Centaurea bruguierana inhibits cell proliferation,causes cell cycle arrest,and induces apoptosis in human MCF-7 breast carcinoma cells

Molecular Biology Reports - Centaurea bruguierana, of the Asteraceae family, has a long history of use in traditional medicines for the treatment of various ailments. However, the anticancer...     

Phytochemical Fingerprints and Bioactivities of Ripe Disseminules (Fruit-Seeds) of Seventeen Gundelia (Kenger-Kereng Dikeni) Species from Anatolia with Chemometric Approach

Gundelia species are known as “Kenger-kereng dikeni” in Anatolia, and their aerial parts are consumed as food. Also, roots and seeds (disseminules) of the Gundelia species are used to prepare gum and coffee. The chemical contents of ethanol and hexane extracts of disseminules of 17 Gundelia species, 13 of them are endemic, were studied using LC/MS/MS and GC/MS. Additionally, their antioxidant potential and enzyme inhibitory capacity against acetyl- and butyryl-cholinesterase, urease, and tyrosinase were determined. The unsaturated fatty acid ratios of Gundelia species were higher than their saturated fatty acid ratio. The highest sum of oleic and linoleic acid was detected in G. tournefortii var. tenuisecta (70.42 %). β-Sitosterol, α-amyrin, 3-acetyllupeol were identified in 17 Gundelia species by GC/MS, while chlorogenic acid and luteolin by LC/MS/MS as major compounds. The ethanol and hexane extracts of G. siirtica, G. rosea, and G. mesopotamica indicated good cholinesterase inhibitory activity. Among all species, ethanol extract of G. colemerikensis exhibited the best activity in ABTS (IC₅₀: 32.30±0.98 μg/mL), DPPH (IC₅₀: 59.91±0.89 μg/mL), and CUPRAC (A_0.5: 57.41±1.03 μg/mL) assays. Ethanol extract of G. colemerikensis also displayed the highest inhibitory activity against butyrylcholinesterase (51.14±0.25 % at 200 μg/mL), urease (51.71±1.75 % at 200 μg/mL), and tyrosinase (39.50±0.85 % at 200 μg/mL) enzymes. According to the chemometric analysis of fatty acids, four groups were observed. Therefore, it is suggested that G. colemerikensis can be used in the pharmaceutical, food, and cosmetic industries due to its antioxidant and enzyme inhibition properties.     

Computational drug screening against the SARS-CoV-2 Saudi Arabia isolates through a multiple-sequence alignment approach

COVID-19 is a rapidly emerging infectious disease caused by the SARS-CoV-2 virus currently spreading throughout the world. To date, there are no specific drugs formulated for it, and researchers around the globe are racing against the clock to investigate potential drug candidates. The repurposing of existing drugs in the market represents an effective and economical strategy commonly utilized in such investigations. In this study, we used a multiple-sequence alignment approach for preliminary screening of commercially-available drugs on SARS-CoV sequences from the Kingdom of Saudi Arabia (KSA) isolates. The viral genomic sequences from KSA isolates were obtained from GISAID, an open access repository housing a wide variety of epidemic and pandemic virus data. A phylogenetic analysis of the present 164 sequences from the KSA provinces was carried out using the MEGA X software, which displayed high similarity (around 98%). The sequence was then analyzed using the VIGOR4 genome annotator to construct its genomic structure. Screening of existing drugs was carried out by mining data based on viral gene expressions from the ZINC database. A total of 73 hits were generated. The viral target orthologs were mapped to the SARS-CoV-2 KSA isolate sequence by multiple sequence alignment using CLUSTAL OMEGA, and a list of 29 orthologs with purchasable drug information was generated. The results showed that the SARS CoV replicase polyprotein 1a had the highest sequence similarity at 79.91%. Through ZINC data mining, tanshinones were found to have high binding affinities to this target. These compounds could be ideal candidates for SARS-CoV-2. Other matches ranged between 27 and 52%. The results of this study would serve as a significant endeavor towards drug discovery that would increase our chances of finding an effective treatment or prevention against COVID19.     

