ mice to identify the role of oxytocin in this process. RESULTS: The regions activated by fear empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, paraventricular nucleus (PVN), lateral habenula, and ventral and dorsal hippocampus. The regions activated by pain empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, and lateral habenula. We found that increasing the activity of oxytocin neurons in the PVN region enhanced the response to fear empathy. This enhancement may be mediated through oxytocin receptors. LIMITATIONS: This study included only male animals, which restricts the broader interpretation of the findings. Further investigations on circuit function need to be conducted. CONCLUSION: The brain regions implicated in the regulation of fear and pain empathy exhibit distinctions; the activity of PVN neurons was positively correlated with empathic behaviour in mice. These findings highlight the role of the PVN oxytocin pathway in regulating fear empathy and suggest the importance of oxytocin signalling in mediating empathetic responses.
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Empatia , Medo , Camundongos Endogâmicos C57BL , Neurônios , Ocitocina , Núcleo Hipotalâmico Paraventricular , Animais , Ocitocina/metabolismo , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , Medo/fisiologia , Empatia/fisiologia , Neurônios/metabolismo , Camundongos , Receptores de Ocitocina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Dor/fisiopatologia , Dor/psicologia , Camundongos TransgênicosRESUMO
BACKGROUND: Due to the high level of organic acids - primarily citric acid - black, red, and white currants have an excessively sour taste, making taste adjustment during processing challenging. This study investigated and evaluated the effects of an inoculation dose of the acid-reducing yeast Issatchenkia terricola WJL-G4 on several aspect such as physicochemical properties, chromaticity, active substances, and antioxidant capacity. A sensory evaluation was also conducted. RESULTS: The results indicated that, when the inoculation dose increased from 2% to 12%, the total phenol, total flavonoid, and total anthocyanin content, and antioxidant capacity in currant juice decreased. A low inoculation dose (2-4%) was beneficial for preserving the total phenol and total flavonoid content. Although the levels of most phenolic compounds decreased, the concentrations of caffeic acid, p-coumaric acid, ferulic acid, rutin, and epicatechin were significantly higher than the control after fermentation. Overall acceptability and taste scores of fermented currants improved compared with those of the control group. CONCLUSION: This experiment provided an effective solution, with a theoretical basis, to the problems of the sour taste and harsh flavor of currant juice. © 2024 Society of Chemical Industry.
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Antocianinas , Antioxidantes , Fermentação , Sucos de Frutas e Vegetais , Fenóis , Ribes , Paladar , Ribes/química , Antioxidantes/análise , Antioxidantes/química , Sucos de Frutas e Vegetais/análise , Humanos , Fenóis/análise , Fenóis/química , Antocianinas/análise , Antocianinas/química , Flavonoides/análise , Frutas/química , Saccharomycetales/metabolismo , CorRESUMO
OBJECTIVE: In this study, we aimed to evaluate the efficacy of the Magnetic Scope Guide Assist (ScopeGuide) in enhancing the procedural competence of endoscopists and reducing patient discomfort during colonoscopy. METHODS: This was a retrospective study with 88 trainee participants. The study participants were trained on patients who underwent colonoscopy without anesthesia. Both ScopeGuide-assisted training and conventional training (without ScopeGuide) were utilized for colonoscopy instruction. The outcomes of training were compared, with a particular emphasis on the competency of looping resolution. RESULTS: ScopeGuide-assisted training was superior to conventional training in multiple aspects, including looping resolution ( Z =-3.681, P <0.001), pain scores ( Z =-4.211, P <0.001), time to reach the cecum ( Z =-4.06, P <0.001), willingness to undergo repeat colonoscopy ( Z =-4.748, P <0.001), competence of positional changes ( Z =-4.079, P <0.001), and the effectiveness of assisted compression ( Z =-3.001, P =0.003). Further stratified analysis revealed that the ScopeGuide-assisted training mode was more beneficial for junior endoscopists ( P <0.05 in all parameters) but not for intermediate endoscopists ( P >0.05) and partially beneficial for senior endoscopists ( P <0.05 for all parameters except looping resolution). CONCLUSION: ScopeGuide-assisted training can significantly facilitate endoscopists in resolving loops and reducing patient pain, thereby enhancing their colonoscopy abilities.
