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1.
Braz J Med Biol Res ; 57: e13368, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38775547

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.


Assuntos
Biomarcadores Tumorais , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Neoplasias de Cabeça e Pescoço/genética , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Pessoa de Meia-Idade
2.
Braz. j. med. biol. res ; 57: e13368, fev.2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1557313

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.

3.
Int Orthop ; 48(2): 547-553, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37782331

RESUMO

PURPOSE: The search for more effective and safe treatment methods for cervical spondylotic radiculopathy (CSR) has led to the rapid development and increasing popularity of minimally invasive posterior cervical foraminotomy (MI-PCF). This study aims to compare two important approaches for MI-PCF surgery: the channel-assisted cervical key hole technology combined with ultrasonic bone osteotome (CKH-UBO) and posterior percutaneous endoscopic cervical foraminotomy (PPECF). METHODS: Data from patients treated with single-level CKH-UBO (n = 35) or PPECF (n = 40) were analyzed. Clinical outcomes, including visual analogue scale (VAS) scores for neck and arm pain, Neck Disability Index (NDI), and modified Macnab criteria, were assessed preoperatively, as well as at three days, three months, and one year postoperatively. RESULTS: The percentages of patients with excellent and good outcomes were 97.14% and 92.5%, respectively. The average surgical time in the CKH-UBO group was significantly shorter than in the PPECF group (p < 0.001), while the average incision length in the PPECF group was significantly smaller than in the CKH-UBO group. There were no significant differences between the two groups in terms of blood loss, hospital stay, and clinical outcomes at three days, three months, and 12 months postoperatively. CONCLUSION: CKH-UBO can achieve the same surgical outcomes as PPECF for the treatment of CSR. However, CKH-UBO saves more time but requires patients to undergo larger incisions.


Assuntos
Foraminotomia , Radiculopatia , Espondilose , Humanos , Foraminotomia/efeitos adversos , Foraminotomia/métodos , Estudos Retrospectivos , Ultrassom , Resultado do Tratamento , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Espondilose/cirurgia , Radiculopatia/cirurgia , Discotomia/métodos
4.
Cancer Med ; 12(11): 12622-12638, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37076985

RESUMO

BACKGROUND: As a nucleolar protein associated with ribosome biogenesis in multiple cancer types, PES1 has been reported to be overexpressed, promoting cancer cell proliferation and invasion. However, in head and neck squamous cell carcinoma (HNSCC), the role of PES1 on the prognosis and immune infiltration remains unknown. METHODS: Multiple databases and qRT-PCR evaluated the expression of PES1 in HNSCC. The prognostic potential of PES1 in HNSCC patients was analyzed by Cox regression and Kaplan-Meier curves. Then, we used LASSO regression and stepwise multivariate Cox regression to construct the PES1-related risk assessment model. In addition, the association between PES1 and tumor immune microenvironment and drug sensitivity was explored by R packages. Finally, we used cell function assays to explore in HNSCC if PES1 influences tumor growth and metastasis. RESULTS: PES1 was significantly up-regulated in HNSCC and closely correlated with HPV status, tumor stage, clinical grade, and TP53 mutation status. Survival analysis suggested that PES1 is associated with worse survival outcomes, acting as an independent prognostic indicator for HNSCC. Our model also performed well in terms of prognosis prediction. Furthermore, tumor-infiltrating immune cells and antitumor drug susceptibility were negatively related to PES1 expression. Functionally, as for HNSCC cell lines in vitro, the knockdown of PES1 could inhibit proliferation, migration, and invasion. CONCLUSION: We have demonstrated that PES1 may be a promoter of tumor growth. PES1 holds excellent promise as a novel biomarker to assess the prognosis of patients with HNSCC and may guide immunotherapy.


Assuntos
Neoplasias de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Microambiente Tumoral/genética , Biomarcadores , Proliferação de Células , Neoplasias de Cabeça e Pescoço/genética , Prognóstico , Proteínas de Ligação a RNA
5.
Int J Oncol ; 62(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36484384

RESUMO

Adenoid cystic carcinoma (ACC) usually arises in the salivary glands, and is a rare tumor, accounting for 1% of all head and neck cancer cases. According to estimates, there are 3­4.5 cases of ACC for every one million individuals. Numerous studies have reported the association between ACC and microRNAs (miRNAs/miRs). miRNAs are endogenous, non­coding small RNAs, 19­25 nt in length, that can regulate target gene expression at the post­transcriptional level. The aberrant expression of miRNAs may be associated with the prognosis and treatment of patients, as well as with tumorigenesis and tumor development. miRNAs are becoming reliable biomarkers for disease detection due to their varied characteristics, and miRNA target­based therapies are increasingly being used in clinical practice. The present review provides a brief introduction to ACC and the biogenesis of miRNAs. A summary of the miRNAs that have been validated by in vitro or in vivo studies is then presented, describing their role in ACC.


