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关键词： somatic embryogenesis   somaclonal variation   AFLP   metAFLP   triterpenoids   Araliaceae  

摘要： Polyscias filicifolia (Araliaceae) is broadly used in traditional medicine in Southeast Asia due to its antimicrobial, immunomodulating and cytotoxic activities. The main groups of compounds responsible for pharmacological effects are believed to be oleanolic triterpene saponins. However, Polyscias plants demonstrate relatively slow growth in natural conditions, which led to applying a developing sustainable source of plant material via primary (PSE), secondary (DSE) and direct somatic embryogenesis from DSE (TSE). The AFLP and metAFLP genotyping resulted in 1277 markers, amplified by a total of 24 pairs of selective primers. Only 3.13% of the markers were polymorphic. The analysis of variance showed that the PSE and TSE regenerants differed only in terms of root number, while the DSE plantlets differed for all studied morphological characteristics. Further, the chemical analysis revealed that oleanolic acid (439.72 mu g/g DW), ursolic acid (111.85 mu g/g DW) and hederagenin (19.07 mu g/g DW) were determined in TSE regenerants. Our results indicate that direct somatic embryogenesis ensures the production of homogeneous plant material, which can serve as a potential source of triterpene compounds. Plants obtained via somatic embryogenesis could also be reintroduced into the natural environment to protect and preserve its biodiversity.

关键词： COVID-19   Hepatology consultation   Liver biochemistries   Diagnosis  

摘要： Background Coronavirus disease 2019 (COVID-19) is associated with elevated liver biochemistries in approximately half of hospitalized patients, with many possible etiologies. Aim To assess agreement on the etiology of abnormal liver biochemistries and diagnostic recommendations in COVID-19. Methods Twenty hepatology consultations were reviewed by three senior hepatologists who provided a differential diagnosis and diagnostic recommendations. Kappa agreement on the primary etiology was calculated. Results Kappa agreement between hepatologists on the primary etiology of elevated liver biochemistries was 0.10 (p = 0.03). Agreement was greater around drug-induced liver injury 0.51 (p < 0.0001) and SARS-CoV-2-related liver injury 0.17 (p = 0.03). Serial liver biochemistries were recommended in all consultations over other evaluations. Conclusion In COVID-19, elevated liver biochemistries present a diagnostic challenge and can often be monitored conservatively.

关键词： Candida   Candida glabrata   Meningitis   Fluconazole   B-d-glucan   Hypercalcemia  

摘要： Candida infections of the central nervous system (CNS) are rare. We report a case of Candida glabrata meningitis successfully treated with combination antifungal therapy followed by step-down therapy with fluconazole. Newonset hypercalcaemia, an uncommon side effect of the prolonged fluconazole treatment, prompted early treatment cessation. A negative cerebrospinal fluid (CSF) beta-d-glucan supported the decision of treatment cessation despite incomplete resolution of CSF biochemical parameters. No disease relapse was encountered after 2 years post-treatment.

关键词： Microplastics   Microalgae   Photosynthesis   Protein   Lipid   Carbohydrate  

摘要： Microplastics have been widely detected in different aquatic ecosystems. The toxicity of microplastics has been extensively evaluated on aquatic animals;however, there is limited information on their influence on microalgal growth and metabolism. This study investigates the effect of different concentrations (0, 5, 10, 15, 25, 100, 125, 200, and 250 mg L-1), of microplastics namely high-density polyethylene, polypropylene, and polyvinyl chloride exposure on growth, photosynthesis, and biochemical composition of Acutodesmus obliquus. The highest growth inhibition ratio of 42.7% was observed for high-density polyethylene (250 mg L-1) supplemented medium followed by polyvinyl chloride (41.6%) and polypropylene (37.7%) microplastics. The results revealed that during the early log phase, the photosynthetic efficiency (F-v/F-m) decreased at higher concentrations on microplastics exposure. However, the microalga was able to adapt to the microplastics supplemented medium and did not show any significant effect on F-v/F-m in the late-log phase. There was no significant effect on the lipid (14.6-17.9%) and carbohydrate (14.59-18.24%) content for all types of microplastic treatments as compared to the control growth medium. Protein content was observed to decrease significantly at higher concentrations of microplastics (100-250 mg L-1). Scanning electron microscopy investigations revealed the microplastic aggregates on the algal surface. The effect on cellular metabolites composition of A. obliquus with different microplastics was also analyzed using infrared spectroscopy. The present study showed that microalga A. obliquus has the ability to adapt in the microplastics supplemented medium, however, higher concentrations could exert metabolic changes in the organism. The findings of the present study could form the basis for future investigations on the exploration of mechanisms of the microplastic toxicity and adaptation in microalgal species.

