Effect of TLR3/dsRNA complex inhibitor on Poly(I:C)-induced airway inflammation in Swiss albino mice.

Rhinovirus infection frequently causes COPD and asthma exacerbations. Impaired anti-viral signaling and reduced viral clearance have both been seen in sick bronchial epithelium, potentially increasing exacerbations. Polyinosinic:polycytidylic acid (Poly(I:C)), a Toll-like receptor-3 (TLR3) ligand, has been shown to cause a viral exacerbation of severe asthma by detecting double-stranded RNA (dsRNA). The purpose of this work was to determine the effect of a TLR3/dsRNA complex inhibitor-Calbiochem drug in the prevention of Poly(I:C)-induced airway inflammation following TLR3 activation and to uncover a potential pathway for the cure of asthma through TLR3 inhibition. Mice were sensitized with Poly(I:C) as an asthma model before being challenged by PBS and ovalbumin (OVA) chemicals. The mice were administered a TLR3/dsRNA complex inhibitor. Throughout the trial, the mice's body weight was measured after each dosage. Biochemical methods are used to analyze the protein as well as enzyme composition in airway tissues. BALF specimens are stained using Giemsa to identify inflammatory cells and lung histopathology to determine morphological abnormalities in lung tissues. By using the ELISA approach, cytokine levels such as TNF-α, IL-13, IL-6, IL-5, and IgE antibody expression in lung tissue and blood serum were assessed. TLR3/dsRNA complex inhibitor drug significantly lowered the number of cells in BALF and also on Giemsa staining slides. It also downregulated the level of TNF-α and IL-6 in contrast to OVA and Poly(I:C) administered in animals. A TLR3/dsRNA complex inhibitor decreased the fraction of oxidative stress markers (MDA, GSH, GPx, and CAT) in lung tissues while keeping the mice's body weight constant during the treatment period. By decreasing alveoli, bronchial narrowing, smooth muscle hypertrophy, and granulocyte levels, the TLR3/dsRNA complex blocker significantly reduced the histopathological damage caused by OVA and Poly(I:C) compounds. In an animal model utilizing ovalbumin, TLR3/dsRNA complex inhibitors similarly reduced the bronchial damage produced by Poly(I:C). A novel TLR3/dsRNA complex inhibitor is expected to be employed in clinical studies since it suppresses airway inflammation without inducing antiviral approach resistance.

Metabolomics of neurological disorders in India.

Metabolomics is the comprehensive study of the metabolome and its alterations within biological fluids and tissues. Over the years, applications of metabolomics have been explored in several areas, including personalised medicine in diseases, metabolome-wide association studies (MWAS), pharmacometabolomics and in combination with other branches of omics such as proteomics, transcriptomics and genomics. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the major analytical techniques widely employed in metabolomics. In addition, MS is coupled with chromatography techniques like gas chromatography (GC) and liquid chromatography (LC) to separate metabolites before analysis. These analytical techniques have made possible identification and quantification of large numbers of metabolites, encompassing characterization of diseases and facilitating a systematic and rational therapeutic strategy based on metabolic patterns. In recent years, the metabolomics approach has been used to obtain a deeper insight into the underlying biochemistry of neurodegenerative disorders and the discovery of biomarkers of clinical implications. The current review mainly focuses on an Indian perspective of metabolomics for the identification of metabolites and metabolic alterations serving as potential diagnostic biomarkers for neurological diseases including acute spinal cord injury, amyotrophic lateral sclerosis, tethered cord syndrome, spina bifida, stroke, Parkinson's disease, glioblastoma and neurological disorders with inborn errors of metabolism.

1 H NMR metabolomic profiling elucidated attenuation of neurometabolic alterations by lercanidipine in MCAo model in rats.

OBJECTIVES: Stroke is a leading cause of death and disability worldwide with limited therapeutic interventions. The current study explored proton nuclear magnetic resonance spectroscopy (1 H NMR)-based metabolomic approach to elucidate the effect of lercanidipine on neurometabolic alterations in transient model of ischaemic stroke in rats. METHODS: In the present investigation, male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) for 2 h followed by reperfusion using intraluminal filament method. Rats were randomly divided into three groups as vehicle-treated sham control, vehicle-treated MCAo control and lercanidipine-treated MCAo. Vehicle or lercanidipine (0.5 mg/kg, i.p.) was administered 120 min post-reperfusion. The rat brain cortex tissues were isolated 24 h post-MCAo and were investigated by 1 H NMR spectroscopy through perchloric extraction method. KEY FINDINGS: A total of 23 metabolites were altered significantly after cerebral ischaemic-reperfusion injury in MCAo control as compared to sham control rats. Lercanidipine significantly reduced the levels of valine, alanine, lactate, acetate and tyrosine, while N-acetylaspartate, glutamate, glutamine, aspartate, creatine/phosphocreatine, choline, glycerophosphorylcholine, taurine, myo-inositol and adenosine di-phosphate were elevated as compared to MCAo control. CONCLUSIONS: Present study illustrates effect of lercanidipine on neurometabolic alterations which might be mediated through its antioxidant, anti-inflammatory, vasodilatory and anti-apoptotic property in MCAo model of stroke.

Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats.

Oxidative stress and inflammation are implicated as cardinal mechanisms of neuronal death following stroke. In the present study citalopram (Cit) was investigated in a 2 h middle cerebral artery occlusion (MCAo) model of stroke in male Wistar rats. Pretreatment, posttreatment (Post Cit) and pre plus posttreatment (Pre + Post Cit) with Cit were evaluated for its neuroprotective effect. In pretreatment protocol, effect of Cit at three doses (2, 4, and 8 mg/kg) administered i.p., 1 h prior to MCAo was evaluated using neurological deficit score (NDS), motor deficit paradigms, and cerebral infarction 24 h post-MCAo. In posttreatment and pre plus posttreatment protocol, the effective dose of Cit (4 mg/kg) was administered i.p., 0.5 h post-reperfusion (Post Cit) only, and 1 h prior to MCAo and again at 0.5 h post-reperfusion (Pre + Post Cit), respectively. These two groups were assessed for NDS and cerebral infarction. Though NDS was significantly reduced in both Post Cit and Pre + Post Cit groups, significant reduction in cerebral infarction was evident only in Pre + Post Cit group. Infarct volume assessed by magnetic resonance imaging was significantly attenuated in Pre + Post Cit group (10.6 ± 1.1%) compared to MCAo control group (18.5 ± 3.0%). Further, Pre + Post Cit treatment significantly altered 17 metabolites along with attenuation of malondialdehyde, reduced glutathione, matrix metalloproteinases, and apoptotic markers as compared to MCAo control. These results support the neuroprotective effect of Cit, mediated through amelioration of oxidative stress, inflammation, apoptosis, and altered metabolic profile.