Search

Plants are major source for discovery and development of anticancer drugs. Several plant-based anticancer drugs are currently in clinical use. Fagonia indica is a plant of medicinal value in the South Asian countries. Using mass spectrometry and NMR spectroscopy, several compounds were purified from the F. indica extract. We have used one of the purified compounds quinovic acid (QA) and found that QA strongly suppressed the growth and viability of human breast and lung cancer cells. QA did not inhibit growth and viability of non-tumorigenic breast cells. QA mediated its anticancer effects by inducing cell death. QA-induced cell death was associated with biochemical features of apoptosis such as activation of caspases 3 and 8 as well as PARP cleavage. QA also upregulated mRNA and protein levels of death receptor 5 (DR5). Further investigation revealed that QA did not alter DR5 gene promoter activity, but enhanced DR5 mRNA and protein stabilities. DR5 is one of the major components of the extrinsic pathway of apoptosis. Accordingly, Apo2L/TRAIL, the DR5 ligand, potentiated the anticancer effects of QA. Our results indicate that QA mediates its anticancer effects, at least in part, by engaging DR5-depentent pathway to induce apoptosis. Based on our results, we propose that QA in combination with Apo2L/TRAIL can be further investigated as a novel therapeutic approach for breast and lung cancers.

Presenilin proteins make the catalytic component of γ-secretase, a multiprotein transmembrane protease, and are type II transmembrane proteins. Amyloid protein, Notch, and beta catenin are among more than 90 substrates of Presenilins. Mutations in Presenilins lead to defects in proteolytic cleavage of its substrate resulting in some of the most devastating pathological conditions including Alzheimer disease (AD), developmental disorders, and cancer. In addition to catalytic roles, Presenilin protein is also shown to be involved in many non-catalytic roles, i.e., calcium homeostasis, regulation of autophagy, and protein trafficking, etc. These proteolytic proteins are highly conserved and are present in almost all the major eukaryotic groups. Studies, performed on a wide variety of organisms ranging from human to unicellular dictyostelium, have shown the important catalytic and non-catalytic roles of Presenilins. In this study, we infer the evolutionary patterns and history of Presenilins as well as of other γ-secretase proteins. We show that Presenilins are the most ancient of the γ-secretase proteins and that Presenilins may have their origin in the last common ancestor (LCA) of Eukaryotes. We also demonstrate that Presenilin proteins generally lack diversifying selection during the course of their evolution. Through evolutionary trace analysis, we show that Presenilin protein sites that undergo mutations in Familial Alzheimer disease, are highly conserved in metazoans. Finally, we discuss the evolutionary, physiological, and pathological implications of our findings and propose that the evolutionary profile of Presenilins supports the loss of function hypothesis of AD pathogenesis.

Crocus sativus, a medicinally important herbaceous plant, has been traditionally used to cure coughs, colds, insomnia, cramps, asthma, and pain. Moreover, the therapeutic applications of saffron include its immunomodulatory and anticancer properties. The current experimental analysis was performed to explore the potential nutraceutical efficacy of corm, leaf, petal, and stigma of saffron ethanolic extracts as analgesic, anti-inflammatory, anticoagulant, and antidepressant using hot plate, carrageenan-induced paw edema, capillary tube and forced swim test, respectively in mice. The results indicated that among all the extracts, stigma ethanolic extract (SEE) represented maximum latency activity (72.85%) and edema inhibition (77.33%) followed by petal ethanolic extract (PEE) with latency activity and edema inhibition of 64.06 and 70.50%, respectively. Corm ethanolic extract (CEE) and leaf ethanolic extract (LEE) displayed mild analgesic activity of 22.40% and 29.07%, respectively. Additionally, LEE (53.29%) and CEE (47.47%) exhibited mild to moderate response against inflammation. The coagulation time of SEE (101.66 s) was almost equivalent to the standard drug, aspirin (101.66 s), suggesting a strong anticoagulant effect followed by PEE (86.5 s). LEE (66.83 s) represented moderate inhibitory effect on coagulation activity while CEE (42.83 s) showed neutral effect. Additionally, PEE and SEE also expressed itself as potential antidepressants with immobility time ≤76.66 s, while CEE (96.50 s) and LEE (106.83 s) indicated moderate to mild antidepressant efficacy. Based on the in vivo activities, saffron extract, particularly SEE and PEE, can be used as a potential nutraceutical and therapeutic agent due to its significant pharmacological activities., Competing Interests: The authors declare no conflict of interest.

Background: Diabetes mellitus is a chronic disease characterized by hyperglycemia that may occur due to genetic, environmental or lifestyle factors. Natural remedies have been used to treat diabetes since long and many antidiabetic compounds of varied efficacies have been isolated from medicinal plants. Rhazya stricta has been used for decades for the treatment of diabetes mellitus and associated ailments. Considering the folkloric use of R. stricta against diabetes, it was aimed to investigate the effectiveness of its root extracts against diabetes through in vitro assays and in vivo studies using animal model along with phytochemical profiling through GCMS., Methods: Various fractions of Rhazya stricta obtained through column chromatography were evaluated for a variety of assays including α-glucosidase, Dipeptidyl peptidase-IV (DPP-IV), β-secretase and Glucagon-like peptide-1 (GLP-1) secretion studies. For the in vivo studies the alloxan-induced diabetic mice were treated with root extracts and blood glucose levels, HbA1C, and other biochemical markers along with the histological study of the liver were done. The phytochemical identification was performed using an Agilent 7890B GC coupled to a 7010 Triple Quadrupole (MS/MS) system. GraphPad Prism software version 5.01 was used for statistical analysis., Results: Majority of the extract fractions showed excellent results against diabetes by inhibiting enzymes DPP-IV (Up to 61%) and β-secretase (Up to 83%) with IC 50s 979 μg/ml and 169 μg/ml respectively with increase in the GLP1 secretion. The results of in vivo studies indicated a marked reduction in blood glucose and HbA1c levels along with positive effects on other parameters like lipid profile, liver functions and renal functions of extract-treated mice as compared to control. The histological examination of the liver demonstrated hepatoprotective effects against diabetes led changes and various classes of phytochemicals were also identified through GCMS in different fractions., Conclusion: The results revealed strong antidiabetic activity of R. stricta root with the potential to protect body organs against diabetic changes. Moreover, a variety of phytochemicals has also been identified through GCMS that might be responsible for the antidiabetic potential of Rhazya stricta root.

Over the last three decades, functional endoscopic sinus surgery (FESS) has become one of the most common surgical techniques, with significant data supporting its efficacy in treating chronic rhinosinusitis (CRS). However, despite this initial published success rate, approximately 10-15% of them will require a subsequent revision surgery. The severity of the disease, the comorbidities and the anatomical variation that are not addressed adequately in the primary surgery, are considered the main factors that cause the failure of the primary surgery. Our objective is to report anatomical findings that may contribute to recurrent disease to improve the success rate in the primary surgery. PATIENTS AND METHODS: A prospective cross sectional study was conducted for 24 patients presenting for revision functional endoscopic sinus surgery (FESS). Lund-kennedy and Lund-Mackay score systems, pre and intraoperative CT scan and endoscopic assessments utilized, respectively, to delineate the causes of the primary surgery's failure. The most common finding was persistent frontoethmoidal cell, anterior and posterior ethmoid cell: 81.2%, 72.9%, 70.8%, respectively. Bony osteitis and scarred frontal recess were visible in 66.7%. Recirculation phenomena, resected concha bullosa and persistent Onodi cell, were the least noticeable findings: 6.25%, 8.3%, 8.30% consecutively CONCLUSIONS: The recurrence of the CRS that needs revision FESS is multifactorial in etiology ranging from sever mucosal disease to anatomical variations that is not addressed precisely in primary surgery. Trials of studies with a larger number of patient series comparing the anatomical variations that impact on recurrence of CRS with and without polyp are required.

