Relationship between Urinary AD7c-NTP with Cerebral Microbleeds Based on APOE Genotype

Objective. This study was performed to investigate the association between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) with cerebral microbleeds (CMBs) based on the apolipoprotein E (APOE) genotypes. Methods. A total of 471 patients with acute cerebral infarction screened by magnetic sensitive imaging were enrolled in this study. Among them, twenty-seven cases of mixed CMBs were excluded. A total of 444 patients were divided into two groups according to the presence or absence of CMBs: CMBs group ( n = 92 ) and noncerebral microbleeds group (nCMBs) ( n = 352 ). Urine AD7c-NTP levels were measured using a human enzyme immunoassay kit. Results. In patients with lobar CMBs, there was an interaction between urine AD7c-NTP levels and APOE genotypes ( p = 0.01 ). In patients with APOE ε3/ε3 allele, the odds ratio of lobar CMBs per standard deviation of urinary AD7c-NTP levels was 0.92 (95% CI: 0.70-1.19). In patients with APOE ε2+ or ε4+ allele, the multivariate-corrected odds ratio of lobar CMBs per standard deviation of urinary AD7c-NTP levels was 2.95 (95% CI: 1.38-6.27). Conclusion. A higher level of urinary AD7c-NTP is involved in lobar CMBs, not deep CMBs.

Simulation of the Interactions of Arginine with Wild-Type GALT Enzyme and the Classic Galactosemia-Related Mutant p.Q188R by a Computational Approach

Classic galactosemia is an inborn error of metabolism associated with mutations that impair the activity and the stability of galactose-1-phosphate uridylyltransferase (GALT), catalyzing the third step in galactose metabolism. To date, no treatments (including dietary galactose deprivation) are able to prevent or alleviate the long-term complications affecting galactosemic patients. Evidence that arginine is able to improve the activity of the human enzyme expressed in a prokaryotic model of classic galactosemia has induced researchers to suppose that this amino acid could act as a pharmacochaperone, but no effects were detected in four galactosemic patients treated with this amino acid. Given that no molecular characterizations of the possible effects of arginine on GALT have been performed, and given that the samples of patients treated with arginine are extremely limited for drawing definitive conclusions at the clinical level, we performed computational simulations in order to predict the interactions (if any) between this amino acid and the enzyme. Our results do not support the possibility that arginine could function as a pharmacochaperone for GALT, but information obtained by this study could be useful for identifying, in the future, possible pharmacochaperones for this enzyme.

Fungal Depsides—Naturally Inspiring Molecules: Biosynthesis, Structural Characterization, and Biological Activities

Fungi represent a huge reservoir of structurally diverse bio-metabolites. Although there has been a marked increase in the number of isolated fungal metabolites over the past years, many hidden metabolites still need to be discovered. Depsides are a group of polyketides consisting of two or more ester-linked hydroxybenzoic acid moieties. They possess valuable bioactive properties, such as anticancer, antidiabetic, antibacterial, antiviral, anti-inflammatory, antifungal, antifouling, and antioxidant qualities, as well as various human enzyme-inhibitory activities. This review provides an overview of the reported data on fungal depsides, including their sources, biosynthesis, physical and spectral data, and bioactivities in the period from 1975 to 2020. Overall, 110 metabolites and more than 122 references are confirmed. This is the first review of these multi-faceted metabolites from fungi.

Investigating ADAMTS7 and ADAMTS12 levels in prediabetic and Type 2 diabetic patients

Background: This study aims to investigate the role of ADAMTS7 and ADAMTS12 on atherosclerosis and inflammation in prediabetic and diabetic patients. Patients & methods: Serum ADAMTS7 and ADAMTS12 levels were compared with the atherosclerotic and inflammatory markers in diabetic (n = 65, female 30.9%, mean age = 53 years), prediabetic (n = 55, female 36.6%, mean age = 49 years) and control groups (n = 55, females 32.5%, mean age = 49 years). Serum ADAMTS levels were determined by a human enzyme-liked immunoassay. Results: In terms of ADAMTS7, there was no significant difference between diabetic, prediabetic and control groups (50.93, 44.34, 59.07, respectively; p > 0.05). ADAMTS12 is lower in diabetics (p < 0.05), whereas it is similar in prediabetics and controls (14.53, 20.76, 25.05, respectively; p > 0.05). ADAMTS7 and ADAMTS12 levels did not differ in diabetic nephropathy, retinopathy and neuropathy (p > 0.05). Conclusion: While ADAMTS12 was significantly lower in diabetics and prediabetics, ADAMTS7 and ADAMTS12 were not related to diabetic complications (nephropathy, retinopathy and neuropathy).

