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BACKGROUND: Nasal and paranasal sinus abnormalities may be related to nasolacrimal duct obstructive disease but are strongly debated. Data of acute disease stage are lacking. OBJECTIVE: The purpose of this study was to determine if there are correlations between radiologic signs of sinus inflammation and acute dacryocystitis (AD). METHODS: This cross-sectional controlled study was conducted at Wenzhou, Zhejiang Province, China from February 2021 to November 2023. Forty-four consecutive patients with AD and 50 consecutive patients with orbital tumors (the control group), who completed preoperative computed tomography scans, were enrolled to evaluate the extent of their inflammatory sinonasal disease by the modified Lund-Mackay score system. RESULTS: The inflammation signs of the paranasal sinuses (total mean sinus scores, 95% CI [0.00, 2.00]; P < 0.001), namely the anterior ethmoid sinus(95% CI [0.00, 1.00]; P < 0.001), the posterior ethmoid sinus(95% CI [0.00, 0.00]; P = 0.003), the frontal sinus (95% CI [0.00, 0.00]; P = 0.02), and the ostiomeatal complex (P < 0.001) were more extensive in patients with AD when compared with the controls. The disease course was negatively correlated with the anterior ethmoid (P = 0.03) and frontal scores (P = 0.01). The symptom of eyelid swelling was positively correlated with the anterior ethmoid (P = 0.03), ostiomeatal complex (P = 0.004), and total sinus scores (P = 0.005). CONCLUSION: Inflammatory sinus disease was found to be more frequent in patients with AD, which was gradually alleviated with the prolongation of the disease course. The mutual spread of inflammation particularly in the acute course may play an important role in lacrimal duct obstructive disease.
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Optic nerve injuries are severely disrupt the structural and functional integrity of the retina, often leading to visual impairment or blindness. Despite the profound impact of these injuries, the molecular mechanisms involved remain poorly understood. In this study, we performed a comprehensive whole-transcriptome analysis of mouse retina samples after optic nerve crush (ONC) to elucidate changes in gene expression and regulatory networks. Transcriptome analysis revealed a variety of molecular alterations, including 256 mRNAs, 530 lncRNAs, and 37 miRNAs, associated with metabolic, inflammatory, signaling, and biosynthetic pathways in the injured retina. The integrated analysis of co-expression and protein-protein interactions identified an active interconnected module comprising 5 co-expressed proteins (Fga, Serpina1a, Hpd, Slc38a4, and Ahsg) associated with the complement and coagulation cascades. Finally, 5 mRNAs (Fga, Serpinala, Hpd, Slc38a4, and Ahsg), 2 miRNAs (miR-671-5p and miR-3057-5p), and 6 lncRNAs (MSTRG. 1830.1, Gm10814, A530013C23Rik, Gm40634, MSTRG.9514.1, A330023F24Rik) were identified by qPCR in the injured retina, and some of them were validated as critical components of a ceRNA network active in 661W and HEK293T cells through dual-luciferase reporter assays. In conclusion, our study provides comprehensive insight into the complex and dynamic biological mechanisms involved in retinal injury responses and highlights promising potential targets to enhance neuroprotection and restore vision.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Ratones Endogámicos C57BL , Traumatismos del Nervio Óptico , ARN Mensajero , Retina , Animales , Ratones , Traumatismos del Nervio Óptico/metabolismo , Traumatismos del Nervio Óptico/genética , Retina/metabolismo , ARN Mensajero/genética , Modelos Animales de Enfermedad , Transcriptoma , MicroARNs/genética , Regulación de la Expresión Génica/fisiología , Masculino , Humanos , ARN Largo no Codificante/genéticaRESUMEN
Background: Both high-fat diet (HFD) and 4-nonylphenol (4-NP) could affect fat formation in adipose tissue individually. We investigated whether HFD promote abnormal adipose tissue formation caused by early exposure to 4-NP in life and preliminarily explore the possible mechanisms involved. Methods: The first-generation rats were treated with HFD on postnatal day after pregnant rats exposure to 5 ug/kg/day 4-NP. Then, the second generation rats started to only receive normal diet without 4-NP or HFD. We analyzed organ coefficient and histopathology of fat tissues, biochemical index, and gene level involved in lipid metabolism in female offspring rats. Results: HFD and 4-NP interaction synergistically increased birth weight, body weight, and organ coefficients of adipose tissue in offspring female rats. HFD accelerately aggravated abnormal lipid metabolism and increased the adipocyte mean areas around the uterus of the offspring female rats induced by prenatal exposure to 4-NP. HFD also facilitate the regulation of gene expression involved lipid metabolism in offspring female rats induced by perinatal exposure to 4-NP, even passed on to the second generation of female rats. Moreover, HFD and 4-NP interaction synergistically declined the gene and protein expression of estrogen receptor (ER) in the adipose tissue of second-generation female rats. Conclusion: HFD and 4-NP synergistically regulate the expression of lipid metabolism genes in adipose tissue of F2 female rats and promote adipose tissue generation, leading to obesity in offspring rats, which is closely related to low expression of ER. Therefore, ER genes and proteins may be involved in the synergistic effect of HFD and 4-NP.
