Breast cancer is one of the common tumors occurring in woman and despite treatment, the prognostic is poor. Genistein, a soy isoflavone, has been reported to have chemopreventive\chemotherapeutic ...potential in multiple tumor types. Here, we investigated the genistein antiproliferative effect in MCF-7 breast cancer, underlying the molecular mechanisms involved in this effect. MCF-7 cancer and CCD1059sK fibroblast cells were treated with estradiol (10 nM) or genistein (0.01–100 μM) for 24, 48, and 72 h and the cell proliferation was investigated by MTT; membrane cell permeability was evaluated by LDH and PI incorporation; apoptosis was investigated by externalization of phosphatidylserine by FACS; and presence of autophagy was detected by LC3A/B immunostaining. The expression of apoptotic proteins and antioxidant enzymes was evaluated by qPCR. The results demonstrate that genistein (100 μM) for 72 h of treatment selectively reduced MCF-7 cell proliferation independent of estrogen receptor activation, while no cytotoxicity was observed in fibroblast cells. Further experiments showed that genistein induced phosphatidylserine externalization and LC3A/B immunopositivity in MCF-7 cells, indicating apoptosis and autophagy cell death. Genistein increased in three times proapoptotic BAX/Bcl-2 ratio and promoted a parallel downregulation of 20 times of antiapoptotic survivin. In addition, genistein promoted a decrease of 5.5, 9.3, and 3.6 times of MnSOD, CuZnSOD, and TrxR mRNA expression, respectively, while the GPx expression was increased by 6.5 times. These results suggest that the antitumor effect of genistein involved the modulation of antioxidant enzyme and apoptotic signaling expression, which resulted in apoptosis and progression of autophagy.
The number of paleoprecipitation records from the South American Monsoon domain that cover the last millennium has increased substantially in past years. However, hitherto most studies focused only ...on regional aspects, thereby neglecting the role of large‐scale monsoon variability and the mechanisms that link proxy locations in space and time. Here we decompose the South American Monsoon into its main modes of variability by applying a Monte Carlo principal component analysis to a compilation of 11 well‐dated summer paleoprecipitation records from tropical South America. The first mode represents changes in precipitation over the core monsoon domain, while the second mode is characterized by high loadings along the fringes of the South American Monsoon over Southeastern South America and the northern monsoon limit. Composite analysis reveals an enhanced monsoon with a wider, rather than a southward displaced, South Atlantic Convergence Zone during the early Little Ice Age, in contrast to previous interpretations.
Plain Language Summary
The South American Monsoon is responsible for more than 70% of the annual precipitation falling over tropical South America. Due to the lack of data prior to the middle of the twentieth century, the long‐term variability of the monsoon is poorly understood. Yet there are concerns that increasing greenhouse gas concentrations may significantly modify monsoon behavior in the 21st century. To better understand how the monsoon responds to such perturbations, detailed knowledge of how it varied in the past is crucial. This will facilitate improvements to Earth System Models that are used to project future rainfall changes in the region. Here 11 paleoprecipitation records that span the last millennium are analyzed using statistical techniques that allow extracting the shared variability from all records. Our result highlight how the monsoon responded in space and time to large‐scale perturbations of the climate system, associated with the Little Ice Age and the Medieval Climate Anomaly.
Key Points
We use high‐resolution δ18O records to decompose the South American Monsoon into its main modes of variability during the last millennium
The first mode shows an enhanced monsoon during the Little Ice Age and a weakening during the Medieval Climate Anomaly
The second mode represents monsoon variability along the fringes of the monsoon area and indicates periods of widening/contractions of the monsoon axis
Cancer-associated fibroblasts (CAFs) promote tumor malignancy, but the precise transcriptional mechanisms regulating the acquisition of the CAF phenotype are not well understood. We show that the ...upregulation of SOX2 is central to this process, which is repressed by protein kinase Cζ (PKCζ). PKCζ deficiency activates the reprogramming of colonic fibroblasts to generate a predominant SOX2-dependent CAF population expressing the WNT regulator Sfrp2 as its top biomarker. SOX2 directly binds the Sfrp1/2 promoters, and the inactivation of Sox2 or Sfrp1/2 in CAFs impaired the induction of migration and invasion of colon cancer cells, as well as their tumorigenicity in vivo. Importantly, recurrence-free and overall survival of colorectal cancer (CRC) patients negatively correlates with stromal PKCζ levels. Also, SOX2 expression in the stroma is associated with CRC T invasion and worse prognosis of recurrence-free survival. Therefore, the PKCζ-SOX2 axis emerges as a critical step in the control of CAF pro-tumorigenic potential.
