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BACKGROUND: Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. METHODS: The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. RESULTS: Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (Pâ =â .013) and an increased expression of vimentin (Pâ =â .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (Pâ =â .026), positive lymph node metastasis (Pâ =â .010), osseous metastasis (Pâ =â .004), and Gleason score (Pâ =â .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (Pâ =â .002) than patients with a low level of PTHrP. CONCLUSION: The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.
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Caderinas , Proteína Relacionada ao Hormônio Paratireóideo , Neoplasias da Próstata , Vimentina , Humanos , Masculino , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Prognóstico , Idoso , Vimentina/metabolismo , Caderinas/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Antígeno Prostático Específico/sangue , Metástase LinfáticaRESUMO
Necrotizing fasciitis is a rare, severe, rapidly progressing disease with a high mortality rate. We report a case of a 72-year female with erythematous pemphigus who developed erythema, swelling and ulceration on right vulva, groin, and thigh. The early clinical manifestations of the patient were nonspecific and easily misdiagnosed as cellulitis. However, upon the occurrence of ulceration and necrosis, deep fungal infection, pyoderma gangrenosum or lymphoproliferative disorders were considered. The pathology suggested IgG4-related diseases, plasmacytoma et al. But at last, surgical exploration and postoperative pathology confirmed the diagnosis of necrotizing fasciitis. The patient recovered after multiple aggressive surgical debridement procedures and antibiotic therapy and the patient has been followed up for 2 years without recurrence. Clinicians should be vigilant about the possibility of necrotizing fasciitis in patients with erythema, pain, rapid ulceration of skin and soft tissue, particularly in immunocompromised individuals with long-term use of immunosuppressive agents. It is crucial for saving life by early multi-disciplinary consultation, prompt diagnosis, and aggressive treatment.
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The treatment strategy for nonsmall cell lung cancer (NSCLC) has always been a hot topic of concern, and its treatment strategies are also emerging. This experiment wants to know the effects of apolipoprotein C1 (APOC1) in immunotherapy of NSCLC. APOC1 mRNA and protein expression were upregulated in lung cancer tissue of patients with NSCLC. programmed cell death protein 1 (PD-1) mRNA expression was negatively correlated with PD-1 mRNA expression in patients. The survival rate of APOC1 high expression was lower than that of low expression in patients with NSCLC. APOC1 gene reduced the transformation of M2 into M1 macrophages (TMMM). APOC1 gene promoted cell growth, and the gene reduced ferroptosis of NSCLC. APOC1-induced nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (NRF2/HO-1) signaling pathway. Sh-APOC1 gene reduced cell growth in mice of NSCLC through the inhibition of NRF2/HO-1 signaling pathway. The inhibition of NRF2 reduced the TMMM by APOC1. The activation of NRF2 reduced the TMMM by si-APOC1. In conclusion, APOC1 reduced anti-PD-1 immunotherapy of NSCLC via the TMMM by ferroptosis by NRF2/HO-1, suggesting that targeting this mechanism of APOC1 may be a feasible strategy for anti-PD-1 immunotherapy for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Receptor de Morte Celular Programada 1 , Apolipoproteína C-I/metabolismo , Apolipoproteína C-I/farmacologia , Macrófagos , Heme Oxigenase-1/genética , RNA Mensageiro/metabolismo , ImunoterapiaRESUMO
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a well-known complex multicomponent disease characterized by systemic inflammation that frequently coexists with other conditions. We investigated the relationship between some inflammatory markers and complications in COPD patients to explore the possible roles of inflammation in these comorbidities. METHODS: This study used cross-sectional and case-control methods. We included 336 hospitalized COPD patients, 64 healthy controls, and 42 major depression patients and evaluated all participants using the Hamilton Rating Scale. C-reactive protein (CRP), red blood cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were collected and measured in the study population. Statistical methods were used to analyze the association of inflammatory markers with COPD comorbidities. RESULTS: Cor pulmonale and psychological comorbidities (depression and anxiety) were more common in this study on COPD patients. We found that MLR (OR = 2.054, 95 % CI 1.129-3.735, p = 0.018) and RDW (OR = 1.367, 95 % CI 1.178-1.586, p = 0.000) were related to COPD patients complicated with cor pulmonale, while IL-6 (OR = 1.026, 95 % CI 1.001-1.053, p = 0.045) and RDW (OR = 1.280, 95 % CI 1.055-1.552, p = 0.012) were related to depression symptoms. CONCLUSION: MLR, RDW and IL-6 were closely related to cor pulmonale and depression in COPD patients. IL-1 ß and IL-6 are closely related to depression in humans.
