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BACKGROUND: Hypophosphatemia is mainly characterized by hypophosphatemia and a low level of 1alpha,25-Dihydroxyvitamin D2 (1,25-(OH)2 D2) and/or 1alpha,25-Dihydroxyvitamin D3 (1,25-(OH)2 D3) in the blood. Previous studies have demonstrated that variants in PHEX and FGF23 are primarily responsible for this disease. Although patients with variants of these two genes share almost the same symptoms, they exhibit the different hereditary pattern, X-link dominant and autosome dominant, respectively. Three-dimensional (3D) printing is a method which can accurately reconstruct physical objects, and its applications in orthopedics can contribute to realizing a more accurate surgical performance and a better outcome. METHODS: An X-linked hypophosphatemia (XLH) family was recruited, with four patients across three generations. We screened candidate genes and filtered a duplication variant in PHEX. Variant analysis and co-segregation confirmation were then performed. Before the operation of our patient, a digital model of our patient's leg had been rebuilt upon the CT scan data, and a polylactic acid (PLA) model had been 3D-printed. RESULTS: A novel duplication PHEX variant c.574dupG (p.A192GfsX20) was identified in a family with XLH. Its pathogenicity was confirmed by the co-segregation assay and online bioinformatics database. The preoperative plan was made with the help of the PLA model. Then, arch osteotomy and transverse osteotomy were performed under the guidance of the previous simulation. The appearance of the surgical-intervened leg was satisfactory. CONCLUSIONS: This study identified a novel PHEX variant and showed that 3D printing tech is a very promising approach for corrective osteotomies.
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Raquitismo Hipofosfatêmico Familiar , Hipofosfatemia , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/cirurgia , Testes Genéticos , Humanos , Hipofosfatemia/genética , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Impressão TridimensionalRESUMO
In Expt 1, a Zn-unsupplemented basal diet (control) and the basal diet supplemented with one of four different Zn sources, including ZnSO4, Zn-amino acid chelate with a weak chelation strength (Zn-AA W), Zn-protein chelate with a moderate chelation strength (Zn-Pro M) and Zn-protein chelate with a strong chelation strength (Zn-Pro S) were fed to broiler chickens from days 14 to 28. On day 28, Zn content in plasma from the hepatic portal vein increased (P0·05) and Zn-AA W(P<0·04) were higher than those for ZnSO4. These findings indicate that organic Zn absorption (especially Zn-Pro S) in intact living broilers was more effective than that of inorganic Zn; organic Zn absorption in the ligated duodenal segment was a saturable carrier-mediated process similar to that of ZnSO4. Moreover, except for MT, there might be other Zn transporters involved in Zn absorption that are affected by different Zn sources.
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Galinhas/metabolismo , Absorção Intestinal/efeitos dos fármacos , Zinco/metabolismo , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Absorção Intestinal/fisiologia , Intestino Delgado/metabolismo , Cinética , Metalotioneína/genética , Metalotioneína/metabolismo , Fenolsulfonaftaleína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Zinco/química , Zinco/farmacologiaRESUMO
To investigate the effect of Mn on antioxidant status and on the expressions of heat shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21±1°C, and high, 32±1°C)×3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in any of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease Cu Zn superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased Mn superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase in malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expressions of heat shock factor 1 (HSF1) and HSF3 mRNA and heat shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels compared with those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70, HSF1 and HSF3 expressions in the tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance the heart's antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.
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Proteínas Aviárias/metabolismo , Galinhas/fisiologia , Proteínas de Ligação a DNA/metabolismo , Dieta/veterinária , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico , Manganês/administração & dosagem , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Animais , Proteínas Aviárias/genética , Biomarcadores/metabolismo , Quelantes/administração & dosagem , Galinhas/crescimento & desenvolvimento , China , Proteínas de Ligação a DNA/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Choque Térmico HSP70/genética , Ventrículos do Coração/enzimologia , Ventrículos do Coração/crescimento & desenvolvimento , Ventrículos do Coração/metabolismo , Fatores de Transcrição de Choque Térmico , Proteínas de Choque Térmico/genética , Absorção Intestinal , Fígado/enzimologia , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Manganês/metabolismo , Compostos de Manganês/administração & dosagem , Músculo Esquelético/enzimologia , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Sulfatos/administração & dosagem , Transativadores/genética , Fatores de Transcrição/genéticaRESUMO
To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.
