Rapid Bioassay-Guided Isolation of Antibacterial Clerodane Type Diterpenoid from Dodonaea viscosa (L.) Jaeq.

Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6ß-hydroxy-15,16-epoxy-5ß, 8ß, 9ß, 10α-cleroda-3, 13(16), 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC) = 64-128 µg/mL) against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa.

Impact of the COVID-19 Pandemic on the Management of Gallbladder, Biliary Tract, and Pancreatic Diseases.

Introduction Biliary diseases are a major acute general surgical burden. Laparoscopic cholecystectomy is the gold standard surgical procedure, although it was discontinued during an outbreak. Effective management permits decisive therapy, symptom alleviation, and fewer hospitalizations and complications. Throughout the initial COVID-19 situation, surgical procedures for patients were delayed. Invasive services were required to employ conservative or non-operative therapy, which could lead to increased recurring presentations and biliary-pancreatic problems. Aim Examining the impact of COVID-19 on the outcomes and hospitalizations of patients suffering from gallstone, biliary tract, and pancreatic diseases.  Methods The retrospective analysis included patients with the following ICD-10 codes who presented to our unit: cholelithiasis (K80), cholecystitis (K81), and acute pancreatitis (K85). We compared the interval of the first COVID-19 pandemic wave, from March to August 2020, with the period before the pandemic, referred to as Pre-COVID-19. After applying exclusion criteria, a total of 868 patients were enrolled in the trial, having initially recruited around 1,400 individuals using these codes. Patients with inaccurate coding, cancer, or non-stone disease were excluded (e.g., alcoholic pancreatitis). The demographic information, admission details, investigations, surgical therapy, operating specifics, and postoperative complications of the patients were noted. Changes in surgical management, patient representation, and postoperative complications were the key outcomes. Results A statistically significant (p<0.05) rise was seen in repeat presentations in the COVID group, most likely due to the failure of definitive treatment. The other outcome is the distribution of presentations was comparable, patients with acute cholecystitis and gallstone pancreatitis showed statistically significant (p<0.05) lower rates of definitive therapy. Conclusion During the COVID period, all surgeries except those for cancer were halted. Unknown causes led to several consequences related to the gallbladder, biliary tract, and pancreas. Patients with cholecystitis, gallstone pancreatitis, and pancreatic inflammation experienced a lower probability of treatment. The increase in hospitalizations and self-presentations indicated that definitive therapy, designed to restrict COVID-19 exposure, actually increased patient risk. Despite this risk, we had no COVID-19 instances in our cohort. The evaluation of the long-term consequences of the pandemic on acute pancreatitis and its care will require a large-scale, multicenter investigation.

Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production.

Increased Abeta42 production has been linked to the development of Alzheimer disease. We now identify a number of compounds that raise Abeta42. Among the more potent Abeta42-raising agents identified are fenofibrate, an antilipidemic agent, and celecoxib, a COX-2-selective NSAID. Many COX-2-selective NSAIDs tested raised Abeta42, including multiple COX-2-selective derivatives of two Abeta42-lowering NSAIDs. Compounds devoid of COX activity and the endogenous isoprenoids FPP and GGPP also raised Abeta42. These compounds seem to target the gamma-secretase complex, increasing gamma-secretase-catalyzed production of Abeta42 in vitro. Short-term in vivo studies show that two Abeta42-raising compounds increase Abeta42 levels in the brains of mice. The elevations in Abeta42 by these compounds are comparable to the increases in Abeta42 induced by Alzheimer disease-causing mutations in the genes encoding amyloid beta protein precursor and presenilins, raising the possibility that exogenous compounds or naturally occurring isoprenoids might increase Abeta42 production in humans.

Pollution, Toxicity and Carcinogenicity of Organic Dyes and their Catalytic Bio-Remediation.

