Proteomics and Visual Health Research: Proteome of the Human Sclera Using High-Resolution Mass Spectrometry.

Eye disorders and resulting visual loss are major public health problems affecting millions of people worldwide. In this context, the sclera is an opaque, thick outer coat covering more than 80% of the eye, and essential in maintaining the shape of the eye and protecting the intraocular contents against infection and the external environment. Despite efforts undertaken to decipher the scleral proteome, the functional and structural picture of the sclera still remain elusive. Recently, proteomics has arisen as a powerful tool that enables identification of proteins playing a critical role in health and disease. Therefore, we carried out an in-depth proteomic analysis of the human scleral tissue using a high-resolution Orbitrap Fusion Tribrid mass spectrometer. We identified 4493 proteins using SequestHT and Mascot as search algorithms in Proteome Discoverer 2.1. Importantly, the proteins, including radixin, synaptopodin, paladin, netrin 1, and kelch-like family member 41, were identified for the first time in human sclera. Gene ontology analysis unveiled that the majority of proteins were localized to the cytoplasm and involved in cell communication and metabolism. In sum, this study offers the largest catalog of proteins identified in sclera with the aim of facilitating their contribution to diagnostics and therapeutics innovation in visual health and autoimmune disorders. This study also provides a valuable baseline for future investigations so as to map the dynamic changes that occur in sclera in various pathological conditions.

Central dopaminergic system plays a role in the analgesic action of paracetamol: Preclinical evidence.

OBJECTIVE: Even after 100 years of discovery, the exact mechanisms for the analgesic action of paracetamol are under scanner. It was recently proposed that paracetamol may act through different mechanisms, especially altering the serotoninergic system. The main objective of this preclinical study was to verify the role of drugs modulating dopaminergic system (l-dopa, bromocriptine, olanzapine) on the analgesic effect of paracetamol. MATERIALS AND METHODS: Thirty adult male albino mice were divided into five groups: distilled water (0.5 ml/25 g), paracetamol (200 mg/kg), levodopa (10 mg/kg) + paracetamol, bromocriptine (5 mg/kg) + paracetamol (200 mg/kg), and olanzapine (2 mg/kg) + paracetamol (200 mg/kg). All drugs were administered orally for 14 days. Eddy's hot plate and tail immersion tests were used to determine analgesic activity. Tests were conducted 1 h after the drug administration on the 14th day. After that, animals were sacrificed and brains were dissected out, to measure the levels of dopamine. Statistical comparisons among the groups were performed by one-way analysis of variance followed by Tukey-Kramer test. RESULTS: Coadministration of l-dopa and bromocriptine with paracetamol increased the antinociceptive activity of paracetamol significantly, whereas coadministration of olanzapine with paracetamol decreased the analgesic activity of paracetamol in the Eddy's hot plate and tail immersion tests considerably. There was a significant increase (P < 0.001) in the levels of dopamine in the brains of mice, which received levodopa, bromocriptine, and paracetamol. However, it was opposite in the brains of animals which received olanzapine. CONCLUSION: The results suggest that analgesic action of paracetamol is influenced by dopaminergic system.

Preclinical screening of phyllanthus amarus ethanolic extract for its analgesic and antimicrobial activity.

BACKGROUND: To discover a new agent which possesses dual property of analgesic and antimicrobial activity, thereby reducing the burden of polypharmacy. Phyllanthus amarus was screened for its analgesic and antimicrobial activities. OBJECTIVES: The objective was to evaluate the analgesic and antimicrobial activity, of P. amarus ethanolic extract (PAEE). MATERIALS AND METHODS: The ethanolic extract of P. amarus was prepared using Soxhlet apparatus. An in vivo study using Swiss albino mice was done to screen the central and peripheral analgesic activity of P. amarus extract. The extract was administered at a dose of 100 mg/kg body weight orally. The peripheral analgesic activity was assessed using acetic acid induced writhing test. The central analgesic activity was assessed using Eddy's hot plate apparatus. An in vitro study was carried out to study the antimicrobial activity of the above extract using selected species of Streptococcus mutans, and S. salivarius. The antimicrobial activities were determined using the agar well method. RESULTS: The ethanolic extract of P. amarus showed significant (P < 0.05) peripheral and central analgesic activity. In vitro antimicrobial screening indicated that the ethanolic extract had shown a zone of inhibition against S. mutans and S. salivarius in the agar wells. CONCLUSION: This study showed that PAEE exhibited significant analgesic and antimicrobial activities.