Trends in nanotechnology patents applied to the health sector

The aim of the article is to present a method for identifying trends in patent applications for nanotechnology applied to the health sector around the world, based on the International Patent Classification. This classification divides the sector into: dental care, drugs, diagnostic kits, and medical apparatus & medical care. The Derwent database was mined for patent documents using nanotechnology terms associated with the IPC subclasses from the health subsectors. The number of patents was found to be rising, led by the United States, particularly universities and R centers. In the dental care subsector, nanotechnology was found to be used in composite material for manufacturing dental appliances. In drugs, the focus is on the use of nanoparticulate compositions comprising agents that are useful for a variety of diseases. In diagnostic kits, nanostructures have been patented that are capable of detecting target analytes. Meanwhile, in medical apparatus & medical care, patent applications have been made for nanocapsules and/or nanocomposite materials inserted in devices and guide catheters. A study was also made of patents in Brazil, where the same assignees and the same country (United States) as in the survey of global patents were found to be the leading patent applicants / holders.     

Recovery of Components from Shrimp (Xiphopenaeus kroyeri) Processing Waste by Enzymatic Hydrolysis

ABSTRACT:  Industrial shrimp waste is a good source of protein, chitin, and carotenoids. In general, this waste is discarded with no attempt to use it, thus contributing to environmental pollution. This study was aimed at recovering the 3 main components of industrial shrimp waste, protein, chitin, and astaxanthin, using enzymatic treatment with Alcalase and pancreatin. An increase in the degree of hydrolysis (DH) from 6% to 12% resulted in 26% to 28% protein recovery. Alcalase was more efficient than pancreatin, increasing the recovery of protein from 57.5% to 64.6% and of astaxanthin from 4.7 to 5.7 mg astaxanthin/100 g of dry waste, at a DH of 12%. The enzymatic hydrolysis of the industrial waste from Xiphopenaeus kroyeri shrimp using Alcalase allowed for 65% protein recovery in the form of hydrolysates, in addition to providing suitable conditions for the recovery of astaxanthin and chitin.     

Influence of Pressure and Temperature on the Velocity of a Turbulent Jet Flow 3D

To investigate the influence of pressure and temperature on the jet velocity of a three-dimensional flow was the main goal of this study. Using a precipitation chamber with approximate capacity of 600 mL, it was studied the thermodynamic behavior of supercritical carbon dioxide mixture, dichloromethane and grape seed extract via SAS （supercritical antisolvent process）. For the numerical solution, the Navier-Stokes equations were used along with the model of turbulence k-ε and Peng-Robinson equation of state with quadratic mixing rules of Van der Waals. The method of Chung was employed to determine the viscosity, thermal conductivity and mass diffusivity of the flow numerically solved through commercial code based on CFD （computational fluid dynamics）. Simulations for pressures between 80 bar and 160 bar and temperatures between 308.15 K and 318.15 K showed large variations in the jet velocity, an important property in the dynamic mixing process that involves the size, size distribution and particle morphology.     

Effect of the mimic structure on the molecular recognition properties of molecularly imprinted polymers for ochratoxin A prepared by a fragmental approach

In this work the fragmental approach was used to prepare several molecularly imprinted ethylene dimethacrylate-co-methacrylic acid polymers with molecular recognition towards the mycotoxin ochratoxin A, with the aim of searching for simpler mimic templates than the well-known N-(4-chloro-1-hydroxy-2-naphthoylamido)-(l)-phenylalanine. The screening for binding of two different kinds of ochratoxin-related molecules was performed by HPLC analysis. Ochratoxin A and the mimic templates were eluted in acetonitrile–acetic acid (0.1% v/v) and the imprinting factor was measured for all the ligands on all the columns packed with the imprinted polymers. The experimental results show that changes to the amino acidic sub-structure or the presence/absence of a chlorine atom in position 4 on the naphthalene ring system does not affect the molecular recognition of ochratoxin A by the resulting imprinted polymer. On the contrary, the presence of the bulky naphthalene ring system in the mimic template seems to be necessary to preserve the molecular recognition of ochratoxin. This binding behavior was found to be compatible with in silico simulations of the complexation between some of the mimic templates and molecules of methacrylic acid. The use of the mimic template N-(1-hydroxy-2-naphthoylamido)-(L)-phenylalanine seems to represent a synthetically simple approach to the preparation of imprinted polymers with molecular recognition properties towards ochratoxin A.     

Investigating heavy metal resistance, bioaccumulation and metabolic profile of a metallophile microbial consortium native to an abandoned mine

Contaminated sites represent new ecological niches where historical pollution has originated an unusual microbial biodiversity. The knowledge of these microorganisms contributes to the discovery of new pathways and metabolic networks and may offer potential solutions for damaged areas. In the present work seven microbial consortia have been isolated from an abandoned mine of blend and galena (Ingurtosu, Italy) through a selection for resistance to zinc (tested up to 40 mM in solution). All the consortia were able to accumulate zinc and the best accumulator, named Ing5, has been studied for the following characteristics: resistance and accumulation of Zn, Cd, Hg, bioaccumulation mechanisms of Zn, and influence of Zn and Cd on the metabolic profile. The results indicate that the consortium Ing5 bears resistance systems for Cd and Hg as well as Zn and that, for some of the 5 isolates belonging to Ing5, the resistance thresholds are higher in consortium than in pure culture. The prevalent mechanism for zinc accumulation can be reasonably considered to be metabolism-dependent, inducible and regulated by metal concentrations. The study on the metabolic profile, carried out by the Biolog system, shows that Zn exerts a very low influence on the metabolic profile and that this influence can also be positive; Cd has a stronger negative influence but that, despite this, the consortium is able to maintain a wide metabolic potential in the presence of heavy metals. These features of Ing5 make it a good candidate for biotechnological applications and for further investigation of the degradation of organic pollutants in the presence of metals.     

