Hypoxia-induced CTCF promotes EMT in breast cancer.

Cancer cells experiencing hypoxic stress employ epithelial-mesenchymal transition (EMT) to undergo metastasis through rewiring of the chromatin landscape, epigenetics, and importantly, gene expression. Here, we showed that hypoxia modulates the epigenetic landscape on CTCF promoter and upregulates its expression. Hypoxia-driven epigenetic regulation, specifically DNA demethylation mediated by TET2, is a prerequisite for CTCF induction. Mechanistically, in hypoxic conditions, Hypoxia-inducible factor 1-alpha (HIF1α) binds to the unmethylated CTCF promoter, causing transcriptional upregulation. Further, we uncover the pivotal role of CTCF in promoting EMT as loss of CTCF abrogated invasiveness of hypoxic breast cancer cells. These findings highlight the functional contribution of HIF1α-CTCF axis in promoting EMT in hypoxic breast cancer cells. Lastly, CTCF expression is alleviated and the potential for EMT is diminished when the HIF1α binding is particularly disrupted through the dCas9-DNMT3A system-mediated maintenance of DNA methylation on the CTCF promoter. This axis may offer a unique therapeutic target in breast cancer.

Small nuclear RNAs enhance protein-free RNA-programmable base conversion on mammalian coding transcripts.

Endogenous U small nuclear RNAs (U snRNAs) form RNA-protein complexes responsible for eukaryotic processing of pre-mRNA into mature mRNA. Previous studies have demonstrated the utility of guide-programmable U snRNAs in targeted exon inclusion and exclusion. We investigated whether snRNAs can also enhance conversion of RNA bases over state-of-the-art RNA targeting technologies in human cells. When compared to adenosine deaminase acting on RNA (ADAR)-recruiting circular RNAs, we find that guided A>I snRNAs consistently increase adenosine-to-inosine editing efficiency for genes with higher exon counts, perturb substantially fewer genes in the transcriptome, and localize more persistently to the nucleus where ADAR is expressed. A>I snRNAs can also edit pre-mRNA 3' splice sites to promote splicing changes. Finally, snRNA fusions to H/ACA box snoRNAs (U>Ψ snRNAs) increase targeted RNA pseudouridylation efficiency. Altogether, our results advance the protein-free RNA base conversion toolbox and enhance minimally invasive RNA targeting technologies to treat genetic diseases.

Social media influenced self-application of cyanoacrylate for double chin reduction in an adolescent girl: an unusual case of post-inflammatory hyperpigmentation.

Introduction: Cyanoacrylate, used as a topical adhesive for wound closure in clinical settings, can result in poor cosmetic outcome on application to skin. Lack of formal medical or dermatological training among social media influencers poses risks of improper diagnosis, incorrect treatments, ineffective home remedies, and potential self-injury or long-term skin effects, especially among adolescents. Case presentation: The authors present a case of a young girl with a persistent post-inflammatory hyperpigmentation after using cyanoacrylate on her chin as a home remedy to reduce her double chin problem after learning from a video on social media. Biopsy findings were consistent with post-inflammatory hyperpigmentation in dermis. Clinical discussion: Application of cyanoacrylate over skin can result in allergic reactions, burn injuries, infections, itching, skin blistering, and aesthetic issues. Persistent post-inflammatory hyperpigmentation can be a poor cosmetic outcome on application of cyanoacrylate over skin. Conclusion: Inadequate social media safety regulations require healthcare professionals to be aware of social trends among adolescents and to encourage them for open conversations and professional help-seeking during times of distress in this digital era.

Microbial electrosynthesis of acetate from CO2 in three-chamber cells with gas diffusion biocathode under moderate saline conditions.