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Antioxidantes/metabolismo , Dieta , Proteínas de Choque Térmico/metabolismo , Temperatura Alta , Manganês/administração & dosagem , Temperatura , Animais , Galinhas , Feminino , Proteínas de Choque Térmico/genética , Fígado/enzimologia , Malondialdeído/metabolismo , Manganês/farmacocinética , Miocárdio/enzimologia , RNA/metabolismo , Superóxido Dismutase/metabolismo , Distribuição TecidualRESUMO
The content characteristics, pollution evaluation and source identification of 6 heavy Metals (Cd, Pb, Cr, As, Cu and Zn) in filtered water and 9 heavy Metals (Cd, Pb, Cr, Ni, Cu, V, Co, Zn and Mn) in suspended particles from 10 sampling sites such as Zhaojunfuqiao (S1) and Baotoufuqiao (S2), etc. from Gansu, Ningxia and Inner Mongolia sections of the Yellow River in 2012 Wet Season were studied to understand the condition of the heavy metal pollution in Gansu, Ningxia and Inner Mongolia Sections of the Yellow River by using high resolution inductively coupled plasma-mass spectrometry (HR-ICP-MS). Multivariate geochemical approaches and statistical analysis were also exploited for assessing the level of heavy metals in filtered water and suspended particles from studied area. The results showed that in filtering water, only the concentrations of Cr exceeded the standard value of Environmental Quality Standard for Surface Water (GB3838-2002) and were the highest (74.8-94.7 µg x L(-1)) among all elements in 10 sampling sites; Single factor pollution index (I(i)) results suggested that the water quality in all sampling sites were contaminated by both Cr and total nitrogen (TN), with the exception of TN in Baotoufuqiao (S2); Integrated Nemerow pollution index (I) indicated that the I values in all sampling sites were between 1-2 (light pollution), which implied that the water quality in Gansu, Ningxia and Inner Mongolia sections, especially downstream sections (S1-S6) of the Yellow River wasn't an ideal source for drinking and using in aquaculture any more. In suspended particles, concentrations of heavy metals were relatively higher than their soil background values in 10 sampling sites, except Ni in S10 (34.7 µg x L(-1)). Index of geo-accumulation (I(geo)) indicated that the I(geo) values of Pb, Cr, Ni, Cu, V, Co, Zn and Mn in all sampling sites were less than 1 (unpolluted or unpolluted-moderately polluted), respectively, while I(geo)Cd were the highest in 10 sampling sites among all heavy metals and with the moderately to strong contamination in Zhaojunfuqiao (S1), Baotoufuqiao (S2), Wuhai (S5) and Dongdagouruhuanghekou (S8). The results of this paper would help to supply reliable experimental data for researching of distribution, migration and effective protection of heavy metals in study area.
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So far, many investigations had been made on the concentration and species distribution of heavy metals in aquatic environments. However, there are only a few studies on heavy metals in upper reaches of the Yellow River, especially in Gansu, Ningxia and Inner Mongolia sections. We have literatures related to the Yellow River, in this work, we remarkably discussed about the contents, speciation and potential risks of Cd, Pb, Cr, V, Co, Ni, Cu, and Zn in surface sediments from 12 sampling sites in Gansu, Ningxia, and Inner Mongolia sections of the Yellow River of China in 2011 year wet season by high resolution inductively coupled plasma mass spectrometer (HR-ICP-MS) and sequential extraction procedure of BCR method. The results indicated that the metals contents were arranged as Cr > V > Zn > Cu > Ni > Pb > Co > Cd in all sites. Comparing with the background value of soil in local section, Cd showed the highest level at S5 (1.30 µg x g(-1)), which was almost 13 times higher than the background value (0.103 µg x g(-1)). Pollution assessment indicated that Cd presented a strong polluted status with the geo-accumulation index (I(geo)) value of 3.08 at S5, moderately to strong polluted status with the I(geo) ranged from 2.02 to 2.90 in Inner Mongolia section (S1-S4). Moreover, enrichment factor (EF) showed that all heavy metals in these sediments have been influenced by anthropogenic activities. According to potential ecological risk index (RI), S5 and S3 demonstrated high ecologic risk of heavy metals, while other sampling sites showed moderately ecological risk. The results of BCR exhibited that Cd was the most available metal, followed by Co and Ni, while V and Cr were unavailable in the sediments. Risk assessment code (RAC) exhibited high risk for Cd at S1-S4 and very high risk at S5, while medium risk for Ni and Co at all sites. The results and conclusions may be important information and therefore of interest to the relevant departments of the governments.
