Effect of herbal combination of triphala and garcinia cambogia extracts on anthropometric measurements and lipid profile in high fat diet induced obesity in rats

Background: Obesity, occurring at epidemic rates globally, is a major risk factor for DM and CVD. Despite advances in understanding its pathogenesis, the pharmacotherapy for obesity remains limited for achievable weight loss, safety and tolerability of the medicines. Almost all approved medications for long term use in obesity treatment result in health issues. Due to the ADRs associated with many antiobesity drugs, the drug trials have focused on screening herbal medicines that are reportedly used in the treatment of obesity and which have minimal side effects.Methods: In this study rats were divided into eight groups of six rats each. In the first approach, the rats were first made obese by feeding HFD for three weeks. In the second, treatment with the herbal extracts was given simultaneously with the HFD to the experimental rats. Rat were fed HFD for six weeks along with treatment of herbal extracts and the effect on their body weight, daily food intake and lipid-profile were evaluated.Results: Results showed that rats fed HFD for a six week period, supplemented with herbal preparations of triphala and G. cambogia presented with significant reduction in body weight, energy intake, and improved the lipid-profile as compared to the rats fed with HFD group.Conclusions: Our findings suggest that triphala and G. cambogia can counter the effects of HFD intake and have the potential for use as antiobesity agents with desirable body weight, food intake, fluid intake, and lipid-profile modulating properties

Factors Associated with Coverage and Usage of Long-Lasting Insecticidal Nets in Madagascar

In October 2007, long-lasting insecticidal nets (LLINs) were distributed in 59 of the 111 districts in Madagascar as part of a nationwide child survival campaign. A community-based cross-sectional survey was conducted six months post-campaign to evaluate net ownership, use and equity. Here, we examined the effects of socioeconomic factors on LLIN ownership and usage in districts with and without net distribution during the campaign. Our data demonstrated that in districts with LLIN distribution, LLIN ownership was similar across all wealth groups in households with at least one child under the age of five years (90.5% versus 88.6%); in districts without net distribution, 57.8% of households in the poorest tertile compared to 90.1% of households in the least poor tertile owned at least one LLIN. In contrast, in LLIN-owning households, both in districts with and without net distribution, higher socio-economic status was not associated with use among children under five years. These findings suggest that socio-economic status contributes to the household net ownership but once a household owns a net, socio-economic status is not associated with net use

Effect of herbal combination of triphala and Garcinia cambogia extracts on liver function test and kidney function test in high fat diet induced obesity in rats

Background: Obesity, a global epidemic, is a major risk factor for diabetes mellitus and cardio vascular diseases. Despite advances, the pharmacotherapy for obesity remains limited. Almost all medications for long term management of obesity have health issues. Due to the adverse drug reactions (ADRs) associated with many antiobesity medicines, the clinical trials are focussing on screening herbal medicines for use in the treatment of obesity, which have minimal ADRs.Methods: Rats were divided into eight groups of six each. The rats were first made obese by feeding high fat diet (HFD) for three weeks. Then treatment with the herbal extracts was given simultaneously with the HFD to the experimental groups. Rats were fed HFD for six weeks along with herbal extracts and the effect on their liver function test and kidney function test were evaluated.Results: The rats fed HFD and supplemented with herbal preparations of Triphala and G. cambogia for six weeks, showed significant improvement in liver function test and kidney function test related parameters as compared to the control group rats fed with HFD alone.Conclusions: Triphala and G. cambogia can counter the effects of HFD intake and have the potential for use as anti-obesity agents with desirable liver function test and kidney function test related parameters modulating properties

The Anointed Son, The Hired Gun, and the Chai Wala: Enemies and Insults in Politicians’ Tweets in the Run-Up to the 2019 Indian General Elections

This study seeks to assess the prevalence, style, and impact of antagonistic messaging on Twitter in the two years preceding the 2019 Indian General Elections. Focusing on the leadership of the two key parties – the ruling BJP, with Prime Minister Narendra Modi and party president Amit Shah, and the opposition INC’s president Rahul Gandhi, we attempt to understand how the politicians sought to portray each other on Twitter, and how their followers reacted to these characterizations, through the lens of Murray Edelman’s work on the ‘Political Enemy’. By thematically coding tweets and quantitatively analyzing their retweets, we find that negative tweets by and large are significantly more popular for all three politicians, and that the opposition leader allocated a significantly larger proportion of his tweets to attacks. We conclude that while leaders in power and those in opposition may take different stances with messaging, Twitter as a social networking site can perpetuate the online reward for attacking behavior

