•mRNA is a safe and precise vaccine technology.•Over 140 clinical trials can be found using mRNA vaccines.•Scalability and cost-effectiveness in mRNA manufacturing is still a bottleneck.•Continuous ...manufacturing can potentially be used in the mRNA technology manufacturing.
Vaccines are one of the most important tools in public health and play an important role in infectious diseases control. Owing to its precision, safe profile and flexible manufacturing, mRNA vaccines are reaching the stoplight as a new alternative to conventional vaccines. In fact, mRNA vaccines were the technology of choice for many companies to combat the Covid-19 pandemic, and it was the first technology to be approved in both United States and in Europe Union as a prophylactic treatment. Additionally, mRNA vaccines are being studied in the clinic to treat a number of diseases including cancer, HIV, influenza and even genetic disorders.
The increased demand for mRNA vaccines requires a technology platform and cost-effective manufacturing process with a well-defined product characterisation. Large scale production of mRNA vaccines consists in a 1 or 2-step in vitro reaction followed by a purification platform with multiple steps that can include Dnase digestion, precipitation, chromatography or tangential flow filtration. In this review we describe the current state-of-art of mRNA vaccines, focusing on the challenges and bottlenecks of manufacturing that need to be addressed to turn this new vaccination technology into an effective, fast and cost-effective response to emerging health crises.
•Plastics used in daily life are of extreme scientific and societal concern.•PE, PP, PET, PS, PA and PVC are the most common polymers used in our daily life.•Plastics can be found in the environment ...and food sources (exposure routes).•Daily use of plastics can cause toxic impacts on environment and human health.•Additives are more toxic than monomers to human-beings and wildlife.
Plastics are indispensable and persistent materials used in daily life that can be fragmented into micro- or nanoplastics. They are long polymer chains mixed with additives that can be toxic when in contact with distinct species. The toxicity can result from polymer matrix, additives, degradation products and adsorbed contaminants. Notwithstanding, there is still an immense gap of information concerning the individual and mixed impacts of plastics. Hence, in this study, we characterize the most common plastic materials widely used in our daily life by its polymer type and compile the environmental and human health hazards of these polymers including the impacts of monomers, additives, degradation products and adsorbed contaminants based on literature review. In summary, polyvinyl chloride is the most toxic polymer type used daily (monomer and additives); additives are more toxic than monomers to wildlife and humans; and the most toxic additives are benzene, phthalates and lead stabilisers.
Impaired function of NPC1 or NPC2 lysosomal proteins leads to the intracellular accumulation of unesterified cholesterol, the primary defect underlying Niemann-Pick type C (NPC) disease. In addition, ...glycosphingolipids (GSLs) accumulate in lysosomes as well. Intralysosomal lipid accumulation triggers the activation of a set of genes, including potential biomarkers. Transcript levels of Gpnmb have been shown to be elevated in various tissues of an NPC mouse model. We speculated that Gpnmb could serve as a marker for visceral lipid accumulation in NPC disease. We report that Gpnmb expression is increased at protein level in macrophages in the viscera of Npc1nih/nih mice. Interestingly, soluble Gpnmb was also found to be increased in murine and NPC patient plasma. Exposure of RAW264.7 macrophages to the NPC-phenotype-inducing drug U18666A also upregulated Gpnmb expression. Inhibition of GSL synthesis with the glucosylceramide synthase (GCS) inhibitor N-butyl-1-deoxynojirimycin prevented U18666A-induced Gpnmb induction and secretion. In summary, we show that Gpnmb is upregulated in NPC mice and patients, most likely due to GSL accumulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
First Observation of B 20 and B 21 Leblond, S.; Marqués, F. M.; Gibelin, J. ...
Physical review letters,
12/2018, Letnik:
121, Številka:
26
Journal Article
Toxic heavy metals are priority pollutants in wastewater, commonly present in dangerous concentrations in many places across the globe. Although in trace quantities copper is a heavy metal essential ...to human life, in excess it causes various diseases, whereby its removal from wastewater is a necessity. Among several reported materials, chitosan is a highly abundant, non-toxic, low-cost, biodegradable polymer, comprising free hydroxyl and amino groups, that has been directly applied as an adsorbent or chemically modified to increase its performance. Taking this into account, reduced chitosan derivatives (RCDs 1-4) were synthesised by chitosan modification with salicylaldehyde, followed by imine reduction, characterised by RMN, FTIR-ATR, TGA and SEM, and used to adsorb Cu(II) from water. A reduced chitosan (RCD3), with a moderate modification percentage (43%) and a high imine reduction percentage (98%), proved to be more efficient than the remainder RCDs and even chitosan, especially at low concentrations under the best adsorption conditions (pH 4,
= 2.5 mg mL
). RCD3 adsorption data were better described by the Langmuir-Freundlich isotherm and the pseudo-second-order kinetic models. The interaction mechanism was assessed by molecular dynamics simulations, showing that RCDs favour Cu(II) capture from water compared to chitosan, due to a greater Cu(II) interaction with the oxygen of the glucosamine ring and the neighbouring hydroxyl groups.
We describe 19B in terms of a 17B-n-n three-body system, where the two-body subsystems 17B-n and n-n are unbound (virtual) states close to the unitary limit. The energy of 19 B ground state is well ...reproduced and two low-lying resonances are predicted. Their eventual link with the Efimov physics is discussed. This model can be extended to describe the recently discovered resonant states in 20,21B.
The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological ...involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2). Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/-) mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs), one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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