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1.
Adela Markota agalj Branka Marinovi Zrinka Bukvi Mokos 《International journal of molecular sciences》2022,23(7)
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease deriving from the hair follicles. The formation of inflammatory nodules, abscesses, fistulas, and sinus tracts is characterized by a large inflow of key pro-inflammatory mediators, such as IFN-γ, TNF-α, IL-1, IL-17, and IL-12/23. Adalimumab is currently the only Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved biologic therapy for moderate to severe HS in adults and adolescents. However, the long-term effectiveness of this TNF-α inhibitor in HS patients has shown to be highly variable. This review aims to review the evidence for emerging therapies that target the main pro-inflammatory cytokines in HS pathogenesis. A review of the literature was conducted, using the PubMed and Google Scholar repositories, as well as Clinicaltrials.gov. Presently, the most promising biologics in phase III trials are anti-IL-17 antibodies, secukinumab, and bimekizumab. Furthermore, an anti-IL-1 biologic, bermekimab, is currently in phase II trials, and shows encouraging results. Overall, the clinical efficacies of all new targeted therapies published up to this point are limited. More studies need to be performed to clarify the precise molecular pathology, and assess the efficacy of biological therapies for HS. 相似文献
2.
Mora-Gutierrez A Farrell HM Attaie R McWhinney VJ Wang C 《The Journal of dairy research》2007,74(3):356-366
Bovine and caprine milks have a similar overall gross composition, but vary considerably in the ratios of their casein components. These differences cause significant changes in the ability of caseins to bind and stabilize calcium (Ca). It might be expected that these in vitro variations, which are thought to be due to differences in casein phosphopeptides (CPP) content, could lead to in vivo differences in the digestion and absorption of Ca. To test this hypothesis three milks with different casein ratios [bovine (B), caprine high in alphas1-casein (CH) and caprine low in alphas1-casein (CL)] were compared with regard to Ca absorption and deposition in growing male rats. For comparison, each milk was Ca-fortified (BCa-milk, CHCa-milk, and CLCa-milk) and CPP, prepared by enzymatic hydrolysis from the respective caseins (extrinsic CPP), were added to both native and Ca-milks. The effects of added CPP (extrinsic) could then be compared with intrinsic CPP released from the gastrointestinal digestion of caseins. Total gastric Ca was sampled at 15, 30 and 60 min after ingestion. No differences were found among the native milks with or without CPP, but the Ca from all Ca-milks (regardless of casein type) appeared to clear the stomach more rapidly and this was enhanced by the extrinsic CPP. The total intestinal Ca was not different among the native milks+/-CPP, however, it rose more rapidly with Ca fortification, and was higher at 30 min for all CPP-Ca-milks. At 60 min the total intestinal Ca level fell for the CPP-Ca-milks while all others continued to rise. These observations suggest that the CPP in Ca-milks enhance gastric clearance and uptake from the intestine. Ca availability from BCa-milk, CHCa-milk, and CLCa-milk with and without CPP was estimated by both plasma and femur uptake of 45Ca. Ca availability was enhanced at 5 h in the plasma in each case by added CPP. In all cases CPP stimulated Ca availability in the femur, but the CL-CPP was higher (P<0.05) than that of either CH-CPP or B-CPP (extrinsic CPP). Based on the results of this study we can conclude that the addition of CPP will have beneficial effect on the absorption of Ca in growing rats from CaCO3 added to bovine and caprine milks. 相似文献
3.
Sara da Mata Joana Ferreira Inmaculada Nicols Susana Esteves Gonalo Esteves Sofia Lrias Fernanda Silva Adela Saco Daniela Cochicho Mrio Cunha Marta del Pino Jaume Ordi Ana Flix 《International journal of molecular sciences》2021,22(5)
The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; p = 0.032) were associated with better survival. HPV16 (HR: 0.63; p = 0.0174) and α-9 genera (HR: 0.57; p = 0.0286) were associated with less relapse. In the multivariate analysis, only the International Federation of Gynecology and Obstetrics (FIGO) stage retained an independent prognostic value. HPV16, α-9 genera and p16 overexpression were associated with better survival, although not as independent prognostic factors. Patients with p16-negative HPV-associated CC were older, presented with advanced disease and had worse prognosis. 相似文献
4.