The industrial adoption of microbial electrosynthesis (MES) is hindered by high overpotentials deriving from low electrolyte conductivity and inefficient cell designs. In this study, a mixed microbial consortium originating from an anaerobic digester operated under saline conditions (∼13 g L-1 NaCl) was adapted for acetate production from bicarbonate in galvanostatic (0.25 mA cm-2) H-type cells at 5, 10, 15, or 20 g L-1 NaCl concentration. The acetogenic communities were successfully enriched only at 5 and 10 g L-1 NaCl, revealing an inhibitory threshold of about 6 g L-1 Na+. The enriched planktonic communities were then used as inoculum for 3D printed, three-chamber cells equipped with a gas diffusion biocathode. The cells were fed with CO2 gas and operated galvanostatically (0.25 or 1.00 mA cm-2). The highest production rate of 55.4 g m-2 d-1 (0.89 g L-1 d-1), with 82.4% Coulombic efficiency, was obtained at 5 g L-1 NaCl concentration and 1 mA cm-2 applied current, achieving an average acetate production of 44.7 kg MWh-1. Scanning electron microscopy and 16S rRNA sequencing analysis confirmed the formation of a cathodic biofilm dominated by Acetobacterium sp. Finally, three 3D printed cells were hydraulically connected in series to simulate an MES stack, achieving three-fold production rates than with the single cell at 0.25 mA cm-2. This confirms that three-chamber MES cells are an efficient and scalable technology for CO2 bio-electro recycling to acetate and that moderate saline conditions (5 g L-1 NaCl) can help reduce their power demand while preserving the activity of acetogens.

Epigenetic Regulation During Hypoxia and Its Implications in Cancer.

Hypoxia is defined as a cellular stress condition caused by a decrease in oxygen below physiologically normal levels. Cells in the core of a rapidly growing solid tumor are faced with the challenge of inadequate supply of oxygen through the blood, owing to improper vasculature inside the tumor. This hypoxic microenvironment inside the tumor initiates a gene expression program that alters numerous signaling pathways, allowing the cancer cell to eventually evade adverse conditions and attain a more aggressive phenotype. A multitude of studies covering diverse aspects of gene regulation has tried to uncover the mechanisms involved in hypoxia-induced tumorigenesis. The role of epigenetics in executing widespread and dynamic changes in gene expression under hypoxia has been gaining an increasing amount of support in recent years. This chapter discusses, in detail, various epigenetic mechanisms driving the cellular response to hypoxia in cancer.

Sulphonated graphene catalyst incorporation with sludge enhanced the microbial activities for biomethanization of crude rice straw.

Biomethanization of crude rice straw (RS) was enhanced by a coupled effectiveness of sulphonated graphene (SGR) with sludge rich anaerobes (SRA). A reduction of 19.2 ± 1.32% for cellulose, 40.8 ± 3.7% for hemicellulose and 30.8 ± 2.4% for lignin was achieved with addition of SRA after fermentation of 60 days. The abundance of hydrolytic microbes in SRA i.e. Acidobacteria, Bacteroidetes, Chloroflexi and Proteobacteria caused RS structure liquefaction and dissolution. The reduction of cellulose, hemicellulose and lignin boosted to 92.3 ± 1.5, 84.9 ± 3.5 and 97.0 ± 1.8% respectively with SGR catalyst addition of 100 mg/gVS. Reducing sugars, phenols and volatile fatty acids (VFAs) were subsequently utilized by bacteria and archaea species of Methanosphaera, Methanocella, Candidatus Methanoregula, Methanolinea and Methanosaeta. The biogas yield was 92 ± 3.1 mL/gRS and methane content amounted to 68 ± 4.6% % at SGR catalyst of 80 mg/gVS. These findings show the potential of using SRA/SGR to improve the RS fermentation with a novel application for biogas productivity.

Unraveling the metabolic shift in anaerobic digestion pathways associated with the alteration of onion skin waste concentration.