Objective: During cardiovascular disease progression, molecular systems of myocardium (e.g., a proteome) undergo diverse and distinct changes. Dynamic, temporally-regulated alterations of individual molecules underlie the collective response of the heart to pathological drivers and the ultimate development of pathogenesis. Advances in high-throughput omics technologies have enabled cost-effective, temporal profiling of targeted systems in animal models of human diseases. However, computational analysis of temporal patterns from omics data remains challenging. In particular, bioinformatic pipelines involving unsupervised statistical approaches to support cardiovascular investigations are lacking, which hinders one's ability to extract biomedical insights from these complex datasets., Approach and Results: We developed a non-parametric data analysis platform to resolve computational challenges unique to temporal omics datasets. Our platform consists of three modules. Module I preprocesses the temporal data using either cubic splines or principal component analysis (PCA), and it simultaneously accomplishes the tasks on missing data imputation and denoising. Module II performs an unsupervised classification by K-means or hierarchical clustering. Module III evaluates and identifies biological entities (e.g., molecular events) that exhibit strong associations to specific temporal patterns. The jackstraw method for cluster membership has been applied to estimate p-values and posterior inclusion probabilities (PIPs), both of which guided feature selection. To demonstrate the utility of the analysis platform, we employed a temporal proteomics dataset that captured the proteome-wide dynamics of oxidative stress induced post-translational modifications (O-PTMs) in mouse hearts undergoing isoproterenol (ISO)-induced hypertrophy., Conclusion: We have created a platform, CV.Signature.TCP, to identify distinct temporal clusters in omics datasets. We presented a cardiovascular use case to demonstrate its utility in unveiling biological insights underlying O-PTM regulations in cardiac remodeling. This platform is implemented in an open source R package (https://github.com/UCLA-BD2K/CV.Signature.TCP)., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The world is experiencing a cancer epidemic and an increase in the prevalence of the disease. Cancer remains a major killer, accounting for more than half a million deaths annually. There is a wide range of natural products that have the potential to treat this disease. One of these products is artemisinin; a natural product from Artemisia plant. The Nobel Prize for Medicine was awarded in 2015 for the discovery of artemisinin in recognition of the drug's efficacy. Artemisinin produces highly reactive free radicals by the breakdown of two oxygen atoms that kill cancerous cells. These cells sequester iron and accumulate as much as 1000 times in comparison with normal cells. Generally, chemotherapy is toxic to both cancerous cells and normal cells, while no significant cytotoxicity from artemisinin to normal cells has been found in more than 4000 case studies, which makes it far different than conventional chemotherapy. The pleiotropic response of artemisinin in cancer cells is responsible for growth inhibition by multiple ways including inhibition of angiogenesis, apoptosis, cell cycle arrest, disruption of cell migration, and modulation of nuclear receptor responsiveness. It is very encouraging that artemisinin and its derivatives are anticipated to be a novel class of broad-spectrum antitumor agents based on efficacy and safety. This review aims to highlight these achievements and propose potential strategies to develop artemisinin and its derivatives as a new class of cancer therapeutic agents.

Species of the genus Nicotiana (Solanaceae), commonly referred to as tobacco plants, are often cultivated as non-food crops and garden ornamentals. In addition to the worldwide production of tobacco leaves, they are also used as evolutionary model systems due to their complex development history tangled by polyploidy and hybridization. Here, we assembled the plastid genomes of five tobacco species: N. knightiana, N. rustica, N. paniculata, N. obtusifolia and N. glauca . De novo assembled tobacco plastid genomes had the typical quadripartite structure, consisting of a pair of inverted repeat (IR) regions (25,323-25,369 bp each) separated by a large single-copy (LSC) region (86,510-86,716 bp) and a small single-copy (SSC) region (18,441-18,555 bp). Comparative analyses of Nicotiana plastid genomes with currently available Solanaceae genome sequences showed similar GC and gene content, codon usage, simple sequence and oligonucleotide repeats, RNA editing sites, and substitutions. We identified 20 highly polymorphic regions, mostly belonging to intergenic spacer regions (IGS), which could be suitable for the development of robust and cost-effective markers for inferring the phylogeny of the genus Nicotiana and family Solanaceae. Our comparative plastid genome analysis revealed that the maternal parent of the tetraploid N. rustica was the common ancestor of N. paniculata and N. knightiana , and the later species is more closely related to N. rustica . Relaxed molecular clock analyses estimated the speciation event between N. rustica and N. knightiana appeared 0.56 Ma (HPD 0.65-0.46). Biogeographical analysis supported a south-to-north range expansion and diversification for N. rustica and related species, where N. undulata and N. paniculata evolved in North/Central Peru, while N. rustica developed in Southern Peru and separated from N. knightiana, which adapted to the Southern coastal climatic regimes. We further inspected selective pressure on protein-coding genes among tobacco species to determine if this adaptation process affected the evolution of plastid genes. These analyses indicate that four genes involved in different plastid functions, including DNA replication ( rpo A) and photosynthesis ( atp B, ndh D and ndhF ), came under positive selective pressure as a result of specific environmental conditions. Genetic mutations in these genes might have contributed to better survival and superior adaptations during the evolutionary history of tobacco species., Competing Interests: Ibrar Ahmed is employed by Alpha Genomics Private Limited. The authors declare there are no competing interests., (©2020 Mehmood et al.)

Within the family Solanaceae, Withania is a small genus belonging to the Solanoideae subfamily. Here, we report the de novo assembled chloroplast genome sequences of W. coagulans, W. adpressa , and W. riebeckii. The length of these genomes ranged from 154,162 to 154,364 base pairs (bp). These genomes contained a pair of inverted repeats (IRa and IRb) ranging from 25,029 to 25,071 bp that were separated by a large single-copy (LSC) region of 85,635-85,765 bp and a small single-copy (SSC) region of 18,457-18,469 bp. We analyzed the structural organization, gene content and order, guanine-cytosine content, codon usage, RNA-editing sites, microsatellites, oligonucleotide and tandem repeats, and substitutions of Withania plastomes, which revealed high similarities among the species. Comparative analysis among the Withania species also highlighted 10 divergent hotspots that could potentially be used for molecular marker development, phylogenetic analysis, and species identification. Furthermore, our analyses showed that even three mutational hotspots ( rps 4- trn T, trn M- atp E, and rps 15) were sufficient to discriminate the Withania species included in current study.

Cancer is one of the greatest causes of mortality worldwide. The prevalence rates of different types of cancer is increasing around the world as well. Limitations in chemotherapy and radiotherapy, owing to multiple side effects including cytotoxic effects of antitumor compounds on normal cells as well as the development of resistance to these treatment options in patients, create a serious threat to successful treatment of cancer. The use of natural compounds to prevent and treat cancers has been found to be quite effective, with fewer adverse effects found in patients. Umbelliprenin (UMB) is a naturally occurring sesquiterpene compound found in Ferula species and recently in Artemisia absinthium . Many studies have highlighted the antitumor potential of UMB in different cancer cell lines as well as in animal models. UMB exerts its anticancer actions by regulating extrinsic and intrinsic apoptotic pathways; causing inhibition of the cell cycle at the G0/G1 phase; and attenuating migration and invasion by modulating the Wnt signaling, NF-ĸB, TGFβ, and Fox3 signaling pathways. UMB also affects the key hallmarks of tumor cells by attenuating tumor growth, angiogenesis, and metastasis. This review provides an insight into the role of UMB as a potential antitumor drug for different malignancies and highlights the signaling cascades affected by UMB treatment in diverse tumor cell lines and preclinical models.