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Doença Pulmonar Obstrutiva Crônica , Doença Cardiopulmonar , Humanos , Citocinas , Interleucina-6 , Biomarcadores , Estudos Transversais , Linfócitos , Inflamação , Neutrófilos , Estudos RetrospectivosRESUMO
INTRODUCTION AND IMPORTANCE: Neurofibromatosis Type 1 (NF1) is a rare autosomal dominant genetic disorder that affects multiple organs and systems, including the nervous system, integumentary system, and connective tissues. Spontaneous hemothorax occurs infrequently in patients with NF1 and is associated with high fatality rates. However, it is commonly overlooked or misdiagnosed. CASE PRESENTATION: We present the case of a 29-year-old woman with NF1 who complained of chest pain and was detected with hemothorax on radiographic examination. No bleeding sites were identified following thrombectomy. The patient's condition deteriorated with conservative treatment over nine days, posing a potentially life-threatening risk. After a diagnostic evaluation using computerized tomography angiography (CTA) and digital subtraction angiography (DSA) of the neck vasculature, the patient was diagnosed with spontaneous rupture of the vertebral artery (VA) and subclavian artery (SuA) aneurysm. Following a multidisciplinary discussion and extensive investigations, the patient underwent successful endovascular treatment. A VIABAHN covered stent was implanted in the left SuA to overlay the emergent orifice. The endovascular treatment challenge due to the inaccessible of the proximal of left VA. To prevent retrograde flow into the VA aneurysm, the coils were used to embolize the left VA via the right vertebral artery-basilar artery (VA-BA) passage. The patient was alive at the 5-year follow-up without further complications. CLINICAL DISCUSSION: The CTA examination led to the diagnosis of vascular rupture due to NF1, and endovascular treatment was performed to occlude the vascular lumen. There have been no recurrences during the five-year follow-up period. CONCLUSION: Vasculopathy is the second leading cause of death in patients with NF1 after malignancy. Early diagnosis of spontaneous hemothorax in patients with NF1 is crucial, as misdiagnosis can result in missed treatment opportunities. CTA plays a vital role in preliminarily diagnosing the cause of spontaneous hemothorax, while endovascular treatment offers a new therapeutic option for such patients.
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The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.
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Colite Ulcerativa , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Interleucina-10 , Metabolômica/métodos , Cromatografia Líquida de Alta PressãoRESUMO
PURPOSE: This study was designed to investigate the association between fibulin-1(FBLN1) and thyroid-associated ophthalmopathy (TAO). METHOD: The plasma FBLN1 levels were measured in 80 participants, including 30 active TAO patients, 25 inactive TAO patients, and 25 Graves disease (GD) patients without TAO using enzyme-linked immunosorbent assay (ELISA). RESULTS: TAO patients had significantly higher TRAb level than GD patients (p < 0.05). The active TAO patients consumed more tobacco and had higher CAS than inactive TAO patients (all p < 0.05). No significant differences were found in age, sex, and the level of FT3, FT4, and TSH between TAO and GD patients, and between the active and inactive TAO patients (all p > 0.05). The plasma FBLN1 level in TAO patients was higher than that in GD patients, and that in active patients was higher than that in inactive patients (all p < 0.05). Furthermore, the plasma FBLN1 level showed strong association with clinical activity score (CAS) of TAO (r = 0.67, p < 0.01). By receiver operator characteristic (ROC) curve analysis, FBLN1 demonstrated good efficiency for predicting disease activity at the cut-off value > 625.33 pg/ml with a sensitivity of 93.3% and a specificity of 88.0% (AUC:0.92, p < 0.01). CONCLUSION: The plasma FBLN1 levels correlated with TAO activity and a value >625.33 pg/ml was associated with active disease. Our results suggest that the plasma FBLN1 level could be a novel biomarker for predicting disease activity of TAO.