Onion skin waste (OSW) is common waste in developing countries, which can cause severe environmental pollution when not properly treated. Value-added products can be chemically extracted from OSW; however, that process is not economically feasible. Alternatively, dry anaerobic digestion (DAD) of OSW is a promising approach for both energy recovery and environment protection. The main hurdles during DAD of OSW can be the hydrolysis and acidification. In batch tests, sludge digestate (SD) rich with methanogens was co-digested with different fractions of OSW for enhancing hydrolysis and raising biogas productivity. The cumulative biogas production (CBP) was 36.6 ± 0.3 mL for sole DAD of SD (100% SD) and increased up to 281.9 ± 14.1 mL for (50% SD: 50% OSW) batch. Self-delignification of OSW took place by SD addition, where the lignin removal reached 75.3 ± 10.5% for (85% SD: 15% OSW) batch. Increasing the fraction of OSW (45% SD: 55% OSW) reduced the delignification by a value of 68.8%, where initial lignin concentration was 9.48 ± 1.6% in dry weight. Lignin breaking down resulted a high fraction of phenolic compounds (345.6 ± 58.8 mg gallic acid equivalent/g dry weight) in the fermentation medium, causing CBP drop (219.0 ± 28.5 mL). The presence of elements (K, Ca, Mg, Fe, Zn, Mn, S and P) in OSW improved the enzymatic activity, facilitated phenolic compounds degradation, shifted the metabolism towards acetate fermentation pathway, and raised biogas productivity. Acidogenesis was less affected by phenolic compounds than methanogenesis, causing higher H2 contents and lower CH4 contents, at batches with high share of OSW.

ERK1/2-EGR1-SRSF10 Axis Mediated Alternative Splicing Plays a Critical Role in Head and Neck Cancer.

Aberrant alternative splicing is recognized to promote cancer pathogenesis, but the underlying mechanism is yet to be clear. Here, in this study, we report the frequent upregulation of SRSF10 (serine and arginine-rich splicing factor 10), a member of an expanded family of SR splicing factors, in the head and neck cancer (HNC) patients sample in comparison to paired normal tissues. We observed that SRSF10 plays a crucial role in HNC tumorigenesis by affecting the pro-death, pro-survical splice variants of BCL2L1 (BCL2 Like 1: BCLx: Apoptosis Regulator) and the two splice variants of PKM (Pyruvate kinase M), PKM1 normal isoform to PKM2 cancer-specific isoform. SRSF10 is a unique splicing factor with a similar domain organization to that of SR proteins but functions differently as it acts as a sequence-specific splicing activator in its phosphorylated form. Although a body of research studied the role of SRSF10 in the splicing process, the regulatory mechanisms underlying SRSF10 upregulation in the tumor are not very clear. In this study, we aim to dissect the pathway that regulates the SRSF10 upregulation in HNC. Our results uncover the role of transcription factor EGR1 (Early Growth Response1) in elevating the SRSF10 expression; EGR1 binds to the promoter of SRSF10 and promotes TET1 binding leading to the CpG demethylation (hydroxymethylation) in the adjacent position of the EGR1 binding motif, which thereby instigate SRSF10 expression in HNC. Interestingly we also observed that the EGR1 level is in the sink with the ERK1/2 pathway, and therefore, inhibition of the ERK1/2 pathway leads to the decreased EGR1 and SRSF10 expression level. Together, this is the first report to the best of our knowledge where we characterize the ERK 1/2-EGR1-SRSF10 axis regulating the cancer-specific splicing, which plays a critical role in HNC and could be a therapeutic target for better management of HNC patients.

Strengthen "the sustainable farm" concept via efficacious conversion of farm wastes into methane.

With escalating global demand for renewable energy, exploitation of farm wastes (i.e., agriculture straw wastes (ASWs), livestock wastewater (LW) and sewage sludge (SS)) has been considered to attain maximum methane yield (MY) via anaerobic digestion (AD). Results pointed that mixture of SS and LW as anaerobes' source with 20 g of ASWs/300 mL of working volume achieved maximum MY and volatile solid (VS) removal efficiency of 0.44 (±0.05) L/gVS and 51.4 (±4.1)%, respectively. This was mainly because of emerging heavy duty bacterial species (i.e., Syntrophorhabdaceae and Synergistaceae) and archaeal community (i.e, Methanosarcina and Methanoculleus) after 70 days of anaerobic incubation. This was acquired along with boosting enzymatic activity, especially xylanase, cellulase and protease up to 71.5(±7.9), 179.3(±14.3) and 207.2(±16.2) U/100 mL, respectively. Furthermore, the digestate contained high concentrations of NH4+ (960.1±(76.8) mg/L), phosphorus (126.3±(10.1) mg/L) and trace metals, making it a good candidate as organic fertilizer.

