Astrocytic tumors are known for their high progression capacity and high mortality rates; in this regard, proteins correlated to prognosis can aid medical conduct. Although several genetic changes ...related to progression from grade 2 to grade 4 astrocytoma are already known, mRNA copies do not necessarily correlate with protein abundance and therefore could shadow further comprehension about this tumor's biology. This motivates us to seek for complementary strategies to study tumor progression at the protein level. Here we compare the proteomic profile of biopsies from patients with grade 2 (diffuse, n = 6) versus grade 4 astrocytomas (glioblastomas, n = 10) using shotgun proteomics. Data analysis performed with PatternLab for proteomics identified 5,206 and 6,004 proteins in the 2- and 4-grade groups, respectively. Our results revealed seventy-four differentially abundant proteins (p < 0.01); we then shortlist those related to greater malignancy. We also describe molecular pathways distinctly activated in the two groups, such as differences in the organization of the extracellular matrix, decisive both in tumor invasiveness and in signaling for cell division, which, together with marked contrasts in energy metabolism, are determining factors in the speed of growth and dissemination of these neoplasms. The degradation pathways of GABA, enriched in the grade 2 group, is consistent with a favorable prognosis. Other functions such as platelet degranulation, apoptosis, and activation of the MAPK pathway were correlated to grade 4 tumors and, consequently, unfavorable prognoses. Our results provide an important survey of molecular pathways involved in glioma pathogenesis for these histopathological groups.
Species from the Annona (Anonaceae) genus are used in traditional medicine for the treatment of various diseases. Ethnobotanical studies provide information regarding the plant part and the ...preparation method being used, while scientific studies such as in vitro, in vivo, and clinical tests can provide evidence supporting ethnopharmacological reports, directing studies towards the isolation of compounds which may be active for specific pathologies. Annona muricata and Annona squamosa were the most commonly reported species from those studied, with Annona cherimola and Annona classiflora also standing out. Acetogenins were the most commonly isolated metabolite class due to their cytotoxic properties, with flavonoids, alkaloids, steroids, and peptides also being reported. Many species from the Annona genus have proven biological activities, such as antitumor, antioxidant, antimicrobial and antifungal. The present review had as its objective to facilitate access to ethnobotanical, chemical and biological information in order to direct future researches.
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•New twenty-three hybrids bisnaphthoquinone x 1,2,3-1H-triazole were developed.•All compounds were screened against breast cancer cell lines MCF-7 and MDA-MB-231.•Some compounds ...presented as potential new drugs for cancer treatment.•Two of them (12g and 12h) two of them were selective with low toxicity.•12g and 12h are novel AMPK activators presenting selective antitumor effects.
The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for cancer treatment. The antitumor activity of the novel compounds was tested using the breast cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased reactive oxygen species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects.
Ortho
-Quinones represent a special class of redox active compounds associated with a spectrum of pronounced biological activities, including selective cytotoxicity and antimicrobial actions. The ...modification of the quinone ring by simple nitrogen and sulphur substitutions leads to several new classes of compounds with their own, distinct redox behaviour and equally distinct activities against cancer cell lines and
Trypanosoma cruzi
. Some of the compounds investigated show activity against
T. cruzi
at concentrations of 24.3 and 65.6 μM with a selectivity index of around 1. These results demonstrate that simple chemical modifications on the
ortho
-quinone ring system, in particular, by heteroatoms such as nitrogen and sulphur, transform these simple redox molecules into powerful cytotoxic agents with considerable "potential", not only in synthesis and electrochemistry, but also, in a broader sense, in health sciences.
New quinoidal compounds were prepared and evaluated against
T. cruzi
and cancer cell lines for the identification of new bioactive agents.
Summary
Several new direct‐acting antiviral (DAA) drugs are in development for chronic hepatitis C viral (HCV) infection, and NS3‐NS4A serine protease and the NS5B RNA‐dependent RNA polymerase have ...been the major targets. HCV variants displaying drug‐resistant phenotypes have been observed both in vitro and during clinical trials. Our aim was to characterize amino acid changes at positions previously associated with resistance in protease (NS3) and polymerase (NS5B) regions from treatment‐naïve HCV patients infected with genotypes 1a, 1b and 3a. All 1383 NS3 protease sequences (genotype 1a = 680, 1b = 498 and 3a = 205) and 806 NS5B polymerase sequences (genotypes 1a = 471, 1b = 329, 3a = 6) were collected from Los Alamos databank. Genotype 3a protease sequences showed the typical low‐level resistance mutation V36L. NS3 sequences from other genotypes presented mutations on positions 36, 39, 41, 43, 54, 80, 109, 155 and 168 in a frequency lower than 2%, except for the mutation Q80R found in 35% of genotype 1a isolates. Polymerase sequences from genotype 3a patients showed five typical mutations: L419I, I424V, I482L, V499A and S556G. Two positions presented high polymorphism in the NS5B region from genotype 1a (V499A) and genotype 1b (C316N) subjects. Our results demonstrated a natural profile of genotype 3a that can be associated with the pre‐existence of HCV variants resistant to first‐generation protease inhibitors and to non‐nucleoside polymerase inhibitors. Likewise, genotype 1b isolates and genotype 1a sequences exhibited pre‐existing mutations associated with resistance to Palm II and Thumb I polymerase inhibitors, respectively.
