Synthetic Catalysts for Selective Glycan Cleavage from Glycoproteins and Cells.

In situ modification of glycans requires extraordinary molecular recognition of highly complex and subtly different carbohydrates, followed by reactions at precise locations on the substrate. We here report synthetic catalysts that under physiological conditions cleave a predetermined oligosaccharide block such as a branched trimannose or the entire N-glycan of a glycoprotein, while nontargeted glycoproteins stay intact. The method also allows α2-6-sialylated galactosides to be removed preferentially over the α2-3-linked ones from cell surfaces, highlighting the potential of these synthetic glycosidases for glycan editing.

Making of water soluble curcumin to potentiate conventional antimicrobials by inducing apoptosis-like phenomena among drug-resistant bacteria.

The upsurge of multidrug resistant bacterial infections with declining pipeline of newer antibiotics has made it imperative to develop newer molecules or tailor the existing molecules for more effective antimicrobial therapies. Since antiquity, the use of curcumin, in the form of Curcuma longa paste, to treat infectious lesions is unperturbed despite its grave limitations like instability and aqueous insolubility. Here, we utilized "click" chemistry to address both the issues along with improvisation of its antibacterial and antibiofilm profile. We show that soluble curcumin disrupts several bacterial cellular processes leading to the Fenton's chemistry mediated increased production of reactive oxygen species and increased membrane permeability of both Gram-positive and Gram-negative bacteria. We here report that its ability to induce oxidative stress can be harnessed to potentiate activities of ciprofloxacin, meropenem, and vancomycin. In addition, we demonstrated that the soluble curcumin reported herein even sensitizes resistant Gram-negative clinical isolates to the Gram-positive specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. This work shows that the soluble curcumin can be used to enhance the action of existing antimicrobials against both Gram-positive and Gram-negative bacteria thus strengthening the antibiotic arsenal for fighting resistant bacterial infections for many years to come.

Human immunodeficiency virus and hepatitis C virus coinfection in Nepal.

OBJECTIVES: The study aimed at finding prevalence, mode of transmission, and pattern of CD4 cell count among hepatitis C virus (HCV) coinfected human immunodeficiency virus (HIV)-positive individuals in Nepal. METHODS: This was a descriptive cross-sectional study carried out in three Volunteer Counseling and Testing clinics, one from Dharan and two from Kathmandu, Nepal. Three hundred and thirteen individuals were recruited. RESULTS: Forty-two percent of HIV-infected persons had HCV coinfection. Significant associations with HIV and HCV coinfection were male gender (p <0.001) and injection drug use (IDU) (p <0.001). The mean CD4 cell count was significantly lower in HCV coinfected individuals, compared to those without coinfection, after 1.5 years (p =0.017), 2 years (p =0.0457), 3 years (p =0.011), and 3.5 years (p <0.001) of antiretroviral therapy. CONCLUSION: HCV coinfection was common in HIV-infected individuals in Nepal and was associated with male gender, IDU, and lower CD4 counts.