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Oftalmopatia de Graves , Humanos , BiomarcadoresRESUMO
Background: Lactate has long been considered an intermediate by-product of glucose metabolism. However, in recent years, accumulating evidence reveals that lactate has unique biological activities. In previous studies, lactate signaling was shown to inhibit inflammation. Furthermore, in vitro experiments have shown that lactate can promote the transformation of pro-inflammatory macrophages into anti-inflammatory macrophages. However, no in vivo studies have shown whether lactate can alleviate inflammation. Methods: RAW 264.7 macrophages were stimulated by LPS to induce an M1 phenotype, and cultured with low and high concentrations of lactate. The cells were then observed for phenotypic transformations and expression of inflammatory mediators and surface markers. The expression of inflammatory factors was also analyzed in the cell-free supernatant fraction. Further, a mouse model of DSS-induced colitis was established and treated with lactate. Colonic tissue injury was monitored by histopathological examinations. Results: The in vitro experiments showed that lactate promoted the transformation of activated macrophages to M2 phenotype and decreased the expression of TLR4-mediated NF-κB signaling proteins and inflammatory factors. In the DSS-induced colitis mouse model, lactate promoted the phenotypic transformation of macrophages in colonic tissue, reduced inflammation and organ damage, inhibited the activation of TLR4/NF-κB signaling pathway, decreased the serum levels of pro-inflammatory factors, increased the expression of anti-inflammatory factors, promoted the repair of the intestinal mucosal barrier and reduced the severity of colitis. Conclusions: Lactate inhibits the TLR/NF-κB signaling pathway and the production of pro-inflammatory factors by promoting polarization of macrophages. In addition, lactate promotesthe repair of the intestinal mucosal barrier and protects intestinal tissue in inflammation. Furthermore, lactate is relatively safe. Therefore, lactate is a promising and effective drug for treating inflammation through immunometabolism regulation.
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Colite , NF-kappa B , Camundongos , Animais , Sulfato de Dextrana/toxicidade , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Ácido Láctico/metabolismo , Colite/patologia , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologia , Inflamação/metabolismo , Modelos Animais de DoençasRESUMO
DHCR7 is a rate-limiting enzyme in cholesterol synthesis. The expression pattern and prognostic value of DHCR7 in cervical cancer are unknown. We investigated the relationship between DHCR7 expression and clinicopathological features of cervical cancer patients. The dataset was acquired from TCGA database. The Wilcoxon rank sum test was used to explore DHCR7 expression level in cervical cancer. The Kruskal-Wallis test and the logistic regression were performed to estimate the association between the DHCR7 and clinical features. The Kaplan-Meier and Cox regression analyses were used to evaluate factors that affect cervical cancer prognosis. GSEA was used to screen the DHCR7-related pathways. We found that DHCR7 was increased in cervical cancer samples and increased DHCR7 was correlated with advanced T stage, lymph node invasion, and clinical stage (P < 0.05). Patients with elevated DHCR7 levels had poorer overall survival (P = 0.021), progression-free interval (P = 0.002), and disease-specific survival (P = 0.005). Cox analysis revealed that DHCR7 was an independent prognostic factor in cervical cancer (P = 0.005). WNT activated receptor activity, G2/M checkpoint, mTORC1 signaling, KRAS signaling, regulation of cholesterol biosynthetic, FGF signaling, T-cell receptor signaling, JAK/STAT signaling cascade T cell activation, and macrophage migration were enriched in high DHCR7 phenotype. Our data also showed that DHCR7 moderately correlates with T-cell infiltration, including CD8+ T-cells. Conclusion. Increased DHCR7 expression is associated with poor survival in cervical cancer.
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Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Neoplasias do Colo do Útero , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: Ocular hypertension (OHT) is an important clinical feature of thyroid-associated orbitopathy (TAO).While the prevalence and outcome of OHT in TAO remains unclear. This study investigates this in moderate-severe active TAO. METHODS: Sixty-eight patients with active moderate-severe TAO were recruited, 49 of whom were treated with 12-week GC therapy.The clinical and biochemical parameters were collected.Treatment outcomes were evaluated after GC therapy. RESULTS: The prevalence of OHT was 44.85% in moderate-severe active TAO patients,including 81.97% of mild hypertension, 13.11% of moderate hypertension and 4.92% of severe hypertension. Clinical and biochemical parameters had no significant difference between OHT patients and non-OHT patients,such as age, sex distributions, smoking status, the kind and the duration of thyroid disease,the duration of eye symptoms and the level of FT3,FT4,TSH, TR-Ab, and Tpo-Ab, Tg-Ab(all P > 0.05). After GC therapy,the intraocular pressure(IOP) in OHT eyes decreased significantly (P < 0.05), while IOP in non-OHT eyes remained unchanged (P > 0.05).There was no significant difference in CAS and the effective rate of GC therapy between OHT eyes and non-OHT eyes (P > 0.05). CONCLUSION: In moderate-severe active TAO, the prevalence of OHT was 44.85%, most of which were mild hypertension.OHT was relieved by GC therapy,which had no effect on the efficacy of GC therapy.Our results will enhance physicians' confidence in GC therapy.