Background Acute kidney injury (AKI) is a commonly recognized clinical problem after congenital heart disease (CHD) surgery. Increased perioperative morbidity, development of chronic kidney disease, and increased mortality are the major concerns. We investigated frequency, risk factors, and outcomes of AKI after CHD surgery at our hospital. Methods This study was a retrospective analytic review conducted from January 2013 to October 2016 on patients aged between 1 month and 45 years who underwent cardiopulmonary bypass (CPB) for CHD surgery. The modified Kidney Disease Improving Global Outcomes criteria based on serum creatinine value was adopted to diagnose AKI. We assessed AKI frequency and its staging, and outcomes as AKI resolution, length of stay, and mortality. Stages II and III (plasma creatinine level two or more times the baseline) were labeled as severe AKI. Univariate and multivariate logistic regression analyses were conducted, and results were reported as mean with standard deviation and as frequencies with percentage. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported for factors associated with the development of AKI. Results Of the 840 patients who underwent CHD surgery, 237 (28%) developed AKI. AKI stages II1 and III were seen in 101 (42%) and 103 (43%) patients, respectively. Prolonged CPB time > 120 minutes (adjusted OR [AOR]: 1.87; 95% CI: 1.22-2.88; p = 0.004) and hemoglobin > 16 gm/dL (AOR: 1.80; 95% CI: 1.16-2.78; p = 0.008) were associated with the development of AKI on multivariate analysis. AKI resolved spontaneously in 222 (94%) patients, and 10 (4%) patients who developed AKI died. Conclusions Most patients with AKI showed spontaneous resolution. Prolonged CPB time and increased hemoglobin were found to be significant risk factors. Our study found spontaneous resolution of AKI in most cases. However, preplanning and careful monitoring in patients with expected prolonged CPB time and increased baseline hemoglobin can prevent and identify AKI at an early stage., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Ali et al.)

In search of achieving less toxic and more potent chemotherapeutics, three novel heterocyclic benzimidazole derivatives: 2-(1H-benzo[d]imidazol-2-yl)-4-chlorophenol (BM1), 4-chloro-2-(6-methyl-1H-benzo[d]imidazol-2-yl)phenol (BM2) and 4-chloro-2-(6-nitro-1H-benzo[d]imidazol-2-yl)phenol (BM3) with DNA-targeting properties, were synthesized and fully characterized by important physicochemical techniques. The DNA binding properties of the compounds were investigated by UV-Visible absorption titrations and thermal denaturation experiments. These molecules exhibited a good binding propensity to fish sperm DNA (FS-DNA), as evident from the high binding constants ( K b ) values: 1.9 × 10 5 , 1.39 × 10 5 and 1.8 × 10 4  M ‒1 for BM1, BM2 and BM3, respectively. Thermal melting studies of DNA further validated the absorption titration results and best interaction was manifested by BM1 with Δ T m  = 4.96 °C. The experimental DNA binding results were further validated theoretically by molecular docking study. It was confirmed that the molecules (BM1-BM3) bind to DNA via an intercalative and groove binding mode. The investigations showed a correlation between binding constants and energies obtained experimentally and through molecular docking, indicating a binding preference of benzimidazole derivatives with the minor groove of DNA. BM1 was the preferential candidate for DNA binding because of its flat structure, π-π interactions and less steric hindrance. To complement the DNA interaction, antimicrobial assays (antibacterial & antifungal) were performed. It was observed that compound BM2 showed promising activity against all bacterial strains ( Micrococcus luteus , Staphylococcus aureus , Enterobacter aerogenes and Escherichia coli ) and fungi ( Aspergillus flavus, Aspergillus fumigatus and Fusarium solani ), while rest of the compounds were active against selective strains. The MIC values of BM2 were found to be in the range of 12.5 ± 2.2-25 ± 1.5 µg/mL. Thus, the compound BM2 was found to be the effective DNA binding antimicrobial agent. Furthermore, the preliminary cytotoxic properties of synthesized compounds were evaluated by brine shrimps lethality assay to check their nontoxic nature towards healthy normal cells.Communicated by Ramaswamy H. Sarma.

Artemisia L. is a complex genus of medicinal importance. Publicly available chloroplast genomes of few Artemisia species are insufficient to resolve taxonomic discrepancies at species level. We report chloroplast genome sequences of two further Artemisia species: A. maritima (151,061 bp) and A. absinthium (151,193 bp). Both genomes possess typical quadripartite structure comprising of a large single copy, a small single copy and a pair of long inverted repeats. The two genomes exhibited high similarities in genome sizes, gene synteny, GC content, synonymous and non-synonymous substitutions, codon usage, amino acids frequencies, RNA editing sites, microsatellites, and oligonucleotide repeats. Transition to transversion ratio was <1. Maximum likelihood tree showed Artemisia a monophyletic genus, sister to genus Chrysanthemum. We also identified 20 highly polymorphic regions including rpoC2-rps2, trnR-UCU-trnG-UCC, rps18-rpl20, and trnL-UAG-rpl32 that could be used to develop authentic and cost-effective markers to resolve taxonomic discrepancies and infer phylogenetic relationships among Artemisia species., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier Inc.)

Withania somnifera (L) Dunal, a wonder herb of family Solanaceae, has multiple medicinal properties. Here, we reported the chloroplast genome sequence of Withania somnifera (154,386 bp) which comprises of a large single copy region (85,688 bp), and a small single copy region (18,464 bp), separated by a pair of large inverted repeats (25,117 bp). The chloroplast genome has 132 genes including 86 protein-coding, 37 tRNAs and 8 rRNAs. Comparison of chloroplast genomes of Withania somnifera with four other Solanaceae species revealed similarities in genomic features, including structure, nucleotide content, codon usage, RNA editing sites, simple sequence repeats (SSRs), oligonucleotide repeats, and tandem repeats. We identified 147 simple sequence repeats in protein-coding, and 229 in non-protein-coding regions. We observed numerous post-transcriptional substitutions of Serine to Leucine, specifically at the second nucleotide position of the codon. Maximum likelihood and maximum parsimony tree reconstructed displayed Withania somnifera a sister taxon of Physalis peruviana., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Under different pathological conditions, high levels of reactive oxygen species (ROS) cause substantial damage to multiple organs. To counter these ROS levels in multiple organs, we have engineered highly potent novel terpolymers. We found that combination of FDA-approved polyethylene glycol, fumaric acid moieties and electroactive tetra(aniline) by varying the content of tetra(aniline) results into a novel drug composition with biologically active and tunable intrinsic antioxidant properties. To test the intrinsic antioxidative properties of these novel terpolymers, we used alloxan to induce diabetes in rats where ROS generation is known to be higher. The systemic administration of terpolymers to the diabetic rats showed strong electroactive antioxidant behavior which not only normalized ROS levels, but also improved the levels of enzymatic antioxidants including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). As a proof-of-principle, we here show TANI based novel drug composition of terpolymers with tunable intrinsic antioxidant properties in multiple organs., (Copyright © 2019. Published by Elsevier B.V.)

Previous studies to resolve phylogenetic and taxonomic discrepancies of Hibiscus remained inconclusive. Here, we report chloroplast genome sequence of Hibiscus rosa-sinensis. Hibiscus rosa-sinensis chloroplast genome was 160,951 bp, comprising of large single copy (89,509 bp) and small single copy (20,246 bp) regions, separated by IRa and IRb (25,598 bp each). The genome contained 130 genes including 85 protein-coding genes, 37 transfer RNAs and 8 ribosomal RNAs. Comparative analyses of chloroplast genomes revealed similar structure among 12 species within family Malvaceae. Evolutionary rates of 77 protein-coding genes showed 95% similarities. Analyses of codon usage, amino acid frequency, putative RNA editing sites, and repeats showed a great extent of similarities between Hibiscus rosa-sinensis and Hibiscus syriacus. We identified 30 mutational hotpots including psbZ-trnG, trnK-rps16, trnD-trnY, trnW-trnP, rpl33-rps18, petG-trnW, trnS-trnG, trnH-psbA, atpB-rbcL, and rpl32-trnL that might be used as polymorphic and robust markers to resolve phylogenetic discrepancies in genus Hibiscus., (Copyright © 2019. Published by Elsevier Inc.)