关键词： Neurotransmitter   Transporter   SLC6   Disease variants   Folding   Pharmacochaperoning  

摘要： Neurotransmitters, such as gamma-aminobutyric acid, glutamate, acetyl choline, glycine and the monoamines, facilitate the crosstalk within the central nervous system. The designated neurotransmitter transporters (NTTs) both release and take up neurotransmitters to and from the synaptic cleft. NTT dysfunction can lead to severe pathophysiological consequences, e.g. epilepsy, intellectual disability, or Parkinson's disease. Genetic point mutations in NTTs have recently been associated with the onset of various neurological disorders. Some of these mutations trigger folding defects in the NTT proteins. Correct folding is a prerequisite for the export of NTTs from the endoplasmic reticulum (ER) and the subsequent trafficking to their pertinent site of action, typically at the plasma membrane. Recent studies have uncovered some of the key features in the molecular machinery responsible for transporter protein folding, e.g., the role of heat shock proteins in fine-tuning the ER quality control mechanisms in cells. The therapeutic significance of understanding these events is apparent from the rising number of reports, which directly link different pathological conditions to NTT misfolding. For instance, folding deficient variants of the human transporters for dopamine or GABA lead to infantile parkinsonism/dystonia and epilepsy, respectively. From a therapeutic point of view, some folding-deficient NTTs are amenable to functional rescue by small molecules, known as chemical and pharmacological chaperones. (c) 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Magnetite nano-particles   Adsorption capacity   Growth and economic performance   Hemato-biochemical   Immunohistochemistry   Nile tilapia  

摘要： Among toxic pollutants, Mercury (Hg) is a toxic heavy metal that induces harmful impacts on aquatic ecosystems directly and human being's health indirectly. This study confirmed the in vitro magnetic potential of magnetite Nano-Particles (Fe3O4 NPs) against waterborne Hg exposure-induced toxicity in Nile tilapia (Oreochromis niloticus). We further evaluate the safety profile of Fe3O4 NPs on fish growth, hemato-biochemical, histological parameters, bioaccumulation in muscles, and economy. Magnetite nanoparticles were characterized, adsorption loading to Hg ions was investigated, and testing different concentrations of Fe3O4 NPs (0.2, 0.4, 0.6, 0.8, and 1.0 mg/L) was applied to determine the highest concentration of adsorption. An in vivo experiment includes 120 fish with an average weight of 26.2 +/- 0.26 g were randomly divided into 4 equal groups, each group had three replicates (n = 30 fish/group;10 fish/ replicate). All groups were fed on a reference basal diet and the experiment was conducted for 30 days. The first group (G1) was allocated as a control. The second group (G2) received 1.0 mg/L aqueous suspension of Fe3O4 NPs. The third group (G3) was exposed to an aqueous solution of Hg ions at a concentration of 0.025 mg/L. Meanwhile, the fourth group (G4) acquired an aqueous suspension composed of a mixture of Hg ions and Fe3O4 NPs as previously mentioned. Throughout the exposure period, the clinical signs, symptoms, and mortalities were recorded. The Hg ions-exposed group induced the following consequences;reduced appetite resulting in reduced growth and less economic efficiency;microcytic hypochromic anemia, leukocytosis, lymphopenia, and neutrophilia;sharp and clear depletion in the immune indicators including lysozymes activity, immunoglobulin M (IgM), and Myeloperoxidase activities (MPO);significant higher levels of ALT, AST, urea, creatinine, and Superoxide dismutase (SOD);histological alterations of gill, hepatic and muscular tissues with strong expressi

关键词： Lactation   Mammary epithelial cells   Alpha-lactalbumin   Lactose synthase complex   Beta-1   4-galactosyl transferase   Oligosaccharide  

摘要： Lactose is the primary carbohydrate in the milk of most mammals and is unique in that it is only synthesized by epithelial cells in the mammary glands. Lactose is also essential for the development and nutrition of infants. Across species, the concentration of lactose in milk holds a strong positive correlation with overall milk volume. Additionally, there is a range of examples where the onset of lactose synthesis as well as the content of lactose in milk varies between species and throughout a lactation. Despite this diversity, the precursors, genes, proteins and ions that regulate lactose synthesis have not received the depth of study they likely deserve relative to the significance of this simple and abundant molecule. Through this review, our objective is to highlight the requirements for lactose synthesis at the biochemical, cellular and temporal levels through a comparative approach. This overview also serves as the prelude to a companion review describing the dietary, hormonal, molecular, and genetic factors that regulate lactose synthesis.

