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关键词： Mimosine   β–PA   Willardiine   Isowillardiine   Lathyrine   Serine   OAS   Cysteine synthase   SP STRAIN TAL1145   MIMOSINE-DEGRADING ENZYME   LEUCAENA-LEUCOCEPHALA LAM   LATHYRUS-TINGITANUS   POLYAMINE OXIDASE   L-HOMOARGININE   DNA-SYNTHESIS   IN-VITRO   BIOSYNTHESIS   RHIZOBIUM  

摘要： Plants catalyze the biosynthesis of a large number of non-protein amino acids, which are usually toxic for other organisms. In this review, the chemistry and metabolism of N-heterocyclic non-protein amino acids from plants are described. These N-heterocyclic non-protein amino acids are composed of beta-substituted alanines and include mimosine, beta-pyrazol-1-yl-l-alanine, willardiine, isowillardiine, and lathyrine. These beta-substituted alanines consisted of an N-heterocyclic moiety and an alanyl side chain. This review explains how these individual moieties are derived from their precursors and how they are used as the substrate for biosynthesizing the respective N-heterocyclic non-protein amino acids. In addition, known catabolism and possible role of these non-protein amino acids in the actual host is explained.

关键词： Prostate cancer   Robotic-assisted radical prostatectomy   Prostate-specific antigen nadir   Biochemical recurrence   CAPRA-S SCORE   RETROPUBIC PROSTATECTOMY   SALVAGE RADIOTHERAPY   PREDICTIVE FACTORS   NATURAL-HISTORY   PSA   MORTALITY   SURVIVAL   OUTCOMES   TIME  

摘要： Purpose The aim of the study is to evaluate the impact of having a nadir and persistently detectable ultrasensitive prostate-specific antigen (uPSA) between 0.01 and 0.1 ng/ml post-robot-assisted radical prostatectomy (RARP), on future biochemical recurrence (BCR). Methods We conducted a retrospective analysis of a prospectively maintained cohort of 1359 men who underwent RARP, between 2006 and 2019. Patients were followed with uPSA at 1, 3, 6, 9, 12, 18, 24, 30, 36 months and annually thereafter. We included patients with PSA nadir values between 0.01 and 0.1 ng/ml within 6 months of surgery and with at least 2 follow-up measurements within the same range. We divided patients based on their BCR status and analyzed uPSA changes. Multivariable Cox-regression models (CRMs) were used to analyze variables predicting BCR-free survival (BCR-FS). Results We identified 167 (12.3%) patients for analyses, with a mean follow-up time of 60.2 +/- 31.4 months. In our cohort, 5-year BCR-FS rate was 86%. Overall, 32 (19.1%) patients had BCR, with a mean time to BCR of 43.7 +/- 24.3 months. BCR-free patients had stable mean uPSA values <= 0.033 ng/ml, while patients who developed BCR showed a slowly rising trend over time, with a significant difference between groups starting at 9 months (p < 0.02). In multivariable CRMs, a rising uPSA starting at 9 months was an independent predictor of BCR (HR: 2.7; 95% CI 1.6-3.82;p = 0.013). Conclusion In the present cohort, our results demonstrated that a considerable number of men have detectable uPSA values ranging between 0.01 and 0.1 ng/ml post-RARP. They can still be followed regularly to avoid patients' anxiety and salvage radiotherapy. Close follow-up is still required.

关键词： Sanfilippo syndrome type B   Mucopolysaccharidosis IIIB   Intracerebroventricular enzyme replacement therapy (ICV-ERT)   Heparan sulfate   Neonatal mice   MUCOPOLYSACCHARIDOSIS TYPE IIIA   ALPHA-N-ACETYLGLUCOSAMINIDASE   HEPARAN-SULFATE ACCUMULATION   BMN 250 NAGLU-IGF2   LYSOSOMAL-ENZYME   CNS   DELIVERY   TRANSPLANTATION   RECOMBINANT   BIOMARKERS  