Phytochemical Investigations and In Vitro Bioactivity Screening on Melia azedarach L. Leaves Extract from Nepal.

Melia azedarach is a common tree used in the traditional medicine of Nepal. In this work, leaves were considered as source of bioactive constituents and composition of methanol extract was evaluated and compared with starting plant material. Flavonoid glycosides and limonoids were identified and quantified by HPLC-DAD-MSn approaches in dried leaves and methanolic extract, while HPLC-APCI-MSn and GC/MS analysis were used to study phytosterol and lipid compositions. ß-Sitosterol and rutin were the most abundant constituents. HPLC-APCI-MSn and HPLC-DAD-MSn analysis revealed high levels of phytosterols and flavonoids in methanolic extract accounting 9.6 and 7.5 % on the dried weight, respectively. On the other hand, HPLC/MSn data revealed that limonoid constituents were in minor amount in the extract <0.1 %, compared with leaves (0.7 %) indicating that degradation occurred during extraction or concentration procedures. The methanol extract was subjected to different bioassays, and antioxidant activity was evaluated. Limited inhibitory activity on acetyl and butyryl cholinesterase, as well as on amylase were detected. Moreover, tyrosinase inhibition was significant resulting in 131.57±0.51 mg kojic acid equivalents/g of dried methanol extract, suggesting possible use of this M. azedarach extract in skin hyperpigmentation conditions. Moderate cytotoxic activity, with IC50 of 26.4 µg/mL was observed against human ovarian cancer cell lines (2008 cells). Our findings indicate that the Nepalese M. azedarach leaves can be considered as valuable starting material for the extraction of phenolics and phytosterols, yielding extracts with possible cosmetic and pharmaceutical applications.

Phytochemical constituents, distributions and traditional usages of Arnebia euchroma: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The present study has indicated phytochemical composition, distribution and ethno-medicinal uses of Arnebia euchroma (Royle) I.M. Johnst, which is commonly known as "Ratanjot" in the Indian subcontinent. It has widely been used in the traditional systems of the Unani, Ayurvedic and Chinese medicines recipes due to its anti-fungal and anti-microbial properties. Instead, the gap of earlier studies is well defined that will be helpful for researchers to carry out more analysis and increase medicinal importance of this plant. AIM OF STUDY: The main aim of this review study is to demonstrate the phytochemical composition and traditional ethno-medicinal uses of A. euchroma all over the world. Earlier studies related to this plant have been discussed in the present study and on that basis, future perspective of A. euchroma is also proposed. MATERIALS AND METHODS: The information of A. euchroma has been gathered from various electronic database, reference books and available literature. RESULTS: The study has indicated that Arnebia euchroma owing to anti-microbial and anti-inflammatory properties is used in the traditional medicines and pharmaceutical industries for the treatment of hair problems, remitting, chronic diseases, burnt limbs, cough and cold, etc., and besides as a vegetable colorant and dyeing of cloths. The important phytochemical constituents viz., shikonin, acetyl-shikonin, iso-butyryl-shikonin, ß,ß-di-methylacryl-shikonin, isovaleryl-shikonin, ß-hydroxy-isovaleryl-shikonin, deoxy-shikonin, isobutyl-shikonin, arnebinone, arnebin-7, stigmasterol, etc., isolated from the roots of Arnebia euchroma are used for curing various harmful diseases. CONCLUSIONS: The earlier studies have confirmed that Arnebia euchroma is having wound healing, anti-microbial and anti-bacterial properties and thus used for the treatment of several diseases. Although, a little works is done on the experimental study regarding anti-HIV, anti-cancer diseases, etc., so there is a requirement of more exploration via analytical studies on phytochemical compounds to treat such diseases. Moreover, the information of its clinical and pharmacokinetics uses is also limited. Therefore, further research is needed to understand bioavailability and pharmacokinetics of this species. In-situ and ex-situ conservations for the management of this endangered species are also lacking in the Himalayan perspective. Such studies will emphasize to explore the possibilities for its conservation and development of agro-technological protocol.