Assuntos
Carcinoma Adenoide Cístico , MicroRNAs , Humanos , MicroRNAs/genética , Carcinoma Adenoide Cístico/genética
6.
Cancer Med ; 12(3): 3773-3785, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35920349

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common and highly heterogeneous malignancies worldwide. Increasing studies have proven that hypoxia and related long non-coding RNA (lncRNA) are involved in the occurrence and prognosis of HNSCC. The goal of this work is to construct a risk assessment model using hypoxia-related lncRNAs (hrlncRNAs) for HNSCC prognosis prediction and personalized treatment. METHODS: Transcriptome expression matrix, clinical follow-up data, and somatic mutation data of HNSCC patients were obtained from The Cancer Genome Atlas (TCGA). We used co-expression analysis to identify hrlncRNAs, then screened for differentially expressed lncRNAs (DEhrlncRNAs), and paired these DEhrlncRNAs. The risk model was established through univariate, least absolute shrinkage and selection operator (LASSO), and stepwise multivariate Cox regression. Finally, we assessed the model from multiple perspectives of tumor mutation burden (TMB), tumor immune infiltration, chemotherapeutic sensitivity, immune checkpoint inhibitor (ICI), and functional enrichment. RESULTS: The risk assessment model included 14 hrlncRNA pairs. The risk score was observed to be a reliable prognostic factor. The high-risk patients had an unfavorable prognosis and significant differences from the low-risk group in TMB and tumor immune infiltration. In the high-risk patients, the common immune checkpoints were down-regulated, including CTLA4 and PDCD1, and the sensibility to paclitaxel and docetaxel was higher. The functional enrichment analysis suggested that the low-risk group was accompanied by activated immune function. CONCLUSIONS: The risk assessment model of 14-hrlncRNA-pairs demonstrated a promising prognostic prediction for HNSCC patients and can guide personalized clinical treatment.


Assuntos
Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Prognóstico , Hipóxia
7.
Front Genet ; 13: 1081519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531252

RESUMO

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in immune and inflammatory signaling. TYK2 is overexpressed in several types of cancers and promotes the invasion and proliferation of cancer cells. Nevertheless, the roles of TYK2 in the prognosis and immune infiltration of head and neck squamous cell carcinoma (HNSCC) remain to be elucidated. In this study, the expression of TYK2 in HNSCC was evaluated based on the data retrieved from multiple databases and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The prognostic potential of TYK2 in patients with HNSCC was analyzed by Kaplan-Meier curves and Cox regression analysis. A TYK2-related risk assessment model was subsequently constructed by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and stepwise multivariate Cox regression analysis. The association between the expression of TYK2 and the tumor immune microenvironment, immune checkpoints, and drug sensitivity was explored various packages in R. Cell function assays were finally used for exploring the effects of TYK2 on the growth and metastasis of HNSCC tumors. The expression of TYK2 was significantly upregulated in HNSCC and was found to be closely correlated with HPV status, gender, clinical grade, and TP53 mutation status. Survival analysis suggested that TYK2 is associated with better survival outcomes and acts as an independent prognostic indicator of HNSCC. The model constructed herein also performed well in terms of predicting patient prognosis. The expression of TYK2 was positively associated with the population of tumor-infiltrating immune cells, expression of immune checkpoint genes, and antitumor drug susceptibility. Functionally, TYK2 knockdown significantly promoted the proliferation, migration, and invasion of HNSCC cell lines in vitro. The findings demonstrated that TYK2 could serve as a suppressor of tumor growth and holds significant promise as a novel biomarker for assessing the prognosis of patients with HNSCC and aid in immunotherapy against HNSCC.

