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BACKGROUND: Qingzhuan dark tea polysaccharides (QDTP) have been complexed with Zinc (Zn) to form the Qingzhuan dark tea polysaccharides-Zinc (QDTP-Zn) complex. The present study investigated the protective effects of QDTP-Zn on ulcerative colitis (UC) in mice. The UC mouse model was induced using dextran sodium sulfate (DSS), followed by oral administration of QDTP-Zn (0.2 and 0.4 g kg-1 day-1). RESULTS: QDTP-Zn demonstrated alleviation of UC symptoms in mice, as evidenced by a decrease in disease activity index scores. QDTP-Zn also regulated colon tissue injury by upregulating ZO-1 and occludin protein expression, at the same time as downregulating tumor necrosis factor-α and interleukin-6ß levels. Furthermore, QDTP-Zn induced significant alterations in the abundance of bacteroidetes and firmicutes and notably increased levels of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, and butyric acid. CONCLUSION: In summary, QDTP-Zn exhibits therapeutic potential in alleviating enteritis by fortifying the colonic mucosal barrier, mitigating inflammation and modulating intestinal microbiota and SCFAs levels. Thus, QDTP-Zn holds promise as a functional food for both the prevention and treatment of UC. © 2024 Society of Chemical Industry.
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Colitis Ulcerosa , Sulfato de Dextran , Polisacáridos , Zinc , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Animales , Sulfato de Dextran/efectos adversos , Ratones , Zinc/administración & dosificación , Zinc/metabolismo , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/administración & dosificación , Masculino , Humanos , Té/química , Colon/metabolismo , Colon/efectos de los fármacos , Colon/patología , Modelos Animales de Enfermedad , Camellia sinensis/química , Microbioma Gastrointestinal/efectos de los fármacos , Ratones Endogámicos C57BL , Ácidos Grasos Volátiles/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , SulfatosRESUMEN
Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.
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Flavonoides , Estrés Oxidativo , Flavonoides/farmacología , Flavonoides/uso terapéuticoRESUMEN
Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.
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Hipertensión , Hiperuricemia , Resistencia a la Insulina , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Ácido Úrico , Hipertensión/complicaciones , Glucosa , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Triglicéridos , Bilirrubina , Colesterol , Glucemia/metabolismoRESUMEN
Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways.
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Neoplasias , ARN Largo no Codificante , Empalme Alternativo/genética , Transformación Celular Neoplásica , Humanos , Neoplasias/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN MensajeroRESUMEN
An iron-promoted oxidative tandem alkylation/cyclization of ynones with 4-alkyl-substituted 1,4-dihydropyridines for the efficient synthesis of 2-alkylated indenones is described. The process occurs via oxidative homolysis of a C-C σ-bond in 1,4-dihydropyridines to generate an alkyl radical followed by the addition of C-C triple bonds in ynones and intramolecular cyclization. A wide range of alkyl radicals could be efficiently transferred to generate a series of synthetically useful 2-alkylated indenones with excellent selectivity under mild conditions.
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Dihidropiridinas , Alquilación , Ciclización , Dihidropiridinas/química , Hierro/química , Estrés OxidativoRESUMEN
BACKGROUND: Folliculocentric basaloid proliferation (FBP) is a benign and reactive proliferation which can histopathologically mimic basal cell carcinomas (BCCs). The incidental presence of FBP during the excision of a BCC can occasionally lead to excessive tissue removal. One distinguishing feature of BCCs is that they invade the stroma, whereas FBPs generally do not. METHODS: Matrilin-2 is an extracellular matrix protein associated with tumor invasion, and we compared the expression of matrilin-2 in peritumoral cells of BCC and FBP. RESULTS: We found increased matrilin-2 expression within the peritumoral stroma of 41 of 42 BCCs (97.7%), with strong expression in all (100%) cases of infiltrative subtypes and in 21 of 25 (84%) nodular subtypes of BCC. We found no expression of peritumoral matrilin-2 in any of the seven cases of FBP. CONCLUSION: Our results suggest that immunolabeling with the matrilin-2 antibody may help distinguish BCCs from FBPs.