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Levofloxacin (LVFX) is widely used in clinical treatment due to it has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria. Human serum albumin (HSA) is the most abundant protein in plasma and constitutes approximately half of the protein founds in human blood. And more than 90% of the drugs used in people are bound to HSA. So it is commonly used for the investigation of drug-serum albumin interaction because the binding will significantly influence the absorption, distribution, metabolism excretion, stability and toxicity of the drugs. Therefore, detailed investigating the interaction of LVFX with HSA is very important to understand the pharmacokinetic behavior of the LVFX. In this paper, the interaction of LVFX and HSA has been studied fluorescence, UV, Fourier transform infrared (FT-IR) and molecular modeling method. The results indicated that LVFX induced the intrinsic fluorescence quenching of HSA though a static quenching procedure, and the effective binding constants (K(a)) were calculated to be 9.44 x 10(4) L x mol(-1) (294 K) and 2.74 x 10(4) L x mol(-1) (310 K) by used of the Stern-Volmer equation. According to the Vant's Hoff equation, the reaction was characterized by negative enthalpy (deltaH = -59.00 kJ x mol(-1)) and negative entropy (delta S = - 105.38 J x mol(-1) x K(-1)), indicated that the predominant forces in the LVFX-HSA complex were hydrogen bonding and van der Waals forces. By displacement measurements, the specific binding of LVFX in the vicinity of Site I of HSA was clarified. The binding distance of 3.66 nm between Trp214 and HSA was obtained by the Förster theory on resonance energy transfer. Furthermore, the binding details between LVFX and HSA were further confirmed by molecular docking studies, which were consistent with the experimental results. The alternations of protein secondary structure were calculated from FT-IR spectra. Upon formation of LVFX-HSA complexes, the amount of alpha-helical structures were decrease, but the numbers of beta-sheet structures, beta-turn structures and random structures were increase, respectively. This result indicated that LVFX induced unfolding of the polypeptides of HSA.
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Levofloxacino/química , Albumina Sérica/química , Fluorescência , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Ligação Proteica , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaRESUMO
Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.
Assuntos
Glutationa Transferase , Acidente Vascular Cerebral Hemorrágico , Animais , Camundongos , Antioxidantes , Hemorragia Cerebral/genética , Modelos Animais de Doenças , Glutationa , Glutationa Transferase/genética , Hemina/farmacologia , Neurônios , RNA MensageiroRESUMO
Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.
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In the present study, two experiments were conducted to investigate the effect of Mn source on Mn transport and the expression of a Mn transporter, divalent metal transporter 1 (DMT1), in the small intestine of broilers. In Expt 1, in situ ligated duodenal loops from Mn-deficient chicks (29-d-old) were perfused with solutions containing 0-8.74 mmol Mn/l from either MnSO4, or one of two organic chelates of Mn and amino acids with moderate (OM) or strong (OS) chelation strength (Q(f)) up to 30 min. In Expt 2, Mn-deficient intact broilers (14-d-old) were fed a control diet (12.45 mg Mn/kg) or the control diet supplemented with 100 mg Mn/kg as one of all Mn sources for 14 d. The uptake kinetics of Mn from different Mn sources in the ligated duodenal loops followed a saturable process as determined by regression analysis of concentration-dependent uptake rates. The maximum transport rate (Jmax) and K(m) values, and DMT1 mRNA levels in the ligated duodenal loops were higher (P < 0.01) for OM and OS than for MnSO4. DMT1 mRNA levels were much higher (P < 0.01) in the duodenum than in the jejunum and ileum. Both DMT1 mRNA levels in the duodenum and plasma Mn contents from the hepatic portal vein of intact chicks on day 14 post-feeding increased (P < 0.05) in the following order: control < MnSO4 < OM < OS. These results indicated that organic Mn sources with stronger Q(f) showed higher Mn transport and absorption, and DMT1 might be involved in the regulation of organic Mn transport in the proximal small intestine of broilers.