A nickel oxide-decorated in situ grown 3-D graphitic forest engrained carbon foam electrode for microbial fuel cells.

A facile and single-step nickel oxide-dispersed in situ grown 3-D graphitic forest engrained carbon foam (NiO-CNF-CF)-based electrode was fabricated for high-performance microbial fuel cells (MFCs). The metal oxide, graphitic contents, biocompatibility, stability and large surface area available in the material for biofilm formation rendered the prepared electrode competent for wastewater treatment and bioenergy (0.79 V and 1.955 W m-2) generation with a coulombic efficiency of 85.66%.

Human health and snails.

Snails can provide a considerable variety of bioactive compounds for cosmetic and pharmaceutical industries, useful for the development of new formulations with less toxicity and post effects compared to regular compounds used for the purpose. Compounds from crude extract, mucus, slime consist of glycans, polypeptides, proteins, etc., and can be used for curing diseases like viral lesions, warts, and different dermal problems. Some particular uses of snails involve treating post-traumatic stress. Micro RNA of Lymnaea stagnalis, was known to be responsible for the development of long-term memory and treatment of Alzheimer's and Dementia like diseases. This review explores the application of various bioactive compounds from snails with its potential as new translational medicinal and cosmetic applications. Snail bioactive compounds like ω-MVIIA, µ-SIIIA, µO-MrVIB, Xen2174, δ-EVIA, α-Vc1.1, σ-GVIIA, Conantokin-G, and Contulakin-G, conopeptides can be used for the development of anti-cancer drugs. These compounds target the innate immunity and improve the defense system of humans and provide protection against these life-threatening health concerns.AbbreviationsFDA: Food and Drug Administration; UTI: urinal tract infection; nAChRs: nicotinic acetylcholine receptors; NMDA: N-methyl-D-aspartate; CNS: central nervous system; CAR T: chimeric antigen receptors therapy; Micro RNA: micro ribonucleic acid.

Hypoxia-induced TGF-ß-RBFOX2-ESRP1 axis regulates human MENA alternative splicing and promotes EMT in breast cancer.

Hypoxic microenvironment heralds epithelial-mesenchymal transition (EMT), invasion and metastasis in solid tumors. Deregulation of alternative splicing (AS) of several cancer-associated genes has been instrumental in hypoxia-induced EMT. Our study in breast cancer unveils a previously unreported mechanism underlying hypoxia-mediated AS of hMENA, a crucial cytoskeleton remodeler during EMT. We report that the hypoxia-driven depletion of splicing regulator ESRP1 leads to skipping of hMENA exon 11a producing a pro-metastatic isoform, hMENAΔ11a. The transcriptional repression of ESRP1 is mediated by SLUG, which gets stimulated via hypoxia-driven TGF-ß signaling. Interestingly, RBFOX2, an otherwise RNA-binding protein, is also found to transcriptionally repress ESRP1 while interacting with SLUG. Similar to SLUG, RBFOX2 gets upregulated under hypoxia via TGF-ß signaling. Notably, we found that the exosomal delivery of TGF-ß contributes to the elevation of TGF-ß signaling under hypoxia. Moreover, our results show that in addition to hMENA, hypoxia-induced TGF-ß signaling contributes to global changes in AS of genes associated with EMT. Overall, our findings reveal a new paradigm of hypoxia-driven AS regulation of hMENA and insinuate important implications in therapeutics targeting EMT.

Himalayan Nettle Girardinia diversifolia as a Candidate Ingredient for Pharmaceutical and Nutraceutical Applications-Phytochemical Analysis and In Vitro Bioassays.