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Carcinoma Basocelular , Proteínas Matrilinas , Neoplasias Cutáneas , Carcinoma Basocelular/patología , Proliferación Celular , Humanos , Proteínas Matrilinas/análisis , Neoplasias Cutáneas/patología , Coloración y EtiquetadoRESUMEN
The successful treatment of human cancers by immunotherapy has been made possible by breakthroughs in the discovery of immune checkpoint regulators, including CTLA-4 and PD-1/PD-L1. However, the immunosuppressive effect of the tumor microenvironment still represents an important bottleneck that limits the success of immunotherapeutic approaches. The tumor microenvironment influences the metabolic crosstalk between tumor cells and tumor-infiltrating immune cells, creating competition for the utilization of nutrients and promoting immunosuppression. In addition, tumor-derived metabolites regulate the activation and effector function of immune cells through a variety of mechanisms; in turn, the metabolites and other factors secreted by immune cells can also become accomplices to cancer development. Immune-metabolic checkpoint regulation is an emerging concept that is being studied with the aim of restoring the immune response in the tumor microenvironment. In this review, we summarize the metabolic reprogramming of various cell types present in the tumor microenvironment, with a focus on the interaction between the metabolic pathways of these cells and antitumor immunosuppression. We also discuss the main metabolic checkpoints that could provide new means of enhancing antitumor immunotherapy.
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Inmunoterapia , Neoplasias/patología , Microambiente Tumoral , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/inmunología , Antígeno CTLA-4/metabolismo , Humanos , Células Supresoras de Origen Mieloide/citología , Células Supresoras de Origen Mieloide/metabolismo , Neoplasias/inmunología , Neoplasias/terapia , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Macrófagos Asociados a Tumores/citología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismoRESUMEN
PURPOSE: In order to control the corona virus disease-2019 (COVID-19) pandemic, many countries have adopted social quarantine policies, with older adults in Wuhan suffering the longest and most severe conditions. But few studies have explored the impact of this on the mental health of older adults in Wuhan. The purpose of this paper is to examine changes in the residential status and mental health of this group when 1 year after the social isolation policies in Wuhan. METHOD: A cross-sectional study with convenience sampling was conducted to assess the questionnaire of older adults in a total of 21 streets in 5 central and 2 distant urban districts of Wuhan. Using a self-compiled living status questionnaire, the Patient Health Questionnaire-9, the General Anxiety Disorder-7, the PTSD Checklist-Civilian Version, the UCLA Loneliness Scale and the Social Support Rating Scale, our survey evaluated the living status, depression, anxiety, post-traumatic stress symptoms, loneliness and social support of all the participants. RESULTS: A total of 400 valid samples were obtained. One year after experiencing social isolation, older adults had not changed much from their pre-epidemic living status and mostly lived with their partners. They had satisfactory social support (33.86 ± 6.92) and low levels of depression (3.12 ± 4.30), anxiety (1.52 ± 3.19) and post-traumatic stress symptoms (21.41 ± 7.39), but there were moderate levels of loneliness (38.27 ± 9.31). Among them, depression, anxiety and post-traumatic stress symptoms were significantly higher (ps < 0.05) in older adults who were COVID-19 close contacts while experiencing social isolation. CONCLUSION: One year after experiencing Wuhan's harsh social isolation, older adults in the Wuhan community did not experience significant symptoms of depression, anxiety or post-traumatic stress, but loneliness has increased and the mental health of older adults who were COVID-19 close contacts needs attention.
