Display omitted
Cancer is a disease with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. The hallmarks of cancer evidence the acquired cells characteristics that ...promote the growth of malignant tumours, including genomic instability and mutations, the ability to evade cellular death and the capacity of sustaining proliferative signalization. Poly(ADP-ribose) polymerase-1 (PARP1) is a protein that plays key roles in cellular regulation, namely in DNA damage repair and cell survival. The inhibition of PARP1 promotes cellular death in cells with homologous recombination deficiency, and therefore, the interest in PARP protein has been rising as a target for anticancer therapies. There are already some PARP1 inhibitors approved by Food and Drug Administration (FDA), such as Olaparib and Niraparib. The last compound presents in its structure an indazole core. In fact, pyrazoles and indazoles have been raising interest due to their various medicinal properties, namely, anticancer activity. Derivatives of these compounds have been studied as inhibitors of PARP1 and presented promising results. Therefore, this review aims to address the importance of PARP1 in cell regulation and its role in cancer. Moreover, it intends to report a comprehensive literature review of PARP1 inhibitors, containing the pyrazole and indazole scaffolds, published in the last fifteen years, focusing on structure–activity relationship aspects, thus providing important insights for the design of novel and more effective PARP1 inhibitors.
Cancer is a complex and multifaceted group of diseases with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. Dysregulation of normal signalling pathways in cancer ...contributes to the different hallmarks of this disease. The signalling pathway of which phosphatidylinositol 3-kinase (PI3K) is a part is not an exception. In fact, dysregulated activation of PI3K signalling pathways can result in unbridled cellular proliferation and enhanced cell survival, thereby fostering the onset and advancement of cancer. Therefore, there is substantial interest in developing targeted therapies specifically aimed at inhibiting the PI3K enzyme and its associated pathways. Also, the therapeutic interest on pyrazoles and indazoles has been growing due to their various medicinal properties, namely, anticancer activity. Derivatives of these compounds have been studied as PI3K inhibitors, and they showed promising results. There are already some PI3K inhibitors approved by Food and Drug Administration (FDA), such as Idelalisib (Zydelig®) and Alpelisib (Piqray®). In this context, this review aims to address the importance of PI3K in cellular processes and its role in cancer. Additionally, it aims to report a comprehensive literature review of PI3K inhibitors, containing the pyrazole and indazole scaffolds, published in the last fifteen years, focusing on structure-activity relationship aspects, thus providing important insights for the design of novel and more effective PI3K inhibitors.
Display omitted
•PI3K plays crucial roles in cell regulation and carcinogenesis.•The target inhibition of PI3K has emerged as a cancer therapy.•Interest in pyrazoles and indazoles comes from their diverse medicinal properties.•Pyrazoles and indazoles show promise as PI3K inhibitors for cancer therapy.•PI3K inhibition relies heavily on Val851 amino acid interaction.
Brazil is a large complex country that is undergoing rapid economic, social, and environmental change. In this Series of six articles, we have reported important improvements in health status and ...life expectancy, which can be ascribed largely to progress in social determinants of health and to implementation of a comprehensive national health system with strong social participation. Many challenges remain, however. Socioeconomic and regional disparities are still unacceptably large, reflecting the fact that much progress is still needed to improve basic living conditions for a large proportion of the population. New health problems arise as a result of urbanisation and social and environmental change, and some old health issues remain unabated. Administration of a complex, decentralised public-health system, in which a large share of services is contracted out to the private sector, together with many private insurance providers, inevitably causes conflict and contradiction. The challenge is ultimately political, and we conclude with a call for action that requires continuous engagement by Brazilian society as a whole in securing the right to health for all Brazilian people.
Microalgae are considered a promising resource of proteins, lipids, carbohydrates, and other functional biomolecules for food and feed markets. Competitive drying solutions are required to meet ...future demands for high-quality algal biomass while ensuring proper preservation at reduced costs. Since often used drying methods, such as freeze or spray drying, are energy and time consuming, more sustainable processes remain to be developed. This study tested an indirect and hybrid solar dryer as an alternative to conventional freeze drying of industrially produced Tetraselmis chui and Nannochloropsis oceanica wet paste. The effects of the drying method on biomass quality parameters, including biochemical profiles, functional properties, and microbial safety, were assessed. No significant differences were found between the applied drying technologies for total proteins, carbohydrates, lipids, and fatty acid profiles. On the other hand, some pigments showed significant differences, displaying up to 44.5% higher contents in freeze-dried samples. Minor differences were also registered in the mineral profiles (<10%). Analyses of microbial safety and functional properties of the solar-dried biomass appear adequate for food and feed products. In conclusion, industrial solar drying is a sustainable technology with a high potential to preserve high-quality microalgal biomass for various markets at expected lower costs.
The Internet of Things (IoT) fosters the development of smart city systems for sustainable living and increases comfort for people. One of the current challenges for sustainable buildings is the ...optimization of energy management. Temperature monitoring in buildings is of prime importance, as heating account for a great part of the total energy consumption. Here, a solar optical temperature sensor is presented with a thermal sensitivity of up to 1.23% °C−1 based on sustainable aqueous solutions of enhanced green fluorescent protein and C‐phycocyanin from biological feedstocks. These photonic sensors are presented under the configuration of luminescent solar concentrators widely proposed as a solution to integrate energy‐generating devices in buildings, as windows or façades. The developed mobile sensor is inserted in IoT context through the development of a self‐powered system able to measure, record, and send data to a user‐friendly website.
A sustainable solar optical temperature sensor with thermal sensitivity up to 1.23% °C−1 based on aqueous solutions of enhanced Green Fluorescent Protein and C‐phycocyanin is presented. These sensors can be applied as smart windows as the developed sensor is inserted in IoT context through the development of a self‐powered system able to measure and send data to a user‐friendly website.
Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed ...in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16-/- without treatment, group II: treated HPV16-/-, group III: HPV16+/- without treatment and group IV: treated HPV16+/-). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wild-type animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers.
Sambucus nigra L., popularly known as elderberry, is renowned for its amazing therapeutic properties, as well as its uses as a food source, in nutraceuticals, and in traditional medicine. This ...study’s aim was to investigate the effects of an elderberry extract (EE) on mice for 29 days, as well as the safety of the extract when used as a natural colorant. Twenty-four FVB/n female mice (n = 6) were randomly assigned to one of four groups: control, 12 mg/mL EE (EE12), 24 mg/mL EE (EE24), or 48 mg/mL EE (EE48). The predominant anthocyanins detected were cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside. Food and drink intake were similar between groups, with the exception of EE48, who drank significantly less compared with the Control. Biochemical analysis of the liver showed that the changes observed in histological analysis had no pathological significance. The EE, at doses of 24 and 48 mg/mL, significantly reduced the oxidative DNA damage compared with the non-supplemented group. The S. nigra extract showed a favorable toxicological profile, affording it potential to be used in the food industry.
PDF