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Ceco , Colonoscopia , Humanos , Estudos Retrospectivos , Dor/etiologia , Dor/prevenção & controle , Competência ClínicaRESUMO
Tea (Camellia sinensis) is a well-known beverage crop rich in polyphenols with health benefits for humans. Understanding how tea polyphenols participate in plant resistance is beneficial to breeding resistant varieties and uncovering the resistance mechanisms. Here, we report that a Colletotrichum infection-induced 'pink ring' symptom appeared outside the lesion, which is highly likely to occur in resistant cultivars. By identifying morphological feature-specific metabolites in the pink ring and their association with disease resistance, and analysis of the association between metabolite and gene expression, the study revealed that the accumulation of anthocyanin-3-O-galactosides, red phytotoxin compounds resistant to anthracnose, plays a pivotal role in the hypersensitive response surrounding infection sites in tea plants. The results of genetic manipulation showed that the expression of CsF3Ha, CsANSa, CsUGT78A15, CsUGT75L43, and CsMYB113, which are involved in anthocyanin biosynthesis, is positively correlated with anthracnose-resistance and the formation of the pink ring. Further phosphorus quantification and fertilization experiments confirmed that phosphate deficiency caused by anthracnose is involved in the occurrence of the pink ring. Genetic manipulation studies indicated that altering the expression levels of Pi transporter proteins (CsPHT2-1, CsPHT4;4) and phosphate deprivation response transcription factors (CsWRKY75-1, CsWRKY75-2, CsMYB62-1) enhances resistance to anthracnose and the formation of the pink ring symptom in tea plants. This article provides the first evidence that anthocyanin-3-O-galactosides are the anthracnose-resistant phytoalexins among various polyphenols in tea plants, and this presents an approach for identifying resistance genes in tea plants, where genetic transformation is challenging.
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Supramolecular organic frameworks (SOFs) have emerged as a promising class of organic porous materials with vast potential as nanocarriers for combination therapy. Here, we successfully construct an anionic flexible supramolecular organic framework (TPP-SOF) by leveraging multiple host-guest interactions. TPP-SOF is fabricated by the hierarchical orthogonal assembly between anionic water-soluble dimacrocyclic host (P5CD), porphyrin photosensitizers (TPP), and ROS-sensitive thioketal linked adamantane dimer (Ada-S-Ada). TPP-SOF exhibits pH-dependent activation of 1O2 production, which further facilitates the cleavage of Ada-S-Ada linker and promotes the disintegration of the framework. Moreover, leveraging electrostatic and hydrophobic interactions, the anionic TPP-SOF serves as an effective platform for loading cationic photosensitizer IR780 and chemotherapeutic prodrug PhenPt(IV), leading to the formation of supramolecular nanoparticles (IR780/Pt@TPP-SOF) for synergistic therapy. The obtained nanoparticles exhibit good stability, efficient generation of 1O2, and photothermal performance. In vitro and in vivo studies indicate that IR780/Pt@TPP-SOF exhibits remarkable synergistic chemo/PDT/PTT effects under 808 and 660 nm light irradiation. This study showcases a deep insight for the development of SOFs and a new approach for delivering cationic drugs and constructing synergistic combination therapy systems. STATEMENT OF SIGNIFICANCE: In this work, a pH/ROS-responsive anionic flexible supramolecular organic framework, TPP-SOF, was innovatively designed by the hierarchical orthogonal assembly, to co-deliver cationic photosensitizer IR780 and prodrug PhenPt(IV) for synergistic cancer therapy. The drug-loaded TPP-SOF is termed IR780/Pt@TPP-SOF, in which the photoactivity of porphyrin within TPP-SOF could be activated under acidic conditions, the 1O2 generated by the photosensitizers could break the thioketal bonds in Ada-S-Ada, leading to the disassembly of the framework and releasing the drugs. This supramolecular drug delivery system displays good biocompatibility and exhibits remarkable synergistic chemo/PDT/PTT effects.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Pró-Fármacos , Humanos , Fármacos Fotossensibilizantes/química , Pró-Fármacos/química , Espécies Reativas de Oxigênio/química , Polímeros/química , Nanopartículas/química , Porfirinas/farmacologia , Porfirinas/química , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológicoRESUMO
Colon cancer is one of the most prevalent cancers and exhibits high mortality worldwide. Despite the certain success in the immunotherapy of many tumor types, the limited response of colon cancer to immunotherapy remains a difficult problem. Retinoic acid-inducible gene-I (RIG-I) is a crucial component in innate antiviral immunity, but its role in antitumor immunity remains unclear. Here, in this report, we found that silencing RIG-I decreased resistance to tumor cells killed by T cells and attenuated colon tumor growth in immunocompetent mice. Meanwhile, overexpressing RIG-I promoted tumor progression, and high expression of RIG-I sensitized cells to anti-programmed cell death protein-1 (PD-1) therapy in vivo. Interestingly, we found that RIG-I influenced programmed cell death ligand 1 (PD-L1) expression to promote colon cancer immune evasion without relying on type I interferon stimulation. Mechanistically, RIG-I could compete with Speckle Type POZ protein (SPOP) to bind PD-L1, leading to attenuation of the polyubiquitination and proteasomal degradation of PD-L1. Collectively, our work reveals new insights into the contribution of RIG-I to driving immune evasion by maintaining the stability of PD-L1 through post-translational modification and provides a promising biomarker of the efficacy of immunotherapy in colon cancer.