Tuberculosis (TB) is one of the major infectious diseases caused by Mycobacterium tuberculosis. The development of an effective and economical vaccine for controlling TB is essential especially for developing countries. Edible plants can serve as biofactories to produce vaccine antigens. In this study, 6 kDa early secretory antigenic target (ESAT-6) of M. tuberculosis was expressed in Brassica oleracea var. italica via Agrobacterium-mediated transformation to facilitate oral delivery of antigen. ESAT-6 gene was cloned using Gateway® cloning strategy. Transformation and presence of transgene was confirmed through PCR. Expression level of transgene was calculated via quantitative real-time PCR (qRT-PCR) and the maximum integrated transgene number was two. Maximum amount of total soluble fraction of ESAT-6 was evaluated by immunoblotting, estimated to accumulate up to 0.5% of total soluble protein. The recombinant ESAT-6 protein was further purified and detected using silver staining and Western blotting. ESAT-6 protein induced humoral immune response in mice immunized orally and subcutaneously. The expression of M. tuberculosis antigen in edible plants could aid in the development of cost-effective and oral delivery of an antigen-based subunit vaccine against TB. To the best our knowledge, it is the first report of expression of a vaccine antigen in broccoli., (© 2019 International Union of Biochemistry and Molecular Biology, Inc.)

Cancer is the second death causing disease worldwide after cardiovascular abnormalities. The difficulty in treating tumor cells with more precise targeted interventions and recurrence of cancer after treatment may pose great difficulty in developing sustainable therapeutic regimens. These limitations have prompted the need to explore several compounds with ability to cease tumor growth while at the same time induce apoptosis of tumor cells. Several studies have emphasized the use of natural compounds as antitumor agents due to their high efficacy against cancer cells and low toxicity in normal cells. Salvianolic acid B (SAB), a naturally occurring phenolic compound extracted from the radix of Chinese herb Salvia miltiorrhiza can induce apoptosis in different types of tumor cells. It can be used to treat cardiovascular and neurodegenerative disorders, hepatic fibrosis, and cancers. Several studies have shown that SAB can mitigate tumorigenesis by modulating MAPK, PI3K/AKT, and NF-ĸB signaling pathways. It also sensitizes the tumor cells to different anti-cancer agents by reversing the multi-drug resistance mechanisms found in tumor cells. This review summarizes the studies showing antitumor potential of SAB in different types of cancer cell lines, animal models and highlights the possible mechanisms through which SAB can induce apoptosis, inhibit growth and metastasis in tumor cells. Moreover, the possible role of nano-technological approaches to induce targeted delivery of SAB to eradicate tumor cells has been also discussed., Competing Interests: The authors declare that there are no conflicts of interest., (© The Author(s) 2020.)

A new protocol for the synthesis of chromeno[ b ]pyridine derivatives is described via a three-component reaction of 4-aminocoumarin, aromatic aldehydes and malononitrile catalyzed by TiO 2 nanoparticles immobilized on carbon nanotubes (TiO 2 -CNTs) as an efficient heterogeneous catalyst under ultrasonic irradiation in water. The sustainable and economic benefits of the protocol are the high yields of products, short reaction time, simple work-up procedure, and use of a non-toxic and reusable catalyst., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Mycobacterium tuberculosis causes tuberculosis in humans. The major disease burden of tuberculosis lies in developing countries. Lack of an effective vaccine for adults is one of the major hurdles for controlling this deadly disease. In the present study, 6 kDa early secretory antigenic target (ESAT-6) of M. tuberculosis was inducibly expressed in chloroplasts of Nicotiana tabacum. The expression of ESAT-6 in chloroplasts was controlled by T7 promoter that was activated by nuclear-generated signal peptide. Tobacco plants, containing nuclear component, were transformed via biolistic bombardment with pEXP-T7-ESAT-6 obtained by Gateway® cloning. Transformation and homoplasmic status of transplastomic plants was confirmed by polymerase chain reaction and Southern blotting. Plants were induced for protein expression by spraying with 5% ethanol for 1 day, 3 days, 7 days and 10 days. ESAT-6 protein was detected by immunoblot analysis and maximum protein was obtained for 10 days induced plants that was estimated to accumulate up to 1.2% of total soluble fraction of protein. Transplastomic plants showed completely normal morphology. Transplastomic and untransformed plants became slightly chlorotic upon prolonged exposure to ethanol until 10 days. Taken together, this data could help in the development of an antigen-based subunit vaccine against tuberculosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hepatitis C virus (HCV) infection is one of the leading causes of morbidity and mortality worldwide. Mortality linked with HCV infection can be lowered with effective and prompt diagnosis in early stages of infection. In this study potential of Raman spectroscopy to differentiate between healthy and HCV infected serum samples was investigated. Clear differences were observed in the Raman spectra of HCV infected and healthy sera samples. Using the analysis of variance (ANOVA) and t-test (p < 0.001) on Raman spectra of diseased and healthy samples, we observed eleven unique Raman bands at 676, 825, 853, 936, 1029, 1105, 1155, 1305, 1620, 1654 and 1757 cm -1 associated with only HCV infected sera and have not been reported in earlier studies. In addition, six Raman bands at 556, 585, 716, 815, 1273 and 1142 cm -1 were observed in healthy sera only. Three Raman bands at 1330, 1526 and 1572 cm -1 were observed in both type of samples but their intensity was drastically reduced in diseased samples. Various multivariate analysis techniques were employed to demonstrate the robustness of the results. We employed multivariate and unsupervised principal component analysis (PCA) in conjunction with supervised classification linear discriminant analysis (LDA), using ten-fold jackknife cross-validation, in order to develop effective diagnostic algorithm technique (PCA-LDA). Our PCA-LDA model yielded sufficient sensitivity and specificity i.e. correctly identified all infected samples included in this study. Ours results indicate that these unique Raman bands have the potential to be used as biomarkers for optical diagnosis of HCV infection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Inappropriate application of pesticides is quite common in the study area, causing health issues and in some cases fatalities. The intent of the current study is to gauge the farmers' level of knowledge on the safe usage of pesticides and biosafety to keep the famers healthy through the focused extension programs., Methodology: The study is carried out in 41 union councils of Tehsil Sahiwal, District Sahiwal, Punjab, Pakistan. Data are collected through a cluster sampling technique by conducting face-to-face interviews. Statistical analysis is used to determine relationships and interpret them., Results: The findings show that the majority of farmers (87.2%) earn their livelihoods from farming and 2.1% are traders. More than half of the respondents (51.8%) own small land-holdings with an area of 4-8 ha, with only 16.4% having a land area of more than 12 ha. The results also reveal that the majority of respondents obtain information from private agents and only about one third (34.4%) respondents get information on the safe usage of pesticides from the Department of Agriculture (Extension). The internet has emerged as a fast and reliable source of information in the new paradigm; however, only 14.4% of the respondents take advantage of this economical and fast information tool/medium. The findings also reveal that the farmers employ unhealthy and poor practices by not following the recommendations regarding the safe usage of pesticides. The study also reveals that more than half of the farmers (54.4%) use unsafe storage practices on their farms, and about 48.2% do not follow the instructions., Conclusions: Inappropriate application of pesticides can have negative effects on human health and the adoption safety measures are necessary to avoid the harmful effects of pesticides. Due to high illiteracy in the area, farmers mainly seek advice of neighboring farmers, having ignorance on the biosafety issues. Variables like education level, land ownership, total land size and the trainings on safe pesticide usage significantly influence the knowledge level of farmers on the safe usage of pesticides., Recommendations: Farmers do not follow the recommendations of the extension department or the instructions printed on pesticide bottles/containers, therefore educational (formal and informal) and training programs are necessary on the safe pesticide usage to upgrade their skills and expertise on safe usage of pesticides and the importance of biosafety., (© 2019 Production and hosting by Elsevier B.V. on behalf of King Saud University.)