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COVID-19 , Salud Mental , Humanos , Anciano , Cuarentena , COVID-19/epidemiología , Estudios Transversales , Soledad/psicologíaRESUMEN
OBJECTIVE: The present study aims to explore the effects of enteral nutrition (EN) semi-curing feeding on nutritional diarrhoea in the patients with stroke. METHODS: The patients admitted to the neurological intensive care unit of a tertiary care hospital with stroke- and EN-related diarrhoea between May 2019 and October 2020 were included in the study. The 60 patients, who met the inclusion criteria were divided into the two groups (30 patients each), the experimental group (EN solution+probiotics+90 ml of pectin) and the control group (EN solution+probiotics), in accordance with the random number table method. The stool number, total stool amount, perineal skin score, and time required to achieve the nutritional target of each patient were recorded at admission and on days 1, 3, and 7 of pectin intervention. The lymphocyte count and the haemoglobin, serum pre-albumin (PA), and total cholesterol (TC) levels were measured in order to assess the patients' nutritional statuses. RESULTS: The stool number and total stool amount on days 1 and 3 of pectin intervention in the experimental group were better than in the control group; the differences were statistically significant (p <0.05). On day 7 of the intervention, the stool number, total stool amount, and perineal skin score had decreased in the experimental group; the differences were statistically significant, when compared to the control group (p <0.05). Furthermore, the PA levels increased, and TC levels decreased in the experimental group; the differences were statistically significant, when compared to the control group (p <0.05). On day 3 of the intervention, the PA levels in the experimental group were increased compared to the control group; the difference was statistically significant (p <0.05). CONCLUSION: EN semi-curing feeding could improve EN-related diarrhoea and nutritional status levels in patients with stroke (Tab. 3, Ref. 9).
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Nutrición Enteral , Accidente Cerebrovascular , Diarrea/terapia , Nutrición Enteral/métodos , Humanos , Estado Nutricional , Albúmina Sérica , Accidente Cerebrovascular/complicacionesRESUMEN
Acute myeloid leukaemia (AML) with chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukaemia (MLL) is an aggressive subtype with low overall survival. Bortezomib (Bort) is first applied in multiple myeloma. However, whether bort possesses anti-self-renewal and leukemogenesis of leukaemia stem cell (LSC) in AML with MLL rearrangements is still unclear. Here, we found that bort suppressed cell proliferation and decreased colony formation in human and murine leukaemic blasts. Besides, bort reduced the frequency and function of LSC, inhibited the progression, and extended the overall survival in MLL-AF9 (MF9) -transformed leukaemic mice. Furthermore, bort decreased the percentage of human LSC (CD34+ CD38- ) cells and extended the overall survival in AML blasts-xenografted NOD/SCID-IL2Rγ (NSG) mice. Mechanistically, cyclin dependent kinase 6 (CDK6) was identified as a bort target by RNA sequencing. Bort reduced the expressions of CDK6 by inhibiting NF ĸB recruitment to the promoter of CDK6, leading to the abolishment of NF ĸB DNA-binding activity for CDK6 promoter. Overexpression of CDK6 partially rescued bort-induced anti-leukemogenesis. Most importantly, bort had little side-effect against the normal haematological stem and progenitor cell (HSPC) and did not affect CDK6 expression in normal HSPC. In conclusion, our results suggest that bort selectively targets LSC in MLL rearrangements. Bort might be a prospective drug for AML patients bearing MLL rearrangements.