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Oftalmopatia de Graves , Hipertensão , Hipertensão Ocular , Glucocorticoides/uso terapêutico , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/epidemiologia , TireotropinaRESUMO
Objective: To evaluate HIF2α polymorphisms and glucose metabolism in a group of women with polycystic ovary syndrome (PCOS) or unexplained infertility (UI). Patients: The infertile group (n=148) consisted of 96 women with PCOS, 52 women with UI, and176 women without infertility as a healthy control group. Intervention: We genotyped 29 single nucleotide polymorphisms (SNPs) of HIF2α by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based genotyping technology. The genetic associations were analyzed statistically. Main outcome measures: Allele frequency, genotype distribution and haplotype analyze of the HIF2α polymorphisms were performed. Body mass index (BMI), waist circumference, uric acid (UA), high-sensitivity C-reactive protein (hsCRP), lipids, glucose and insulin tolerance - were also measured. Results: Infertile women with PCOS had a higherBMI and waist circumference, elevated hsCRP and uric acid (UA) levels, impaired glucose tolerance, and increased levels of plasma insulin compared to UI patients and healthy women. SNP analysis of HIF2α revealed that the allele and genotype frequencies of rs4953361 were significantly associated with infertile women with PCOS. Haplotype analysis of the HIF2α polymorphism identified haplotypes TGG and TGA as being associated with infertile women with PCOS. Women with the AA genotype of rs4953361 had a significantly higher BMI and post load plasma glucose and insulin levels than those of women with the GG genotype. Conclusion: Infertile women with PCOS more commonly have metabolic disturbances than those with UI. This is the first study to report an association between HIF2α polymorphisms (rs4953361) and the risk of infertile women with PCOS, not UI, in Han Chinese population. These results require replication in larger populations.In this observational study, we did not report the results of a health care intervention on human participants. The study was approved by the Human Research Ethics Committee of the First Affiliated Hospital of Chongqing Medical University. Clinical data and peripheral blood samples were collected only after explaining the objectives of the study and obtaining a signed informed consent form.
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Infertilidade Feminina , Insulinas , Síndrome do Ovário Policístico , Glicemia/metabolismo , Proteína C-Reativa , Feminino , Humanos , Infertilidade Feminina/genética , Lipídeos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/genética , Ácido ÚricoRESUMO
Background: Oxidative stress, cholinergic deficiency, and neuroinflammation are hallmarks of most neurodegenerative disorders (NDs). Lipids play an important role in brain development and proper functioning. Marine-derived lipids have shown good memory-improving potentials, especially those from fish and microalgae. The cultivated macroalga Hizikia fusiforme is healthy food and shows benefits to memory, but the study is rare on the brain healthy value of its oil. Previously, we had reported that the Hizikia fusiforme functional oil (HFFO) contains arachidonic acid, 11,14,17-eicosatrienoic acid, phytol, and other molecules displaying in vitro acetylcholinesterase inhibitory and nitroxide scavenging activity; however, the in vivo effect remains unclear. In this study, we further investigated its potential effects against lipopolysaccharides (LPS)- or aluminum trichloride (AlCl3)-induced memory deficiency in zebrafish and its drug-related properties in silica. Methods: We established memory deficit models in zebrafish by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS) (75 ng) or aluminum trichloride (AlCl3) (21 µg), and assessed their behaviors in the T-maze test. The interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), acetylcholine (ACh), and malondialdehyde (MDA) levels were measured 24 h after the LPS/AlCl3 injection as markers of inflammation, cholinergic activity, and oxidative stress. Furthermore, the interaction of two main components, 11,14,17-eicosatrienoic acid and phytol, was investigated by molecular docking, with the important anti-inflammatory targets nuclear factor kappa B (NF-κB) and cyclooxygenase 2 (COX-2). Specifically, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of HFFO were studied by ADMETlab. Results: The results showed that HFFO reduced cognitive deficits in zebrafish T-maze induced by LPS/AlCl3. While the LPS/AlCl3 treatment increased MDA content, lowered ACh levels in the zebrafish brain, and elevated levels of central and peripheral proinflammatory cytokines, these effects were reversed by 100 mg/kg HFFO except for MDA. Moreover, 11,14,17-eicosatrienoic acid and phytol showed a good affinity with NF-κB, COX-2, and HFFO exhibited acceptable drug-likeness and ADMET profiles in general. Conclusion: Collectively, this study's findings suggest HFFO as a potent neuroprotectant, potentially valuable for the prevention of memory impairment caused by cholinergic deficiency and neuroinflammation.
