Background
Wei Le San (WLS) is a Chinese herbal formula comprised of 9 herbs selected for their putative anti‐inflammatory effects.
Objectives
To evaluate the effects of WLS administration in horses ...with nonglandular gastric ulcers.
Animals
Ten mixed breed mares (aged 7‐21 years, 401‐567 kg body weight).
Methods
Experimental design was a blinded, prospective, 2‐period crossover study. All horses received a placebo (25 mL dextrose‐based syrup; n = 10) and the treatment (WLS, 5 g in 25 mL dextrose‐based syrup; n = 10), administered twice daily. Horses underwent a 1‐week, alternating feed‐deprivation period to induce or worsen existing ulcers; treatment began on day 7. Gastroscopic examination was performed on d0, d6, and d35, with gastric fluid pH obtained on d6 and d35. Gastric ulcer scores assigned by 3 masked observers were averaged for each examination.
Results
Ulcer number scores for horses treated with WLS (median = 0; range, 0‐4) was not different from the untreated controls (median = 0.5; range, 0‐4; P = .81) by the end of the treatment period. Ulcer severity score for treated horses (median = 0; range, 0‐1) was also unchanged compared to the control group (median = 0.5; range, 0‐1; P = .85). Gastric pH was not altered by either treatment, with a median of 2.1 (range, 1.9‐4.1) for the horses treated with WLS and 2.8 (range, 1.6‐7.2) in the untreated controls (P = .46).
Conclusions and Clinical Importance
The experimental model used to induce gastric ulceration was unable to discern a difference between the herbal supplement and the placebo in normal horses.
Flowslides and debris flows in granular soils pose a serious threat to human life and man-made structures. Due to rainwater infiltrating into superficial unsaturated soils, rainfall is the most ...common triggering factor of such landslides, causing a decrease in matric suction and hence in soil shear strength. Early warning systems based on accurate analyses of groundwater response to meteorological factors are widely used to mitigate landslide risk. In such a context, the accuracy of the model adopted to calculate the groundwater field is closely related to the reliability and meaningfulness of hydraulic soil characterization. In this paper, an extensive laboratory investigation regarding the hydraulic behaviour of pyroclastic unsaturated deposits from a vegetated slope monitored on Mount Faito (Campania, Southern Italy) is presented to highlight the importance of hydraulic hysteresis and the presence of roots in shallow soils. Water retention properties and hydraulic conductivity functions were determined, focusing on a drying–wetting cycle. Tests on specimens sampled in the top ten centimetres of the soil profile were also carried out to assess the effects of plant roots on soil hydraulic properties. Inverse analyses were used to estimate the parameters of a hysteretic hydraulic model. Finally, parametric numerical analyses, carried out via a finite element code, were used to highlight the potential effects of the hydraulic characterization on the stability of sloping pyroclastic covers, including all above factors.
•Hydraulic hysteresis was investigated for some Italian pyroclastic unsaturated soils.•Experimentally, permeability of root-permeated soil is higher than in bare soils.•The model was adapted to consider the effect of roots on the hydraulic behaviour.•The wetting front progression from ground surface was modelled in unsaturated soils.
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•Development time is minimized at intermediate protein to carbohydrate (P:C) ratios.•The highest P:C ratios confer maximum body/ovary size and survival.•Larvae regulate their nutrient ...intake towards intermediate P:C ratios.•Females lay their eggs in low P:C ratios.
Organisms from slime moulds to humans carefully regulate their macronutrient intake to optimize a wide range of life history characters including survival, stress resistance, and reproductive success. However, life history characters often differ in their response to nutrition, forcing organisms to make foraging decisions while balancing the trade-offs between these effects. To date, we have a limited understanding of how the nutritional environment shapes the relationship between life history characters and foraging decisions. To gain insight into the problem, we used a geometric framework for nutrition to assess how the protein and carbohydrate content of the larval diet affected key life history traits in the fruit fly, Drosophila melanogaster. In no-choice assays, survival from egg to pupae, female and male body size, and ovariole number – a proxy for female fecundity – were maximized at the highest protein to carbohydrate (P:C) ratio (1.5:1). In contrast, development time was minimized at intermediate P:C ratios, around 1:2. Next, we subjected larvae to two-choice tests to determine how they regulated their protein and carbohydrate intake in relation to these life history traits. Our results show that larvae targeted their consumption to P:C ratios that minimized development time. Finally, we examined whether adult females also chose to lay their eggs in the P:C ratios that minimized developmental time. Using a three-choice assay, we found that adult females preferentially laid their eggs in food P:C ratios that were suboptimal for all larval life history traits. Our results demonstrate that D. melanogaster larvae make foraging decisions that trade-off developmental time with body size, ovariole number, and survival. In addition, adult females make oviposition decisions that do not appear to benefit the larvae. We propose that these decisions may reflect the living nature of the larval nutritional environment in rotting fruit. These studies illustrate the interaction between the nutritional environment, life history traits, and foraging choices in D. melanogaster, and lend insight into the ecology of their foraging decisions.