Allosteric Inhibition of Neutral Sphingomyelinase 2 (nSMase2) by DPTIP: From Antiflaviviral Activity to Deciphering Its Binding Site through In Silico Studies and Experimental Validation

Flavivirus comprises globally emerging and re-emerging pathogens such as Zika virus (ZIKV), Dengue virus (DENV), and West Nile virus (WNV), among others. Although some vaccines are available, there is an unmet medical need as no effective antiviral treatment has been approved for flaviviral infections. The development of host-directed antivirals (HDAs) targeting host factors that are essential for viral replication cycle offers the opportunity for the development of broad-spectrum antivirals. In the case of flaviviruses, recent studies have revealed that neutral sphingomyelinase 2, (nSMase2), involved in lipid metabolism, plays a key role in WNV and ZIKV infection. As a proof of concept, we have determined the antiviral activity of the non-competitive nSMase2 inhibitor DPTIP against WNV and ZIKV virus. DPTIP showed potent antiviral activity with EC₅₀ values of 0.26 µM and 1.56 µM for WNV and ZIKV, respectively. In order to unravel the allosteric binding site of DPTIP in nSMase2 and the details of the interaction, computational studies have been carried out. These studies have revealed that DPTIP could block the DK switch in nSMase2. Moreover, the analysis of the residues contributing to the binding identified His463 as a crucial residue. Interestingly, the inhibitory activity of DPTIP on the H463A mutant protein supported our hypothesis. Thus, an allosteric cavity in nSMase2 has been identified that can be exploited for the development of new inhibitors with anti-flaviviral activity.     

Low Sulfur Amino Acid,High Polyunsaturated Fatty Acid Diet Inhibits Breast Cancer Growth

Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability. We used in vitro models of BC (MCF7 and MDA-MB-231) that were maintained with a low amount of sulfur amino acids (SAAs) and a high amount of oxidizable polyunsatured fatty acids (PUFAs). Treatment with anti-apoptotic, anti-ferroptotic and antioxidant drugs were used to determine the modality of cell death. We reproduced these conditions in vivo by feeding BC-bearing mice with a diet poor in proteins and SAAs and rich in PUFAs (LSAA/HPUFA). Western blot analysis, qPCR and histological analyses were used to assess the anti-cancer effects and the molecular pathways involved. We found that BC cells underwent oxidative damage to DNA and proteins and both apoptosis and ferroptosis were induced. Along with caspases-mediated PARP1 cleavage, we found a lowering of the GSH-GPX4 system and an increase of lipid peroxides. A LSAA/HPUFA diet reduced tumor mass and its vascularization and immune cell infiltration, and induced apoptosis and ferroptotic hallmarks. Furthermore, mitochondrial mass was found to be increased, and the buffering of mitochondrial reactive oxygen species limited GPX4 reduction and DNA damage. Our results suggest that administration of custom diets, targeting the dependency of cancer cells on certain nutrients, can represent a promising complementary option for anti-cancer therapy.     

Discovery of New Phenylacetone Monooxygenase Variants for the Development of Substituted Indigoids through Biocatalysis

Indigoids are natural pigments obtained from plants by ancient cultures. Romans used them mainly as dyes, whereas Asian cultures applied these compounds as treatment agents for several diseases. In the modern era, the chemical industry has made it possible to identify and develop synthetic routes to obtain them from petroleum derivatives. However, these processes require high temperatures and pressures and large amounts of solvents, acids, and alkali agents. Thus, enzyme engineering and the development of bacteria as whole-cell biocatalysts emerges as a promising green alternative to avoid the use of these hazardous materials and consequently prevent toxic waste generation. In this research, we obtained two novel variants of phenylacetone monooxygenase (PAMO) by iterative saturation mutagenesis. Heterologous expression of these two enzymes, called PAMO_HPCD and PAMO_HPED, in E. coli was serendipitously found to produce indigoids. These interesting results encourage us to characterize the thermal stability and enzyme kinetics of these new variants and to evaluate indigo and indirubin production in a whole-cell system by HPLC. The highest yields were obtained with PAMO_HPCD supplemented with L-tryptophan, producing ~3000 mg/L indigo and ~130.0 mg/L indirubin. Additionally, both enzymes could oxidize and produce several indigo derivatives from substituted indoles, with PAMO_HPCD being able to produce the well-known Tyrian purple. Our results indicate that the PAMO variants described herein have potential application in the textile, pharmaceutics, and semiconductors industries, prompting the use of environmentally friendly strategies to obtain a diverse variety of indigoids.     

Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury

The incidence of traumatic brain injury (TBI) has increased over the last years with an important impact on public health. Many preclinical and clinical studies identified multiple and heterogeneous TBI-related pathophysiological mechanisms that are responsible for functional, cognitive, and behavioral alterations. Recent evidence has suggested that post-TBI neuroinflammation is responsible for several long-term clinical consequences, including hypopituitarism. This review aims to summarize current evidence on TBI-induced neuroinflammation and its potential role in determining hypothalamic-pituitary dysfunctions.