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Because breast cancer cells such as MCF-7, exhibit vital and developmental signs by exosome secretion, diagnosing them in the blood can provide a good index of the presence of breast cancer. However, accurate and inexpensive detection of exosomes in clinical practice faces challenges. Therefore, in the presents study, an aptasensor based on CD63 aptameriron oxide-copper ion nanozymes (Fe3O4-Cu2+-NZs) was designed with the ability of the CD63 aptamer to interact with the exosome and the release of the Fe3O4-Cu2+-NZs for peroxidase-like activity on the tetramethylbenzidine (TMB). After fabrication of CD63 aptamer-Fe3O4-Cu2+-NZs based on hydrothermal method, their physicochemical properties were investigated with the SEM, TEM, DLS, Zeta, XRD and magnetization. To investigate the interaction of CD63 aptamer-Fe3O4-Cu2+-NZs with exosomes, the required exosomes were extracted from cultured MCF-7 cells. The performance of CD63 aptamer-Fe3O4-Cu2+-NZs on TMB degradation in the presence and absence of exosomes was investigated through UV-vis adsorption and ocular observations based on colour changes on laboratory and real samples. The results show that the absence of exosomes significantly inhibited the peroxidase-like activity of CD63 aptamer-Fe3O4-Cu2+-NZs due to the aptamer coating. Under optimal conditions, the designed CD63 aptamer-Fe3O4-Cu2+-NZs is capable of detecting exosomes in the range of 1.4 × 104-5.6 × 105 particles/µL with a detection limit of 5.91 × 10³ particles/µL. Also, this method showed a satisfactory outcome in detection of cancer cells in real samples. Overall, this colorimetric aptasensor can be used to diagnose breast cancer cells based on a simple and inexpensive approach.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Neoplasias da Mama , Exossomos , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Colorimetria/métodos , Exossomos/química , Exossomos/metabolismo , Feminino , Humanos , Peroxidases/análise , Peroxidases/metabolismoRESUMO
Objective: Programmed cell death protein-1 (PD-1) inhibitors are widely used for the treatment of hepatocellular carcinoma (HCC). Thyroid dysfunction is common in patients treated with this therapy, although the dynamic changes in thyroid function and sonographic features remain unclear. Methods: We analyzed 38 patients with HCC who received anti-PD-1 therapy at our hospital. Demographic, clinical, laboratory, and ultrasound data were extracted from electronic medical records. The grading of thyroid nodules was based on the American College of Radiology Thyroid Imaging Reporting and Data System classification. Statistical analyses were performed using GraphPad Prism 5.0. Results: Fifteen patients (40%) had hypothyroidism, among which six had hypothyroidism at baseline, three had overt hypothyroidism, and six had subclinical hypothyroidism after anti-PD1 therapy. The proportion of patients with euthyroid function and thyroid antibody positivity was significantly lower than that of patients with thyroid dysfunction (10% vs 39%, P < 0.05). Nine patients (24%) had irregular echo patterns on sonographic imaging, six of whom had irregular echo patterns present during the treatment, but only one had them persist until the end of treatment. At baseline, the classification of most thyroid nodules was grade 3, with a significant increase in grade 4A and 4B classifications during treatment, though most nodules remained grade 3 at the end of treatment. There were no significant differences in survival rates between the euthyroid and thyroid dysfunction groups. Conclusion: Anti-PD-1 therapy-induced thyroid dysfunction was accompanied by changes in thyroid function, antibodies, and ultrasonography. Therefore, in patients receiving anti-PD-1 therapy, close, dynamic monitoring of thyroid function, antibodies, and ultrasonographic characteristics is necessary.