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•PKCζ is lost in the stroma of poor-prognosis mesenchymal human CMS4 CRC•Stromal loss of PKCζ upregulates SOX2 to promote the CAF phenotype•Selective deletion of PKCζ in fibroblast activates the SOX2/SFRP1/2 axis in vivo•Stromal SOX2 negatively correlates with PKCζ and predicts poor survival in CRC
Kasashima et al. describe a molecular mechanism whereby the loss of PKCζ in the stroma upregulates SOX2 to activate the reprogramming of colonic fibroblasts generating a SFRP1/2-expressing CAF population. This population supports epithelial tumor progression, revealing vulnerabilities in mesenchymal CMS4 colorectal cancer.
Most reconstructions of the South American Monsoon System (SAMS) over the last two millennia are based on δ18O records from locations at high‐elevation sites in the Andes, which are not influenced by ...the South Atlantic Convergence Zone (SACZ). Yet the SACZ is a key driver of SAMS variability over much of Brazil. Here we use two new δ18O records from speleothems sampled in the central and southwestern portions of the SACZ core to show that the SAMS was not varying in phase over the entire tropical continent during the last two millennia. In fact, speleothem records located to the northeast of the SACZ record precipitation variations that are antiphased with similar records on the opposite side of the SACZ, in particular during the Little Ice Age period, while records close to the core of the SACZ axis show no significant departure from the mean state during this period.
Plain Language Summary
The South American Monsoon System (SAMS) is responsible for most rainfall occurring over tropical South America. Within this monsoon system the South Atlantic Convergence Zone (SACZ) is considered a key driver of SAMS variability over Brazil. By analyzing the chemical composition of stalagmites we can track the history of rainfall in the region where these stalagmites grew. Using stalagmites from caves in the SACZ region of Brazil that formed during the last two millennia, we can reconstruct the behavior of the SACZ, and consequently the rainfall distribution over Brazil during this period, which includes global climate changes that significantly affected human history, such as the Medieval Climate Anomaly and the Little Ice Age. Understanding the nature of these past changes in climate is fundamental for putting current climate changes in a longer‐term perspective and for differentiating between natural and anthropogenic causes of current and future climate change.
Key Points
A new and expanded network of speleothem records from eastern Brazil recorded the movement of the South Atlantic Convergence Zone over the last 2,000 years
The new network shows that precipitation did not vary in phase throughout the entire monsoon domain during the last millennium over Brazil
Variations in location and intensity of the South Atlantic Convergence Zone represent a main driver of hydrologic variability over Brazil
Plant-based diets have emerged as athletic performance enhancers for various types of exercise. Therefore, the present study evaluated the effectiveness of plant-based diets on aerobic and ...strength/power performances, as well as on BMI of physically active individuals. This systematic review and meta-analysis was conducted and reported according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A systematic search of electronic databases, including PubMed, Web of Science and SPORTDiscus, was performed. On the basis of the search and inclusion criteria, four and six studies evaluating the effects of plant-based diets on aerobic and strength/power performances in humans were, respectively, included in the systematic review and meta-analysis. Plant-based diets had a moderate but positive effect on aerobic performance (0·55; 95 % CI 0·29, 0·81) and no effect on strength/power performance (-0·30; 95 % CI -0·67, 0·07). The altogether analyses of both aerobic and strength/power exercises revealed that athletic performance was unchanged (0·01; 95 % CI -0·21, 0·22) in athletes who adopted plant-based diets. However, a small negative effect on BMI (-0·27; 95 % CI -0·40, -0·15) was induced by these diets. The results indicate that plant-based diets have the potential to exclusively assist aerobic performance. On the other hand, these diets do not jeopardise strength/power performance. Overall, the predicted effects of plant-based diets on physical performance are impactless, even though the BMI of their adherents is reduced.
Background
Several tests may be used to assess exercise intolerance in cystic fibrosis (CF), including the gold standard cardiopulmonary exercise test (CPET) and the Modified Shuttle Test (MST).
...Objective
To evaluate the use of the MST as a predictor of peak oxygen uptake (VO2peak) and to compare VO2peak and maximal heart rate (HRmax) obtained in both tests.
Methods
Cross‐sectional study including individuals with CF aged between 6 and 20 years old. Participants who were unable to perform the tests and/or presented signs of pulmonary exacerbation were excluded. Demographic, anthropometric, clinical and spirometric values were collected. CPET and the MST were performed in two consecutive outpatient visits. HRmax, peripheral oxygen saturation, dyspnea, and VO2peak measured and estimated were compared.
Results
Twenty‐four patients, mean age 15.7 ± 4.2 years and FEV1 (% predicted) 76.4 ± 23.8, were included. Mean values of HRmax (bpm) and HRmax in percent of predicted (HRmax%) were lower (P = 0.01) in the MST (171.6 ± 14.5 and 87.1 ± 7.5) compared to CPET (180.9 ± 10.0 and 91.9 ± 5.4). However, there was no significant differences between tests in the variation (delta) for HRmax and HRmax% (P = 0.17). A strong correlation (r = 0.79; P < 0.0001) was found between distance achieved (MST) and VO2peak (CPET). The regression model to estimate VO2peak resulted in the following equation: VO2(mL · kg−1 · min−1) = 20.301 + 0.019 × MST distance (meters). There was no difference (P = 0.50) between VO2peak measured (CPET) and estimated by the equation.