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Adipogénesis , Efectos Tardíos de la Exposición Prenatal , Embarazo , Ratas , Animales , Femenino , Humanos , Dieta Alta en Grasa/efectos adversos , Tejido Adiposo/metabolismo , Fenoles/farmacología , Efectos Tardíos de la Exposición Prenatal/metabolismoRESUMEN
BACKGROUND: Low dose of NP exposure can alter adipose tissue formation, and the intake of high-fat diet (HFD) can also lead to the fatty liver disease. We investigated the combined effect of NP and HFD on the first offspring of rats, and whether this effect can be passed to the next generation and the possible mechanisms involved. METHODS: Pregnant rats had access to be treated with 5 µg/kg/day NP and normal diet. The first generation rats were given normal diet and HFD on postnatal day 21, respectively. Then the second generation rats started to only receive normal diet without NP or HFD. Body weight, organ coefficient of liver tissues, lipid profile, biochemical indexes and the expression of genes involved in lipid metabolism, as well as liver histopathology were investigated in male offspring of rats. RESULTS: NP and HFD interaction had significant effect on the birth weight, body weight and liver tissue organ coefficient of first generation male rats. And HFD aggravated abnormal lipid metabolism, even abnormal liver function and liver histopathological damage of first generation male rats produced by the NP. And this effect can be passed on to the second generation rats. HFD also accelerated the mRNA level of fatty acid synthesis genes such as Lpl, Fas, Srebp-1 and Ppar-γ of first generation rats induced by perinatal exposure to NP, even passed on to the second generation of male rats. NP and HFD resulted in synergistical decrease of the protein expression level of ERα in liver tissue in F2 male rats. CONCLUSION: HFD and NP synergistically accelerated synthesis of fatty acids in liver of male offspring rats through reducing the expression of ERα, which induced abnormal lipid metabolism, abnormal liver function and hepatic steatosis. Moreover, all of these damage passed on to the next generation rats.
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Dieta Alta en Grasa , Disruptores Endocrinos/toxicidad , Ácidos Grasos/metabolismo , Hígado/efectos de los fármacos , Fenoles/toxicidad , Efectos Tardíos de la Exposición Prenatal , Animales , Disruptores Endocrinos/sangre , Receptor alfa de Estrógeno/metabolismo , Acido Graso Sintasa Tipo I/genética , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Lipoproteína Lipasa/genética , Hígado/metabolismo , Hígado/patología , Masculino , Intercambio Materno-Fetal , PPAR gamma/genética , Fenoles/sangre , Embarazo , Ratas Wistar , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
Adaptation of hepatitis C virus (HCV) to CD8+ T cell selection pressure is well described; however, it is unclear if HCV differentially adapts in different populations. Here, we studied HLA class I-associated viral sequence polymorphisms in HCV 1b isolates in a Chinese population and compared viral substitution patterns between Chinese and German populations. We identified three HLA class I-restricted epitopes in HCV NS3 with statistical support for selection pressure and found evidence for differential escape pathways between isolates from China and Germany depending on the HLA class I molecule. The substitution patterns particularly differed in the epitope VTLTHPITK1635-1643 , which was presented by HLA-A*03 as well as HLA-A*11, two alleles with highly different frequencies in the two populations. In Germany, a substitution in position seven of the epitope was the most frequent substitution in the presence of HLA-A*03, functionally associated with immune escape and nearly absent in Chinese isolates. In contrast, the most frequent substitution in China was located at position two of the epitope and became the predominant consensus residue. Moreover, substitutions in position one of the epitope were significantly enriched in HLA-A*11-positive individuals in China and associated with different patterns of CD8+ T cell reactivity. Our study confirms the differential escape pathways selected by HCV that depended on different HLA class I alleles in Chinese and German populations, indicating that HCV differentially adapts to distinct HLA class I alleles in these populations. This result has important implications for vaccine design against highly variable and globally distributed pathogens, which may require matching antigen sequences to geographic regions for T cell-based vaccine strategies.