Girardinia diversifolia, also known as Himalayan nettle, is a perennial herb used in Nepal to make fiber as well as in traditional medicine for the treatment of several diseases. To date, phytochemical studies and biological assays on this plant are scarce. Thus, in the present work, the G. diversifolia extracts have been evaluated for their potential pharmaceutical, cosmetic and nutraceutical uses. For this purpose, detailed phytochemical analyses were performed, evidencing the presence of phytosterols, fatty acids, carotenoids, polyphenols and saponins. The most abundant secondary metabolites were ß- and γ-sitosterol (11 and 9% dw, respectively), and trans syringin (0.5 mg/g) was the most abundant phenolic. Fatty acids with an abundant portion of unsaturated derivatives (linoleic and linolenic acid at 22.0 and 9.7 mg/g respectively), vitamin C (2.9 mg/g) and vitamin B2 (0.12 mg/g) were also present. The antioxidant activity was moderate while a significant ability to inhibit acetylcholinesterase (AChE), butyrilcholinesterase (BuChE), tyrosinase, α-amylase and α-glucosidase was observed. A cytotoxic effect was observed on human ovarian, pancreatic and hepatic cancer cell lines. The effect in hepatocarcinoma cells was associated to a downregulation of the low-density lipoprotein receptor (LDLR), a pivotal regulator of cellular cholesterol homeostasis. These data show the potential usefulness of this species for possible applications in pharmaceuticals, nutraceuticals and cosmetics.

Hypoxia-induced changes in intragenic DNA methylation correlate with alternative splicing in breast cancer.

The tumor microenvironment is marked by gradients in the level of oxygen and nutrients, with oxygen levels reaching a minimum at the core of the tumor, a condition known as tumor hypoxia. Mediated by members of the HIF family of transcription factors, hypoxia leads to a more aggressive tumor phenotype by transactivation of several genes as well as reprogramming of pre-mRNA splicing. Intragenic DNA methylation, which is known to affect alternative splicing in cancer, could be one of several reasons behind the changes in splicing patterns under hypoxia. Here, we have tried to establish a correlation between intragenicDNA methylation and alternative usage of exons in tumor hypoxia. First, we have generated a customhypoxia signature consisting of 34 genes that are upregulated under hypoxia and are direct targets of HIF-1α. Using this gene expression signature, we have successfully stratified publicly available breast cancer patient samples into hypoxia positive and hypoxia negative groups followed by mining of differentially spliced isoforms between these groups. The Hypoxia Hallmark signature from MSigDB was also used independently to stratify the same tumor samples into hypoxic and normoxic.We found that 821 genes were showing differential splicing between samples stratified using a custom signature, whereas, 911 genes were showing differential splicing between samples stratified using the MSigDB signature. Finally, we performed multiple correlation tests between the methylation levels (ß) of microarray probes located within 1 kilo base pairs of isoform-specific exons using those exons' expression levels in the same patient samples in which the methylation level was recorded. We found that the expression level of one of the exons ofDHX32 and BICD2 significantly correlated with the methylation levels, and we were also able to predict patient survival (p-value: 0.02 for DHX32 and 0.0024 for BICD2). Our findings provide new insights into the potential functional role of intragenic DNA methylation in modulating alternative splicing during hypoxia.

Carbonic anhydrase modification for carbon management.

Carbonic anhydrase modification (chemical and biological) is an attractive strategy for its diverse application to accelerate the absorption of CO2 from a flue gas with improved activity and stability. This article reports various possibilities of CA modification using metal-ligand homologous chemistry, cross-linking agents, and residue- and group-specific and genetic modifications, and assesses their role in carbon management. Chemically modified carbonic anhydrase is able to improve the absorption of carbon dioxide from a gas stream into mediation compounds with enhanced sequestration and mineral formation. Genetically modified CA polypeptide can also increase carbon dioxide conversion. Chemical modification of CA can be categorized in terms of (i) residue-specific modification (involves protein-ligand interaction in terms of substitution/addition) and group-specific modifications (based on the functional groups of the target CA). For every sustainable change, there should be no/limited toxic or immunological response. In this review, several CA modification pathways and biocompatibility rules are proposed as a theoretical support for emerging research in this area.

Phytochemical Fingerprinting and In Vitro Bioassays of the Ethnomedicinal Fern Tectaria coadunata (J. Smith) C. Christensen from Central Nepal.

