Tumor-associated lymph vessels and lymph node involvement are critical staging criteria in several cancers. In skin squamous cell carcinoma, lymph vessels play a role in cancer development and ...metastatic spread. However, their relationship with the cancer stem cell niche at early tumor stages remains unclear. To address this gap, we studied the lymph vessel localization at the cancer stem cell niche and observed an association from benign skin lesions to malignant stages of skin squamous cell carcinoma. By co-culturing lymphatic endothelial cells with cancer cell lines representing the initiation and promotion stages, and conducting RNA profiling, we observed a reciprocal induction of cell adhesion, immunity regulation, and vessel remodeling genes, suggesting dynamic interactions between lymphatic and cancer cells. Additionally, imaging analyses of the cultured cells revealed the establishment of heterotypic contacts between cancer cells and lymph endothelial cells, potentially contributing to the observed distribution and maintenance at the cancer stem cell niche, inducing downstream cellular responses. Our data provide evidence for an association of lymph vessels from the early stages of skin squamous cell carcinoma development, opening new avenues for better comprehending their involvement in cancer progression.
Abstract Bay snook (Petenia splendida) is a carnivorous cichlid species with excellent economic value in Southeast Mexico. Although this species presents an excellent potential for commercial ...aquaculture, the information about its nutritional, physiological, and reproductive metabolic pathways is meager. The current study focuses on the expression of glucose transporter 2 (glut2) in embryos and larvae at 5, 10, 15-, 20-, 25-, and 30-days post-hatch (dph) and in the liver, intestine, kidney, muscle, heart, testicle, gill, stomach, pancreas, and brain of adult fish. The partial sequence of glut2 was obtained, and specific qPCR primers were designed. In embryos, the expression was lower compared to larvae at 5, 15, and 20 dph. The highest expression in larvae occurred at 20 dph and the lowest at 25 and 30 dph. Maximum expression levels in adults occurred in the liver and intestine. Our results show that glut2 is expressed differentially across tissues of adult bay snook, and it fluctuates during larval development.
Resumen La mojarra tenguayaca (Petenia splendida) es una especie de cíclido carnívoro con excelente valor comercial en el sureste de México. A pesar de su potencial para la acuicultura, existe muy poca información sobre sus rutas metabólicas relacionadas con su nutrición, fisiología y reproducción. El presente estudio se enfoca en la expresión del transportador de glucosa (glut2) en embriones y larvas de 5, 10, 15, 20, 25 y 30 días post eclosión (dph) y en el hígado, intestino, riñón, músculo, corazón, testículo, branquias, estómago, páncreas y cerebro en peces adultos. Se diseñaron cebadores de qPCR específicos para glut2. La expresión en los embriones fue menor que en larvas a los 5, 15 y 20 dph. La expresión máxima en larvas se observó a los 20 dph y la mínima a los 25 y 30 dph. La expresión más alta en los adultos ocurrió en el hígado y el intestino. Nuestros resultados muestran que el gen glut2 se expresa de manera diferencial en los tejidos de adultos de la mojarra tenguayaca y su expresión fluctúa durante el desarrollo larvario.
Lymphatic vessels are essential for skin fluid homeostasis and immune cell trafficking. Whether the lymphatic vasculature is associated with hair follicle regeneration is, however, unknown. Here, ...using steady and live imaging approaches in mouse skin, we show that lymphatic vessels distribute to the anterior permanent region of individual hair follicles, starting from development through all cycle stages and interconnecting neighboring follicles at the bulge level, in a stem cell‐dependent manner. Lymphatic vessels further connect hair follicles in triads and dynamically flow across the skin. At the onset of the physiological stem cell activation, or upon pharmacological or genetic induction of hair follicle growth, lymphatic vessels transiently expand their caliber suggesting an increased tissue drainage capacity. Interestingly, the physiological caliber increase is associated with a distinct gene expression correlated with lymphatic vessel reorganization. Using mouse genetics, we show that lymphatic vessel depletion blocks hair follicle growth. Our findings point toward the lymphatic vasculature being important for hair follicle development, cycling, and organization, and define lymphatic vessels as stem cell niche components, coordinating connections at tissue‐level, thus provide insight into their functional contribution to skin regeneration.
Synopsis
Like blood vasculature, lymphangiogenesis may have an impact on epithelial tissue development. Combined morphological profiling and genetic analyses now show structural and functional association between lymph vessels (LV) and the hair follicles (HF), providing new insights into principles of niche organization during skin regeneration and maintenance.
LVs in the mouse back skin associate with HFs in a polarized manner, interconnecting HF triads throughout the hair cycle.
Depletion of Wnt ligands in HF stem cells disrupts LV‐HF association.