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Presentación de Antígeno , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/genética , Antígenos HLA-A/inmunología , Hepacivirus/genética , Proteínas no Estructurales Virales/genética , Alelos , China , Epítopos de Linfocito T/inmunología , Alemania , Antígenos HLA-A/genética , Antígeno HLA-A11/genética , Antígeno HLA-A11/inmunología , Antígeno HLA-A3/genética , Antígeno HLA-A3/inmunología , Hepacivirus/inmunología , Hepatitis C/etnología , Hepatitis C/inmunología , Humanos , Evasión Inmune , Mutación , Selección Genética , Proteínas no Estructurales Virales/inmunologíaRESUMEN
UNLABELLED: CD8+ T cells are an essential component of successful adaptive immune responses against hepatitis C virus (HCV). A major obstacle to vaccine design against HCV is its inherent viral sequence diversity. Here, we test the hypothesis that different sequence variants of an immunodominant CD8+ T cell epitope, all binding with high affinity to HLA class I, target different T cell receptor repertoires and thereby influence the quality of the CD8+ T cell response. The impacts of sequence differences in the HLA-A*02-restricted HCV NS31406-1415 epitope on in vitro priming of naive CD8+ T cells from seronegative donors and cross-reactivity of primed T cells with other epitope variants were characterized. Although the six epitope variants tested were all high-affinity binders to HLA-A*02:01, substantial differences in priming and cross-reactivity of CD8+ T cells were observed. The variant associated with the most reproducible priming and induction of T cells with broad cross-reactivity was a genotype 1b variant (KLSALGLNAV) that is more common in HCV isolates collected in Asia but is rare in sequences from Europe and North America. The superior immunogenicity and cross-reactivity of this relatively rare epitope variant were confirmed by using HCV-specific memory CD8+ T cells from people who inject drugs, who are frequently exposed to HCV. Collectively, the data suggest that sequence differences at the epitope level between HCV isolates substantially impact CD8+ T cell priming and the degree of cross-reactivity with other epitope variants. IMPORTANCE: The results have important implications for vaccine design against highly variable pathogens and suggest that evidence-based selection of the vaccine antigen sequence may improve immunogenicity and T cell cross-reactivity. Cross-reactive CD8+ T cells are likely beneficial for immune control of transmitted viruses carrying epitope variants and for prevention of immune escape during acute infection. To this end, rare epitope variants and potentially even altered epitope sequences associated with priming of broadly cross-reactive T cell receptors should be considered for vaccine design and need further testing.
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Antígenos Virales/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , Antígeno HLA-A2/inmunología , Hepacivirus/inmunología , Secuencia de Aminoácidos , Antígenos Virales/química , Antígenos Virales/genética , Linfocitos T CD8-positivos/virología , Células Cultivadas , Reacciones Cruzadas , Epítopos de Linfocito T/genética , Expresión Génica , Variación Genética , Antígeno HLA-A2/genética , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/virología , Humanos , Inmunidad Celular , Activación de Linfocitos , Datos de Secuencia Molecular , Unión Proteica , Abuso de Sustancias por Vía Intravenosa/inmunología , Abuso de Sustancias por Vía Intravenosa/virología , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunologíaRESUMEN
Phosphatidylinositide 3-kinase (PI3K)/protein kinase B (PKB, Akt) pathway plays a major role in proliferation and survival of many types of cells. The inhibitory effect of LY294002, widely applied as an inhibitor of PI3K, in combination with gemcitabine on proliferation of PANC-1 cells was investigated. The expression of PI3K, phosphorylated Akt (p-Akt) and multidrug-resistance like protein (MRP) in normal pancreas tissues, chronic pancreatitis tissues and pancreatic carcinoma tissues was detected. The effects of LY294002 combined with gemcitabine on proliferation of PANC-1 cells and protein levels of p-Akt and MRP were detected. The results showed that the positive expression rate of PI3K, p-Akt and MRP in pancreatic carcinoma tissues was significantly higher than that in normal pancreas tissues and chronic pancreatitis tissues (P<0.01 and P<0.05 respectively). LY294002 could effectively enhance the inhibitory effect of gemcitabine on proliferation of PANC-1 cells. Furthermore, Western blotting revealed that LY294002 combined with gemcitabine reduced the protein levels of p-Akt and MRP, which contributed to the inhibition of proliferation. It is concluded that LY294002 in combination with gemcitabine may represent an alternative therapy for pancreatic carcinoma.