Comparative phenotypic characterization identifies few differences in the metabolic capacity between Escherichia coli ST131 subclones

BackgroundExtraintestinal pathogenic Escherichia coli (ExPEC) is responsible for causing many infections such as urinary tract infections (UTIs). The current dissemination of the multidrug resistant (MDR) ExPEC clone, Escherichia coli sequence type 131 (E. coli ST131), poses a real threat to public health worldwide. This study aimed to determine and compare the metabolic capacity of a collection of ExPEC isolates including ST131, non-ST131 and various ST131 subclones, and sought to assess the association between antimicrobial resistance and metabolic capacity of ST131 isolates.MethodsThe metabolic activity of forty urine E. coli isolates, collected from in-patients hospitalized at tertiary hospital in Riyadh, was tested using KB009 Hi carbohydrate kit, and then statistically analysed to assess the difference in the metabolic profiles between ST131 and non-ST131 isolates, and between ST131 subclones.ResultsThe data of this study found almost similar metabolic profiles between ST131 and non-ST131, suggesting that ST131 is not a metabolically unique clone of ExPEC. There was also no link between antimicrobial susceptibility profiles and high metabolic capacity of ST131 isolates. Testing the biochemical activity of isolates belonging to ST131 subclones found higher activity of H30 subclone than non-H30 isolates, however it revealed few significant differences between these subclones.ConclusionThis study demonstrated no difference in the metabolism of ST131 and non-ST131, although it uncovered the presence of few significant differences in the metabolic capacity between ST131 subclones. Carrying out whole-genome based studies on ST131 and its main subclones is essential to elucidate the genetic factors responsible for the success of particular ST131 subclones.     

Structure insights of SARS-CoV-2 open state envelope protein and inhibiting through active phytochemical of ayurvedic medicinal plants from Withania somnifera

Coronaviruses have been causing pandemic situations across the globe for the past two decades and the focus is on identifying suitable novel targets for antivirals and vaccine development. SARS-CoV-2 encodes a small hydrophobic envelope (E) protein that mediates envelope formation, budding, replication, and release of progeny viruses from the host. Through this study, the SARS-CoV-2 E protein is studied for its open and closed state and focused in identifying antiviral herbs used in traditional medicine practices for COVID-19 infections. In this study using computational tools, we docked the shortlisted phytochemicals with the envelope protein of the SARS-CoV-2 virus and the results hint that these compounds interact with the pore-lining residues. The molecular level understanding of the open state is considered and the active inhibitors from the phytochemicals of Ayurvedic medicinal plants from Withania somnifera. We have thus identified a potential phytochemical compound that directly binds with the pore region of the E protein and thereby blocks its channel activity. Blocking the ion channel activity of E protein is directly related to the inhibition of virus replication. The study shows encouraging results on the usage of these phytochemicals in the treatment/management of SARS-CoV-2 infection.     

Correlations among oligonucleotide repeats,nucleotide substitutions,and insertion–deletion mutations in chloroplast genomes of plant family Malvaceae

The co‐occurrence of mutational events including substitutions and insertions–deletions (InDels) with oligonucleotide repeats has previously been reported for a limited number of prokaryotic, eukaryotic, and organelle genomes. In this study, the correlations among these mutational events in chloroplast genomes of species in the eudicot family Malvaceae were investigated. This study also reported chloroplast genome sequences of Hibiscus mutabilis, Malva parviflora, and Malvastrum coromandelianum. These three genomes and 16 other publicly available chloroplast genomes from 12 genera of Malvaceae were used to calculate the correlation coefficients among the mutational events at family, subfamily, and genus levels. In these comparisons, chloroplast genomes were pairwise aligned to record the substitutions and the InDels in mutually exclusive, 250nucleotide long bins. Taking one among the two genomes as a reference, the coordinate positions of oligonucleotide repeats in the reference genome were recorded. The extent of correlations among repeats, substitutions, and InDels was calculated and categorized as follows: very weak (0.1–0.19), weak (0.20–0.29), moderate (0.30–0.39), and strong (0.4–0.69). The extent of correlations ranged 0.201–0.6 between “InDels and single‐nucleotide polymorphism (SNP)”, 0.182–0.513 between “InDels and repeat” and 0.055–0.403 between “SNPs and repeats”. At family‐ and subfamily‐level comparisons, 88%–96% of the repeats showed co‐occurrence with SNPs, whereas at the genus level, 23%–86% of the repeats co‐occurred with SNPs in same bins. Our findings support the previous hypothesis suggesting the use of oligonucleotide repeats as a proxy for finding the mutational hotspots.     