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Antineoplásicos/farmacología , Bortezomib/farmacología , Autorrenovación de las Células/efectos de los fármacos , Quinasa 6 Dependiente de la Ciclina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , FN-kappa B/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Animales , Línea Celular Tumoral , Biología Computacional , Quinasa 6 Dependiente de la Ciclina/genética , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Orden Génico , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Ratones , Pronóstico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Circular RNAs (circRNAs) are widely expressed in human cells and are closely associated with cancer development. However, they have rarely been investigated in the context of nasopharyngeal carcinoma (NPC). METHODS: We screened a new circRNA, circRNF13, in NPC cells using next-generation sequencing of mRNA. Reverse transcription polymerase chain reaction and RNA fluorescence in situ hybridization were used to detect circRNF13 expression in 12 non-tumor nasopharyngeal epithelial (NPE) tissues and 36 NPC samples. Cell proliferation was detected using MTT and flow cytometry assays, and colony formation capability was detected using colony formation assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. Cell glycolysis was analyzed using the Seahorse glycolytic stress test. Glucose transporter type 1 (GLUT1) ubiquitination and SUMOylation modifications were analyzed using co-immunoprecipitation and western blotting. CircRNF13 and Small Ubiquitin-like Modifier 2 (SUMO2) interactions were analyzed using RNA pull-down and luciferase reporter assays. Finally, to test whether circRNF13 inhibited NPC proliferation and metastasis in vivo, we used a xenograft nude mouse model generated by means of subcutaneous or tail vein injection. RESULTS: We found that circRNF13 was stably expressed at low levels in NPC clinical tissues and NPC cells. In vitro and in vivo experiments showed that circRNF13 inhibited NPC proliferation and metastasis. Moreover, circRNF13 activated the SUMO2 protein by binding to the 3'- Untranslated Region (3'-UTR) of the SUMO2 gene and prolonging the half-life of SUMO2 mRNA. Upregulation of SUMO2 promotes GLUT1 degradation through SUMOylation and ubiquitination of GLUT1, which regulates the AMPK-mTOR pathway by inhibiting glycolysis, ultimately resulting in the proliferation and metastasis of NPC. CONCLUSIONS: Our results revealed that a novel circRNF13 plays an important role in the development of NPC through the circRNF13-SUMO2-GLUT1 axis. This study implies that circRNF13 mediates glycolysis in NPC by binding to SUMO2 and provides an important theoretical basis for further elucidating the pathogenesis of NPC and targeted therapy.
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Carcinoma Nasofaríngeo/genética , ARN Circular/genética , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética , Ubiquitina-Proteína Ligasas/genética , Regiones no Traducidas 3' , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Modelos Animales de Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Genes Reporteros , Transportador de Glucosa de Tipo 1/metabolismo , Glucólisis , Humanos , Hibridación Fluorescente in Situ , Ratones , Modelos Biológicos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Invasividad Neoplásica , Metástasis de la Neoplasia , Interferencia de ARN , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/metabolismo , Ubiquitinación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
LESSONS LEARNED: Administration of autologous invariant natural killer T (iNKT) cells was safe and well-tolerated in patients with hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage B/C). Expanded iNKT cells produced T-helper 1-like responses with possible antitumor activity. No severe adverse events were observed in any of the enrolled patients, including one patient who received 1010 in vitro-expanded autologous iNKT cells as a single infusion. BACKGROUND: Invariant natural killer T cells co-express T-cell antigen receptor and natural killer (NK) cell receptors. Invariant natural killer T (iNKT) cells exhibit antitumor activity, but their numbers and functions are impaired in patients with hepatocellular carcinoma (HCC). The adoptive transfer of iNKT cells might treat advanced HCC. METHODS: This phase I study (NCT03175679) enrolled 10 patients with HCC (Barcelona Clinic Liver Cancer [BCLC] stage B/C) at Beijing YouAn Hospital (April 2017 to May 2018). iNKT cells isolated from peripheral blood mononuclear cells (PBMCs) were expanded and alpha-galactosylceramide (α-GalCer)-pulsed. Dosage escalated from 3 × 107 to 6 × 107 to 9 × 107 cells/m2 (3+3 design). An exploratory dose trial (1 × 1010 cells/m2 ) was conducted in one patient. RESULTS: Expanded iNKT cells produced greater quantities of T-helper 1 (Th1) cytokines (e.g., interferon-gamma, perforin, and granzyme B) but less interleukin-4 than nonexpanded iNKT cells. Circulating numbers of iNKT cells and activated NK cells were increased after iNKT cell infusion. Most treatment-related adverse events were grade 1-2, and three grade 3 adverse events were reported; all resolved without treatment. Four patients were progression-free at 5.5, 6, 7, and 11 months after therapy, and one patient was alive and without tumor recurrence at the last follow-up. Five patients died at 1.5 to 11 months after treatment. CONCLUSION: Autologous iNKT cell treatment is safe and well-tolerated. Expanded iNKT cells produce Th1-like responses with possible antitumor activity. The antitumor effects of iNKT cell infusion in patients with advanced HCC merit further investigation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Células T Asesinas Naturales , Traslado Adoptivo , Carcinoma Hepatocelular/terapia , Humanos , Inmunoterapia , Neoplasias Hepáticas/terapia , Recurrencia Local de NeoplasiaRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women at childbearing age. Several circular RNAs (circRNAs) have been demonstrated to be involved in PCOS. In this study, we aimed to explore the function and mechanism of circ_0043532 in PCOS. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of circ_0043532, miR-182 and serum/glucocorticoid regulated kinase family member 3 (SGK3). Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Flow cytometry analysis was employed to evaluate cell cycle and cell apoptosis. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the association between miR-182 and SGK3. Western blot assay was carried out to determine the protein level of SGK3. RESULTS: Circ_0043532 was markedly elevated in PCOS granulosa cells (GCs) and KGN cells. Silencing of circ_0043532 suppressed cell proliferation and cell cycle process and promoted cell apoptosis in PCOS GCs and KGN cells. For mechanistic analysis, circ_0043532 was identified as a sponge of miR-182 and SGK3 was confirmed to be a target gene of miR-182. Inhibition of miR-182 rescued the impacts of circ_0043532 interference on PCOS GCs and KGN cell progression. Moreover, miR-182 overexpression suppressed cell proliferation and cell cycle process and promoted cell apoptosis in PCOS GCs and KGN cells by targeting SGK3. CONCLUSION: Deficiency of circ_0043532 suppressed cell proliferation and induced cell cycle arrest and cell apoptosis in PCOS by modulation of miR-182/SGK3 axis.
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Proliferación Celular/fisiología , Células de la Granulosa/metabolismo , MicroARNs/biosíntesis , Síndrome del Ovario Poliquístico/metabolismo , Proteínas Serina-Treonina Quinasas/biosíntesis , ARN Circular/biosíntesis , Adulto , Movimiento Celular/fisiología , Femenino , Células de la Granulosa/patología , Humanos , MicroARNs/genética , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/patología , Proteínas Serina-Treonina Quinasas/genética , ARN Circular/genética , Adulto JovenRESUMEN
Epstein-Barr virus (EBV) infection leads to cancers with an epithelial origin, such as nasopharyngeal cancer and gastric cancer, as well as multiple blood cell-based malignant tumors, such as lymphoma. Interestingly, EBV is also the first virus found to carry genes encoding miRNAs. EBV encodes 25 types of pre-miRNAs which are finally processed into 44 mature miRNAs. Most EBV-encoded miRNAs were found to be involved in the occurrence and development of EBV-related tumors. However, the function of EBV-miR-BART12 remains unclear. The findings of the current study revealed that EBV-miR-BART12 binds to the 3'UTR region of Tubulin Polymerization-Promoting Protein 1 (TPPP1) mRNA and downregulates TPPP1, thereby promoting the invasion and migration of EBV-related cancers, such as nasopharyngeal cancer and gastric cancer. The mechanism underlying this process was found to be the inhibition of TPPP1 by EBV-miRNA-BART12, which, in turn, inhibits the acetylation of α-tubulin, and promotes the dynamic assembly of microtubules, remodels the cytoskeleton, and enhances the acetylation of ß-catenin. ß-catenin activates epithelial to mesenchymal transition (EMT). These two processes synergistically promote the invasion and metastasis of tumor cells. To the best of our knowledge, this is the first study to reveal the role of EBV-miRNA-BART12 in the development of EBV-related tumors as well as the mechanism underlying this process, and suggests potential targets and strategies for the treatment of EBV-related tumors.