Worldwide, food waste is one of the prime issues threatening food security and the Kingdom of Saudi Arabia (KSA) is not an exception. With 427 kg of food wasted per capita per year, the country ranks among the top food wasters. Ironically, the Kingdom has limited arable lands and scarce water resources to support mass-scale agriculture and to feed its increasing population, KSA relies heavily on imports and subsidized food to meet needs. Yet, food is wasted at restaurants, caterers, cafeterias and, especially, by households such that food waste is the single-largest component of the landfills. The review article is based on the grey and scientific literature published in the English and Arabic languages on the issue of food waste in Saudi Arabia. Information sources like Web of knowledge, online resources and the databases available through the King Saud University, Saudi Arabia were accessed and used to collect information on food waste, its social, cultural, economic and environmental impacts and related topics. Since food items and groceries are abundantly available to all living in KSA and they are highly subsidized, the residents take food for granted. According to a recent survey, about 78% of food purchased in KSA is discarded each week in order to make room for new groceries. The factors responsible for food waste include: lack of awareness; and insufficient and inappropriate planning when shopping. Food waste in restaurants, celebrations, social events and occasions are enormous. Waste is common in festivals and special events where the customs is to provide more food than required. There is a need to change society's food culture, particularly among the women and the youth, as they are largest segment of the society and the prime food wasters. The analysis of the factors responsible for food waste, identified in this article suggests a "Stop Wasting Food" campaign should be launched. It is also recommended to determine and activate the role of extension education to reduce food waste in the KSA through vibrant capacity building programs for youth and women, in particular, and society in general., (© 2018 King Saud University.)

In vitro suspension culture techniques are cost effective for large-scale production of secondary metabolites. In the present study, firstly, suspension cultures of untransformed Lactuca sativa were prepared using different hormonal combinations and were subjected to different pH, temperature and salt concentrations. Maximum biomass was obtained for suspensions supplemented with 1.5 mg/L BAP and 0.1 mg/L NAA, at pH 5.8, temperature 28 °C and 0 mM NaCl concentration. Using these parameters, suspensions were produced for rol ABC- and rol C -transformed lines of L. sativa . All the transgenic lines showed prominent increase in fresh weight (FW) and dry weight (DW) with maximum values for rol ABC 2 line producing 169.8 mg/mL FW and 25.3 mg/mL DW. The exudates of transformed and untransformed plants were tested for the antioxidant activity and in vivo assays on rats. Maximum phenolic content (261 μg/mL) and flavonoid content (637.6 μg/mL) were obtained for rol C 1 transgenic line. Total antioxidant capacity was found maximum (1451.7 μg/mL) for untransformed lettuce, whereas rol C 1 showed maximum total reducing power activity (637.6 μg/mL). In DPPH assay, maximum activity (104.7 μg/mL) was shown by rol ABC 3 line. In rats analgesic assay, maximum activity (74.9%) was shown by rol C 2. Line rol C 1 showed maximum anti-inflammatory activity (69.2%) and maximum antidepressant activity (minimum immobility time of 55 s). Maximum anticoagulant activity was observed for rol ABC 2 with maximum clotting time of 130 s. The present study could help in using lettuce suspension culture as platform for the enhanced production of important metabolites., Competing Interests: Conflict of interestThe author declares that they have no competing interests.

Integration of multi-omics in cardiovascular diseases (CVDs) presents high potentials for translational discoveries. By analyzing abundance levels of heterogeneous molecules over time, we may uncover biological interactions and networks that were previously unidentifiable. However, to effectively perform integrative analysis of temporal multi-omics, computational methods must account for the heterogeneity and complexity in the data. To this end, we performed unsupervised classification of proteins and metabolites in mice during cardiac remodeling using two innovative deep learning (DL) approaches. First, long short-term memory (LSTM)-based variational autoencoder (LSTM-VAE) was trained on time-series numeric data. The low-dimensional embeddings extracted from LSTM-VAE were then used for clustering. Second, deep convolutional embedded clustering (DCEC) was applied on images of temporal trends. Instead of a two-step procedure, DCEC performes a joint optimization for image reconstruction and cluster assignment. Additionally, we performed K-means clustering, partitioning around medoids (PAM), and hierarchical clustering. Pathway enrichment analysis using the Reactome knowledgebase demonstrated that DL methods yielded higher numbers of significant biological pathways than conventional clustering algorithms. In particular, DCEC resulted in the highest number of enriched pathways, suggesting the strength of its unified framework based on visual similarities. Overall, unsupervised DL is shown to be a promising analytical approach for integrative analysis of temporal multi-omics., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

World is facing the largest refugee crisis of its time due to continuously outgoing wars, conflicts and natural disasters. One of the important aspects of refugees and migrants is health. Till date, no comprehensive data was available related to health status of Afghan refugees and internally displaced persons (IDPs) in Pakistan. Here, we present health status for Afghan refugees for last seven years and for IDPs for 2-4 years. For Afghan refugees the data was provided by Commissionerate Afghan Refugee (CAR), Pakistan, whereas data for IDPs was collected from hospitals and Basic health units (BHUs) of different districts of Khyber Pakhtunkhwa namely Peshawar, Dera Ismail Khan and Bannu. Highest number of Afghan refugee's deaths occurred due to cardiovascular problems. Most prevalent reported infections were respiratory tract infections (48.05%). Skin diseases and Diarrhea collectively affected 21.08% of Afghan refugees. Overall, disease burden was more in females than males in Afghan refugee's population. To the best of our knowledge, this is the first comprehensive report on health and disease status of Afghan refugees and IDPs in Pakistan.

The original version of this article unfortunately contained a mistake in the image of Figure 1 and in Table 4. The corrected version of the figure and table is shown here.

Embryonic stem cells provide an ideal system to study various therapies for serious human diseases such as juvenile diabetes, neurodegenerative diseases, heart diseases and cancer. Synthetic or natural compounds that affect cell proliferation and/or differentiation of embryonic stem cells are of great value. Focus of the current project was upon the isolation and evaluation of natural components from a medicinal plant; Rhazya stricta on proliferation/ differentiation potential of embryonic stem cells. For this purpose, after a series of fractionation and purification steps, 7 compounds named as RS1-RS7 were isolated from aerial parts of the plant. The effects of these compounds were evaluated on the morphology and rate of cell proliferation of mouse naive embryonic stem cells. Only RS7 inhibited the proliferation of cell and reduced the induction of differentiation of cell. The qPCR analysis confirmed that the expression of the selected pluripotency markers (Oct4, Nanog and Sox2) was down regulated by RS7 treatment as compared to control. Furthermore, upon withdraw of Leukemia inhibitory factor (lif) from medium; effect of RS7 to promote differentiation was enhanced. Through structure elucidation studies, RS7 was found to be ursolic acid. This study first time shows the effect of natural compounds of Rhazya stricta Decne. on mouse embryonic stem cells.