Production and sale of botanical insecticides depend on knowing the potential opportunities for these products. Essential oils from plants secondary metabolism can control pests, especially in ...agricultural systems where synthetic insecticides are limited, as in organic agriculture. The objective of this study was to evaluate the toxicity of essential oils to Diaphania hyalinata (Lepidoptera: Crambidae) and to show regions with the potential to use Cinnamomum zeylanicum, Citrus sinensis, and Syzygium aromaticum in the formulation and commercialization of insecticides to control this insect. The C. zeylanicum oil was more toxic to larvae and pupae and the S. aromaticum to eggs of D. hyalinata. Essential oils are an alternative for the management of D. hyalinata. The production of pesticides from essential oils of C. zeylanicum, C. sinensis, and S. aromaticum to control D. hyalinata has high potential in America. Also, Asia, Africa, Europe, the Middle East, and Asia can extract these plants to formulate insecticide molecules for the America countries.
Cheeses are able to serve as suitable matrices for supplying probiotics to consumers, enabling appropriate conditions for bacteria to survive gastric transit and reach the gut, where they are assumed ...to promote beneficial processes. The present study aimed to evaluate the microbiological, immunological, and histological changes in the gut of Salmonella Enteritidis-challenged rats fed goat cheese supplemented with the probiotic strain Lactobacillus rhamnosus EM1107. Thirty male albino Wistar rats were randomly distributed into 5 experimental groups with 6 animals each: negative (NC) and positive (PtC) control groups, control goat cheese (CCh), goat cheese added with L. rhamnosus EM1107 (LrCh), and L. rhamnosus EM1107 only (EM1107). All animals, except NC group were challenged with Salmonella Enteritidis (109 cfu in 1 mL of saline through oral gavage). Microbial composition was assessed with high-throughput 16S rRNA sequencing by means of Illumina MiSeq (Illumina, San Diego, CA). Nuclear factor kappa B (NF-κB) from the animal cecum tissue was determined by real-time PCR and interleukins (TNF-α, IL-1β, IL-10, and IFN-γ) by means of ELISA. Myeloperoxidase and malondialdehyde levels were determined biochemically. The administration of the L. rhamnosus EM1107 probiotic strain, either as a pure culture or added to a cheese matrix, was able to reduce Salmonella colonization in the intestinal lumen and lessen tissue damage compared with rats from PtC group. In addition, the use of cheese for the probiotic strain delivery (LrCh) was associated with a marked shift in the gut microbiota composition toward the increase of beneficial organisms such as Blautia and Lactobacillus and a reduction in NF-κB expression. These findings support our hypothesis that cheeses might be explored as functional matrices for the efficacious delivery of probiotic strains to consumers.
We report the synthesis of 47 new quinone-based derivatives
via
click chemistry and their subsequent evaluation against cancer cell lines and the control L929 murine fibroblast cell line. These ...compounds combine two redox centers, such as an
ortho
-quinone/
para
-quinone or quinones/selenium with the 1,2,3-triazole nucleus. Several of these compounds present IC
50
values below 0.5 μM in cancer cell lines with significantly lower cytotoxicity in the control cell line L929 and good selectivity index. Hence, our study confirms the use of a complete and very diverse range of quinone compounds with potential application against certain cancer cell lines.
Quinone-based frameworks with antitumor activities were described. We identified compounds with IC
50
values below 0.5 μM in cancer cells lines with significantly lower cytotoxicity in the control cell line L929.
We investigated the effect of including palm kernel cake (PKC) at the levels of 0, 80, 160 and 240 g kg
in the diet of lactating goats on the quality and sensory parameters of Minas Frescal cheese. ...Twelve goats were used in a triple 4 × 4 Latin square design. The dietary addition of PKC was associated with a reduction in moisture (
= 0.004), which compromised the cheese yield (
= 0.030). The ether extract content showed a quadratic response. There was a decrease in caproic (
= 0.014), caprylic (
= 0.011), capric (
= 0.003) and palmitic (
= 0.049) acids and an increase in lauric (
= 0.012) and myristic (
= 0.02) acids. Monounsaturated fatty acids increased (
= 0.008), whereas the ratio of polyunsaturated to saturated fatty acids (
= 0.022) and thrombogenicity index (
= 0.023) decreased. Principal component analysis indicated that control treatment and the treatment with 80 g kg
PKC were the most acceptable to the cheese tasters. The use of palm kernel cake is a good alternative for lactating goats when added to the diet at levels up to 80 g kg
.
The ground beetle, Neoaulacoryssus speciosus (Coleoptera: Carabidae) is of high relevance to field because it has been recorded as a pest of seeds and young plants of vegetables and other crops and a ...predator in agricultural crops, forest and weeds in Brazil. However, natural habitat changes are increasing agriculture and forest insect outbreaks in urban areas. A N. speciosus population outbreak occurred in October and November 2018 simultaneously in 12 neighboring municipalities at the beginning of the rainy season in the northern region of Minas Gerais State, Brazil. The objectives of this study were to report a sudden and simultaneous population outbreak of N. speciosus and to describe the factors of habitat change that could have contributed to this invasion in 12 municipalities in the northern region of Minas Gerais State in the Caatinga biome of Brazil. In addition, female and male genitals were described and illustrated, the scientific classification revised and common names of N. speciosus listed. Thousands of males and females of N. speciosus agglomerated in shady, humid places during the day and night for about 15 days. Neoaulacoryssus speciosus has been identified and illustrated, its scientific classification revised and four common names listed for this species.
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