Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The ...substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.
Coinfection of HPgV-1 with hepatitis C virus (HCV) is common due to shared modes of transmission, with a prevalence of HPgV-1 viremia of approximately 20% among individuals with chronic HCV ...infection. The aim of the present study was to estimate the prevalence of HPgV-1 RNA and circulating genotypes in patients with hepatitis C from a health service located in the city of Belém, in the state of Pará, Northern Brazil. A total of 147 samples were included in the study from February to December 2019. Among the participants, 72.1% (106/147) were monoinfected with HCV, with detectable HCV viral RNA, and 27.9% (41/147) were coinfected with HCV/HPgV-1. The most frequently found genotypes were HPgV-1 genotypes 1 and 2 (36.6% and 63.4%), respectively. While for HCV there was a predominance of genotypes 1 and 3 (58.5% and 41.5%). No significant differences were found when comparing any risk, sociodemographic, or clinical factors between groups. Also, there was no statistically significant difference when relating the viral genotypes of both agents. This study indicated that the prevalence of infection by HPgV-1 is high in HCV carriers in Belém, Pará, and probably does not change the clinical course of HCV infection, however, further studies are still needed.
Background Epidermal growth factor receptor (EGFR) overexpression has been considered a poor prognostic factor in breast cancer. Methodology A prospective study of 206 women with breast cancer ...analysed by stages (I, II, III and IV) and by immunohistochemical subtype (Luminal A, Luminal B, HER2+ and triple-negative (TN)); 89 healthy controls with normal recent mammography were included. The EGFR measured in the serum (sEGFR) was detected by the Enzyme-Linked Immunosorbent Assay (ELISA) method (R&D Systems kit DY231) collected by blood before any treatment in patients. Kaplan–Meier method and Cox regression were carried out to obtain the prognostic value, considering significance if p < 0.05. Results With a median follow-up of 36.6 months, 47 deaths occurred. Multivariable Cox regression showed difference of overall survival (OS) associated with sEGFR levels (sEGFR ≤ or > 47.8 ng/mL) in patients with TN cancers, but not of Luminal A, Luminal B or HER2+ subtypes; adjusted by stage, the death risk increased by approximately 415% hazard ratio (HR): 5.149 (1.900–13.955), p = 0.001 for patients with sEGFR > 47.8 ng/mL compared to patients with a lower sEGFR value. There was no significant correlation of sEGFR with staging, histological tumour grade (G1/G2/G3), Ki67 (< or ≥14%) or body mass index. Conclusions Increased sEGFR expression in patients with TN tumours is a significant predictor of lower OS and its quantification is inexpensive and straightforward.
Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in ...vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms.
Tumour lymphovascular invasion is not routinely assessed in all pathology services, and whether reporting it quantitatively or qualitatively is the main factor associated with the loss of this ...prognostic event. This study aimed to analyse the prognostic value of qualitatively reported lymphovascular invasion in patients with invasive breast ductal carcinoma.
This was a retrospective, single-center study, enrolling a total of 426 patients with invasive ductal carcinoma of the breast with a report of lymphovascular invasion, with a median follow-up of approximately 4.5 years. Kaplan-Meier and Cox regression was performed to obtain the predictive value of lymphovascular invasion. Propensity score matching was performed to reduce bias by standardising factors with significant differential distribution of lymphovascular invasion status.
Lymphovascular invasion was present in 197 (49.2%) patients. Multivariate Cox regression showed that lymphovascular invasion independently increases the risk of death by almost two times (adjusted hazard ratio (HR): 2.045 (1.226-3.406),
= 0.006) and the risk of distant metastasis by more than two times (adjusted HR: 2.373 (1.404-4.010),
= 0.001). Subgroup analysis after matching by propensity score in adjuvant-only patients showed that the lymphovascular invasion is a factor of increased death in N- patients (adjusted HR: 12.597 (1.624-97.728),
= 0.015) and of distant metastasis-free survival in N+ patients (adjusted HR: 4.862 (1.649-14.335),
= 0.004) and almost for N- patients (adjusted HR 7.905 (0.969-64.509),
= 0.004).
The presence of lymphovascular invasion is a predictor of worse prognosis in patients with invasive ductal carcinoma of the breast, even with metastatic lymph node disease (N1-N3).
Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for ...evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.
The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several ...structural variations with the same numbers of carbon and nitrogen atoms. Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds. In this review, the authors explored aspects of patents for the 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011.
