Telmisartan exerts beneficial effects in an acetic acid model of colitis in rats. These effects may be due to accelerated termination of the acute inflammatory phase, indicated by decreased TNF-α and increased production of IL-10 and low expression of RANKL and RANK.
Microbial resistance to conventional antibiotics is a public health problem worldwide, motivating the search for new therapeutic alternatives in varied natural sources. Cationic peptides without disulfide bridges from scorpions have been targeted in this context, mainly due to their multifunctional action and the limited ability of microorganisms to develop resistance against them. The present study was focused on Stigmurin and TsAP-2, cationic peptides found in the transcriptome of the venom gland from the scorpion Tityus stigmurus. The aims were: to assess the secondary structure of TsAP-2 and the structural stability of both peptides by circular dichroism; to evaluate their antiproliferative effect, and antimicrobial activities in vitro, ex vivo and in vivo; and to investigate their therapeutic potential in a murine model of polymicrobial sepsis. Stigmurin and TsAP-2 secondary structures responded similarly to environment polarity changes, and were stable to temperature and pH variation. Both peptides showed antiproliferative effect on tumor cells. TsAP-2 showed lower cytotoxicity to normal cells, and had a mitogenic activity on murine macrophages. Stigmurin demonstrated bactericidal and bacteriostatic activity, depending on the microorganism, whereas TsAP-2 had bactericidal action upon different bacterial strains analyzed. Both peptides were able to reduce leukocyte migration, TNF-α levels and microorganism load in the peritoneal cavity after induction of experimental sepsis, decreasing inflammation in the lung and cecum of septic animals. TsAP-2 also reduced the release of nitric oxide in the peritoneal cavity. Taken together, these data suggest that Stigmurin and TsAP-2 are structurally stable molecules and are efficient in the control of the infectious focus in polymicrobial sepsis, with potential use as a prototype for the rational design of novel therapeutic agents.
In this paper, principal component analysis (PCA), successive projections algorithm (SPA), and genetic algorithm (GA) followed by support vector machines (SVM), combined with Fourier-transform mid-infrared (FT-MIR) spectroscopy were presented as complementary or alternatives tools to the traditional methods for prostate cancer screening and classification. These approaches were applied to analyze tissue samples, and their performances were compared within dependent SVM models and with traditional methods of diagnosis, according to class separation interpretability, time consumption, and figures of merit. The results showed that variable reduction and selection methods followed by SVM can reduce drawbacks of independent SVM analysis. The potential biomarkers indicated by PCA-SVM, SPA-SVM, and GA-SVM were amide I, II, and III; as well as protein regions (1400-1585 cm −1 ), followed by DNA/RNA (O-P-O symmetric stretch) (1080 cm −1 ) and DNA (O-P-O asymmetric stretch) (1230 cm −1 ) regions. GA-SVM was the best classification approach, with higher sensitivity (100%) and specificity (80%), particularly in early stages, being better than traditional methods of diagnosis. KEYWORDSFT-MIR, prostate cancer, SVM, tissue 1 | INTRODUCTION Currently, prostate cancer recognition follows some phases. First of all, the proctologist evaluates the prostate by Digital Rectal Examination (DRE), which allows palpation of only 40% to 50% of the prostate, and it is mainly affected by intraobserver and inter-observer variability, resulting in DRE sensitivity and specificity of about 21% to 37% and 71% to 91%, respectively. 1-5 Concomitantly, a measurement of serum prostatic specific antigen levels is performed which have about 21% and 64% sensitivity and specificity in earliest stages, respectively, and about 32% and 93% sensitivity and specificity in high grade prostate cancers, respectively. When combined with DRE, sensitivity and specificity increase from 51% to 68% and from 92% to 94%, respectively 1-8 ; however, this measurement can be affected by other factors beyond prostate cancer, such as ejaculation, bacterial prostatitis, biopsy, and acute urinary retention, which may elevate prostatic specific antigen levels. 3,[5][6][7][8] According to the results of these exams, a biopsy coupled with an anatomopathological examination can be indicated in order to identify cancer stage. Trans-rectal ultrasound (TRUS)-guided biopsy is currently the gold standard, characterized by 39% to 52% sensitivity and 81% to 82% specificity. 9 The anatomopathological examination by Gleason score system classifies biopsy samples according to tumor aggressiveness and provides a prognostic idea. It defines Gleason 1 (best differentiation and most favorable prognosis) to Gleason 5 (least differentiation and poor prognosis). [10][11][12] The sum of the primary (most architectural atypia) and secondary (least architectural atypia) patterns leads to the Gleason score (eg, Gleason 3 + Gleason 4 is equivalent to a Gleason score 3 + 4 = 7). 12 In 2014, a new Gleaso...
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