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Movimiento Celular/genética , Proteínas del Citoesqueleto/genética , Herpesvirus Humano 4/genética , MicroARNs/genética , Carcinoma Nasofaríngeo/virología , Neoplasias Gástricas/virología , Factores de Transcripción/genética , Regiones no Traducidas 3'/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo/genética , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/virología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Carcinoma Nasofaríngeo/genética , Polimerizacion , ARN Viral/genética , Neoplasias Gástricas/genética , beta Catenina/genéticaRESUMEN
Epstein-Barr virus (EBV) is a tumorigenic virus that can cause various human malignancies such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature micro (mi)RNAs, mostly exhibiting oncogenic properties and promoting cancer progression. However, we have previously found that one EBV-encoded miRNA, namely EBV-miR-BART6-3p, acts as a tumor suppressor by inhibiting metastasis and invasion. Here, we report that EBV-miR-BART6-3p inhibits the proliferation of EBV-associated cancers, NPC, and GC, by targeting and downregulating a long non-coding RNA (lncRNA), LOC553103. Through proteomics analysis, we determined that stathmin (STMN1) is affected by EBV-miR-BART6-3p and LOC553103. Further, via RNA immunoprecipitation and luciferase reporter assay, we confirmed that LOC553103 directly binds and stabilizes the 3'UTR region of STMN1 mRNA. These results indicate that the EBV-miR-BART6-3p/LOC553103/STMN1 axis regulates the expression of cell cycle-associated proteins, which then inhibit EBV-associated tumor cell proliferation. These findings provide potential targets or strategies for novel EBV-related cancer treatments, as well as contributes new insights into the understanding of EBV infection-related carcinogenesis.
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Proliferación Celular/genética , Infecciones por Virus de Epstein-Barr/genética , Herpesvirus Humano 4/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Estatmina/genética , Regiones no Traducidas 3'/genética , Animales , Carcinogénesis/genética , Línea Celular , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células HEK293 , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , ARN Viral/genética , Neoplasias Gástricas/genéticaRESUMEN
A nitrogen-centered radical-mediated carbon-carbon bond cleavage strategy is described to synthesize functionalized 3-acylcoumarins. The strategy is enabled by the visible-light-induced acylation/cyclization of alkynoates with various acyl oxime compounds in acetonitrile. The difunctionalization of carbon-carbon triple bonds precedes the generation of iminyl radicals, which is followed by the formation of acyl radicals. The acyl radicals then attack the carbon-carbon triple bonds, followed by 5-exo-trig cyclization and 1,2-ester migration. This strategy has wide substrate adaptability and good substituent tolerance.
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Non-coding RNAs do not encode proteins and regulate various oncological processes. They are also important potential cancer diagnostic and prognostic biomarkers. Bioinformatics and translation omics have begun to elucidate the roles and modes of action of the functional peptides encoded by ncRNA. Here, recent advances in long non-coding RNA (lncRNA) and circular RNA (circRNA)-encoded small peptides are compiled and synthesized. We introduce both the computational and analytical methods used to forecast prospective ncRNAs encoding oncologically functional oligopeptides. We also present numerous specific lncRNA and circRNA-encoded proteins and their cancer-promoting or cancer-inhibiting molecular mechanisms. This information may expedite the discovery, development, and optimization of novel and efficacious cancer diagnostic, therapeutic, and prognostic protein-based tools derived from non-coding RNAs. The role of ncRNA-encoding functional peptides has promising application perspectives and potential challenges in cancer research. The aim of this review is to provide a theoretical basis and relevant references, which may promote the discovery of more functional peptides encoded by ncRNAs, and further develop novel anticancer therapeutic targets, as well as diagnostic and prognostic cancer markers.