Optimization of caulogenesis in Populus nigra under lead (Pb) stress via response surface methodology (RSM) and desirability function analysis

Plant Cell, Tissue and Organ Culture (PCTOC) - Polyethylene glycol (PEG)-mediated transient expression system in plant protoplasts has been widely used in a variety of plants for gene function...     

Ca2+ Influx through Store-operated Calcium Channels Replenishes the Functional Phosphatidylinositol 4,5-Bisphosphate Pool Used by Cysteinyl Leukotriene Type I Receptors

Oscillations in cytoplasmic Ca²⁺ concentration are a universal mode of signaling following physiological levels of stimulation with agonists that engage the phospholipase C pathway. Sustained cytoplasmic Ca²⁺ oscillations require replenishment of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP₂), the source of the Ca²⁺-releasing second messenger inositol trisphosphate. Here we show that cytoplasmic Ca²⁺ oscillations induced by cysteinyl leukotriene type I receptor activation run down when cells are pretreated with Li⁺, an inhibitor of inositol monophosphatases that prevents PIP₂ resynthesis. In Li⁺-treated cells, cytoplasmic Ca²⁺ signals evoked by an agonist were rescued by addition of exogenous inositol or phosphatidylinositol 4-phosphate (PI4P). Knockdown of the phosphatidylinositol 4-phosphate 5 (PIP5) kinases α and γ resulted in rapid loss of the intracellular Ca²⁺ oscillations and also prevented rescue by PI4P. Knockdown of talin1, a protein that helps regulate PIP5 kinases, accelerated rundown of cytoplasmic Ca²⁺ oscillations, and these could not be rescued by inositol or PI4P. In Li⁺-treated cells, recovery of the cytoplasmic Ca²⁺ oscillations in the presence of inositol or PI4P was suppressed when Ca²⁺ influx through store-operated Ca²⁺ channels was inhibited. After rundown of the Ca²⁺ signals following leukotriene receptor activation, stimulation of P2Y receptors evoked prominent inositol trisphosphate-dependent Ca²⁺ release. Therefore, leukotriene and P2Y receptors utilize distinct membrane PIP₂ pools. Our findings show that store-operated Ca²⁺ entry is needed to sustain cytoplasmic Ca²⁺ signaling following leukotriene receptor activation both by refilling the Ca²⁺ stores and by helping to replenish the PIP₂ pool accessible to leukotriene receptors, ostensibly through control of PIP5 kinase activity.     

Population Structure and Development of Resistance to Hymexazol Among Fusarium solani Populations from Date Palm,Citrus and Cucumber

A study was conducted to investigate genetic diversity and sensitivity to hymexazol among 80 isolates of Fusarium solani complex obtained from date palm (30), citrus (31) and cucumber (19). Characterization based on sequences of the EF1α and ITS rRNA showed that isolates belong to F. solani complex MLST type 3 + 4. AFLP analysis produced 980 polymorphic loci, 80 AFLP genotypes and moderate levels of genetic diversity (H = 0.2494). Clustering of the isolates was not related to the host or the geographical origin of the isolates. Analysis of molecular variance (amova ) indicated the existence of a low level of genetic differentiation among populations obtained from different hosts (F_st = 0.0162) and regions (F_st = 0.0066). This may provide evidence for frequent movement of inoculum among hosts and regions in Oman, which could be attributed to cultural practices employed by farmers. Isolates of F. solani displayed variation in sensitivity to hymexazol, with EC₅₀ values ranging from 2 to 5745 μg/ml (mean = 878 μg/ml); 19% of the isolates have an EC₅₀ value of more than 1000 μg/ml. Findings are discussed in terms of the factors that affect diversity in F. solani isolates. The study reports for the first time the development of resistance to hymexazol among F. solani isolates from date palm, citrus and cucumber.