The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities. More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases. This review emphasizes recent perspective and advances in the therapeutically active 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals. Many studies have focused on these compounds as target structures and evaluated them in several biological targets.
The preparation of 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives brings to light several issues. There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability. New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these new diseases. Of great urgency is finding prototypes against bacteria that continue to increase resistance and for neglected diseases that affect a large part of humanity, especially the poor and vulnerable.
This research aimed to study the effects of the nanosilica supply on Si absorption and the physiological and nutritional aspects of beet plants with N and P deficiencies cultivated in a nutrient ...solution. Two experiments were performed with treatments arranged in a 2 × 2 factorial scheme in randomized blocks with five replications. The first experiment was carried out on plants under a N deficiency and complete (complete solution with all nutrients), combined with the absence of Si (0 mmol L
) and the presence of Si (2.0 mmol L
). In the other experiment, the plants were cultivated in a nutrient solution with a P deficiency and complete, combined with the absence (0 mmol L
) and the presence of Si (2.0 mmol L
). The beet crop was sensitive to the N and P deficiencies because they sustained important physiological damage. However, using nanosilica via fertigation could reverse the damage. Using nanotechnology from nanosilica constituted a sustainable strategy to mitigate the damage due to a deficiency in the beet crop of the two most limiting nutrients by optimizing the physiological processes, nutritional efficiency, and growth of the plants without environmental risks. The future perspective is the feasibility of nanotechnology for food security.
The differentiation between the main crop and weeds is an important step for selective spraying systems to avoid agrochemical waste and reduce economic and environmental impacts. In this sense, this ...study aims to classify and map the area occupied by weeds, determine the percentage of area occupied, and indicate treatment control strategies to be adopted in the field. This study was conducted by using a yellow Bourbon cultivar (IAC J10) with 1 year of implementation on a commercial coffee plantation located at Minas Gerais, Brazil. The aerial images were obtained by a remotely piloted aircraft (RPA) with an embedded multispectral sensor. Image processing was performed using PIX4D, and data analysis was performed using R and QGIS. The random forest (RF) and support vector machine (SVM) algorithms were used for the classification of the regions of interest: coffee, weed, brachiaria, and exposed soil. The differentiation between the study classes was possible due to the spectral differences between the targets, with better classification performance using the RF algorithm. The savings gained by only treating areas with the presence of weeds compared with treating the total study area are approximately 92.68%.
BackgroundThe luminal subtype accounts for ~70% of newly diagnosed breast cancer patients. Although it has a better prognosis, approximately 30% of them develop a late relapse. Identifying those ...patients is of interest to improve treatment decisions.MethodsA retrospective observational, single-centre study based on data from medical records of 572 non-metastatic (I–III) invasive ductal breast carcinoma patients, 448 with luminal tumours and 124 with triple-negative tumours. Kaplan–Meier, Cox regression and time-dependent Cox regression were carried out to obtain the prognosis value of risk factors.ResultsDuring a median observation of 5.5 years, 105 distant metastasis events and 105 all-cause deaths were observed. In addition to known clinicopathological factors (i.e., age, tumour size and lymph node metastasis), the high semi-quantitative expression of both hormone receptors was associated with distant metastasis-free survival (DMFS) (adjusted hazard ratio (HaR): 0.524 (0.316–0.867), p = 0.012) and overall survival (OS) (adjusted HaR: 0.486 (0.286–0.827), p = 0.008). The stratified analysis made it possible to identify risk modification factors. Subsequent stratification by histological grade, Ki-67 and semi-quantitative PR expression or, mainly, the composite semi-quantitative expression of hormone receptors (cHR) enabled the identification of luminal breast cancer patients of adjuvant schema at higher risk for metastasis and death. However, initial analyses including patients of neoadjuvant therapy pointed to a path of subsequent stratification by cHR and histological grade, also enabling grouping of luminal breast cancer patients with similar prognosis for DMFS (cHR ≤ 4+ G2 or G3 versus triple-negative, adjusted HaR: 0.703 (0.415–1.189), p = 0.189) and OS (cHR ≤4+ G2 or G3 versus triple-negative, adjusted HaR: 0.662 (0.403–1.088), p = 0.104).ConclusionThe semi-quantitative expression of both cHR, Ki-67 proliferation index and histological grade can identify luminal breast cancer patients at greater risk of developing metastasis and death when combined in a hierarchical fashion, and could be useful for a better prognosis stratification in services from low- and middle-income countries.
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