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Introduction: The incidence of anastomotic leakage is relatively high (6-26%) in esophagogastrocervical anastomosis. The traditional anastomotic mode has high tissue tension in the process of anastomosis, which can easily cause tissue tear in the anastomotic area and increase the incidence of anastomotic leakage. Aim: To investigate the usefulness of reversely connecting circular stapler technique for reducing anastomotic tension and injury of the esophageal and gastric wall, preventing anastomotic leakage in minimally invasive McKeown esophagectomy. Material and methods: A total of 133 patients with esophageal cancer who underwent minimally invasive McKeown esophagectomy from January 2021 to December 2021 were collected. Characteristics, surgical data, and outcomes of patients were recorded and retrospectively analyzed. There were 83 patients in the reverse order connecting circular stapler group and 50 patients in the conventional order connecting group. Results: Anastomotic leakage was observed in 2 (2.4%) cases in the reverse order connecting circular stapler group. Compared with the conventional connection group, the reverse connecting group had lower incidence of anastomotic leakage, shorter anastomotic time, shorter hospital stay, and lower incidence of pulmonary and chest infections and hoarseness. Conclusions: The reversely connecting circular stapler technique could reduce the incidence of anastomotic leakage. The technique is simple to perform and easy to learn. Therefore, it is useful for the prevention of anastomotic leakage.
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The tea plant (Camellia sinensis) is rich in polyphenolic compounds. Particularly, flavan-3-ols and proanthocyanidins (PAs) are essential for the flavor and disease-resistance property of tea leaves. The fifth subgroup of R2R3-MYB transcription factors comprises the primary activators of PA biosynthesis. This study showed that subgroup 5 R2R3-MYBs in tea plants contained at least nine genes belonging to the TT2, MYB5, and MYBPA types. Tannin-rich plants showed an expansion in the number of subgroup 5 R2R3-MYB genes compared with other dicotyledonous and monocot plants. The MYBPA-type genes of tea plant were slightly expanded. qRT-PCR analysis and GUS staining analysis of promoter activity under a series of treatments revealed the differential responses of CsMYB5s to biotic and abiotic stresses. In particular, CsMYB5a, CsMYB5b, and CsMYB5e responded to high-intensity light, high temperature, MeJA, and mechanical wounding, whereas CsMYB5f and CsMYB5g were only induced by wounding. Three genetic transformation systems (C. sinensis, Nicotiana tabacum, and Arabidopsis thaliana) were used to verify the biological function of CsMYB5s. The results show that CsMYB5a, CsMYB5b, and CsMYB5e could promote the gene expression of CsLAR and CsANR. However, CsMYB5f and CsMYB5g could only upregulate the gene expression of CsLAR but not CsANR. A series of site-directed mutation and domain-swapping experiments were used to verify functional domains and key amino acids of CsMYB5s responsible for the regulation of PA biosynthesis. This study aimed to provide insight into the induced expression and functional diversity model of PA biosynthesis regulation in tea plants.
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Lung adenocarcinoma (LUAD) is one of the most common types of lung cancer, which affects the life and health of patients. The role of ATP-binding cassette subfamily A member 3 (ABCA3) in the occurrence and development of LUAD is unclear; therefore, ABCA3 expression in LUAD and other tumors was analyzed in the present study. In addition, ABCA3 expression in patients with LUAD and their survival were analyzed using a public database. ABCA3 co-expressed genes were identified and their enriched pathways were analyzed. Furthermore, ABCA3 expression was knocked down in LUAD cell lines. The proliferation, invasion and migration of cells, and the process of epithelial-mesenchymal transition (EMT), were studied through cytological and molecular biology experiments. Compared with that in normal lung tissues, ABCA3 expression was significantly reduced in tumor tissues. Patients with low ABCA3 expression had a markedly worse overall survival compared with those with high ABCA3 expression. Notably, abnormal ABCA3 expression has been observed in a variety of tumors. Subsequently, multiple pathophysiological pathways enriched by ABCA3 and its co-expressed genes were explored. Furthermore, the malignant behavior of tumor cells was enhanced when ABCA3 expression was knocked down, and the EMT process was activated after ABCA3 expression was knocked down. In conclusion, as a tumor suppressor gene, ABCA3 serves a protective role in the development of tumors, and may have a potential role in clinical applications, and thus, is worthy of further study.
