RESUMO
The World Health Organization estimates that more than 23 million individuals worldwide suffer from rheumatoid arthritis (RA), a chronic systemic autoimmune disease and experts predict that the number of RA patients may double by 2030. A substantial portion of RA patients do not respond effectively to the treatment that are already available therefore there is an urgent need of innovative new drugs. Over the past several years, Peptidyl Arginine Deiminase Type 4 (PAD4) receptors have become potential therapeutic targets for the treatment of RA. The main objective of the present study is to identify potential PAD4 inhibitors from edible fruits Morinda citrifolia. Structure based virtual screening (VS) of 60 compounds from M. citrifolia were performed to identify PAD4 inhibitors. The virtual screening of compounds resulted ten hits having XP-Glide score greater than the co-ligand (XPGS: - 8.341 kcal/mol). Three hits NF_15, NF_34, and NF_35 exhibited admirable MM-GBSA dG binding energy - 52.577, - 46.777, and - 60.711 kcal/mol, respectively. These three compounds were chosen for 100 ns molecular dynamics (MD) simulations in order to evaluate the stability and interactions. The protein-ligand complex with the highest level of stability was revealed to be NF_35. Therefore, M. citrifolia fruits may be beneficial in the treatment and prevention of rheumatoid arthritis since it contains potential hits. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00147-3.
RESUMO
BACKGROUND: Hepatitis E virus (HEV) is an important cause of acute liver failure (ALF) in Bangladesh with pregnant mothers being more vulnerable. As HEV occurs in epidemics, it limits medical capabilities in this resource-poor country. Cerebral oedema, resulting in raised intracranial pressure (ICP), is an important cause of morbidity and mortality. Practical treatments are currently few. To study the baseline characteristics and clinical outcome of HEV-induced ALF in a recent HEV epidemicTo detect raised ICP clinically and observe response to mannitol infusion.This was a prospective cohort study from June until August 2018 of 20 patients admitted to the intensive care unit (ICU) of a major Bangladeshi Referral Hospital with HEV-induced ALF. We diagnosed HEV infection by detecting serum anti-HEV IgM antibody. All were negative for hepatitis B surface antigen and hepatitis A IgM antibody. Data were collected on 5-day outcome after admission to ICU, monitoring all patients for signs of raised ICP. An intravenous bolus of 20% mannitol was administered at a single time point to patients with raised ICP. RESULTS: Twenty patients were included in the study. Ten (50%) patients, seven (70%) females, received mannitol infusion. HE worsened in eight (40%): seven female and three pregnant. Glasgow Coma scores deteriorated in six (30%): all (100%) females and three pregnant. Consciousness status was not significantly different between pregnant and non-pregnant subjects, nor between those who received mannitol and those who did not. Six patients met King's College Criteria for liver transplantation. CONCLUSIONS: Female patients had a worse outcome, but pregnancy status was not an additional risk factor in our cohort. Mannitol infusion was also not associated with a significant difference in outcome.
RESUMO
Naturally occurring new iridoids and secoiridoids published during 2005-2008 are reviewed with available physical and spectral data: mp, [alpha](D), UV, IR, (1)H- and (13)C-NMR and plant source. The works on biological and pharmacological activity of naturally occurring iridoids and secoiridoids reported during 2005-2008 are also reviewed. Bioactivities like antibacterial, anticancer, anticoagulant, antifungal, anti-inflammatory, antioxidative, antiprotozoal, hepatoprotective and neuroprotective activities are highlighted.