Water pollution due to waste effluents of the textile industry is seriously causing various health problems in humans. Water pollution with pathogenic bacteria, especially Escherichia coli (E. coli) and other microbes is due to the mixing of fecal material with drinking water, industrial and domestic sewage, pasture and agricultural runoff. Among the chemical pollutants, organic dyes due to toxic nature, are one of the major contaminants of industrial wastewater. Adequate sanitation services and drinking quality water would eliminate 200 million cases of diarrhea, which results in 2.1 million less deaths caused by diarrheal disease due to E. coli each year. Nanotechnology is an excellent platform as compared to conventional treatment methods of water treatment and remediation from microorganisms and organic dyes. In the current study, toxicity and carcinogenicity of the organic dyes have been studied as well as the remediation/inactivation of dyes and microorganism has been discussed. Remediation by biological, physical and chemical methods has been reviewed critically. A physical process like adsorption is cost-effective, but can't degrade dyes. Biological methods were considered to be ecofriendly and cost-effective. Microbiological degradation of dyes is cost-effective, eco-friendly and alternative to the chemical reduction. Besides, certain enzymes especially horseradish peroxidase are used as versatile catalysts in a number of industrial processes. Moreover, this document has been prepared by gathering recent research works related to the dyes and microbial pollution elimination from water sources by using heterogeneous photocatalysts, metal nanoparticles catalysts, metal oxides and enzymes.

Synthesis of acid-cleavable light isotope-coded affinity tags (ICAT-L) for potential use in proteomic expression profiling analysis.

A convenient synthesis of some homologous light isotope-coded affinity tags (ICAT-L) containing an acid-labile moiety between the affinity component biotin and an electrophilic polar linker is described. These light ICAT reagents give smooth mass spectral signals in tandem mass spectrometry (MS/MS) analyses of some commercially available cysteine-containing peptides. However, these ICAT molecules are designed for use in identification and relative quantification of whole or partially purified cellular and tissue proteomes. Since the biotin moiety can be readily cleaved off the reagent after mass tagging, undesired residual fragmentation patterns caused by biotin of derived peptides, as normally observed using biotin-containing ICAT reagents, are effectively eliminated. This strategy should enhance peptide sequence coverage significantly which, in turn, should result in improving the quality of data obtained during data-dependent peptide mass and tandem mass spectral analysis of whole proteomes.

Design and chemical synthesis of a magnetic resonance contrast agent with enhanced in vitro binding, high blood-brain barrier permeability, and in vivo targeting to Alzheimer's disease amyloid plaques.

Molecular imaging is an important new direction in medical diagnosis; however, its success is dependent upon molecular probes that demonstrate selective tissue targeting. We report the design and chemical synthesis of a derivative of human amyloid-beta (Abeta) peptide that is capable of selectively targeting individual amyloid plaques in the brain of Alzheimer's disease transgenic mice after being intravenously injected. This derivative is based on the sequence of the first 30 amino acid residues of Abeta with asparagyl/glutamyl-4-aminobutane residues (N-4ab/Q-4ab) substituted at unique Asp and Glu positions and with Gd-DTPA-aminohexanoic acid covalently attached at the N-terminal Asp. The Gd[N-4ab/Q-4ab]Abeta30 peptide was homogeneous as shown by high-resolution analytical techniques with a mass of +/-4385 Da determined by electrospray ionization mass spectrometry. This diamine- and gadolinium-substituted derivative of Abeta is shown to have enhanced in vitro binding to Alzheimer's disease (AD) amyloid plaques and increased in vivo permeability at the blood-brain barrier because of the unique Asp/Glu substitutions. In addition, specific in vivo targeting to AD amyloid plaques is demonstrated throughout the brain of an APP, PS1 transgenic mouse after intravenous injection. Because of the magnetic resonance (MR) imaging contrast enhancement provided by gadolinium, this derivative should enable the in vivo MR imaging of individual amyloid plaques in the brains of AD animals or patients to allow for early diagnosis and also provide a direct measure of the efficacy of anti-amyloid therapies currently being developed.