Molecular dynamics directed neuroprotective activity of alcoholic extract of Garuga pinnata Roxb. in experimental rats.

Background: Garuga pinnata Roxb., a member of family Burseraceae, is a commonly grown plant in south east Asia including India in tropical rain forests predominately. Apart from folkloric use, important anti-inflammatory and antiasthamatic activity of this plant has been revealed.

Lycopene potentiates wound healing in streptozotocin-induced diabetic rats.

Background: Diabetes is a growing metabolic disease that is characterized by high blood sugar levels with life-threatening results. Diabetic wounds are a major problem because they do not resolve in few days. Major problems affecting wound healing are infection, age, stress, etc.

A Simple HPTLC Approach of Quantification of Serratol and Tirucallic Acid with Boswellic Acids in Boswellia serrata by Validated Densitometric Method with MS/MS Characterization.

This study was planned to develop a simple high-performance thin-layer chromatography method for qualitative and quantitative estimation of 3-acetyl-11-keto-β-boswellic acid (AKBBA), β-boswellic acid (BBA), 3-oxo-tirucallic acid (TCA) and serratol (SRT) with HPTLC-ESI-MS/MS for characterization in Boswellia serrata Roxb. oleo gum resin extract. The method was developed with hexane-ethyl acetate-toluene-chloroform-formic acid as mobile phase.

Evaluation of wound healing effect of (Lam.) Mull. Arg. by in silico multitargets directed for multiligand approach.

The healing of wound is a tightly-regulated cascade of events, involving interplay of enormous factors. Now a days, pain alleviation and faster wound healing have attracted considerable attention. Several natural compounds have played crucial role in this intriguing process.

Radiation Response of Murine Embryonic Stem Cells.

To understand the mechanisms of disturbed differentiation and development by radiation, murine CGR8 embryonic stem cells (mESCs) were exposed to ionizing radiation and differentiated by forming embryoid bodies (EBs). The colony forming ability test was applied for survival and the MTT test for viability determination after X-irradiation. Cell cycle progression was determined by flow cytometry of propidium iodide-stained cells, and DNA double strand break (DSB) induction and repair by γH2AX immunofluorescence.

The War against Tuberculosis: A Review of Natural Compounds and Their Derivatives.

Tuberculosis (TB), caused by the bacterial organism , pose a major threat to public health, especially in middle and low-income countries. Worldwide in 2018, approximately 10 million new cases of TB were reported to the World Health Organization (WHO). There are a limited number of medications available to treat TB; additionally, multi-drug resistant TB and extensively-drug resistant TB strains are becoming more prevalent.

Cardiomyocytes facing fibrotic conditions re-express extracellular matrix transcripts.

Pathophysiological conditions, such as myocardial infarction and mechanical overload affect the mammalian heart integrity, leading to a stiffened fibrotic tissue. With respect to the pathophysiology of cardiac fibrosis but also in the limelight of upcoming approaches of cardiac cell therapy it is of interest to decipher the interaction of cardiomyocytes with fibrotic matrix. Therefore, we designed a hydrogel-based model to engineer fibrotic tissue in vitro as an approach to predict the behavior of cardiomyocytes facing increased matrix rigidity.

Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells.

Background: Human embryonic stem cells (hESCs) partially recapitulate early embryonic three germ layer development, allowing testing of potential teratogenic hazards. Because use of hESCs is ethically debated, we investigated the potential for human induced pluripotent stem cells (hiPSCs) to replace hESCs in such tests.

Methods: Three cell lines, comprising hiPSCs (foreskin and IMR90) and hESCs (H9) were differentiated for 14 days.

Stem Cell Transcriptome Responses and Corresponding Biomarkers That Indicate the Transition from Adaptive Responses to Cytotoxicity.

Analysis of transcriptome changes has become an established method to characterize the reaction of cells to toxicants. Such experiments are mostly performed at compound concentrations close to the cytotoxicity threshold. At present, little information is available on concentration-dependent features of transcriptome changes, in particular, at the transition from noncytotoxic concentrations to conditions that are associated with cell death.

Novel R-plasmid conjugal transfer inhibitory and antibacterial activities of phenolic compounds from Mallotus philippensis (Lam.) Mull. Arg.

