Parasiticidal effect of synthetic bovine lactoferrin peptides on the enteric parasite Giardia intestinalis.

Giardia intestinalis is the most common infectious protozoan parasite in children. Despite the effectiveness of some drugs, the disease remains a major worldwide problem. Consequently, the search for new treatments is important for disease eradication. Biological molecules with antimicrobial properties represent a promising alternative to combat pathogens. Bovine lactoferrin (bLF) is a key component of the innate host defense system, and its peptides have exhibited strong antimicrobial activity. Based on these properties, we evaluated the parasiticidal activity of these peptides on G. intestinalis. Trophozoites were incubated with different peptide concentrations for different periods of time, and the growth or viability was determined by carboxyfluorescein-succinimidyl-diacetate-ester (CFDA) and propidium iodide (PI) staining. Endocytosis of peptides was investigated by confocal microscopy, damage was analyzed by transmission and scanning electron microscopy, and the type of programmed cell death was analyzed by flow cytometry. Our results showed that the LF peptides had giardicidal activity. The LF peptides interacted with G. intestinalis and exposure to LF peptides correlated with an increase in the granularity and vacuolization of the cytoplasm. Additionally, the formation of pores, extensive membrane disruption, and programmed cell death was observed in trophozoites treated with LF peptides. Our results demonstrate that LF peptides exhibit potent in vitro antigiardial activity.

National Burden and Trends for 29 Groups of Cancer in Mexico from 1990 to 2019: A Secondary Analysis of the Global Burden of Disease Study 2019.

The global burden of cancer is on the rise, with varying national patterns. To gain a better understanding and control of cancer, it is essential to provide national estimates. Therefore, we present a comparative description of cancer incidence and mortality rates in Mexico from 1990 to 2019, by age and sex for 29 different cancer groups. Based on public data from the Global Burden of Disease Study 2019, we evaluated the national burden of cancer by analyzing counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and trends using the annual percentage change from 1990 to 2019. In 2019, cancer resulted in 222,060 incident cases and 105,591 deaths. In 2019, the highest incidence of cancer was observed in non-melanoma skin cancer, prostate cancer, and breast cancer. Additionally, 53% of deaths were attributed to six cancer groups (lung, colorectal, stomach, prostate, breast, and pancreatic). From 1990 to 2019, there was an increasing trend in incidence and mortality rates, which varied by 10-436% among cancer groups. Furthermore, there were cancer-specific sex differences in crude and age-standardized rates. The results show an increase in the national cancer burden with sex-specific patterns of change. These findings can guide national efforts to reduce health loss due to cancer.

Incidence, Mortality, and Trends of Prostate Cancer in Mexico from 2000 to 2019: Results from the Global Burden of Disease Study 2019.

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases and 9.2 thousand (7.7-12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

Vanadium pentoxide increased PTEN and decreased SHP1 expression in NK-92MI cells, affecting PI3K-AKT-mTOR and Ras-MAPK pathways.

Vanadium is an air pollutant that imparts immunosuppressive effects on NK cell immune responses, in part, by dysregulating interleukin (IL)-2/IL-2R-mediated JAK signaling pathways and inducing apoptosis. The aim of the present study was to evaluate effects of vanadium pentoxide (V2O5) on other IL-2 receptor-mediated signaling pathways, i.e. PI3K-AKT-mTOR and Ras-MAPK. Here, IL-2-independent NK-92MI cells were exposed to different V2O5 doses for 24 h periods. Expression of PI3K, Akt, mTOR, ERK1/2, MEK1, PTEN, SHP1, BAD and phosphorylated forms, as well as caspases-3, -8, -9, BAX and BAK in/on the cells were then determined by flow cytometry. The results show that V2O5 was cytotoxic to NK cells in a dose-related manner. Exposure increased BAD and pBAD expression and decreased that of BAK and BAX, but cell death was not related to caspase activation. At 400 µM V2O5, expression of PI3K-p85 regulatory subunit increased 20% and pPI3K 50%, while that of the non-pPI3K 110α catalytic subunit decreased by 20%. At 200 µM, V2O5 showed significant decrease in non-pAkt expression (p < 0.05); the decrease in pAkt expression was significant at 100 µM. Non-pmTOR expression displayed a significant downward trend beginning at 100 µM. Expressions of pMEK-1/2 and pERK-1/2 increased substantially at 200 µM V2O5. No differences were found with non-phosphorylated ERK-1/2. PTEN expression increased significantly at 100 µM V2O5 exposure whereas pPTEN decreased by 18% at 25 µM V2O5 concentrations, but remained unchanged thereafter. Lastly, V2O5 at all doses decreased SHP1 expression and increased expression of its phosphorylated form. These results indicated a toxic effect of V2O5 on NK cells that was due in part to dysregulation of signaling pathways mediated by IL-2 via increased PTEN and decreased SHP1 expression. These results can help to explain some of the known deleterious effects of this particular form of vanadium on innate immune responses.

Vanadium pentoxide prevents NK-92MI cell proliferation and IFNγ secretion through sustained JAK3 phosphorylation.

Vanadium is a major air pollutant with toxic and carcinogenic effects; it also exercises immunosuppressive effects on the adaptive immune response. Its effect on the innate immune response is poorly explored. The aim of this study was to identify if vanadium pentoxide (V2O5) impairs the function of immunoregulatory NK cells and to determine possible mechanisms associated with this effect. Interleukin-2-independent NK-92MI cells were exposed to different V2O5 concentrations for 6, 12, or 24 h periods. Cell proliferation was then evaluated using CFSE staining, apoptosis by Annexin V binding, and necrosis by 7-AAD staining. The release of IL-2, -4, -6, -10, -17A, IFNγ, and TNFα by the cells were assessed using a human CBA kit. Expression of CD45, SOCS1, JAK3, pJAK3, STAT5, pSTAT5, IL-2R, IL-15R, Fas, and FasL in/on the cells was determined by flow cytometry; JAK3 and pJAK3 expression were also evaluated via confocal microscopy. The results indicated that V2O5 could inhibit NK-92MI cell proliferation and induce cell apoptosis in a dose- and time-related manner. V2O5 also inhibited IL-2, IL-10, and IFNγ secretion but mostly only after 24 h of exposure and with primarily the higher doses tested. V2O5 had no effect on expression of JAK3 and STAT5, but did cause an increase in pJAK3 and appeared to lead (trend) to reductions in levels of phosphorylated STAT5. V2O5 increased the expression of IL-2R, IL-15R, Fas, and FasL at concentrations above the 50-100 µM range. V2O5 had no effect on expression of the CD45 membrane phosphatase, but it did cause an increase in the expression of SOCS1. These results indicate that a key toxic effect of V2O5 on NK cells is a dysregulation of signaling pathways mediated by IL-2. These effects could help to explain the previously-reported deleterious effects on innate immune responses of hosts exposed to inhaled V2O5.