Embryonic and Neonatal Mouse Cochleae Are Susceptible to Zika Virus Infection

Congenital Zika Syndrome (CZS) is caused by vertical transmission of Zika virus (ZIKV) to the gestating human fetus. A subset of CZS microcephalic infants present with reduced otoacoustic emissions; this test screens for hearing loss originating in the cochlea. This observation leads to the question of whether mammalian cochlear tissues are susceptible to infection by ZIKV during development. To address this question using a mouse model, the sensory cochlea was explanted at proliferative, newly post-mitotic or maturing stages. ZIKV was added for the first 24 h and organs cultured for up to 6 days to allow for cell differentiation. Results showed that ZIKV can robustly infect proliferating sensory progenitors, as well as post-mitotic hair cells and supporting cells. Virus neutralization using ZIKV-117 antibody blocked cochlear infection. AXL is a cell surface molecule known to enhance the attachment of flavivirus to host cells. While Axl mRNA is widely expressed in embryonic cochlear tissues susceptible to ZIKV infection, it is selectively downregulated in the post-mitotic sensory organ by E15.5, even though these cells remain infectible. These findings may offer insights into which target cells could potentially contribute to hearing loss resulting from fetal exposure to ZIKV in humans

EFFECTS OF NITROXAZEPINE ON DIASTOLIC BLOOD PRESSURE IN MILD HYPERTENSIVE PATIENTS -A SHORT TERM CLINICAL STUDY

Abstract: In a double blind short term clinical study, nitroxazcpine has been found to be superior over placebo in reducing the diastolic blood pressure in mild hypertensive patients. In short term open clinical trial design nitroxazepine (25 mg PO, HS) has been found to be superior and better tolerated than diazepam (5 mg PO, HS). In open clinical trial design. nitroxazepine (25 mg PO, HS) reduced the diastolic blood pressure to the target level (100 mm Hg and less) effecti'.'ely controlling the uncontrolled hypertensive patients receiving maintenance dose of beta blockers. There was no such beneficial effect in patients receiving maintenance doses of other antihypertensive drugs (piLot studyl. Adverse drug reactions like disturbed sleep in one, uneasiness in 3, palpitation in one and dryness of mouth in one patient have been observed

Data-driven discovery of molecular photoswitches with multioutput Gaussian processes

Photoswitchable molecules display two or more isomeric forms that may be accessed using light. Separating the electronic absorption bands of these isomers is key to selectively addressing a specific isomer and achieving high photostationary states whilst overall red-shifting the absorption bands serves to limit material damage due to UV-exposure and increases penetration depth in photopharmacological applications. Engineering these properties into a system through synthetic design however, remains a challenge. Here, we present a data-driven discovery pipeline for molecular photoswitches underpinned by dataset curation and multitask learning with Gaussian processes. In the prediction of electronic transition wavelengths, we demonstrate that a multioutput Gaussian process (MOGP) trained using labels from four photoswitch transition wavelengths yields the strongest predictive performance relative to single-task models as well as operationally outperforming time-dependent density functional theory (TD-DFT) in terms of the wall-clock time for prediction. We validate our proposed approach experimentally by screening a library of commercially available photoswitchable molecules. Through this screen, we identified several motifs that displayed separated electronic absorption bands of their isomers, exhibited red-shifted absorptions, and are suited for information transfer and photopharmacological applications. Our curated dataset, code, as well as all models are made available at https://github.com/Ryan-Rhys/The-Photoswitch-Dataset

Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe

Ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme (DUB), is a potential drug target in various cancers, and liver and lung fibrosis. However, bona fide functions and substrates of UCHL1 remain poorly understood. Herein, we report the characterization of UCHL1 covalent inhibitor MT16-001 based on a thiazole cyanopyrrolidine scaffold. In combination with chemical proteomics, a closely related activity-based probe (MT16-205) was used to generate a comprehensive quantitative profile for on- and off-targets at endogenous cellular abundance. Both compounds are selective for UCHL1 over other DUBs in intact cells but also engage a range of other targets with good selectivity over the wider proteome, including aldehyde dehydrogenases, redox-sensitive Parkinson’s disease related protein PARK7, and glutamine amidotransferase. Taken together, these results underline the importance of robust profiling of activity-based probes as chemical tools and highlight the cyanopyrrolidine warhead as a versatile platform for liganding diverse classes of protein with reactive cysteine residues which can be used for further inhibitor screening, and as a starting point for inhibitor development

Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2.

Proteolysis-Targeting Chimeras (PROTACs) are heterobifunctional small-molecules that can promote the rapid and selective proteasome-mediated degradation of intracellular proteins through the recruitment of E3 ligase complexes to non-native protein substrates. The catalytic mechanism of action of PROTACs represents an exciting new modality in drug discovery that offers several potential advantages over traditional small-molecule inhibitors, including the potential to deliver pharmacodynamic (PD) efficacy which extends beyond the detectable pharmacokinetic (PK) presence of the PROTAC, driven by the synthesis rate of the protein. Herein we report the identification and development of PROTACs that selectively degrade Receptor-Interacting Serine/Threonine Protein Kinase 2 (RIPK2) and demonstrate in vivo degradation of endogenous RIPK2 in rats at low doses and extended PD that persists in the absence of detectable compound. This disconnect between PK and PD, when coupled with low nanomolar potency, offers the potential for low human doses and infrequent dosing regimens with PROTAC medicines