Common dandelion: a review of its botanical,phytochemical and pharmacological profiles

Phytochemistry Reviews - Phytoalimurgy is a term that derives from Greek and Latin by combination of the words φυτόν, which meaning plant, and alimenta urgentia, indicating...     

Smart process development: Application of machine-learning and integrated process modeling for inclusion body purification processes

The development of a biopharmaceutical production process usually occurs sequentially, and tedious optimization of each individual unit operation is very time-consuming. Here, the conditions established as optimal for one-step serve as input for the following step. Yet, this strategy does not consider potential interactions between a priori distant process steps and therefore cannot guarantee for optimal overall process performance. To overcome these limitations, we established a smart approach to develop and utilize integrated process models using machine learning techniques and genetic algorithms. We evaluated the application of the data-driven models to explore potential efficiency increases and compared them to a conventional development approach for one of our development products. First, we developed a data-driven integrated process model using gradient boosting machines and Gaussian processes as machine learning techniques and a genetic algorithm as recommendation engine for two downstream unit operations, namely solubilization and refolding. Through projection of the results into our large-scale facility, we predicted a twofold increase in productivity. Second, we extended the model to a three-step model by including the capture chromatography. Here, depending on the selected baseline-process chosen for comparison, we obtained between 50% and 100% increase in productivity. These data show the successful application of machine learning techniques and optimization algorithms for downstream process development. Finally, our results highlight the importance of considering integrated process models for the whole process chain, including all unit operations.     

Phylogeography of the Endangered Franciscana Dolphin: Timing and Geological Setting of the Evolution of Populations

Pontoporia blainvillei (Gervais & d’Orbigny, 1844), the franciscana dolphin, is the most endangered small cetacean in the Western South Atlantic. It is an endemic species with a coastal and estuarine distribution that has been divided into four Franciscana Management Areas (FMAs). We used the mitochondrial DNA control region to conduct a phylogeographic analysis to evaluate the population structure of the franciscana and the influence of paleoceanographic events on its biogeographic history. We found nine populations along the entire distribution (Φ_ST?=?0.41, Φ_CT?=?0.38, p?<?10^–5), with estimated migration rates resulting in less than one female per generation. Populations from FMAIII and FMAIV in the south (including the Río de La Plata Estuary) showed higher long-term migration rates and effective population sizes than northern populations. The phylogeographic analysis supports the franciscana origin in the Río de La Plata Estuary, with further dispersal south and northwards. The first lineage split happened around 2.5 Ma, with lineage radiation throughout the Pleistocene until recent fragmentation events shaped current-day populations. We suggest that Pleistocene glaciations influenced the dispersion and population structure of the franciscana. Specifically, that the shift of the Brazil-Malvinas Confluence drove the dispersion northwards. Then, low sea-level periods caused either the isolation in estuarine refugia or local extinctions, followed by re-colonizations.

     

Phosphorus Recovery from Phosphate Rocks Using Phosphate-Solubilizing Bacteria

In this paper, we are presenting a biological process to recover phosphorus by solubilizing low-grade phosphate rocks. To this end, the efficiency of different phosphate-solubilizing microorganism (PSM) species for solubilizing P from phosphate rocks using both pure cultures and associations. Nutritional conditions, phosphate rock concentrations, and reactor designs were tested. The genus Bacillus, especially Bacillus megaterium (ATCC 14581), was found to be the most promising PSM for solubilizing P. Production of organic acids and acidic pH values were shown to be directly related to P solubilizing. However, associations between tested microorganisms did not significantly enhance process efficiency. We conclude that nutritional factors of the medium are important to solubilization, and lower phosphate rock concentrations lead to better solubilization. The Air Lift reactor was promising for B. megaterium (ATCC 14581), but adaptations are needed for further tests.     

Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats

Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO₃) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO₃ groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO₃ 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.     

Body temperature variation controls pre-mRNA processing and transcription of antiviral genes and SARS-CoV-2 replication

Antiviral innate immunity represents the first defense against invading viruses and is key to control viral infections, including SARS-CoV-2. Body temperature is an omnipresent variable but was neglected when addressing host defense mechanisms and susceptibility to SARS-CoV-2 infection. Here, we show that increasing temperature in a 1.5°C window, between 36.5 and 38°C, strongly increases the expression of genes in two branches of antiviral immunity, nitric oxide production and type I interferon response. We show that alternative splicing coupled to nonsense-mediated decay decreases STAT2 expression in colder conditions and suggest that increased STAT2 expression at elevated temperature induces the expression of diverse antiviral genes and SARS-CoV-2 restriction factors. This cascade is activated in a remarkably narrow temperature range below febrile temperature, which reflects individual, circadian and age-dependent variation. We suggest that decreased body temperature with aging contributes to reduced expression of antiviral genes in older individuals. Using cell culture and in vivo models, we show that higher body temperature correlates with reduced SARS-CoV-2 replication, which may affect the different vulnerability of children versus seniors toward severe SARS-CoV-2 infection. Altogether, our data connect body temperature and pre-mRNA processing to provide new mechanistic insight into the regulation of antiviral innate immunity.     

Atrophic cardiac remodeling induced by taurine deficiency in wistar rats

Introduction

Micronutrient deficiency is observed in heart failure patients. Taurine, for example, represents 50% of total free amino acids in the heart, and in vivo studies have linked taurine deficiency with cardiomyopathy.

Methods

Thirty-four male Wistar rats (body weight = 100 g) were weighed and randomly assigned to one of two groups: Control (C) or taurine-deficient (T (-)). Beta-alanine at a concentration of 3% was added to the animals’ water to induce taurine deficiency in the T (-) group. On day 30, the rats were individually submitted to echocardiography; morphometrical and histopathological evaluation and metalloproteinase activity, oxidative stress and inflammation evaluation were performed. Tissue samples were collected to determine the taurine concentration in the heart.

Results

Taurine deficiency led to decreases in: ventricular wall thickness, left ventricle dry weight, myocyte sectional area, left ventricle posterior wall thickness and ventricular geometry. With regard to heart function, the velocity of the A wave, the ratio between the E and A wave, the ejection fraction, fractional shortening and cardiac output values were decreased in T (-) rats, suggesting abnormal diastolic and systolic function. Increased fibrosis, inflammation and increased activation of metalloproteinases were not observed. Oxidative stress was increased in deficient animals.

Conclusions

These data suggest that taurine deficiency promotes structural and functional cardiac alterations with unique characteristics.