Ipomoea carnea Jacq . is an important folklore medicinal plant, assessed for its underexplored biological potential. Antioxidant, cytotoxic, antiproliferative and polyphenolic profile of whole plant was evaluated using various techniques. Maximum extract recovery (29% w/w), phenolic [13.54 ± 0.27 μg GAE/mg dry weight (DW)] and flavonoid (2.11 ± 0.10 μg QE /mg DW) content were recorded in methanol-distilled water (1:1) flower extract. HPLC-DAD analysis quantified substantial amount of six different polyphenols ranging from 0.081 to 37.95 μg/mg extract. Maximum total antioxidant and reducing potential were documented in methanol-distilled water and acetone-distilled water flower extracts (42.62 ± 0.47 and 24.38 ± 0.39 μg AAE/mg DW) respectively. Ethanol-chloroform root extract manifested highest free radical scavenging (IC 50 of 61.22 μg/mL) while 94.64% of the extracts showed cytotoxicity against brine shrimps. Ethanol leaf extract exhibited remarkable activity against THP-1 cell line (IC 50  = 8 ± 0.05 μg/mL) and protein kinases (31 mm phenotype bald zone).

[This corrects the article DOI: 10.3389/fphar.2018.01376.].

Prostate cancer is one of the major causes of cancer-related deaths in men and there is a growing interest in identifying natural compounds for its management. We analyzed bioactive withanolides in Withania coagulans from 11 different sites in Pakistan and evaluated the antiprostate cancer activities of leaf extracts from two sites with the greatest amounts. Total withanolide concentration differed by ~ 17-fold between sites, ranging from 1.01 ± 0.01 mg/g dry weight (mean ± SE) at Jand to 16.83 ± 0.02 mg/g at Mohmand Agency. Different tissues varied in their total withanolide content with roots having the least (0.42 ± 0.07 mg/g dry weight) and leaves the most (2.45 ± 0.45 mg/g). We found strong inverse correlations between site annual precipitation versus withanolide amounts in fruits (r = - 0.84, P = 0.001), leaves (r = - 0.88, P < 0.001), roots (r = - 0.91, P < 0.001), and total (r = - 0.89, P < 0.001), but not stems (r = - 0.20, P = 0.556). Extracts made from Mianwali and Mohmand Agency leaves possessed high anticancer activity in terms of increased induction of apoptosis and decreased cell viability, cell proliferation, invasion, and migration of different prostate cancer cell lines. These results are useful for the selection of withanolide-rich germplasm with potent anticancer properties.

Plant secondary metabolites are protective dietary constituents and rol genes evidently increase the synthesis of these versatile phytochemicals. This study subjected a globally important vegetable, lettuce ( Lactuca sativa ) to a combination of untargeted metabolomics (LC-QTof-MS) and in vitro bioactivity assays. Specifically, we examined the differences between untransformed cultured lettuce (UnT), lettuce transformed with either rolABC (RA) or rolC (RC) and commercially grown (COM) lettuce. Of the 5333 metabolite features aligned, deconvoluted and quantified 3637, 1792 and 3737 significantly differed in RA, RC and COM, respectively, compared with UnT. In all cases the number of downregulated metabolites exceeded the number increased. In vitro bioactivity assays showed that RA and RC (but not COM) significantly improved the ability of L. sativa to inhibit α-glucosidase, inhibit dipeptidyl peptidase-4 (DPP-4) and stimulate GLP-1 secretion. We putatively identified 76 lettuce metabolites (sesquiterpene lactones, non-phenolic and phenolic compounds) some of which were altered by several thousand percent in RA and RC. Ferulic acid levels increased 3033-9777%, aminooxononanoic acid increased 1141-1803% and 2,3,5,4'tetrahydroxystilbene-2-O-β-d-glucoside increased 40,272-48,008%. Compound activities were confirmed using commercially obtained standards. In conclusion, rol gene transformation significantly alters the metabolome of L.sativa and enhances its antidiabetic properties. There is considerable potential to exploit rol genes to modulate secondary metabolite production for the development of novel functional foods. This investigation serves as a new paradigm whereby genetic manipulation, metabolomic analysis and bioactivity techniques can be combined to enable the discovery of novel natural bioactives and determine the functional significance of plant metabolites., Competing Interests: The authors declare no conflict of interest.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues., Competing Interests: The authors declare no conflict of interest.

Aim: 5,10-MTHFR-single nucleotide polymorphisms are important for normal functioning of the enzyme that plays a key role in DNA synthesis, folate metabolism and methylation reactions. Methodology & results: Male infertility association of C665T and A1298C polymorphisms was explored, this topic is still debatable. Infertile men (232) and controls (114) were genotyped and statistically analyzed. Comparison of patients (6180) and controls (5744) of Caucasian populations was performed by meta-analysis. Pooled results showed A1298C minor allele and homozygous genotype to be of a significantly higher frequency in the low-income group. Increase in per capita income has shown an increasing trend in the minor allele frequency in various world populations, potentially due to dietry-folate compensation., Conclusion: A1298C seems more relevant marker than C665T for infertility association in Caucasian populations and may be addressed by improving dietary folate.

Cysteine oxidative modification of cellular proteins is crucial for many aspects of cardiac hypertrophy development. However, integrated dissection of multiple types of cysteine oxidative post-translational modifications (O-PTM) of proteomes in cardiac hypertrophy is currently missing. Here we developed a novel discovery platform that encompasses a customized biotin switch-based quantitative proteomics pipeline and an advanced analytic workflow to comprehensively profile the landscape of cysteine O-PTM in an ISO-induced cardiac hypertrophy mouse model. Specifically, we identified a total of 1655 proteins containing 3324 oxidized cysteine sites by at least one of the following three modifications: reversible cysteine O-PTM, cysteine sulfinylation (CysSO 2 H), and cysteine sulfonylation (CysSO 3 H). Analyzing the hypertrophy signatures that are reproducibly discovered from this computational workflow unveiled four biological processes with increased cysteine O-PTM. Among them, protein phosphorylation, creatine metabolism, and response to elevated Ca 2+ pathways exhibited an elevation of cysteine O-PTM in early stages, whereas glucose metabolism enzymes were increasingly modified in later stages, illustrating a temporal regulatory map in cardiac hypertrophy. Our cysteine O-PTM platform depicts a dynamic and integrated landscape of the cysteine oxidative proteome, through the extracted molecular signatures, and provides critical mechanistic insights in cardiac hypertrophy. Data are available via ProteomeXchange with identifier PXD010336.

Purpose: This study was aimed to evaluate the effect of Hedera nepalensis crude extract (HNC) and its isolated compound lupeol on antioxidant defence system, biochemical parameters and behavioural indices of Alzheimer disease generated in diabetic rats., Methods: To evaluate the effect of the plant extract and lupeol, symptoms of Alzheimer and diabetes were induced in rats by STZ + AlCl 3 treatment. Glucose level was measured with glucometer followed by antioxidant and biochemical assessment of the treated and untreated animals. Behavioural response of the rats was determined by Elevated Plus Maze (EPM) test and Morris Water Maze (MWM) test followed by determination of brain neurotransmitters by HPLC., Results: HNC significantly reduced blood glucose level in a time dependent manner and elevated liver function markers were significantly (P < 0.05) reinstated to normal levels. HNC showed increase in level of catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH). HPLC quantification revealed that HNC treatment led to significant (p < 0.001) elevation in the level of neurotransmitters (dopamine and serotonin) in the midbrain region as compared to Alzheimer control (AC) group. EPM and MWM test showed decrease in cognitive and memory impairment in a rat group treated with HNC as compared to AC group., Conclusion: Overall, results showed that H. nepalensis has therapeutic potential for the treatment of diseases like Alzheimer and diabetes. Graphical abstract Therapeutic effect of Hedera nepalensis K. Koch and lupeol against STZ + AICI 3 induced diabetic rats model.