Guy Bordin Josephine McCourt Fernando Cordeiro Raposo Adela Rodriguez 《The Science of the total environment》1996,180(3):241
Tellinid clams Macoma balthica were sampled every 2 months for 2.5 years at two locations from the Westerschelde estuary (The Netherlands) and submitted to in vitro short-term exposure to Cd, Cu and Zn. Total and heat-stable cytosolic metal concentrations have been measured before and after exposure to study the effects of the sampling season on metal uptake by the bivalve. We observed much higher uptakes of Cd and, to a lesser extent, Cu in winter than in summer, while Zn appears to be constantly regulated. These phenomena are amplified in the cytosol, especially for Cd, a non-essential element, for which the concentrations after exposure can reach 35–45 μg·g−1 (dry wt.) in winter, but only a maximum of 0.5 μg·g−1 in summer, all natural values being between 0.01 and 0.1 μg·g−1 on average. The contents (μg) of the various elements, either at the total or at the cytosolic level, are not constant, hence showing that the seasonal body weight fluctuation of the clams (dilution or concentration effect) is not the only parameter responsible for the metal uptake variability. Furthermore, we have shown that the proportion of cytosolic metal is not constant, but increases with the absolute cytosolic concentration up to 35–40. Therefore, the cytosolic phase of the cells plays a growing role in Cd, Cu and Zn storage as long as their total concentration increases. 相似文献
5.
María A. Vasco-Mogorrn Jos A. Campillo Adela Periago Valentin Cabaas Mercedes Berenguer María C. García-Garay Lourdes Gimeno María F. Soto-Ramírez María D. Martínez-Hernndez Manuel Muro Alfredo Minguela 《International journal of molecular sciences》2021,22(8)
Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PAhigh, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PAhigh at higher risk of progression and death. 相似文献
6.
A. Redondo M. José Villanueva M. Dolores Rodriguez M. Dolores Saco 《European Food Research and Technology》1997,205(6):457-463
Different methods have been used to evaluate variations in the dietary fibre content of carrots and turnips during autoclaving. Autoclaving was carried out at 121°C under pressure for 15 min. The methods used were the gravimetric (neutral and acid detergent fibre) method, the enzymatic-gravimetric method for (insoluble and soluble fibre and the spectrophotometric method for pectic substances. When the methodologies were compared it was observed that in raw carrots and turnips, the neutral detergent fibre and insoluble fibre contents were statistically different (P<0.05). This was not the case for processed samples of the vegetables. The correlation between the different methodologies was studied. A good correlation was found between neutral detergent fibre and insoluble fibre in raw turnips (r = 0.999). Variance analysis indicated that quantitative variations resulting after thermal treatment were statistically significant (P<0.05) for neutral detergent fibre in carrots (raw = 1.97%, processed = 1.68%), and for pectic substances in carrots (raw = 0.54%, processed = 0.47%) and turnips (raw = 0.33%, processed = 0.25%). Optical microscopy has been used to identify different dietary fibre components in raw and processed samples. 相似文献
7.
In this paper, particle size effect on pinewood combustion in a stationary packed bed was investigated. Mass loss rate, temperature profile at different bed locations and gas compositions in the out-of-bed flue gases were measured at a fixed primary air flow rate. Pinewood cubes was fired with size ranging from 5 to 35 mm. A unique numerical model applicable to thermally thick particles was proposed and relevant equations were solved to simulate the non-homogeneous characteristics of the burning process. It is found that at the operating conditions of the current study, smaller particles are quicker to ignite than larger particles and have distinctive combustion stages; burning rate is also higher with smaller fuel size; and smaller fuels have a thinner reaction zone and result in both higher CO and CH4 concentrations in the out-of-bed flue gases; on the other hand, larger particles produced a higher flame temperature and result in higher H2 concentration in the flue gases. Larger particles also cause the combustion process becoming more transient where the burning rate varies for most part of the combustion process. 相似文献
8.
9.
Ljiljana Simovic Petar Skundric Ivana Pajic‐Lijakovic Katarina Ristic Adela Medovic Goran Tasić 《应用聚合物科学杂志》2010,117(3):1424-1430
A mathematical model was developed to estimate the release of gentamicin sulfate from a bioactive textile material as a transdermal system for wound dressing. The gentamicin sulfate released from the antibiotic/chitosan hydrogel complexes was measured in vitro by the Franz diffusion cell technique. The diffusive transport of gentamicin sulfate through three connected compartments, that is, chitosan hydrogel, membrane, and solution, was considered by the formulation of a model based on Fick's second law. Initially, the total amount of gentamicin sulfate was placed within an already swollen chitosan hydrogel. The value of the diffusivity coefficient of the drug through the chitosan hydrogel was calculated for every initial amount of the active substance. For the initial concentration of gentamicin sulfate, which was lower than 2.81 × 104 μg/mL, the diffusion coefficient was approximately constant. A higher amount of gentamicin sulfate in the hydrogel reduced its own transport as a consequence of an increase in the intensity of the interaction field between the molecules of gentamicin sulfate. The model provides the possibility of optimizing the process of drug release by ensuring a compromise between a higher value of the diffusivity coefficient and a desirable amount of gentamicin sulfate and a constant concentration within the solution over 48 h. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 相似文献
10.