Circulating plasma miR-23b-3p as a biomarker target for idiopathic Parkinson's disease: comparison with small extracellular vesicle miRNA.

Background: Parkinson's disease (PD) is an increasingly common neurodegenerative condition, which causes movement dysfunction and a broad range of non-motor symptoms. There is no molecular or biochemical diagnosis test for PD. The miRNAs are a class of small non-coding RNAs and are extensively studied owing to their altered expression in pathological states and facile harvesting and analysis techniques. Methods: A total of 48 samples (16 each of PD, aged-matched, and young controls) were recruited. The small extracellular vesicles (sEVs) were isolated and validated using Western blot, transmission electron microscope, and nanoparticle tracking analysis. Small RNA isolation, library preparation, and small RNA sequencing followed by differential expression and targeted prediction of miRNA were performed. The real-time PCR was performed with the targeted miRNA on PD, age-matched, and young healthy control of plasma and plasma-derived sEVs to demonstrate their potential as a diagnostic biomarker. Results: In RNA sequencing, we identified 14.89% upregulated (fold change 1.11 to 11.04, p < 0.05) and 16.54% downregulated (fold change -1.04 to -7.28, p < 0.05) miRNAs in PD and controls. Four differentially expressed miRNAs (miR-23b-3p, miR-29a-3p, miR-19b-3p, and miR-150-3p) were selected. The expression of miR-23b-3p was "upregulated" (p = 0.002) in plasma, whereas "downregulated" (p = 0.0284) in plasma-derived sEVs in PD than age-matched controls. The ROC analysis of miR-23b-3p revealed better AUC values in plasma (AUC = 0.8086, p = 0.0029) and plasma-derived sEVs (AUC = 0.7278, p = 0.0483) of PD and age-matched controls. Conclusion: We observed an opposite expression profile of miR-23b-3p in PD and age-matched healthy control in plasma and plasma-derived sEV fractions, where the expression of miR-23b-3p is increased in PD plasma while decreased in plasma-derived sEV fractions. We further observed the different miR-23b-3p expression profiles in young and age-matched healthy control.

Identification and characterization of degradation products of indacaterol using liquid chromatography/mass spectrometry.

Indacaterol (IND), 5-[2-[(5,6-Diethyl-2,3-dihydro-1H-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxyquinolin-2(1H)-one, is an active pharmaceutical ingredient (API) which is used to treat chronic obstructive pulmonary disease (COPD). We followed the International Council for Harmonization (ICH) guide lines to study the degradation behavior of IND under various stress conditions. Stressed degradation of the drug was performed under hydrolytic (alkaline, acidic and neutral), photolytic, oxidative and thermal conditions. Identification and characterization of IND and its forced degradation products (DPs) were demonstrated by using LC-HRMS and MS/MS method. A total of three DPs (DP1-DP3) were identified and characterized. The IND was found to be stable under photolytic, oxidative and thermal conditions, whereas it produced three DPs in acidic, basic and neutral hydrolytic stress conditions.

The discovery of antioxidants in marine microorganisms and their protective effects on the hepatic cells from chemical-induced oxidative stress.

The marine environment is emerging as a biodiversity resource for the discovery of natural molecules or chemical scaffolds with pharmaceutical activity. Marine microbes have a tremendous ability to sense and respond to their surroundings to survive in a stressful environment by producing different molecules. As oxidative stress is directly or indirectly involved in various pathological conditions in humans, we believe that marine-derived antioxidant molecules will have a great prospect as a novel antioxidant molecule. We, in this work, explored the marine microbial resources from the Gulf of Mannar, Bay of Bengal, India. High-throughput screening of antioxidant molecule producing marine microbes has revealed that extract from Kocuria marina CDMP 10, can effectively reduce the DPPH free radical. Methanolic crude extract obtained by the freeze-thawing was fractionated and purified by using activity guided purification with the help of reverse phase HPLC and analysed through UPLC-MS. Chemical analysis, as well as MS-spectra, indicated that marine bacteria K. marina CDMP 10 derived antioxidant fraction contains the short peptides. The antioxidant activity of the three highly hydrophobic peptides, (Ser-Ser-Gln, Phe-Glu, Asp-Ile and Leu-Glu) was confirmed by in vitro as well as a cell-based assay. These small peptide molecules are noncytotoxic and can prevent the human cells from chemical-induced oxidative stress. Ser-Ser-Gln peptide demonstrated a potent free radical scavenging activity in Hepatocellular carcinoma cell lines. This study suggests that these short peptides from K. marina CDMP 10 may serve as a potential pharmaceutical candidate with antioxidant activity.

Some proteins of M. tuberculosis that localise to the nucleus of THP-1-derived macrophages.

Host-pathogen dialectics in tuberculosis (TB) via DNA-protein interactions are emerging. We investigated whether proteins produced by Mycobacterium tuberculosis (Mtb) could translocate to the host nucleus. Using lysates of nuclei purified from Mtb-infected THP-1-derived macrophages, we identified at least 15 proteins of Mtb-origin by electrophoretic and chromatographic separation and mass spectrometry. Western blotting confirmed time-dependent accumulation of Mtb EF-Tu, GroEL, GroES and MtrA in the host nucleus. MtrA could pull down at least 16 host proteins. Mtb proteins may have moonlighting functions that affect host gene expression.

Pd-Catalyzed Isocyanide Assisted Reductive Cyclization of 1-(2-Hydroxyphenyl)-propargyl Alcohols for 2-Alkyl/Benzyl Benzofurans and Their Useful Oxidative Derivatization.

An unusual Pd-catalyzed isocyanide assisted 5-exo-dig reductive cyclization of 1-(2-hydroxyphenyl)-propargyl alcohols is achieved for 2-alkyl/benzyl benzofurans. The reaction features a high substrate scope, insensitivity to air, and excellent product yielding. Further, a direct metal-free C-H functionalization (azidation, alkoxylation, and hydroxylation) and selective oxidative cleavage of thus synthesized 2-benzylfurans are described for azido-, alkoxy-, hydroxyl-, amide-, and tetrazolyl adducts.

Synthesis of 3-Sulfonylamino Quinolines from 1-(2-Aminophenyl) Propargyl Alcohols through a Ag(I)-Catalyzed Hydroamination, (2 + 3) Cycloaddition, and an Unusual Strain-Driven Ring Expansion.

We describe herein a silver-catalyzed conversion of 1-(2-aminophenyl)-propargyl alcohols to 4-substituted 3-tosylaminoquinolines using TsN3 as an amino surrogate. Controlled reactions reveal the pathway consisting of Ag(I)-catalyzed 5-exo-dig cyclization, catalyst-free (2 + 3) cycloaddition, and ring-expansive rearrangement via nitrogen expulsion. As a support study, we show that the cyclic enamines in similar conditions produce amidines via a C-C bond migration.