ADAMS-1 and ADAMS-9, novel markers in endometriosis

Objectives: ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin repeats) proteinases, which are released outside the cell (soluble) have very critical roles in damage and repair of extracellular matrix (ECM) processes. Our aim was to analyse the ADAMTS-1 and ADAMTS-9 which were the member of the ADAMTS gene family of metalloproteinases that might had been involved in the cytokines-mediated etiopathogenesis of endometriosis. Methods: A case-control study was performed in an university hospital. Thirty-four patient with endometriosis which was defined via laparoscopy and thirty-three healthy female volunteers were recruited in the present study. Serum ADAMTS-1 and ADAMTS-9 and IL-beta (IL-1 β) and vascular endothelial growth factor (VEGF) levels were determined by a human enzyme-linked immunoassay (ELISA) in all subjects. Results: The demographic characteristics of the patients were significantly higher than healthy control group. The IL-1 β and VEGF levels were significantly higher; ADAMTS-1 and ADAMTS-9 levels were significantly lower in the endometriosis patients compared to the controls. We also found a negative correlation between ADAMTS-1, ADAMTS-9, and IL-1 β, VEGF. Conclusion: The results of the study might suggest that ADAMS-1 and ADAMTS-9 have a role in the pathogenesis of the endometriosis.

Structure of Cystathionine β-Synthase from Toxoplasma gondii, a key enzyme in its H2S production machinery

ABSTRACTCystathionine β-synthase (CBS), the pivotal enzyme of the reverse transsulfuration pathway, catalyzes the pyridoxal-5’-phosphate-dependent condensation of serine with homocysteine to form cystathionine. Additionally, CBS performs alternative reactions that use homocysteine and cysteine as substrates leading to the endogenous biosynthesis of hydrogen sulfide (H2S), an important signal transducer in many physiological and pathological processes. Toxoplasma gondii, the causative agent of toxoplasmosis, encodes a functional CBS (TgCBS) that contrary to human CBS, is not allosterically regulated by S-adenosylmethionine and can use both, Ser and O-acetylserine (OAS) as substrates. TgCBS is also strongly implicated in the production of H2S, and thus involved in redox homeostasis of the parasite. Here, we report its crystal structure, the first CBS from a protozoan described so far. Our data reveals a basal-like fold that unexpectedly differs from the active conformations found in other organisms, but structurally similar to the pathogenic activated mutant D444N of the human enzyme.

Impact of some metal ions on activity of purified human enzyme paraoxonase (hPON1)

Inhibition of enzymes has a great influence on various metabolism activity in the body. The objective of this research has been to assess the impact of some metals and the drug statin on the activity of purified enzyme paraoxonase extracted from human sera (hPON1). The enzyme was purified in consecutive four steps using Ammonium Sulphate, Dialysis, Ion exchange and Gel filtration chromatography, respectively. These four purification steps have approved their credence in obtaining a maximum purification state of the enzyme. The inhibitory impact of some metals ions, i.e. Mg+2, K+1, Mn+2, Na+1, EDTA, and Zn+2, on the activity of purified hPON1 has also been assessed. The result showed the highest inhibitory impact of 10 mMol/L of Sodium Nitrate (NaNO3) on the activity of purified hPON1 while medication atorvastatin had significantly increased the activity of hPON1. It is concluded that any subtle change in the enzyme PON-1 could consequently lead to various diseases. More assessments are required for type two (PON-2) and type three (PON-3) to be explored. Atorvastatin is recommended to regulate cholesterol metabolism by the intestine and to lower the risk of diseases for elder ages.