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Retinoic acid-inducible gene-I (RIG-I) is considered a key sensor for host recognition of RNA virus infections. Recent studies have shown that RIG-I also regulates carcinogenesis. However, the role of RIG-I in esophageal squamous cell carcinoma (ESCC) remains unclear. We investigated the RIG-I expression in ESCC cells using a public database, immunohistochemistry, and Western blotting. We evaluated the proliferative activity of ESCC cells using CCK-8, colony formation, and EdU staining assays. Further, we determined the ESCC cell-cycle changes using flow cytometry and the ubiquitination of p21 in the cells using cycloheximide chase and ubiquitination assays. Finally, we verified the in vivo effects of RIG-I on ESCC cells by constructing xenograft models. RIG-I was highly expressed in ESCC cells and significantly promoted their proliferation and cell-cycle. Moreover, RIG-I knockdown inhibited xenograft growth in nude mice. Furthermore, RIG-I accelerated the cell-cycle by promoting the ubiquitination and degradation of p21. Overall, this study revealed that the increased expression of RIG-I due to ESCC accelerated the progression of esophageal cancer by promoting the ubiquitination and degradation of p21, which is related to the prognosis of ESCC. Thus, RIG-I may be a novel therapeutic target for ESCC treatment.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Camundongos NusRESUMO
OBJECTIVE: Recent studies have shown that the metabolic process-related gene AHSG is involved in multiple pathological processes of tumours. This study will explore the relationship between AHSG and lung adenocarcinoma. MATERIALS AND METHODS: Expression analysis, survival analysis and co-expression analysis of AHSG were performed using a public database, and cytological and molecular biology assays were performed to explore the role of AHSG in lung adenocarcinoma. RESULT: Compared with normal tissues, AHSG expression was significantly higher in cancer tissues in the TCGA-LUAD database, and pan-cancer analysis revealed abnormal AHSG expression in different kinds of tumours. Survival analysis revealed that compared with the low expression group, the patients in the high expression group had a significantly worse overall survival duration in the TCGA-LUAD database, and a subsequent study confirmed that AHSG expression could be an independent prognostic factor of overall survival in lung adenocarcinoma. AHSG-related genes are involved in multiple physiological and pathophysiological pathways. In subsequent cytological and molecular biology experiments, inhibition of AHSG expression suppressed proliferation, migration and invasion in lung adenocarcinoma cell lines, and the EMT process was blocked after knockdown of AHSG. CONCLUSION: AHSG could be used as a prognostic factor for OS in patients with lung adenocarcinoma. It can promote the biological behaviour of lung adenocarcinoma and may become a potential target for treatment, which is worthy of further study.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/metabolismo , Prognóstico , Adenocarcinoma de Pulmão/patologia , Análise de Sobrevida , Proliferação de Células/genética , alfa-2-Glicoproteína-HSRESUMO
BACKGROUND: Tumours with no evidence of neuroendocrine transformation histologically but harbouring neuroendocrine features are collectively referred to as non-small cell lung cancer (NSCLC) with neuroendocrine differentiation (NED). Investigating the mechanisms underlying NED is conducive to designing appropriate treatment options for NSCLC patients. METHODS: In the present study, we integrated multiple lung cancer datasets to identify neuroendocrine features using a one-class logistic regression (OCLR) machine learning algorithm trained on small cell lung cancer (SCLC) cells, a pulmonary neuroendocrine cell type, based on the transcriptome of NSCLC and named the NED index (NEDI). Single-sample gene set enrichment analysis, pathway enrichment analysis, ESTIMATE algorithm analysis, and unsupervised subclass mapping (SubMap) were performed to assess the altered pathways and immune characteristics of lung cancer samples with different NEDI values. RESULTS: We developed and validated a novel one-class predictor based on the expression values of 13,279 mRNAs to quantitatively evaluate neuroendocrine features in NSCLC. We observed that a higher NEDI correlated with better prognosis in patients with LUAD. In addition, we observed that a higher NEDI was significantly associated with reduced immune cell infiltration and immune effector molecule expression. Furthermore, we found that etoposide-based chemotherapy might be more effective in the treatment of LUAD with high NEDI values. Moreover, we noted that tumours with low NEDI values had better responses to immunotherapy than those with high NEDI values. CONCLUSIONS: Our findings improve the understanding of NED and provide a useful strategy for applying NEDI-based risk stratification to guide decision-making in the treatment of LUAD.