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Cromonas/administración & dosificación , Desoxicitidina/análogos & derivados , Morfolinas/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Adulto , Antimetabolitos Antineoplásicos/administración & dosificación , Proliferación Celular/efectos de los fármacos , Desoxicitidina/administración & dosificación , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Inhibidores Enzimáticos/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Células Tumorales Cultivadas , GemcitabinaRESUMEN
This study examined the expression of cell adhesion molecule 1 (CADM1) in pancreatic cancer and the possible mechanism. The expression of CADM1 was detected by immunohistochemistry in tissues of pancreatic cancer, pancreatitis, and normal pancreas. The plasmid pcDNA3.1-Hygro(+)/CADM1 was transfected into PANC-1 cells (a pancreatic cancer cell line). The expression of CADM1 in the transfected cells was determined by RT-PCR and Western blotting. Cell growth was measured by the MTT method and cell apoptosis by flow cytometry. The results showed that CADM1 was weakly expressed in tissues of pancreatic cancer in contrast to its high expression in normal pancreatic and pancreatitis tissues. The expression level of CADM in pancreatic caner was intensely correlated with the differentiation degree, lymph node metastasis and TNM stages. The growth of CADM1-transfected PANC-1 cells was significantly suppressed in vitro by a G1 cell cycle arrest and apoptosis occurrence. It was concluded that re-expression of CADM1 inhibits the growth of pancreatic cancer cells and induces their apoptosis in vitro. As a tumor suppressor gene, CADM1 plays an important role in the occurrence, progression and metastasis of pancreatic cancer.
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Apoptosis , Moléculas de Adhesión Celular/metabolismo , Inmunoglobulinas/metabolismo , Neoplasias Pancreáticas/patología , Proteínas Supresoras de Tumor/metabolismo , Adolescente , Adulto , Anciano , Molécula 1 de Adhesión Celular , Moléculas de Adhesión Celular/genética , Puntos de Control del Ciclo Celular , Proliferación Celular , Femenino , Humanos , Inmunoglobulinas/genética , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugía , Transfección , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor/genética , Adulto JovenRESUMEN
This study examined the expression of cell adhesion molecule 1 (CADM1) in pancreatic cancer and the possible mechanism.The expression of CADM1 was detected by immunohistochemistry in tissues of pancreatic cancer,pancreatitis,and normal pancreas.The plasmid pcDNA3.1-Hygro(+)/CADM1 was transfected into PANC-1 cells (a pancreatic cancer cell line).The expression of CADM1 in the transfected cells was determined by RT-PCR and Western blotting.Cell growth was measured by the MTT method and cell apoptosis by flow cytometry.The results showed that CADM1was weakly expressed in tissues of pancreatic cancer in contrast to its high expression in normal pancreatic and pancreatitis tissues.The expression level of CADM in pancreatic caner was intensely correlated with the differentiation degree,lymph node metastasis and TNM stages. The growth of CADM1-transfected PANC-1 cells was significantly suppressed in vitro by a G1 cell cycle arrest and apoptosis occurrence.It was concluded that re-expression of CADM1 inhibits the growth of pancreatic cancer cells and induces their apoptosis in vitro.As a tumor suppressor gene,CADM1 plays an important role in the occurrence,progression and metastasis of pancreatic cancer.