Investigation of the Synergistic Anti-pyretic and Anti-inflammatory Activity of Sonchus wightianus DC, Paracetamol and Indomethacin Combination in Rat Models

Introduction: In conventional Indian medicine, several plants have long been utilized to treat various ailments. Among these herbal species, Sonchus wightianus DC is known for anti-inflammatory and antipyretic effects attributed to compound found in its leaves such as fatty acid methyl esters, sterol and triterpenoids. Induced pyrexia and inflammation in animal models serves to investigate the potential synergistic interactions between traditional herbal remedies and standard medication. Aims and Objectves: Thus, this research aimed to evaluate the anti-pyretic and anti-inflammatory properties of methanolic extract obtained from Sonchus wightianus DC leaves tested alone and in combination with classic anti-inflammatory agents using the Carrageenan paw edema and anti-pyretic agent using yeast-induced pyrexia in Wistar rats. Methods: Soxhlet extraction was used to obtain the methanolic extract. Inflammation was induced by a 1% (w/v) carrageenan injection, while 20% Brewer\u27s yeast triggered pyrexia in male Wistar rat. The antipyretic activity was evaluated by taking the body temperature at various hours, while the anti-inflammatory activity was assessed by measuring the paw and cytokines (TNF-α, IL-6, IL-1β). Results: The research investigation discovered that the extract of Sonchus wightianus DC along with varying doses of Indomethacin and Paracetamol, considerably reduced raised body temperature and avoided inflammation, exhibiting percentage inhibition. The study further revealed that at a dosage of 300 mg/kg of the plant extract, 300 mg/kg plant extract combined with Paracetamol (150 mg/kg), and 300 mg/kg plant extract combined with Indomethacin (10 mg/kg), there was a marked reduction in paw edema and pyrexia in the experimental models. Moreover, the extract was found to substantially lower serum levels of key inflammatory mediators, including IL-1β, IL-6, and TNF-α. Conclusion: These findings indicates that Sonchus wightianus DC extract has potential therapeutic benefits in managing inflammation and fever, especially when combined with standard drugs like Paracetamol and Indomethacin

Using Biological Photophysics to Map the Excited‐State Topology of Molecular Photosensitizers for Photodynamic Therapy

This study employs TLD1433, a Ru II ‐based photodynamic therapy (PDT) agent in human clinical trials, as a benchmark to establish protocols for studying the excited‐state dynamics of photosensitizers (PSs) in cellulo , in the local environment provided by human cancer cells. Very little is known about the excited‐state properties of any PS in live cells, and for TLD1433, it is terra incognita . This contribution targets a general problem in phototherapy, which is how to interrogate the light‐triggered, function‐determining processes of the PSs in the relevant biological environment, and establishes methodological advances to study the ultrafast photoinduced processes for TLD1433 when taken up by MCF7 cells. We generalize the methodological developments and results in terms of molecular physics by applying them to TLD1433’s analogue TLD1633, making this study a benchmark to investigate the excited‐state dynamics of phototoxic compounds in the complex biological environment

It takes three to tango: The length of the oligothiophene chain determines the nature of the long‐lived excited state and the resulting photocytotoxicity of a ruthenium(II) Photodrug

Abstract TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally‐related Ru(II)‐imidozo[4,5‐f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter‐ or quaterthiophene changes the nature of the long‐lived triplet state from metal‐to‐ligand charge‐transfer to 3 ππ* character. The addition of the third thiophene thus presents a critical juncture which not only determines the photophysics of the complex but most importantly its capacity for 1 O 2 generation and hence the potential of the complex to be used as a photocytotoxic agent

Unveiling Potent Anti-Asthmatic Effect of Curcumin in Combination with Salmeterol in Swiss Albino Mice

Background: Asthma is a long-term inflammatory respiratory condition marked by alterations in the airways and an increase in inflammatory cell infiltration. It has been observed that Curcumin possesses immune-modulating, anti-inflammatory, and relaxing properties for smooth muscle in the airways. Salmeterol is believed to ease the smooth muscles of the airways. Objective: Swiss Albino mice were used in the research to examine the combination anti-asthmatic effects of Curcumin and Salmeterol in asthma produced by ova albumin and milk induced eosinophilia and leucocytosis. Methods: The mice received pre-treatment with Curcumin (10 mg/kg, 20 mg/kg intraperitoneally) as well as Salmeterol (5 mg/kg) after being stimulated with an Ovalbumin (OVA) challenge and milk. After the induction period, various hematological, biochemical, molecular (ELISA), and histological analyses were performed. Results: The findings demonstrated that the combined treatment decreased the animal’s overall leukocyte and eosinophil numbers in a manner that was dose-dependent. Additionally, the therapy reduced albumin and overall protein amount in serum, BALF and lung tissues, facilitated changes in haematological parameters, and reduced the rise of Th2 cytokines (IL-4, TNF-α, IL-13) levels that is induced by OVA in lungs and BALF, total IgE level in serum. The combined action of Curcumin and Salmeterol reduced OVA-induced inflammatory influx and ultrastructural abnormalities, according to histopathological evaluation. Conclusion: The findings of this investigation demonstrate that curcumin and salmeterol together possess anti-asthmatic effects through suppressing Th2 triggered immune response and possessing an anti-inflammatory effect and anti-allergic effect. Thus combination of treatments might be a novel technique for managing asthma