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BACKGROUND: Tea trees originated in southwest China 60 million or 70 million years ago. Written records show that Chinese ancestors had begun drinking tea over 3000 years ago. Nowadays, with the aging of populations worldwide and more people suffering from non-communicable diseases or poor health, tea beverages have become an inexpensive and fine complementary and alternative medicine (CAM) therapy. At present, there are 3 billion people who like to drink tea in the world, but few of them actually understand tea, especially on its development process and the spiritual and cultural connotations. METHODS: We searched PubMed, Google Scholar, Web of Science, CNKI, and other relevant platforms with the key word "tea", and reviewed and analyzed tea-related literatures and pictures in the past 40 years about tea's history, culture, customs, experimental studies, and markets. RESULTS: China is the hometown of tea, tea trees, tea drinking, and tea culture. China has the oldest wild and planted tea trees in the world, fossil of a tea leaf from 35,400,000 years ago, and abundant tea-related literatures and art works. Moreover, tea may be the first Chinese herbal medicine (CHM) used by Chinese people in ancient times. Tea drinking has many benefits to our physical health via its antioxidant, anti-inflammatory, immuno-regulatory, anticancer, cardiovascular-protective, anti-diabetic, and anti-obesity activities. At the moment, COVID-19 is wreaking havoc across the globe and causing severe damages to people's health and lives. Tea has anti-COVID-19 functions via the enhancement of the innate immune response and inhibition of viral growth. Besides, drinking tea can allow people to acquire a peaceful, relaxed, refreshed and cheerful enjoyment, and even longevity. According to the meridian theory of traditional Chinese medicine, different kinds of tea can activate different meridian systems in the human body. At present, black tea (fermented tea) and green tea (non-fermented tea) are the most popular in the world. Black tea accounts for over 90% of all teas sold in western countries. The world's top-grade black teas include Qi Men black in China, Darjeeling and Assam black tea in India, and Uva black tea in Sri Lanka. However, all top ten famous green teas in the world are produced in China, and Xi Hu Long Jing tea is the most famous among all green teas. More than 700 different kinds of components and 27 mineral elements can be found in tea. Tea polyphenols and theaflavin/thearubigins are considered to be the major bioactive components of black tea and green tea, respectively. Overly strong or overheated tea liquid should be avoided when drinking tea. CONCLUSIONS: Today, CAM provides an array of treatment modalities for the health promotion in both developed and developing countries all over the world. Tea drinking, a simple herb-based CAM therapy, has become a popular man-made non-alcoholic beverage widely consumed worldwide, and it can improve the growth of economy as well. Tea can improve our physical and mental health and promote the harmonious development of society through its chemical and cultural elements.
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Aberrant M1/M2 macrophage polarization and dysbiosis are involved in the pathogenesis of ulcerative colitis (UC). Ginsenoside Rg1 exhibits optimal immunomodulatory and anti-inflammatory effects in treating UC of humans and animals, but the action mechanism through the regulation of M1/M2 macrophage polarization and intestinal flora composition remain unclear. Here, experimental colitis was induced in BALB/c mice using dextran sulfate sodium, and Rock1 inhibitor Y27632 was used to explore the action mechanism of ginsenoside Rg1. Following treatment with ginsenoside Rg1 (200 mg/kg/day) and Y27632 (10 mg/kg/day) for 14 consecutive days, the rate of change in mouse body weight, mouse final weight, colonic weight, colonic length, colonic weight index and pathological damage scores of colitis mice were effectively improved, accompanied by less ulcer formation and inflammatory cell infiltration, lower levels of interleukin (IL)-6, IL-33, chemokine (C-C motif) ligand 2 (CCL-2), tumor necrosis factor alpha (TNF-α), and higher IL-4 and IL-10. Importantly, ginsenoside Rg1 and Y27632 significantly down-regulated CD11b+F4/80+, CD11b+F4/80+Tim-1+ and CD11b+F4/80+TLR4+ macrophages, and CD11b+F4/80+iNOS+ M1 macrophages, and significantly up-regulated CD11b+F4/80+CD206+ and CD11b+F4/80+CD163+ M2 macrophages in colitis mice; concomitantly, ginsenoside Rg1 improved the diversity of colonic microbiota and regulated Lachnospiraceae, Staphylococcus, Bacteroide and Ruminococcaceae_UCG_014 at genus level in colitis mice, but the flora regulated by Y27632 was not identical to it. Moreover, ginsenoside Rg1 and Y27632 down-regulated the protein levels of Rock1, RhoA and Nogo-B in colitis mice. These results suggested that ginsenoside Rg1 and Y27632 ameliorated colitis by regulating M1/M2 macrophage polarization and microbiota composition, associated with inhibition of the Nogo-B/RhoA signaling pathway.