LVs transiently increase their caliber at the onset of stem cell activation showing a distinct molecular signature.
Genetic ablation of LVs leads to premature exit from HF growth.
Lymph vessels and the hair follicles are structurally and functionally associated during skin growth and maintenance.
This study was conducted to investigate the effects of dietary fructooligosaccharides (FOS) on the growth, survival rate, digestive enzyms activity, and the expression of intestinal barrier function ...genes in tropical gar (Atractosteus tropicus) larvae. A total of 960 larvae (0.030 ± 0.006 g) were fed three diets supplemented with increasing FOS concentrations (2.5, 5, and 7.5 g kg−1) and a control diet for 15 days. Results revealed that a 7.5 g kg−1 FOS supplementation improved weight gain, specific growth rate, and survival rate (p < 0.05). Furthermore, 5 g kg−1 FOS supplementation increased alkaline protease and amylase activities and induced an upregulation of the claudin-17 gene expression (p < 0.05). Meanwhile, the inclusion of 7.5 g kg−1 FOS induced the upregulation of mucin 2 (muc-2), and the tight junction genes zo-2 and claudin-3 (p < 0.05). In addition, 2.5, 5, and 7.5 g kg−1 FOS promoted the downregulation of the claudin-15 gene expression (p < 0.05). At the same time, FOS inclusion did not increase the pro-inflammatory cytokine il-8 expression. We can conclude that 7.5 g kg−1 FOS supplementation improves growth performance, survival rate, and digestive capacity, and could contribute to the reinforcement of the intestinal barrier function of Tropical gar larvae.
Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response ...to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.
ABSTRACT In the Southeast of Mexico, there are many native cichlids with commercial interest such as redhead cichlid (Vieja melanurus) and twoband cichlid (V. bifasciata), which have a great local ...demand and excellent meat quality. However, it is necessary to implement their culture based on nutrition studies and digestive biochemistry. This study’s objective was to characterize these two cichlids’ digestive proteases (pH, temperature, and inhibitors) through biochemistry techniques. Results showed that V. melanurus and V. bifasciata have a digestive capacity analogous to other omnivore fishes, where the optimal pH values of stomach proteases (4 and 2, respectively) and intestinal proteases (6 and 12, respectively), the optimal temperature of acid (35°C and 55°C, respectively) and alkaline proteases (45°C and 55°C, respectively) are quite similar. Both species presented high thermal and pH stabilities. Inhibition showed that V. melanurus is more sensitive to specific inhibitors for alkaline proteases than V. bifasciata. In conclusion, V. bisfasciata and V. melanurus have different digestive protease patterns. Both species can hydrolyze different protein ingredients to formulate a specific diet. Nevertheless, V. bifasciata is more resistant to the presence of inhibitors, which allow it to include vegetable proteins in its diet.
RESUMEN En el sureste de México, existen muchas especies de cíclidos nativos de interés comercial como el cíclido rojo (Vieja melanurus) y el cíclido de dos bandas (V. bifasciata), los cuales tienen una gran demanda local y tienen una excelente calidad de carne; sin embargo, es necesario implementar su cultivo con base en estudios de nutrición y bioquímica digestiva. El objetivo de este estudio fue caracterizar las proteasas digestivas (pH, temperatura e inhibidores) de estos dos cíclidos nativos mediante técnicas bioquímicas. Los resultados mostraron que V. melanurus y V. bifasciata tienen una capacidad digestiva similar a otros peces omnívoros, donde los valores óptimos de pH de proteasas estomacales (4 y 2, respectivamente) e intestinales (6 y 12, respectivamente), la temperatura óptima de proteasas ácidas (35°C y 55°C, respectivamente) y alcalinas (45°C y 55°C, respectivamente) son muy parecidas. Ambas especies presentaron alta estabilidad térmica y de pH. La inhibición mostró que V. melanurus es más sensible a inhibidores específicos de proteasas alcalinas que V. bifasciata. En conclusión, V. bisfasciata y V. melanurus tienen diferentes patrones de proteasas digestivas, pero ambas especies pueden hidrolizar diversos ingredientes proteicos para formular dietas específicas; sin embargo, V. bifasciata es más resistente a la presencia de inhibidores, lo que permitiría incluir proteínas vegetales en su dieta.
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•Solubility of sulfadiazine (SD) was measured in 1,4-dioxane+water co-solvent mixtures.•Gibbs energy, enthalpy, and entropy of solution and mixing of SD were calculated.•Thermodynamic ...quantities of mixing of SD were also calculated.•Non-linear enthalpy–entropy relationship was observed for SD in the enthalpy vs. Gibbs energy plot.•Preferential solvation of SD by both solvents was analyzed by using the IKBI method.