Antimicrobial resistance severely limits the therapeutic options for many clinically important bacteria. In Gram-negative bacteria, multidrug resistance is commonly facilitated by plasmids that have the ability to accumulate and transfer refractory genes amongst bacterial populations. The aim of this study was to isolate and identify bioactive compounds from the medicinal plant Mallotus philippensis (Lam.

Human Embryonic and Induced Pluripotent Stem Cell Based Toxicity Testing Models: Future Applications in New Drug Discovery.

New drug discovery (NDD) is a fascinating discipline encompassing different facets of medicine, pharmacology, biotechnology and chemistry. NDD is very often restricted by efficacy or safety problems of the new clinical candidate in human patients. Drug regulatory authorities have provided various guidelines for advancement of safe new chemical entities (NCEs) in clinical trials which must be strictly followed.

Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Tox and STOP-Tox tests.

Stem cell-based in vitro test systems can recapitulate specific phases of human development. In the UKK test system, human pluripotent stem cells (hPSCs) randomly differentiate into cells of the three germ layers and their derivatives. In the UKN1 test system, hPSCs differentiate into early neural precursor cells.

Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells.

Background/aims: Embryonic developmental studies under microgravity conditions in space are very limited. To study the effects of altered gravity on the embryonic development processes we established an in vitro methodology allowing differentiation of mouse embryonic stem cells (mESCs) under simulated microgravity within a fast-rotating clinostat (clinorotation) and capture of microarray-based gene signatures.

Methods: The differentiating mESCs were cultured in a 2D pipette clinostat.

Discovery of Novel and Orally Bioavailable Inhibitors of PI3 Kinase Based on Indazole Substituted Morpholino-Triazines.

A new class of potent PI3Kα inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development.

A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors.

Test systems to identify developmental toxicants are urgently needed. A combination of human stem cell technology and transcriptome analysis was to provide a proof of concept that toxicants with a related mode of action can be identified and grouped for read-across. We chose a test system of developmental toxicity, related to the generation of neuroectoderm from pluripotent stem cells (UKN1), and exposed cells for 6 days to the histone deacetylase inhibitors (HDACi) valproic acid, trichostatin A, vorinostat, belinostat, panobinostat and entinostat.

Transcriptomics of Hepatocytes Treated with Toxicants for Investigating Molecular Mechanisms Underlying Hepatotoxicity.

Transcriptomics is a powerful tool for high-throughput gene expression profiling. Transcriptome microarray experiments conducted with RNA isolated from hepatocytes after exposure to toxicants enable a deep insight into the molecular mechanisms of hepatotoxicity. This understanding, along with structure-activity relationships underlying hepatotoxicity, will provide a novel strategy to design cost-effective and safer therapeutics.

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements.

Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance.

Alcoholic extract of Piper betle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with imatinib resistance phenotype. Hydroxy-chavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity.

Antitumor activity of NPB001-05, an orally active inhibitor of Bcr-Abl tyrosine kinase.

Scientists are constantly searching for phytochemical compounds with anti-cancer activity. In this study, activity of plant extract NPB001-05 from Piper betle was tested on human chronic myelogenous leukemia (CML) xenograft models. NPB001-05 was active when dosed orally (500 mg/kg) once or twice a day in xenograft tumor models.

Development and validation of a TLC-densitometric method for the simultaneous quantitation of strychnine and brucine from Strychnos spp. and its formulations.

A simple, sensitive, and specific thin-layer chromatography densitometric method has been developed for the simultaneous quantitation of strychnine and brucine. These two marker compounds are quantitated in the seeds of Strychnos nux-vomica, Strychnos ignatii, and its formulations. The method involves densitometric evaluation of strychnine and brucine after resolving it by high-performance TLC on silica gel plate with toluene-ethyl acetate-diethyl amine-methanol (7:2:1:0.

Rapid densitometric method for simultaneous analysis of umbelliferone, psoralen, and eugenol in herbal raw materials using HPTLC.

The term 'phenolics' refers to a vast array of biologically active compounds ubiquitous in plants, many of which have been used in traditional medicine for thousands of years. Umbelliferone, psoralen, and eugenol are widely occurring phenolic compounds of plant origin, for which many biological activities against chronic diseases have been reported. A simple HPTLC method has been developed for the simultaneous quantification of umbelliferone, psoralen, and eugenol.