Assuntos
Proteínas Aviárias/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Galinhas/metabolismo , Regulação da Expressão Gênica , Absorção Intestinal , Intestino Delgado/metabolismo , Manganês/administração & dosagem , Aminoácidos/química , Ração Animal/análise , Animais , Proteínas Aviárias/genética , Proteínas de Transporte de Cátions/genética , Quelantes/administração & dosagem , Quelantes/química , Galinhas/sangue , Galinhas/crescimento & desenvolvimento , China , Deficiências Nutricionais/dietoterapia , Deficiências Nutricionais/metabolismo , Deficiências Nutricionais/veterinária , Duodeno/crescimento & desenvolvimento , Duodeno/metabolismo , Intestino Delgado/crescimento & desenvolvimento , Cinética , Masculino , Manganês/deficiência , Manganês/metabolismo , Manganês/uso terapêutico , Compostos de Manganês/administração & dosagem , Especificidade de Órgãos , Concentração Osmolar , Doenças das Aves Domésticas/dietoterapia , Doenças das Aves Domésticas/metabolismo , Sulfatos/administração & dosagemRESUMO
Background: The prognostic factors for differentiated thyroid cancer (DTC) patients with pulmonary metastases (PM) remain scantly identified and analyzed. Therefore, this systematic review and meta-analysis were performed to identify and summarize the prognostic factors in adult DTC patients with PM to help distinguish patients with different prognoses and inform the rational treatment regimens. Method: We performed a comprehensive search of the relevant studies published in the Cochrane Library, PubMed, Scopus, Embase, Wanfang database, VIP database, China National Knowledge Infrastructure, and Google Scholar from their inception until February 2021. The pooled hazard ratios (HR) for overall survival and/or progression-free survival (PFS) with 95% confidence intervals were applied to evaluate and identify the potential prognostic factors. Pooled OS at different time points were also calculated for the available data. A random-effects model was used in the meta-analysis. Results: The review and meta-analysis included 21 studies comprising 2722 DTC patients with PM. The prognostic factors for poor OS were: age over 40 years (HR=7.21, 95% confidence interval [CI] 1.52-34.10, P=0.01, N=788), age over 45 years (HR=2.18, 95% CI 1.26-3.77, P<0.01, N=601), male gender (HR=1.01, 95% CI 1.01-1.19, P=0.03, N=1396), follicular subtype of thyroid cancer (HR=1.63, 95% CI 1.36-1.96, P<0.01, N=2110), iodine non-avidity (HR=3.10, 95% CI 1.79-5.37, P<0.01, N=646), and metastases to other organs (HR=3.18, 95% CI 2.43-4.16, P<0.01, N=1713). Factors associated with poor PFS included age over 45 years (HR=3.85, 95% CI 1.29-11.47, P<0.01, N=306), male gender (HR=1.36, 95% CI 1.06-1.75, P=0.02, N=546), iodine non-avidity (HR=2.93, 95% CI 2.18-3.95, P<0.01, N=395), pulmonary metastatic nodule size over 10mm (HR=2.56, 95% CI 2.02-3.24, P<0.01, N=513), and extra-thyroidal invasion (HR=2.05, 95% CI 1.15-3.67, P=0.02, N=271). The pooled 1, 3, 5, 10, 15, and 20-years OS were 95.24%, 88.46%, 78.36%, 64.86%, 56.57%, and 51.03%, respectively. Conclusions: This review and meta-analysis identified the prognostic factors of DTC patients with PM. Notably, FTC, metastases to other organs, and iodine non-avidity were particularly associated with poor prognosis. The identified prognostic factors will help guide the clinical management of DTC patients with PM. Systematic review registration: https://inplasy.com/inplasy-2022-2-0026/, identifier (INPLASY202220026).