The solubility of sulfadiazine (SD) in some 1,4-dioxane+water co-solvent mixtures was measured at five temperatures from 293.15 to 313.15K in all the polarity range. By using the van’t Hoff and Gibbs equations the thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from these data. The maximal solubility of this drug expressed in mole fraction was found in the mixture with 0.85 in mass fraction of 1,4-dioxane (w1=0.85, δ1+2=24.7MPa1/2) and the minimum solubility in pure water (δ=47.8MPa1/2) at almost all the temperatures studied. By using the ideal solubility values reported in literature, the thermodynamic quantities of mixing were also calculated. Non-linear enthalpy–entropy relationship was observed for SD in the plot of enthalpy vs. Gibbs energy of solution with variable positive slopes in the regions with 0.00≤w1≤0.90 and 0.95≤w1≤1.00. Hence, the driving mechanism for SD solution process is the enthalpy in nearly all the compositions. In addition, the preferential solvation of this drug by both solvents was analyzed by means of the inverse Kirkwood–Buff integrals observing that it is preferentially solvated by water in water-rich and 1,4-dioxane-rich mixtures but preferentially solvated by 1,4-dioxane in those mixtures with intermediate compositions.
Aquatic hypoxia is both a naturally-occurring and anthropogenically-generated event. Fish species have evolved different adaptations to cope with hypoxic environments, including gill modifications ...and air breathing. However, little is known about the molecular mechanisms involved in the respiration of embryonic and larval fishes during critical windows of development. We assessed expression of the genes hif-1α, fih-1, nhe1, epo, gr and il8 using the developing tropical gar as a piscine model during three developmental periods (fertilization to hatch, 1 to 6 days post hatch (dph) and 7 to 12 dph) when exposed to normoxia (~7.43 mg/L DO), hypoxia (~2.5 mg/L DO) or hyperoxia (~9.15 mg/L DO). All genes had higher expression when fish were exposed to either hypoxia or hyperoxia during the first two developmental periods. However, fish continuously exposed to hypoxia had increased expression of the six genes by hatching and 6 dph, and by 12 dph only hif-1α still had increased expression. The middle developmental period was the most hypoxia-sensitive, coinciding with several changes in physiology and morphology. The oldest larvae were the most resilient to gene expression change, with little variation in expression of the six genes compared. This study is the first to relate the molecular response of an air-breathing fish to oxygen availability to developmental critical windows and contributes to our understanding of some molecular responses of developing fish to changes in oxygen availability.
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•Regulation of genes varies with time of exposure, type of stressor and developmental time.•Period from fertilization to 6 dph results in higher expression of genes in response to hypoxia/hyperoxia.•Period from 7 to 12 dph resulted as the most resilient with little variation in gene expression.
The COVID-19 outbreak has spread extensively around the world. Loss of smell and taste have emerged as main predictors for COVID-19. The objective of our study is to develop a comprehensive machine ...learning (ML) modelling framework to assess the predictive value of smell and taste disorders, along with other symptoms, in COVID-19 infection. A multicenter case-control study was performed, in which suspected cases for COVID-19, who were tested by real-time reverse-transcription polymerase chain reaction (RT-PCR), informed about the presence and severity of their symptoms using visual analog scales (VAS). ML algorithms were applied to the collected data to predict a COVID-19 diagnosis using a 50-fold cross-validation scheme by randomly splitting the patients in training (75%) and testing datasets (25%). A total of 777 patients were included. Loss of smell and taste were found to be the symptoms with higher odds ratios of 6.21 and 2.42 for COVID-19 positivity. The ML algorithms applied reached an average accuracy of 80%, a sensitivity of 82%, and a specificity of 78% when using VAS to predict a COVID-19 diagnosis. This study concludes that smell and taste disorders are accurate predictors, with ML algorithms constituting helpful tools for COVID-19 diagnostic prediction.
The effect of different lipid levels (10, 15, 20 and 25%) and oil sources (fish oil: FO and soybean lecithin oil: LO) on growth, survival, digestive enzymatic activity, gene expression acetyl CoA ...carboxylase (ACC1) and fatty acid synthase (FAS) of Mayan cichlid larvae Cichlasoma urophthalmus were evaluated by a bi-factorial design. The larvae were fed from hatching with eight different experimental isoproteic diets (45% protein) and a commercial diet for tilapia as a control diet. The results showed that larvae fed the LO15 diet had the highest growth in weight and total length and higher trypsin activity. The lowest values in FAS and ACC1 expression were obtained exclusively with the lipid type (soybean lecithin). It is concluded that the inclusion of soybean lecithin at a concentration of 15% allows the 100% replacement of fish oil in balanced feed for the culture of Mayan cichlid larvae.
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