Thioureas are exquisite building blocks for the construction of five and six membered heterocyclic units, and also display an extensive range of biological activities. 4-Nitro-2-cyano aniline was reacted with the various acid chlorides which were freshly prepared from carboxylic acids to afford the desired products in good yield. All the newly synthesized compounds were evaluated antibacterial, antifungal, antioxidant and α-amylase activity. The compounds showed significant activity against bacteria and fungi. The compound 4e and 4b were found to be most inhibitors of α-amylase having IC 50 9.7 μg/ml and 9.1 μg/ml. Further molecular docking studies were carried out to find out the binding mode of the inhibitors with the enzyme., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Type 2 diabetes is a metabolic disorder, characterized by hyperglycemia and glucose intolerance. Natural products and its derived active compounds may be achievable alternatives for the treatment of type 2 diabetes. In present study we investigated the antidiabetic potential of Ficus microcarpa and isolated bioactive compounds i.e., Plectranthoic acid A (PA-A) and 3,4,5,7-Flavantetrol (FL). Anti-hyperglycemic potential was evaluated via α-glucosidase, α-amylase and dipeptidyl peptidase 4 (DPP-4) assays. 5'AMP-activated kinase (AMPK) activation potential was assessed by using primary hepatocytes. Distribution of PA-A in different parts of Ficus microcarpa was evaluated by using rapid high-performance liquid chromatography (HPLC). Ethyl acetate fraction (FME) exhibited significant inhibition of α-glucosidase, α-amylase, and DPP-4, therefore, was selected for isolation of bioactive compounds. Among isolated compounds PA-A was more potent and possessed pleotropic inhibitory activity with IC 50 values of 39.5, 55.5, and 51.4 μM against α-glucosidase, α-amylase, and DPP-4, respectively. Our results showed that PA-A is also a potent activator of AMPK which is a central hub of metabolic regulation. Molecular docking studies confirmed the activity of PA-A against α-glucosidase, α-amylase, and DPP-4. Rapid HPLC method revealed that maximum concentration of PA-A is present in the stem (2.25 μg/mg dry weight) of Ficus microcarpa . Both in vitro and in silico studies proposed that Ficus microcarpa and its isolated compound PA-A could be an important natural source for alleviating the symptoms of type 2 diabetes mellitus and we suggest that PA-A should be explored further for its ultimate use for the treatment of type 2 diabetes.

Background: Ipomoea batatas L. Lam. is a functional food and belongs to family Convolvulaceae. It is used as an antiinflammatory, aphrodisiac, antiasthmatic, anticonvalescent, antitumor, antanemic and antidiabetic agent by local communities. This study has been planned to evaluate its antiinflammatory and antiarthritic potentials., Methods: Dry powder of I. batatas tuber and roots were extracted with ethyl acetate (IPT-EA, IPR-EA) and methanol (IPT-M, IPR-M), respectively. These extracts were tested for total phenolic and flavonoid contents (TPC and TFC), HPLC finger printing, multidimensional in vitro and in vivo antioxidant potential and albumin denaturation inhibition. Carrageenan-induced paw edema, croton oil-induced ear and anal edema inhibition and Complete Freund's Adjuvant (CFA)-induced antiarthritic assays were executed at a dose of 300 mg/kg body weight on Sprague-Dawley rats. Serum levels of interleukins IL-1β and IL-6 and nitric oxide (NO) were assessed to measure the inhibition of inflammation., Results: Maximal TPC (319.81 ± 14.20 μg GAE/mg dry extract) and TFC (208.77 ± 9.09 μg QE/mg DE) were estimated in IPR-EA extract. IPT-EA and IPR-EA yielded the maximum amounts of rutin (7.3 ± 1.12 and 4.5 ± 0.55), caffeic acid (1.60 ± 0.25 and 2.17 ± 0.26) and myricetin (2.7 ± 0.14 and 1.01 ± 0.08 μg/mg DE), respectively in HPLC-DAD analysis. All extracts showed dose dependent response in in vitro antioxidant assays. Best inhibition (76.92 ± 3.07%) of albumin denaturation was shown by IPT-EA in comparison to ibuprofen (79.48 ± 4.71%). IPR-EA exhibited highest edema inhibition in models of carrageenan-induced paw edema (79.11 ± 5.47%) and croton oil-induced ear and anal edema (72.01 ± 7.80% and 70.80 ± 4.94%, respectively). Significant inhibition of CFA-induced arthritic edema and arthritic score were observed by IPR-EA as compared to ibuprofen. Suppression of pro-inflammatory cytokines (IL-1β, IL-6) and NO levels was shown by IPR-EA and IPT-EA, respectively., Conclusion: These results depict that richness of polyphenols and phytoconstituents in I. batatas ameliorates oxidative stress and inflammation of acute and chronic nature. Dose dependent antioxidant potential and inhibition of inflammatory edema, pro-inflammatory cytokines and hematological, biochemical and histological changes prove I. batatas therapeutic potential as an antiinflammatory and antiarthritic agent.

A robust extraction method against the variations of sample ionic strength viz. ionic liquid-based ultrasound-assisted in situ solvent formation microextraction (IL-UA-ISFME) was coupled for the first time with high-performance liquid chromatography-ultraviolet detection (HPLC-UV), and successfully used as a more sustainable approach for the determination of meloxicam (MEL) in human plasma. Herein, a hydrophobic IL (1-butyl-3-methylimidazolium hexafluorophosphate) was formed by adding a hydrophilic IL (1-butyl-3-methylimidazolium tetrafluoroborate) to aqueous sample solution containing an ion-exchange reagent (sodium hexafluorophosphate). The target analyte was transferred into the IL medium while the extraction solvent was completely dispersed into the sample using ultrasonic irradiation and then, the settled enriched phase was injected to HPLC. Firstly, main factors affecting the microextraction performance were evaluated and optimized. The linearity was in the range of 5-1,500 ng mL-1 with regression coefficient corresponding to 0.997. Limits of detection (LOD; signal-to-noise ratio (S/N) = 3) and quantification (LOQ, S/N = 10) were 1 and 5 ng mL-1, respectively. An acceptable recovery range of 82.1-93.6% and satisfactory intra-assay (3.6-4.8%, n = 6) and inter-assay (3.3-5.1%, n = 9) precision as well as remarkable sample clean up exhibited good efficiency of the method. The freeze-thaw stability study was performed for samples and standard solutions. To study the applicability of the proposed method, it was employed for the determination of MEL in human plasma after oral administration of the drug and some pharmacokinetic data were achieved. The technique proved to be accurate and reliable for the screening intentions., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Epithelial-to-mesenchymal transition (EMT) plays a crucial role in prostate cancer (PCa) metastasis. This has led to a surge in the efforts for identification of safer and more effective compounds which can modulate EMT and consequently inhibiting migration and invasion of PCa cells. We reported previously that Plectranthoic acid (PA), a natural compound isolated from the extracts of Ficus microcarpa, has the capability to induce cell cycle arrest and apoptosis in PCa cells. Here, we determined the effects of PA on EMT, migration, and invasion of PCa cells. Inhibition of EMT induced by different mitogens was effectively inhibited by PA treatment with subsequent decrease in migration of PCa cells. Employing a PCa cell culture model of TGF-β-induced EMT, we showed that PA has the ability to reverse EMT. PA treatment was associated with induction of epithelial markers and decrease in the expression of mesenchymal markers in PCa cells. Proteomic analysis identified Rac1 as the major cadherin signaling protein modulated with PA treatment. In silico studies indicated that PA docked to the CH domain of NEDD9 protein with an estimated free binding energy of -7.34 Kcal/moL. Our studies revealed significant inhibition of Rac1/NEDD9 pathway in PA treated cells thereby providing a molecular basis of the inhibitory effect of PA on PCa cell migration and invasion. In conclusion, our data suggest that PA should be investigated further as an adjuvant treatment in human PCa cells, given its potential as an anti-invasive agent., (© 2018 Wiley Periodicals, Inc.)