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Background: Radioiodine (RAI) therapy plays a vital role in the postoperative treatment of differentiated thyroid cancer (DTC) patients underwent total thyroidectomy (TT). However, even in the presence of capsular invasion and lymph node metastasis prognosis can be excellent and a postoperative RAI treatment might not be necessary for all patients. Therefore, this study explored the criteria for avoiding unnecessary RAI therapy in these patients. Method: We applied response to therapy assessment immediately after surgery and prospectively recruited 179 excellent or indeterminate response DTC patients with capsular invasion and/or LNM who underwent TT without RAI therapy. During the follow-up, thyroglobulin (Tg), thyroglobulin antibody (TgAb) levels, and cervical ultrasonography were collected and analyzed. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. In addition, response to therapy assessments was performed on patients during each follow-up. Results: The mean follow-up period was 29.85 ± 17.44 months, and the 3- and 5-year DFS for all the patients was 99.3% in each. At the last follow-up, 165 (92.2%) patients had excellent responses, while 12 (6.7%) had an indeterminate response, and one (0.6%) each had biochemical and incomplete responses. No significant difference was observed in response to therapy between the subgroups of LNM and tumor invasion (P>0.05). For patients with capsular invasion and a number of metastatic lymph nodes ≤5 and >5, the proportions of recorded excellent responses were 95.9%, 91.0%, and 85.7%, respectively. Better responses were observed in females (excellent response: 95.5%, P=0.023), patients with stimulated Tg (s-Tg) ≤1ng/ml (excellent response: 100%, P<0.001), s-Tg ≤ 2ng/ml (excellent response: 98.4%, P<0.001), and excellent response for the immediate postoperative assessment (excellent response: 98.5%, P=0.004). Conclusions: The current study suggested that the response to therapy assessment immediately applied postoperatively could help avoid unnecessary RAI therapy among DTC patients with capsular invasion and/or LNM. Moreover, excellent response patients and patients with indeterminate response and s-Tg ≤ 2ng/ml could be managed without RAI therapy.
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Accumulating evidence has demonstrated that the immune cells have an emerging role in controlling anti-tumor immune responses and tumor progression. The comprehensive role of mast cell in glioma has not been illustrated yet. In this study, 1,991 diffuse glioma samples were collected from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). xCell algorithm was employed to define the mast cell-related genes. Based on mast cell-related genes, gliomas were divided into two clusters with distinct clinical and immunological characteristics. The survival probability of cluster 1 was significantly lower than that of cluster 2 in the TCGA dataset, three CGGA datasets, and the Xiangya cohort. Meanwhile, the hypoxic and metabolic pathways were active in cluster 1, which were beneficial to the proliferation of tumor cells. A potent prognostic model based on mast cell was constructed. Via machine learning, DRG2 was screened out as a characteristic gene, which was demonstrated to predict treatment response and predict survival outcome in the Xiangya cohort. In conclusion, mast cells could be used as a potential effective prognostic factor for gliomas.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/patologia , Proteínas de Ligação ao GTP/genética , Glioma/patologia , Humanos , Evasão da Resposta Imune , Mastócitos/patologia , RNA-SeqRESUMO
The ubiquitin E3 ligase CUL4A plays important roles in diverse cellular processes including carcinogenesis and proliferation. It has been reported that the expression of CUL4A can be induced by hypoxic-ischemic injury. However, the effect of elevated expression of CUL4A on hypoxia-reoxygenation injury is currently unclear. In this study, human CUL4A (hCUL4A) was expressed in rat pheochromocytoma (PC12) cells using adenoviral vector-mediated gene transfer, and the effects of hCUL4A expression on hypoxia-reoxygenation injury were investigated. In PC12 cells subjected to hypoxia and reoxygenation, we found that hCUL4A suppresses apoptosis and DNA damage by regulating apoptosis-related proteins and cell cycle regulators (Bcl-2, caspase-3, p53 and p27); consequently, hCUL4A promotes cell survival. Taken together, our results reveal the beneficial effects of hCUL4A in PC12 cells upon hypoxia-reoxygenation injury.