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GinsenosídeosRESUMO
Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.
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Ácido Láctico , Neoplasias , Humanos , Inflamação , Ácido Láctico/metabolismo , Ativação de Macrófagos , Macrófagos , Neoplasias/metabolismo , Transdução de SinaisRESUMO
BACKGROUND AND AIMS: Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) also has been reported to be highly activated in HCC. In this study, we aimed to explore the role of AR phosphorylation and its relationship with mTORC1 in hepatocarcinogenesis. APPROACH AND RESULTS: In vitro experiment, we observed that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization, and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen. Furthermore, high ARS96 phosphorylation is observed in human liver steatotic and HCC tissues and is associated with overall survival and disease-free survival, which has been proven as an independent survival predictor for patients with HCC. CONCLUSIONS: AR S96 phosphorylation by mTORC1 drives liver steatosis and HCC development and progression independently and cooperatively with androgen, which not only explains why HCC is man-biased but also provides a target molecule for prevention and treatment of HCC and a potential survival predictor in patients with HCC.
Assuntos
Carcinoma Hepatocelular , Fígado Gorduroso , Neoplasias Hepáticas , Androgênios , Animais , Carcinogênese , Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica , Humanos , Neoplasias Hepáticas/patologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Fosforilação , Receptores Androgênicos/metabolismoRESUMO
Objective: Both primary thyroid lymphoma (PTL) and diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) are two rare malignant tumours with different therapies and prognoses. This study compared their clinical features. Methods: From a retrospective review of the pathologic database at our institute between January 2015 and August 2020, 52 PTL patients and 40 DSVPTC patients were included. Demographic, clinical, laboratory and ultrasound data were extracted from electronic medical records. Statistical analyses were performed using GraphPad Prism 5.0. Results: Both PTL and DSVPTC were more likely to occur in women (83.7 and 67.5%, respectively), but DSVPTC patients were younger (median age: 36 vs 64.5), had fewer compressive symptoms, and more frequently had neck lymph node metastasis than PTL patients. The prevalence of Hashimoto's thyroiditis (HT) and hypothyroidism was significantly higher in PTL patients than in DSVPTC patients (31% vs 17.5%). Hyperthyroidism could only be found in DSVPTC patients, which accounted for 7.5%. Heterogeneous echogenicity and irregular edges were frequently observed in both PTL and DSVPTC. However, compared with PTL, DSVPTC exhibited smaller lesion sizes, higher frequencies of diffuse sonographic patterns and calcification and lower frequencies of hypoechoic features and internal blood flow signal. The overall survival rate with PTL was 77.23%, which was lower than that with DSVPTC (90.91%), but this difference was not significant (P = 0.096). Conclusion: Clinical characteristics such as age, compression symptoms, and sonographic features such as a large mass with heterogeneous echogenicity, hypoechoic, irregular edges, and calcification are helpful for impression diagnosis of PTL and DSVPTC before surgery.
RESUMO
Inflammatory bowel disease (IBD) is typically characterized by the dysregulation of Tfh cell differentiation. we sought to explore the potential mechanism of Ginsenoside Rg1 (G-Rg1) treated IBD by observing the level of the Tfh/Treg cells and the activation of PI3K/Akt signaling pathway in the colitis mice. In the present study, G-Rg1 significantly inhibited the inflammatory response to mice colitis induced by dextran sodium sulfate (DSS), as evidenced by increased body weight and colon length, decreased colon weight, reduced colon weight index and histopathological scores, lower levels of IL-6 and TNF-α, and increased IL-10 levels. Significantly, G-Rg1 effectively decreased the amounts of CD4+CXCR5+IL-9+(Tfh9), CD4+ CXCR5+IL-17+(Tfh17), and increased CD4+CXCR5+Foxp3+(Tfr) and CD4+CD25+ Foxp3+(Treg) cells. Furthermore, G-Rg1 markedly down-regulated PI3K and p-Akt level, and upregulated PTEN expression. These results indicated that G-Rg1 could effectively regulate the balance of Tfh/Treg cells to relieve experimental colitis, which could be potentially related to PI3K/Akt signaling pathway inhibition.