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N4-acetylcytidine (ac4C) is one type of RNA modification found in eukaryotes. RNA acetylation modifications are gradually expanding in oncology. However, the role of RNA acetylation modifications in colorectal cancer and its association with colorectal cancer microsatellite status remain unclear. Using public databases and in vitro experiments, we verified the expression and biological function of NAT10, as the key RNA acetylation modification enzyme, in colorectal cancer. The results showed that NAT10 was highly expressed in colorectal cancer, and significantly promoted colorectal cancer cell proliferation. NAT10 was also involved in several aspects of cell homoeostasis such as ion transport, calcium-dependent phospholipid binding, and RNA stability. NAT10 expression positively correlated with immune infiltration in colorectal cancer. We further constructed a risk regression model for mRNA acetylation in colorectal cancer using acetylation-related differential genes. We found that tumour immune infiltration, microsatellite instability (MSI) proportion, tumour immune mutation burden, and patient response to immunotherapy were positively correlated with risk scores. For the first time, our study showed that the level of mRNA acetylation modification level is elevated in colorectal cancer and positively correlates with immune infiltration and microsatellite status of patients. Based on our findings, NAT10 may be a new target for colorectal cancer treatment.
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Neoplasias do Colo , Neoplasias Colorretais , Humanos , RNA Mensageiro/genética , Acetiltransferases N-Terminal/genética , Acetiltransferases N-Terminal/metabolismo , Acetilação , Metilação de DNA , Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Repetições de MicrossatélitesRESUMO
Rubus chingii Hu is a berry plant of the genus Rubus of the Rosaceae family, which has high nutritional and medicinal value and is rich in flavonoids. Flavonol synthase (FLS) and dihydroflavonol 4-reductase (DFR) compete for the common substrate dihydroflavonols to regulate the metabolic flux of flavonoids. However, the competition between FLS and DFR based on enzyme is rarely reported. Here, we isolated and identified two FLS genes (RcFLS1 and RcFLS2) and one DFR gene (RcDFR) from Rubus chingii Hu. RcFLSs and RcDFR were highly expressed in stems, leaves, and flowers, although the flavonol accumulation in these organs was significantly higher than that of proanthocyanidins (PAs). The recombinant RcFLSs demonstrated bifunctional activities via hydroxylation and desaturation at the C-3α position having a lower Michaelis constant (Km) for dihydroflavonols than RcDFR. We also found that a low concentration of flavonols could significantly inhibit RcDFR activity. To investigate the competitive relationship between RcFLSs and RcDFR, we used a prokaryotic expression system (E. coli) to co-express these proteins. The transgenic cells expressing recombinant proteins were incubated with substrates, and the reaction products were analyzed. Furthermore, two transient expression systems (tobacco leaves and strawberry fruits) and a stable genetic system (Arabidopsis thaliana) were used to co-express these proteins in vivo. The results showed that RcFLS1 was dominant in the competition with RcDFR. Our results demonstrated that the competition between FLS and DFR regulated the metabolic flux distribution of flavonols and PAs, which will be of great significance for the molecular breeding of Rubus plants.
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A 64-year-old man was admitted with paroxysmal left-side thoracic pain. CT scan showed an irregular appearance, expansile, osteolytic lesion of the left seventh rib. Wide en bloc excision of the tumour was performed. Macroscopic examination showed that a 3.5 cm × 3.0 cm × 3.0 cm solid lesion with destruction of bone. Histological examination showed that the tumour cells were arranged in plate shaped and interspersed between the bone trabeculae. Mature adipocytes were noted in the tumour tissues. The immunohistochemical stainings showed that the vacuolated cells were positive for S-100 protein and negative for CD68 and CD34. These clinicopathological features were consistent with intraosseous hibernoma.
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Salicylic acid (SA) is an important plant hormone and signal required for establishing resistance to diverse pathogens and plant diseases. The abundant polyphenols in tea plants also defend plants from biotic and abiotic stresses. However, whether exogenous SA would increase the resistance of tea plants to adversity and the relationship between SA and polyphenols are still poorly understood. Here, we carried out SA treatment on tea seedlings and performed transcriptome sequencing. SA treatment inhibited the phenylpropanoid and flavonoid metabolic pathways but promoted the lignin metabolic pathways. The increased accumulation of lignin in tea leaves after treating with SA indicated that lignin might coordinate SA, enhance, and improve plant defense and disease resistance. Simultaneously, an SA-inducible flavonoid glucosyltransferase (CsUGT0554) specifically involved in 7-OH site glycosylation was characterized in vitro. These results provided valuable information about the effects of SA on tea seedlings and the molecular basis for SA-mediated immune responses.