Conclusion
The MST may be an alternative method to evaluate exercise capacity and to predict VO2peak in children and adolescents with CF.
Whereas pulmonary exacerbations and aerobic fitness play a key role in the prognosis of cystic fibrosis (CF), the use of ventilatory threshold data as markers of exacerbation risk has been scarcely ...addressed. This study sought to examine the association between aerobic fitness, assessed through ventilatory threshold variables recorded during cardiopulmonary exercise testing (CPET), and the risk of exacerbations in individuals with CF.
Participants of this retrospective cohort study were subjects from 6 y of age. Over a 4-y period, the following data were recorded: lung function indicators, CPET variables, time to first exacerbation and antibiotic use, along with demographic, clinical, and anthropometric data.
The mean age of 20 subjects included was 16 ± 5.4 y. Univariate regression analysis revealed that lung function (FEV
: Cox hazard ratio HR 0.97,
= .03; and forced expiratory flow between 25-75% of vital capacity FEF
: Cox HR 0.98,
= .036) and aerobic fitness (oxygen consumption V̇
at ventilatory threshold: Cox HR 0.94,
= .01; and ventilatory equivalent for carbon dioxide V̇
/V̇
at ventilatory threshold: Cox HR 1.13,
= .049) were associated with exacerbation risk, whereas in the multivariate model, only V̇
at the ventilatory threshold (%max) (Cox HR 0.92,
= .01) had a significant impact on this risk. Consistently, individuals experiencing exacerbation had significantly lower V̇
values (%max) at the ventilatory threshold (
= .050) and higher ventilatory equivalent for oxygen consumption (V̇
/V̇
) (
= .040) and V̇
/V̇
(
= .037) values at the ventilatory threshold. Time to exacerbation was significantly correlated with V̇
at the ventilatory threshold (r = 0.50,
= .02), V̇
/V̇
(r = -0.48,
= .02), and V̇
/V̇
(r = -0.50,
= .02).
Our results suggest an association between CPET variables at the ventilatory threshold and exacerbations. Percentage V̇
at the ventilatory threshold could serve as a complementary variable to monitor exacerbations in people with CF.
Sodium monensin is the most frequently used ionophore as a growth promoter in ruminant diets. It has numerous benefits; however its toxic effects have also been observed in several animal species. ...Naturally occurring cases have not yet been reported in goats. This study describes an outbreak of accidental poisoning, characterizing its clinical, laboratory and pathological findings. Thirty-seven of 40 Anglo Nubian goat kids became intoxicated after receiving a diet that was erroneously supplemented with sodium monensin. They ingested an estimated toxic dose between 25 and 39 mg/kg BW. Clinical evolution was monitored (n = 27), followed by serum creatine kinase (CK) and aspartate aminotransferase (AST) activities measurements, and blood gas analysis. Postmortem examinations were performed between 1 and 8 days of evolution (n = 14). Clinical signs began 5 h after ingestion and included reticuloruminal hypomotility, lethargy, anorexia, tachycardia, cardiac arrhythmia, wet cough, pulmonary and tracheal crackles, and serous nasal discharge. The morbidity and lethality rates were 92.5 and 62.1%, respectively. CK and AST activities increased, reaching median values of 10,860 and 1596 U/L, respectively; the hyperchloremic metabolic acidosis was mild. The lesions were characterized by degeneration and necrosis of the cardiac and skeletal muscles, pulmonary congestion and edema, and passive liver congestion. The kids essentially developed cardiomyopathy with left and right congestive heart failures. Unlike in other ruminant species, skeletal muscle functional disability was infrequent. It can be concluded that monensin is toxic to goats and should be used with caution in their diet.
Nitric oxide (NO) is an important molecule involved in the perception of stress induced by toxic compounds such as arsenic (As). The present study investigated the role of NO applied as sodium ...nitroprusside (SNP) in cell signalling and the ability of NO to attenuate the toxic effects of As (in the form of sodium arsenate) in water hyacinth (Eichhornia crassipes). Water hyacinth plants were collected and assigned to one of the following treatments: control; 100 μM SNP; 20 μM As; or 20 μM As + 100 μM SNP. The plants remained under these conditions for 0, 4, 12, and 24 h. After each time interval, the plants were collected and As absorption, production of reactive oxygen species (ROS), integrity of membranes, and antioxidant enzyme activities were evaluated. The plants were able to absorb and accumulate large amounts of As, even after only four hours of exposure to the pollutant. The absorption and bioaccumulation factor of As was even greater when plants were exposed to both As and SNP. The accumulation of As triggered increases in ROS production and cell membrane damage. In the presence of SNP, the tolerance index to As increased and damage was mitigated. Therefore, from the present work, it was possible to conclude that exogenous NO influenced the ability of plants to tolerate As; this finding has implications for phytoremediation in areas contaminated by As.
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