Tectaria coadunata, an ethnomedicinal fern used in Nepal to treat a large number of diseases, has been poorly studied with regard to its phytochemical composition and possible bioactivity. This study was performed with the aim of supporting traditional medicine as a new source of bioactive constituents. Phytochemical compositions of methanol extracts were determined by nuclear magnetic resonance (NMR), liquid chromatography-diode array detector-mass spectrophotometry (LC-DAD-MS), and liquid chromatography-fluorescence-mass spectrometry. Quali-quantitative data revealed large amount of procyanidins, mainly of the A-type, as well as eriodictyol-7-O-glucuronide and luteolin-7-O-glucoronide as main constituents. The antioxidant, cytotoxic, and inhibitory activity of five enzymes that are implicated in human diseases was evaluated for the extract and fractions. High free-radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and inhibitory activities against cholinesterases and tyrosinase were observed. Furthermore, a moderate cytotoxic effect was observed on the 2008 and BxPC3 cell lines. Overall results showed potential usefulness of this fern as a source of phytochemicals for pharmaceutical uses.

LC-MSn and HR-MS characterization of secondary metabolites from Hypericum japonicum Thunb. ex Murray from Nepalese Himalayan region and assessment of cytotoxic effect and inhibition of NF-κB and AP-1 transcription factors in vitro.

Hypericum japonicum Thunb. ex Murray is traditionally used in Nepal to treat several diseases, among whom inflammation and acute pain. Although several secondary metabolites from the same Hypericum species have been already characterized and considered for their pharmacological use, an exhaustive phytochemical characterization of H. japonicum from Nepal is lacking, as well as the assessment of its potential pharmacological properties. Hence, the aims of this study were the characterization of a methanolic extract of H. japonicum (HJME) collected from the Northern region of Nepal by LC-MSn and UPLC-QTOF. The assessment of in vitro inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1) transcription factors and HJME's cytotoxic effect on human cell lines was performed to evaluate the potential use of this herb as a source of anti-inflammatory and cytotoxic lead compounds. Fifty-seven phytoconstituents were identified, being mainly flavonoids, phloroglucinols, phenolic acids and xanthones. Although compounds characteristic of H. japonicum were detected (quercetin, quercetin-7-O-α-l-rhamnoside, quercitrin and hyperoside), several others are here reported for the first time in this species. The results from bioassays indicated that HJME could significantly reduce the viability of human THP-1 cells (IC50 = 5.4 ±â€¯1.1 µg mL-1), showing the promising potential of HJME as anti-tumor agent. Furthermore, HJME significantly decreased the activation of both NF-κB and AP-1 at the concentration of 2 µg mL-1. Overall, these data suggest that H. japonicum from Nepal could be used as a source of potential natural anti-inflammatory and anti-tumor lead compounds.

Wheat straw extracted lignin in silver nanoparticles synthesis: Expanding its prophecy towards antineoplastic potency and hydrogen peroxide sensing ability.

Lignin, is the most abundant, renewable and degradable biopolymer available in the nature. The present study exploited purified lignin from wheat straw as reducing, capping and stabilizing agent for the green synthesis of silver nanoparticles (Li-AgNPs) under optimized conditions. The analytical studies revealed synthesized Li-AgNPs having a face centered cubic crystalline structure, size ranging ~15-20 nm and the biomolecules comprising majorly phenolic, hydroxyl and carboxylic group of lignin coated on the surface of AgNPs. Li-AgNPs showed significant antimicrobial efficacy against human pathogens namely; Staphylococcus aureus and Escherichia coli and also determined their minimum inhibitory and minimum bactericidal concentration (MIC and MBC). Li-AgNPs also displayed substantial antioxidant activity in terms of well-known enzyme marker viz.; ABTS and DPPH free radical scavenging assay relative to commercial AgNPs. In vitro cytotoxicity assay of Li-AgNPs demonstrated dose-dependent toxicity effects in SKOV3 ovarian cancer cell line (LD50; 150 µg/mL) indicative of promising anticancer agent. Further, H2O2 sensing ability of stabilized Li-AgNPs exhibited its vital role in determining reactive oxygen species. Synthesis of Li-AgNPs is a cheap green technology and could exhibit its commercial use in biomedical, cosmetic, and pharmaceutical industry.