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2(IP-4T)](PF6)2 with bpy=2,2′-bipyridine and IP-4T=2-{5′-[3′,4′-diethyl-(2,2′-bithien-5-yl)]-3,4-diethyl-2,2′-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug. © 2020 The Authors. Published by Wiley-VCH Gmb

Ensemble Models for Spoofing Detection in Automatic Speaker Verification

Detecting spoofing attempts of automatic speaker verification (ASV) systems is challenging, especially when using only one modelling approach. For robustness, we use both deep neural networks and traditional machine learning models and combine them as ensemble models through logistic regression. They are trained to detect logical access (LA) and physical access (PA) attacks on the dataset released as part of the ASV Spoofing and Countermeasures Challenge 2019. We propose dataset partitions that ensure different attack types are present during training and validation to improve system robustness. Our ensemble model outperforms all our single models and the baselines from the challenge for both attack types. We investigate why some models on the PA dataset strongly outperform others and find that spoofed recordings in the dataset tend to have longer silences at the end than genuine ones. By removing them, the PA task becomes much more challenging, with the tandem detection cost function (t-DCF) of our best single model rising from 0.1672 to 0.5018 and equal error rate (EER) increasing from 5.98% to 19.8% on the development set

Can working with the private for-profit sector improve utilization of quality health services by the poor? A systematic review of the literature

BACKGROUND: There has been a growing interest in the role of the private for-profit sector in health service provision in low- and middle-income countries. The private sector represents an important source of care for all socioeconomic groups, including the poorest and substantial concerns have been raised about the quality of care it provides. Interventions have been developed to address these technical failures and simultaneously take advantage of the potential for involving private providers to achieve public health goals. Limited information is available on the extent to which these interventions have successfully expanded access to quality health services for poor and disadvantaged populations. This paper addresses this knowledge gap by presenting the results of a systematic literature review on the effectiveness of working with private for-profit providers to reach the poor. METHODS: The search topic of the systematic literature review was the effectiveness of interventions working with the private for-profit sector to improve utilization of quality health services by the poor. Interventions included social marketing, use of vouchers, pre-packaging of drugs, franchising, training, regulation, accreditation and contracting-out. The search for published literature used a series of electronic databases including PubMed, Popline, HMIC and CabHealth Global Health. The search for grey and unpublished literature used documents available on the World Wide Web. We focused on studies which evaluated the impact of interventions on utilization and/or quality of services and which provided information on the socioeconomic status of the beneficiary populations. RESULTS: A total of 2483 references were retrieved, of which 52 qualified as impact evaluations. Data were available on the average socioeconomic status of recipient communities for 5 interventions, and on the distribution of benefits across socioeconomic groups for 5 interventions. CONCLUSION: Few studies provided evidence on the impact of private sector interventions on quality and/or utilization of care by the poor. It was, however, evident that many interventions have worked successfully in poor communities and positive equity impacts can be inferred from interventions that work with types of providers predominantly used by poor people. Better evidence of the equity impact of interventions working with the private sector is needed for more robust conclusions to be drawn

The genome of the emerging barley pathogen Ramularia collo-cygni

Background Ramularia collo-cygni is a newly important, foliar fungal pathogen of barley that causes the disease Ramularia leaf spot. The fungus exhibits a prolonged endophytic growth stage before switching life habit to become an aggressive, necrotrophic pathogen that causes significant losses to green leaf area and hence grain yield and quality. Results The R. collo-cygni genome was sequenced using a combination of Illumina and Roche 454 technologies. The draft assembly of 30.3 Mb contained 11,617 predicted gene models. Our phylogenomic analysis confirmed the classification of this ascomycete fungus within the family Mycosphaerellaceae, order Capnodiales of the class Dothideomycetes. A predicted secretome comprising 1053 proteins included redox-related enzymes and carbohydrate-modifying enzymes and proteases. The relative paucity of plant cell wall degrading enzyme genes may be associated with the stealth pathogenesis characteristic of plant pathogens from the Mycosphaerellaceae. A large number of genes associated with secondary metabolite production, including homologs of toxin biosynthesis genes found in other Dothideomycete plant pathogens, were identified. Conclusions The genome sequence of R. collo-cygni provides a framework for understanding the genetic basis of pathogenesis in this important emerging pathogen. The reduced complement of carbohydrate-degrading enzyme genes is likely to reflect a strategy to avoid detection by host defences during its prolonged asymptomatic growth. Of particular interest will be the analysis of R. collo-cygni gene expression during interactions with the host barley, to understand what triggers this fungus to switch from being a benign endophyte to an aggressive necrotroph