关键词： L-asparaginase   Biopharmaceutical   Food industry   Bioprocess  

摘要： In the past decades, the production of biopharmaceuticals has gained high interest due to its great sensitivity, specificity, and lower risk of negative effects to patients. Biopharmaceuticals are mostly therapeutic recombinant proteins produced through biotechnological processes. In this context, L-asparaginase (L-asparagine amidohydrolase, L-ASNase (E.C. 3.***.1.1)) is a therapeutic enzyme that has been abundantly studied by researchers due to its antineoplastic properties. As a biopharmaceutical, L-ASNase has been used in the treatment of acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), and other lymphoid malignancies, in combination with other drugs. Besides its application as a biopharmaceutical, this enzyme is widely used in food processing industries as an acrylamide mitigation agent and as a biosensor for the detection of L-asparagine in physiological fluids at nano-levels. The great demand for L-ASNase is supplied by recombinant enzymes from Escherichia coli and Erwinia chrysanthemi. However, production processes are associated to low yields and proteins associated to immunogenicity problems, which leads to the search for a better enzyme source. Considering the L-ASNase pharmacological and food importance, this review provides an overview of the current biotechnological developments in L-ASNase production and biochemical characterization aiming to improve the knowledge about its production.

关键词： Intracellular thermometry   Design of experiments   Cellular metabolism   Interfacial resistance   Thermal conductivity   Heat diffusion  

摘要： Temperature is a fundamental thermodynamic property that can serve as a probe of biochemical reactions. Extracellular thermometry has previously been used to probe cancer metabolism and thermoregulation, with measured temperature changes of similar to 1-2 K in tissues, consistent with theoretical predictions. In contrast, previous intracellular thermometry studies remain disputed due to reports of >1 K intracellular temperature rises over 5 min or more that are inconsistent with theory. Thus, the origins of such anomalous temperature rises remain unclear. An improved quantitative understanding of intracellular thermometry is necessary to provide a clearer perspective for future measurements. Here, we develop a generalizable framework for modeling cellular heat diffusion over a range of subcellular-to-tissue length scales. Our model shows that local intracellular temperature changes reach measurable limits (>0.1 K) only when exogenously stimulated. On the other hand, extracellular temperatures can be measurable (>0.1 K) in tissues even from endogenous biochemical pathways. Using these insights, we provide a comprehensive approach to choosing an appropriate cellular thermometry technique by analyzing thermogenic reactions of different heat rates and time constants across length scales ranging from subcellular to tissues. Our work provides clarity on cellular heat diffusion modeling and on the required thermometry approach for probing thermogenic biochemical pathways.

关键词： Neutrophils   Neutrophil extracellular traps   Innate immune response   Autoimmunity   Systemic lupus erythematosus  

摘要： Neutrophil extracellular traps (NETs) are networks of decondensed chromatin loaded with antimicrobial peptides and enzymes produced against microorganisms or biochemical stimuli. Since their discovery, numerous studies made separately have revealed multiple triggers that induce similar NET morphologies allowing to classify them as lytic or non-lytic. However, the variability in NET composition depending on the inducer agent and the local milieu under similar conditions has been scarcely studied. In this work, a comparative study was conducted to evaluate structural and enzymatic divergences in NET composition induced by biochemical (phorbol myristate acetate [PMA] and hypochlorous acid [HOCl]) and microbiologic (Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) stimuli, along with the presence of plasma from healthy donors or patients with systemic lupus erythematosus (SLE). The results showed a differential composition of DNA and the antimicrobial peptide cathelicidin (LL37) and a variable enzymatic activity (neutrophil elastase, cathepsin G, myeloperoxidase) induced by the different stimuli despite showing morphologically similar NETs. Additionally, SLE plasma ' s presence increased DNA and LL37 release during NET induction independently of the trigger stimulus but with no enzymatic activity differences. This work provides new evidence about NET composition variability depending on the inducer stimulus and the local milieu.