Rose bengal is an anionic dye considered as a potential photosensitizer for anticancer photodynamic therapy. The clinical utility of rose bengal is hampered by its short half-life, limited ...transmembrane transport, aggregation, and self-quenching; consequently, efficient drug carriers that overcome these obstacles are urgently required. In this study, we performed multilevel in vitro and in silico characterization of interactions between rose bengal and cationic poly(amidoamine) (PAMAM) and poly(propyleneimine) (PPI) dendrimers of the third and fourth generation and assessed the ability of the resultant complexes to modulate the photosensitizing properties of the drug. We focused on explaining the molecular basis of this phenomenon and proved that the generation- and structure-dependent binding of the dye by the dendrimers increases the cellular uptake and production of singlet oxygen and intracellular reactive oxygen species, leading to an increase in phototoxicity. We conclude that the application of dendrimer carriers could enable the design of efficient photodynamic therapies based on rose bengal.
Polo-like kinase 4 (Plk4), the major regulator of centriole biogenesis, has emerged as a putative therapeutic target in cancer due to its abnormal expression in human carcinomas, leading to ...centrosome number deregulation, mitotic defects and chromosomal instability. Moreover, Plk4 deregulation promotes tumor growth and metastasis in mouse models and is significantly associated with poor patient prognosis. Here, we further investigate the role of Plk4 in carcinogenesis and show that its overexpression significantly potentiates resistance to cell death by anoikis of nontumorigenic p53 knock-out (p53KO) mammary epithelial cells. Importantly, this effect is independent of Plk4's role in centrosome biogenesis, suggesting that this kinase has additional cellular functions. Interestingly, the Plk4-induced anoikis resistance is associated with the induction of a stable hybrid epithelial-mesenchymal phenotype and is partially dependent on P-cadherin upregulation. Furthermore, we found that the conditioned media of Plk4-induced p53KO mammary epithelial cells also induces anoikis resistance of breast cancer cells in a paracrine way, being also partially dependent on soluble P-cadherin secretion. Our work shows, for the first time, that high expression levels of Plk4 induce anoikis resistance of both mammary epithelial cells with p53KO background, as well as of breast cancer cells exposed to their secretome, which is partially mediated through P-cadherin upregulation. These results reinforce the idea that Plk4, independently of its role in centrosome biogenesis, functions as an oncogene, by impacting the tumor microenvironment to promote malignancy.
Melanoma is the deadliest type of skin cancer, with about 61,000 deaths annually worldwide. Late diagnosis increases mortality rates due to melanoma's capacity to metastasise rapidly and patients' ...resistance to the available conventional therapies. Consequently, the interest in natural products as a strategy for drug discovery has been emerging. Propolis, a natural product produced by bees, has several biological properties, including anticancer effects. Propolis from Gerês is one of the most studied Portuguese propolis. Our group has previously demonstrated that an ethanol extract of Gerês propolis collected in 2018 (G18.EE) and its fractions (
-hexane, ethyl acetate, and
-butanol) decrease melanoma cell viability. Out of all the fractions, G18.EE-
-BuOH showed the highest potential as a melanoma pharmacological therapy. Thus, in this work, G18.EE-
-BuOH was fractioned into 17 subfractions whose effect was evaluated in A375
-mutated melanoma cells. The subfractions with the highest cytotoxic activity were analysed by UPLC-DAD-ESI/MS
in an attempt to understand which phenolic compounds could account for the anti-melanoma activity. The compounds identified are typical of the Gerês propolis, and some of them have already been linked with antitumor effectiveness. These results reaffirm that propolis compounds can be a source of new drugs and the isolation of compounds could allow its use in traditional medicine.
Melanoma is the most aggressive and life-threatening skin cancer type. The melanoma genome is the most frequently mutated, with the
mutation present in 40-60% of melanoma cases.