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Apoptose , Proteínas Culina/biossíntese , Hipóxia/enzimologia , Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/biossíntese , Animais , Proteínas Reguladoras de Apoptose/biossíntese , Hipóxia Celular , Proteínas Culina/genética , Dano ao DNA , Humanos , Hipóxia/genética , Hipóxia/patologia , Células PC12 , Ratos , Transcrição Gênica , Ubiquitina-Proteína Ligases/genéticaRESUMO
The prognostic factors and optimal treatment for the elderly patient with glioblastoma (GBM) were poorly understood. This study extracted 4975 elderly patients (≥ 65 years old) with histologically confirmed GBM from Surveillance, Epidemiology and End Results (SEER) database. Firstly, Cumulative incidence function and cox proportional model were utilized to illustrate the interference of non-GBM related mortality in our cohort. Then, the Fine-Gray competing risk model was applied to determine the prognostic factors for GBM related mortality. Age ≥ 75 years old, white race, size > 5.4 cm, frontal lobe tumor, and overlapping lesion were independently associated with more GBM related death, while Gross total resection (GTR) (HR 0.87, 95%CI 0.80-0.94, P = 0.010), radiotherapy (HR 0.64, 95%CI 0.55-0.74, P < 0.001), chemotherapy (HR 0.72, 95%CI 0.59-0.90, P = 0.003), and chemoRT (HR 0.43, 95%CI 0.38-0.48, P < 0.001) were identified as independently protective factors of GBM related death. Based on this, a corresponding nomogram was conducted to predict 3-, 6- and 12-month GBM related mortality, the C-index of which were 0.763, 0.718, and 0.694 respectively. The calibration curve showed that there was a good consistency between the predicted and the actual mortality probability. Concerning treatment options, GTR followed by chemoRT is suggested as optimal treatment. Radiotherapy and chemotherapy alone also provide moderate clinical benefits.
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Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Nomogramas , Idoso , Neoplasias Encefálicas/terapia , Feminino , Glioblastoma/terapia , Humanos , Masculino , Estudos Retrospectivos , Medição de Risco , Programa de SEER , Estados Unidos/epidemiologiaRESUMO
Cartilage is a relatively simple connective tissue that plays a variety of roles in the human body, including joint support and protection, load bearing of the intervertebral discs, joint lubrication, formation of the external structure of the ears and nose and support of the trachea. The maintenance of cartilage homeostasis is therefore crucial. Cartilage-related diseases are difficult to diagnose and treat because their molecular and pathological mechanisms are not fully understood. Melatonin, which has a wide range of physiological effects, is an endocrine hormone mainly secreted by the pineal gland. Its biological effects include its antioxidant, antiaging, analgesic, and hypnotic effects and its ability to stabilize the circadian rhythm. In recent years, research on cartilage homeostasis and melatonin has been increasing, and melatonin has gradually been used in the treatment of cartilage-related diseases. Therefore, this article will briefly review the role of melatonin in cartilage homeostasis, including its anti-inflammatory effects and effects in protecting cartilage from damage by other factors and promoting chondrocyte growth and the expression of cartilage-related genes. Based on the above, the current status and future developmental direction of melatonin in the treatment of cartilage-related diseases are also discussed, demonstrating the broad prospects of melatonin in maintaining cartilage homeostasis and treating cartilage injury-related diseases.
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OBJECTIVE: To study the transformation of Astragaloside IV in bidirectional solid fermenting of Astragalus membranaceus var. mongholicus. METHODS: The chemical components of pre and post-fermenting were comparatively analyzed by techniques of HPLC, column chromatography and spectral identification. Antioxidant effect of transformational product on vascular endothelial cells was researched. RESULTS: In fermenting of Astragalus membranaceus, Astragaloside IV was transformed into 6-O-beta-D-glucoside cycloastragenol, which had significant antioxidant effect. CONCLUSION: Biotransformation of Astragaloside IV in Astragalus membranaceus was occurred after bidirectional solid fermenting with Ganoderma lucidum, and the biotransformation could enhance effect.