摘要： Mucopolysaccharidosis IIIB (MPS IIIB, Sanfilippo syndrome type B) is caused by a deficiency in alpha-N-acetylglucosaminidase (NAGLU) activity, which leads to the accumulation of heparan sulfate (HS). MPS IIIB causes progressive neurological decline, with affected patients having an expected lifespan of approximately 20 years. No effective treatment is available. Recent pre-clinical studies have shown that intracerebroventricular (ICV) ERT with a fusion protein of rhNAGLU-IGF2 is a feasible treatment for MPS IIIB in both canine and mouse models. In this study, we evaluated the biochemical efficacy of a single dose of rhNAGLU-IGF2 via ICV-ERT in brain and liver tissue from Naglu(-/-) neonatal mice. Twelve weeks after treatment, NAGLU activity levels in brain were 0.75-fold those of controls. HS and beta-hexosaminidase activity, which are elevated in MPS IIIB, decreased to normal levels. This effect persisted for at least 4 weeks after treatment. Elevated NAGLU and reduced beta-hexosaminidase activity levels were detected in liver; these effects persisted for up to 4 weeks after treatment. The overall therapeutic effects of single dose ICV-ERT with rhNAGLU-IGF2 in Naglu(-/-) neonatal mice were long-lasting. These results suggest a potential benefit of early treatment, followed by less-frequent ICV-ERT dosing, in patients diagnosed with MPS IIIB. (C) 2021 Elsevier Inc. All rights reserved.

关键词： Gradient consistency test   Amino acid properties   Amino acid usage   Protein evolution  

摘要： Proteins can evolve by accumulating changes on amino acid sequences. These changes are mainly caused by missense mutations on its DNA coding sequences. Mutations with neutral or positive effects on fitness can be maintained while deleterious mutations tend to be eliminated by natural selection. Amino acid changes are influenced by the biophysical, chemical, and biological properties of amino acids. There is a multiplicity of amino acid properties that can influence the function and expression of proteins. Amino acid properties can be expressed into numerical indexes, which can help to predict functional and structural aspects of proteins and allow statistical inferences of selection pressure on amino acid usage. The accuracy of these analyses may be compromised by the existence of several numerical indexes that measure the same amino acid property, and the lack of objective parameters to determine the most accurate and biologically relevant index. In the present study, the gradient consistency test was used in order to estimate the magnitude of directional selection imparted by amino acid biochemical and biophysical properties on protein evolution.

关键词： Antimicrobial protein   L-amino acid oxidase   Interleukin (IL)-4-induced gene 1   Hydrogen peroxide   Metabolites   Biomarker   IMMUNOSUPPRESSIVE ENZYME IL4I1   SNAKE-VENOM ISOLATION   LYSINE ALPHA-OXIDASE   MOLECULAR CHARACTERIZATION   IL-4-INDUCED GENE-1   SKIN MUCUS   RECOMBINANT EXPRESSION   IMMUNE CHECKPOINT   CRYSTAL-STRUCTURE   DENDRITIC CELLS  

摘要： Mucus layer that covers the body surface of various animal functions as a defense barrier against microbes, environmental xenobiotics, and predators. Previous studies have reported that L-amino acid oxidase (LAAO), present in several animal fluids, has potent properties against pathogenic bacteria, viruses, and parasites. LAAO catalyzes the oxidative deamination of specific L-amino acids with the generation of hydrogen peroxide and L-amino acid metabolites. Further, the generated hydrogen peroxide is involved in oxidation (direct effect) while the metabolites activate immune responses (indirect effect). Therefore, LAAO exhibits two different mechanisms of bioactivation. Previously, we described the selective, specific, and local oxidative and potent antibacterial actions of various LAAOs as potential therapeutic strategies. In this review, we focus on their biochemical features, enzymatic regulations, and biomedical applications with a view of describing their probable role as biochemical agents and biomarkers for microbial infections, cancer, and autoimmune-mediated diseases. We consider that LAAOs hold implications in biomedicine owing to their antimicrobial activity wherein they can be used in treatment of infectious diseases and as diagnostic biomarkers in the above-mentioned diseased conditions.

关键词： somatic embryogenesis   somaclonal variation   AFLP   metAFLP   triterpenoids   Araliaceae   IN-VITRO CULTURE   SOMACLONAL VARIATION   DNA METHYLATION   URSOLIC ACID   PLANT-REGENERATION   OLEANOLIC ACID   RAPID MULTIPLICATION   EPIGENETIC VARIATION   STABILITY   AFLP  

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   POLYSTYRENE MICROPLASTICS   PLASTIC NANOPARTICLES   MARINE   BIOMASS   ALGAE   OPTIMIZATION   ENHANCEMENT   TOXICITY   EXPOSURE   FISHES  

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   AMINO-ACID TRANSPORTER   VESICULAR ACETYLCHOLINE TRANSPORTER   HUMAN SEROTONIN TRANSPORTER   MEMBRANE MONOAMINE TRANSPORTER   CONGENITAL MYASTHENIC SYNDROME   SINGLE NUCLEOTIDE POLYMORPHISMS   AMYOTROPHIC-LATERAL-SCLEROSIS   ORGANIC CATION TRANSPORTERS   GLUTAMATE TRANSPORTER   DOPAMINE TRANSPORTER  

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/).