8.
Front Pharmacol ; 13: 949713, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532732

RESUMO

Background: Circular RNA (circRNA) has an important influence on oral squamous cell carcinoma (OSCC) progression as competing endogenous RNAs (ceRNAs). However, the link between ceRNAs and the OSCC immune microenvironment is unknown. The research aimed to find circRNAs implicated in OSCC carcinogenesis and progression and build a circRNA-based ceRNA network to create a reliable OSCC risk prediction model. Methods: The expression profiles of circRNA in OSCC tumors and normal tissues were assessed through RNA sequencing. From the TCGA database, clinicopathological data and expression patterns of microRNAs (miRNAs) and mRNAs were obtained. A network of circRNA-miRNA-mRNA ceRNA was prepared according to these differentially expressed RNAs and was analyzed through functional enrichment. Subsequently, based on the mRNA in the ceRNA network, the influence of the model on prognosis was then evaluated using a risk prediction model. Finally, considering survival, tumor-infiltrating immune cells (TICs), clinicopathological features, immunosuppressive molecules, and chemotherapy efficacy were analyzed. Results: Eleven differentially expressed circRNAs were found in cancer tissues relative to healthy tissues. We established a network of circRNA-miRNA-mRNA ceRNA, and the ceRNA network includes 123 mRNAs, six miRNAs, and four circRNAs. By the assessment of Genomes pathway and Kyoto Encyclopedia of Genes, it is found that in the cellular senescence, PI3K-AKT and mTOR signaling pathway mRNAs were mainly enrichment. An immune-related signature was created utilizing seven immune-related genes in the ceRNA network after univariate and multivariate analysis. The receiver operating characteristic of the nomogram exhibited satisfactory accuracy and predictive potential. According to a Kaplan-Meier analysis, the high-risk group's survival rate was signally lower than the group with low-risk. In addition, risk models were linked to clinicopathological characteristics, TICs, immune checkpoints, and antitumor drug susceptibility. Conclusion: The profiles of circRNAs expression of OSCC tissues differ significantly from normal tissues. Our study established a circRNA-associated ceRNA network associated with OSCC and identified essential prognostic genes. Furthermore, our proposed immune-based signature aims to help research OSCC etiology, prognostic marker screening, and immune response evaluation.

9.
Food Funct ; 12(20): 9979-9993, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34494629

RESUMO

Currently, drug-induced liver injury caused by acetaminophen (APAP) is the second leading cause of human liver transplantation. The only clinical antidote treatment for APAP-induced liver injury is N-acetyl-L-cysteine (NAC), which has many side effects. Chitooligosaccharides (COS) are processed from naturally occurring chitin through chemical desalting and deproteinization, biological enzymatic hydrolysis and other processes. In this study, we constructed in vitro and in vivo models of APAP-induced liver injury to study COS of two molecular weights (MWs), which are COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da). The results showed that COST and COSM can significantly reduce the levels of serum ALT and AST and liver MDA, TNF-α, IL-1ß and IL-6, and increase the levels and activity of GSH, SOD, GSH-Px and CAT. A mechanistic study found that COST and COSM can significantly reduce the expression of liver CYP2E1, Keap1, p-ASK1/ASK1, p-MKK4/MKK4, p-JNK/JNK, Caspase-3 and Bax and increase the expression of Nrf2, HO-1, eNOS, SOD and Bcl-XL. COST and COSM can inhibit toxic APAP metabolism, inhibit oxidative damage and the apoptosis pathway, increase activation of the liver antioxidant pathway, and ultimately ameliorate APAP-induced liver oxidative damage.


Assuntos
Acetaminofen/efeitos adversos , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Quitosana/farmacologia , Oligossacarídeos/farmacologia , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Quitosana/química , Citocromo P-450 CYP2E1/metabolismo , Citocinas/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Oligossacarídeos/química , Estresse Oxidativo/efeitos dos fármacos
10.
Int J Biol Sci ; 17(11): 2853-2870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34345212

RESUMO

In mammals, thermogenic organs exist in the body that increase heat production and enhance energy regulation. Because brown adipose tissue (BAT) consumes energy and generates heat, increasing energy expenditure via BAT might be a potential strategy for new treatments for obesity and obesity-related diseases. Thermogenic differentiation affects normal adipose tissue generation, emphasizing the critical role that common transcriptional regulation factors might play in common characteristics and sources. An understanding of thermogenic differentiation and related factors could help in developing ways to improve obesity indirectly or directly through targeting of specific signalling pathways. Many studies have shown that the active components of various natural products promote thermogenesis through various signalling pathways. This article reviews recent major advances in this field, including those in the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA), cyclic guanosine monophosphate-GMP-dependent protein kinase G (cGMP-AKT), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), transforming growth factor-ß/bone morphogenic protein (TGF-ß/BMP), transient receptor potential (TRP), Wnt, nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κΒ), Notch and Hedgehog (Hh) signalling pathways in brown and brown-like adipose tissue. To provide effective information for future research on weight-loss nutraceuticals or drugs, this review also highlights the natural products and their active ingredients that have been reported in recent years to affect thermogenesis and thus contribute to weight loss via the above signalling pathways.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiologia , Transdução de Sinais/fisiologia , Termogênese/fisiologia , Animais , Peso Corporal , Metabolismo Energético , Humanos , Obesidade
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