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Astragalus propinquus/química , Fermentação , Sapogeninas/química , Saponinas/química , Triterpenos/química , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Ganoderma , Estrutura Molecular , Raízes de Plantas/química , Plantas Medicinais/química , Sapogeninas/metabolismo , Sapogeninas/farmacologia , Saponinas/metabolismo , Triterpenos/metabolismoRESUMO
Background: Hereditary sensory and autonomic neuropathies (HSANs) are a rare and severe group of sensory axonal neuropathies. HSANs have been classified into eight groups based on mode of inheritance, clinical features, and the involved genes. HSAN-VI, perhaps the most notable type, is an autosomal recessive disease, which manifests as the severely impaired pain sensitivity, autonomic disturbances, distal myopathy, spontaneous or surgical amputations, and sometimes early death. Mutations in DST have been identified as the cause of HSAN-VI. DST encodes dystonin, a member of the plakin protein family that is involved in cytoskeletal filament networks. Dystonin has seven major isoforms in nerve, muscle, and epithelium. Material and Methods: The present study investigated a Chinese family with HSAN and explored potential pathogenic variants using whole-exome sequencing (WES). Variants were screened and filtered through bioinformatics analysis and prediction of variant pathogenicity. Co-segregation analysis was subsequently conducted. Results: We identified compound heterozygous variants of DST (c.3304G>A, p.V1102I and c.13796G>A, p.R4599H) in two patients. Conclusion: We reported on a Chinese family with HSAN-VI family and detected the disease-causing variants. Our description expands the spectrum of known DST variants and contributes to the clinical diagnosis of HSAN-VI.
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RATIONALE: Langerhans cell histiocytosis (LCH) involves mainly the skin and bone and rarely the thyroid. Meanwhile, papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. Both LCH and PTC could make the thyroid enlarged and hypermetabolic. The coincidence of these 2 events in a patient is rare, and this paper aimed to report such case. PATIENT CONCERNS: A 40-year-old man presented with polyuria and polydipsia for 5 years. The symptoms had been relieved well by drug therapy for >4 years, until the drugs could not control the symptoms anymore and an extensively enlarged thyroid gland was noticed. DIAGNOSES: Thyroid ultrasound showed a nodule with microcalcification in the upper right lobe, positron emission tomography/computer tomography scan demonstrated thyroid hypermetabolism, and fine needle aspiration (FNA) revealed PTC. Right lobectomy of the thyroid and cervical lymph node biopsy verified the diagnosis "LCH of the thyroid complicated by PTC." INTERVENTIONS: The ultrasound-guided FNA biopsy was performed prior to right lobectomy of the thyroid and cervical lymph node biopsy. Postoperative histopathological examination confirmed the diagnosis, after which the patient received adjuvant chemotherapy. OUTCOMES: After 5 cycles of adjuvant chemotherapy, the patient had been followed up for 2 years. LCH was controlled satisfactorily and there was no significant sign of recurrence or metastasis of PTC. LESSONS: LCH of the thyroid complicated by PTC is rare. Thyroid involvement should always be considered in the differential diagnosis of LCH patients. Surgery for PTC followed by chemotherapy for LCH may be the suitable treatment.
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Carcinoma/complicações , Histiocitose de Células de Langerhans/complicações , Doenças da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/complicações , Adulto , Carcinoma/diagnóstico por imagem , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Carcinoma Papilar , Quimioterapia Adjuvante , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/cirurgia , Humanos , Masculino , Câncer Papilífero da Tireoide , Doenças da Glândula Tireoide/diagnóstico por imagem , Doenças da Glândula Tireoide/tratamento farmacológico , Doenças da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
Non-functioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. The elucidation of the mechanisms of aggressive NFPAs in bone destruction is required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, we investigated the differential proteomics of fibroblasts isolated from clinical specimens of NFPAs with or without bone destruction. Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction NFPAs (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. Furthermore, immunohistochemical staining of the NFPAs clinical samples showed that the expression of caldesmon in stromal cells and the expression of osteopontin in both tumor cells and stroma were significantly increased in BD-NFPAs. Taken together, our results indicate a possible way that osteopontin secreted from both NFPA cells and surrounding fibroblasts modify caldesmon expression and polymerization in fibroblasts, which may contribute to bone destruction in NFPA patients.