-mutated melanomas ...are characterized by a higher aggressiveness and progression. Adjuvant targeted treatments, such as BRAF and MEK inhibitors, are added to surgical excision in
-mutated metastatic melanomas to maximize treatment effectiveness. However, resistance remains the major therapeutic problem. Interest in natural products, like propolis, for therapeutic applications, has increased in the last years. Propolis healing proprieties offer great potential for the development of novel cancer drugs. As the activity of Portuguese propolis has never been studied in melanoma, we evaluated the antitumoral activity of propolis from Gerês (G18.EE) and its fractions (
-hexane, ethyl acetate (EtOAc), and
-butanol) in A375 and WM9 melanoma cell lines. Results from DPPH•/ABTS• radical scavenging assays indicated that the samples had relevant antioxidant activity, however, this was not confirmed in the cell models. G18.EE and its fractions decreased cell viability (SRB assay) and promoted ROS production (DHE/Mitotracker probes by flow cytometry), leading to activation of apoptotic signaling (expression of apoptosis markers). Our results suggest that the
-BuOH fraction has the potential to be explored in the pharmacological therapy of melanoma.
Background Acute respiratory distress syndrome (ARDS) is a severe complication of malaria that remains largely unstudied. We aim to describe the development of ARDS associated with severe P. ...falciparum malaria, its management and impact on clinical outcome. Methods Retrospective observational study of adult patients admitted with severe P. falciparum malaria in an Intensive Care Unit (ICU) of a tertiary care hospital from Portugal from 2008 to 2018. A multivariate logistic regression analysis was used to identify factors associated with the development of ARDS, defined according to Berlin Criteria. Prognosis was assessed by case-fatality ratio, nosocomial infection and length of stay. Results 98 patients were enrolled, of which 32 (33%) developed ARDS, a median of 2 days after starting antimalarial medication (IQR 0-4, range 0-6). Length of stay in ICU and in hospital were significantly longer in patients who developed ARDS: 13 days (IQR 10-18) vs 3 days (IQR 2-5) and 21 days (IQR 15-30.5) vs 7 days (IQR 6-10), respectively. Overall case-fatality ratio in ICU was 4.1% and did not differ between groups. The risk of ARDS development is difficult to establish. Conclusion ARDS is a hard to predict late complication of severe malaria. A low threshold for ICU admission and monitoring should be used. Ideally patients should be managed in a centre with experience and access to advanced techniques.
Renal cell carcinoma (RCC) is the most lethal urological cancer and up to 40% of patients submitted to surgery will relapse. Thus, the study aim was to analyze the associations of
SNPs with RCC ...patients' prognosis, and evaluate their effect on
mRNA levels
The
rs4961280, rs3928672 and rs11996715 polymorphisms and the relative quantification of
mRNA levels were analyzed by real-time PCR.
We observed that
genotypes carriers presented a higher cancer progression risk (odds ratio= 3.13, p < 0.001), a reduced progression-free survival (log rank test, p = 0.003) and an increased risk of an early relapse (hazard ratio= 2.26, p = 0.008). In fact, these patients also presented higher circulating levels of
mRNA (p = 0.043), with the high levels being associated with more aggressive tumors.
The
genotypes are unfavorable RCC prognostic biomarkers, with the
levels being a useful RCC aggressive phenotype biomarker.
Long-linear assets, such as roads and railways, supported by earthworks are susceptible to deterioration caused by weather cycles, that translate into changes in soil hydro-mechanical properties. ...Failures in these earthworks are expected to become more common due to climate change as periods of drought and extreme rainfall events become more frequent. In the present study, the effect of the suction range of the moisture cycle on the soil-water retention curve (SWRC) and soil shrink-swell curve (SSC) of active London clay is investigated. Soil samples compacted at Proctor optimum conditions were subjected to drying-wetting cycles within a variable suction interval. A change in the SSC was observed when the water content reduced below a threshold that approximates to the shrinkage limit. A reduction in the ability of the soil to hold suction was observed with SWRCs becoming less steep, as the Primary Drying Line was steeper than subsequent drying phases (Scanning Drying Lines). Once the Scanning Drying Line intersects the Primary Drying Line, a yielding point is identified, and the soil loses further ability to hold suction. Irreversible deformations were observed associated with changes in the SWRC from drying-wetting cycles.
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