Asunto(s)
Terapia Molecular Dirigida , Neoplasias/terapia , Fragmentos de Péptidos/uso terapéutico , ARN Circular/genética , ARN Largo no Codificante/genética , Animales , Humanos , Neoplasias/genética , Neoplasias/metabolismoRESUMEN
BACKGROUND: Identification of effective diagnostic and prognostic biomarkers of cancer is necessary for improving precision medicine. Long non-coding RNAs (lncRNAs) play an important regulatory role in tumor initiation and progression. The lncRNA LOC284454 is distinctly expressed in various head and neck cancers (HNCs), as demonstrated by our previous bioinformatics analysis. However, the expression levels and functions of LOC284454 in cancer are still unclear. METHODS: We investigated the dysregulation of lncRNAs in HNCs using the GEO database and found that LOC284454 was highly expressed in HNCs. Serum samples from 212 patients with HNCs and 121 normal controls were included in this biomarker study. We measured the expression of LOC284454 in the sera of HNC patients and normal controls using RT-qPCR. Receiver operating characteristics (ROC) analysis is an important statistical method that is widely used in clinical diagnosis and disease screening. ROC was used to analyze the clinical value of LOC284454 in the early diagnosis of HNCs. RESULTS: LOC284454 was significantly upregulated in the sera of patients with nasopharyngeal carcinoma, oral cancer, and thyroid cancer. LOC284454 upregulation had good clinical diagnostic value in these cancers, as evaluated by area under the ROC curve values of 0.931, 0.698, and 0.834, respectively. CONCLUSIONS: LOC284454 may be a valuable serum biomarker for HNCs facilitating the early diagnosis of malignant cancers. Further studies are needed to elucidate the mechanisms underlying the involvement of LOC284454 in HNCs. This study provides the first evidence that LOC284454 may be a serum biomarker for HNCs.
Asunto(s)
Neoplasias de Cabeza y Cuello/genética , ARN Largo no Codificante/sangre , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Femenino , Neoplasias de Cabeza y Cuello/sangre , Humanos , Masculino , Neoplasias de la Boca/sangre , Neoplasias de la Boca/genética , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/genética , ARN Largo no Codificante/genética , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/genética , Regulación hacia ArribaRESUMEN
Nasopharyngeal carcinoma (NPC) is a unique malignant cancer with high metastasis. Because the early symptoms of NPC patients are not obvious, most patients have distant metastases when diagnosed, which makes treatment difficult. Long non-coding RNAs (lncRNAs) are emerging as important regulators in human carcinogenesis. LncRNAs have been increasingly identified but remain largely unknown in NPC. Therefore, we performed gene expression profiling to screen for altered expression of lncRNAs in NPC tissues and adjacent samples. One lncRNA, LOC284454, was upregulated and associated with poor prognosis in NPC. In in vivo and in vitro assays, LOC284454 promoted the migration and invasion capacity of NPC cells. Mass spectrometry combined with bioinformatics suggested that LOC284454 affected the cytoskeletal and adhesion-related Rho/Rac signaling pathways. LOC284454 may be a potential novel treatment target and is expected to be a new diagnostic and prognostic marker in patients with NPC.
Asunto(s)
Movimiento Celular/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Invasividad Neoplásica/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Largo no Codificante/genética , Transducción de Señal/genética , Animales , Carcinogénesis/genética , Línea Celular Tumoral , Biología Computacional/métodos , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Ratones , Ratones Desnudos , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Pronóstico , Regulación hacia Arriba/genéticaRESUMEN
Cancer is a complex disease, which may involve multiple tumor susceptibility genes that mediate the occurrence and development of tumor molecular events. This study aimed to identify new genetic loci using genome-wide linkage analysis and whole-exome sequencing in a rare, large multi-cancer pedigree recently found in China. We performed high-throughput single-nucleotide polymorphism (SNP) array and linkage analyses of 24 core members of this pedigree and found that the disease susceptibility locus in the multi-cancer pedigree was mapped to chromosome 3q24-26. We also used microsatellites to further validate the results of the SNP locus linkage analysis. Furthermore, we sequenced the whole exome of three members in this pedigree and identified a novel mutant of transforming growth factor ß stimulated clone 22 domain family, member 2 (TSC22D2, c.-91T-C) cosegregated with the cancer phenotype. This change was at a highly conserved position, and the exome results were validated using linkage analysis. Moreover, we found the histone H4 transcription factor (HINFP) binds to the promoter region of TSC22D2 and may regulate its transcription. In conclusion, our findings are of great significance to the early pathogenesis of tumors and contribute to the search for molecular targets for the early prevention and treatment of tumors.