An electrophile, N-(1,3-thiazol-2-yl)-2-bromoacetamide (3), was synthesized by the reaction of 1,3-thiazole-2-amine (1) and 2-bromoethanoyl bromide (2) in an aqueous medium. A series of carboxylic acids, 7a-j, were converted into 1,3,4-oxadiazole heterocyclic core, through a series of three steps. The final compounds, 8a-j, were synthesized by stirring 7a-j and 3 in an aprotic polar solvent. The structural elucidation of the synthesized compounds was supported by IR, EI-MS, 1H-NMR, and 13 C-NMR spectral data. Title compounds were evaluated for enzyme inhibition against cholinesterases and α-glucosidase enzymes and their cytotoxic behavior was monitored using brine shrimp assay. The enzyme inhibitor potential of compounds was supported by molecular docking studies.

Cyanobacteria-dominated harmful algal blooms are increasing in occurrence. Many of the taxa contributing to these blooms are capable of fixing atmospheric nitrogen and should be favored under conditions of low nitrogen availability. Yet, synthesizing nitrogenase, the enzyme responsible for nitrogen fixation, is energetically expensive and requires substantial concentrations of iron. Phosphorus addition to nitrogen poor streams should promote nitrogen fixation, but experimental results so far have been inconclusive, suggesting that other factors may be involved in controlling this process. With iron potentially limited in many streams, we examined the influence of phosphorus-iron colimitation on the community structure of nitrogen-fixing organisms. In stream microcosms, using microscopic and molecular sequence data, we observed: (i) the greatest abundance of heterocyst forming nitrogen-fixing cyanobacteria in low nitrogen treatments with high phosphorus and iron and (ii) greater abundance of non-photosynthetic nitrogen-fixing bacteria in treatments with nitrogen compared to those without it. We also found that comparisons between molecular results and those obtained from microscopic identification provided complementary information about cyanobacterial communities. Our investigation indicates the potential for phosphorus-iron colimitation of stream nitrogen-fixing organisms.

Somatic cell reprogramming by exogenous factors requires cooperation with transcriptional co-activators and co-repressors to effectively remodel the epigenetic environment. How this interplay is regulated remains poorly understood. Here, we demonstrate that NCoR/SMRT co-repressors bind to pluripotency loci to create a barrier to reprogramming with the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC), and consequently, suppressing NCoR/SMRT significantly enhances reprogramming efficiency and kinetics. The core epigenetic subunit of the NCoR/SMRT complex, histone deacetylase 3 (HDAC3), contributes to the effects of NCoR/SMRT by inducing histone deacetylation at pluripotency loci. Among the Yamanaka factors, recruitment of NCoR/SMRT-HDAC3 to genomic loci is mostly facilitated by c-MYC. Hence, we describe how c-MYC is beneficial for the early phase of reprogramming but deleterious later. Overall, we uncover a role for NCoR/SMRT co-repressors in reprogramming and propose a dual function for c-MYC in this process.

Artemisinin and its analogues are naturally occurring most effective antimalarial secondary metabolites. These compounds also possess activity against various types of cancer cells, schistosomiasis, and some viral diseases. Artemisinin and its derivatives (A&D) are found in very low amounts in the only natural source i.e. Artemisia plant. To meet the global needs, plant sources have been exploited for the enhanced production of these natural products because their chemical synthesis is not profitable. The generally adopted approaches include non-transgenic (tissue and cell cultures) and transgenic together with the cell, tissue, and whole transgenic plant cultures. The genes targeted for the overproduction of A&D include the biosynthetic pathway genes, trichome development genes and rol genes, etc. Artemisinin is naturally produced in trichomes of leaves. At the same time, transgenic hairy roots are considered a good source to harvest artemisinin. However, the absence of trichomes in hairy roots suggests that artemisinin biosynthesis is not limited to trichomes. Moreover, the expression of the gene involved in trichome development and sesquiterpenoid biosynthesis (TFAR1) in transgenic and non-transgenic roots provokes researchers to look for new insight of artemisinin biosynthesis. Here we discuss and review precisely the various biotechnological approaches for the enhanced biosynthesis of A&D.

Lupeol is a triterpene with various pharmacological properties. This study investigated the effect of lupeol on the in vitro development of bovine embryos. Oocytes (270 per group, 1620 in total) obtained from slaughterhouse-derived ovaries were matured and fertilized in vitro and then cultured for 8 days in a humidified atmosphere of 5% CO 2 in air at 38.5 °C. The in vitro maturation medium was supplemented with 0.5, 1.0, 2.0, 3.0, and 4.0 μM lupeol. Treatment with 2.0 μM lupeol significantly (P < 0.05) improved blastocyst development. Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling showed that treatment with 2.0 μM lupeol improved blastocyst quality by increasing the total cell number and reducing the apoptotic cell number. Confocal microscopy confirmed that treatment with 2.0 μM lupeol significantly (P < 0.05) reduced the level of 8-oxoguanine, an indicator of reactive oxygen species. Lupeol treatment also significantly attenuated protein expression of nuclear factor-kappa B subunit 1 (NFKB1), cyclooxygenase (COX) 2, and CASP3. Real-time PCR analysis of nitric oxide synthase 2, NFKB1, COX2, CASP3, and BCL2-associated X protein supported the immunofluorescence data. In conclusion, lupeol is a potent antioxidant that improves bovine embryo development in vitro., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Teratomas originating from the stomach are extremely rare and account for less than 1% of all cases of teratomas. This site of occurrence has unique diagnostic and management issues., Methods: A single centre case-record review of gastric teratomas presenting between January 2000 and April 2017 was performed., Results: Thirteen children were found to have gastric teratomas. Presenting features were abdominal distension in 12 (92%) and palpable abdominal mass in 9 (69%). At operation, 8 (61%) were exogastric tumors. The tumor was excised with partial gastrectomy (n=7, 54%), total gastrectomy (n=1, 8%), partial gastrectomy and limited transverse colectomy (n=2, 15%), and excision of small part of serosa (mucosal sparing) (n=3, 23%). Histopathologically, these were identified as mature gastric teratomas in 8 (61%). Three (23%) children died postoperatively., Conclusion: Gastric teratomas are rare, with the majority described as exogastric. Partial gastrectomy is always needed, but occasionally complete gastrectomy is necessary. Overall survival is >75% in our experience., Level of Evidence: IV., (Copyright © 2017. Published by Elsevier Inc.)

There is enough data available now to believe that nature has provided cure of almost every ailment through herbal medicine or management. Therefore, now there is lot of emphasis on identification, evaluation, development and characterization of numerous plants and their active constituents against several diseases including depression. Depression is not only one of the most common ailments but also a highly complex condition to study. Even though several antidepressant drugs are available now, yet their effectiveness and usefulness are highly questionable especially because of their side effects. As herbal remedies are generally associated with favourable safety profiles therefore they have the possible potential to deliver effective replacements to currently available synthetic antidepressants. More recently, efforts have been focused on characterization of pharmacologically active ingredients and to identify the mode of action of herbal antidepressant medicines. This review describes a brief introduction of different animal models for depression and discusses the advantages and disadvantages for each approach. Then we have summarized possible plant phytochemicals as antidepressant drug and their underlying mechanisms. In the main body of the review, we have discussed in detail the most frequently used plants (21) being investigated for the treatment of depression. Additionally, we have provided the list of medicinal plants (92) representing their origin, parts used, extraction method, evaluation method and possible active ingredient. In the final part of the review we have presented the summary of clinical trials on the use of medical plants for depression and their active constituents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)