OBJECTIVES:Lung cancer is one of the most common malignancies and the leading cause of cancer-related mortality worldwide, posing a major public health challenge. Flavonoids, a large and diverse group of plant metabolites, exhibit various anticancer properties, making them promising candidates for therapeutic applications. This study evaluated the anticancer efficacy of methoxy flavonoids and elucidated their underlying mechanisms of action in A549 lung cancer cells. METHODS:A549 cells were treated with various flavonoids (AKC1-AKC5), and their effects were analyzed using an MTT assay, DAPI staining, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, colony formation, and wound scratch tests. Molecular docking was also performed to confirm the binding of AKC1 and AKC3 to EGFR, BCL-2, and CDK-2 proteins. RESULTS:AKC1 and AKC3 prevented the growth of A549 lung cancer cells with IC50 of 64.57 and 19.80 μM among 5 methoxy flavonoids. AKC1 and AKC3 triggered notable alterations in the shape and reduced the colony-forming potential of A549 cells. The DAPI staining experiment demonstrated that AKC1 and AKC3 impede the growth of cancer cells through activation of apoptotic cell death. Moreover, the anticancer properties of AKC1 and AKC3 were attributed to significant inhibition of MMP and a notable ROS enhancement in a dose-related pattern. The wound scratch assay demonstrated that AKC1 and AKC3 suppressed A549 lung cancer cell migration, suggesting their anti-metastatic properties. Molecular docking studies confirmed that AKC-1 and AKC-3 bind strongly to EGFR, BCL-2, and CDK2, suggesting a multi-target mechanism that underlies their anti-proliferative and pro-apoptotic effects in A549 cells. CONCLUSIONS:AKC1 and AKC3 exhibited significant anticancer activity against A549 cells and may serve as promising therapeutic drugs for lung cancer treatment.

Since ancient times, herbal medicines have been the most significant type of medicine used in all societies. There have been numerous plants reports that plant extracts exhibit a variety of biological properties, including immunomodulator activity, hepatoprotective activity, antilipidemic activity, etc. Herbosomes are freshly developed herbal preparations that are absorbed more readily than traditional Phyto molecules or botanical extracts, producing improved bioavailability and effects. The integration of polyphenolic compounds into phospholipid-based self-assembled delivery systems, also referred to as Herbosomes, can improve the less oral bioavailability of these compounds. Numerous products, including those made from Ginkgo biloba, Silybum marianum, and Camellia sinensis, contain phytosomal drug delivery systems.

This review explores advancing and refining hydrogels derived from natural gums for heavy metal ion adsorption, focusing on their efficiency, capacity, and influencing parameters. The high adsorption capacity of these hydrogels, with values reaching up to 384.6 mg/g (Pb2+) and 203.7 mg/g (Cu2+), is linked to functional moieties like -COOH and -OH, which bind to metal ions through electrostatic interactions, exchange of ions, and coordination mechanisms. Adsorption efficiency is governed by conditions such as duration of contact, temperature, and pH. Temperature studies imply that adsorption occurs through an endothermic mechanism, with positive ΔH values and negative ΔG values, validating the spontaneity and efficiency of the process. Adsorption isotherms, including Langmuir and Freundlich models, have shown promising fits, with a high correlation coefficient (r2 > 0.9). The kinetic study reveals that the adsorption follows pseudo-second-order kinetics, implying a chemisorption mechanism. The occurrence of interfering ions (e.g., Na+, Ca2+) can reduce adsorption efficiency, but their impact is minimal at lower concentrations. Overall, gum-based hydrogels provide an eco-conscious and reliable approach for metal ion removal in aqueous solutions, showing potential for large-scale environmental applications. Further studies focusing on improving adsorption capacity and scalability are recommended to enhance their practical utility in wastewater treatment.

Artemisinin-based combination therapies recommended by WHO marks Artemisia annua as the only natural source of artemisinin fighting deadly disease, Malaria. In this study, we isolated two transcription factors, AaMYC2 and AaMYC2-LIKE, from A. annua and investigated their role in regulating artemisinin biosynthetic pathway. Our findings depict that both AaMYC2 and AaMYC2-LIKE are transcriptionally active and, when co-transformed in yeast cells, significantly enhance β-galactosidase activity in transactivation assays as compared to their individual transformations. Furthermore, Yeast two-hybrid (Y2H) and Biomolecular fluorescence complementation assays revealed AaMYC2 physically interacts with AaMYC2-LIKE in yeast cells and in the nucleus of onion epidermal cells respectively. Generation of transient transgenic over expression and co-expression lines of AaMYC2 and AaMYC2-LIKE resulted in elevated expression of artemisinin biosynthetic genes and trichome development genes in co-expression lines as compared to individual transgenic lines and wildtype. Importantly, the glandular trichome density and artemisinin content was also significantly higher in co-transformed transgenic lines compared to individual AaMYC2 and AMYC2-LIKE transgenic lines. Conversely, artemisinin content was markedly reduced in AaMYC2-RNAi lines, underscoring the critical role of functional AaMYC2 in synergistic regulation with AaMYC2-LIKE. Altogether the above studies provide valuable insights into the regulatory networks of MYC type bHLH transcription factors in controlling economically and medically important pathway in A. annua.

Cellulose-based hydrogels have garnered significant interest in antimicrobial applications due to their exceptional biocompatibility, biodegradability, and superior mechanical properties. This in-depth investigation explores the various mechanisms and innovative strategies employed by cellulose-based hydrogels to exhibit remarkable antimicrobial activity. Our review aims to provide significant insights into utilizing the full potential of cellulose sources, cross-linking moieties, and polymerization processes on the structure, porosity, and mechanical properties of hydrogels by highlighting the major features and recent advancements in this developing sector. Additionally, we examine alternative functionalization methods for enhancing antimicrobial efficacy, such as incorporating antimicrobial moieties and surface modification. Understanding the mechanisms of action that disrupt microbial cell membranes and cell walls is crucial for comprehending their antimicrobial efficacy. Moreover, we assess the antimicrobial action of these hydrogels against various pathogens, including fungi and bacteria. Finally, we address recent achievements and future goals in this field, emphasizing the importance of continued research and collaboration. This demonstrates the potential of cellulose-based hydrogels as potent weapons in the battle against antimicrobial resistance.

Background: In the expanding field of cancer research, antimutagenic studies hold a promising ground. In recent times these studies have shown a shift towards the diverse flora of nature and its potential to treat cancer. Genus Morina has been extensively used in Chinese, Tibetan, and Indian traditional medicine to cure numerous diseases. The plant Morina coulteriana has been traditionally used to cure eye diseases. Nevertheless, it has been explored for the first time for its antimutagenic/antigenotoxic potential and phytochemical profile. Purpose: The present study aimed to determine the antimutagenic/antigenotoxic potential of Morina coulteriana and the bioassay-guided identification of its bioactive constituents. Methods: The methanol crude extract and its subsequent fractions were tested for antimutagenic/antigenotoxic activity in vitro (Ames assay) and in vivo (Chromosomal aberration assay in Balb/c mice). The active (ethyl acetate) fraction was further investigated to isolate and identify its bioactive compounds utilizing chromatographic purification and detailed spectroscopic techniques respectively. Results: The results revealed that the plant and its fractions were neither mutagenic nor toxic. The ethyl acetate fraction showed significant antimutagenic/antigenotoxic activity (66.13 %) in vitro and (88.15 %) in vivo. Further, four identified major compounds which were also tested in vitro. Our results revealed that the plant is a potent antimutagen. It worked in a dose-dependent manner and its administration decreased the mutagenic load on the cells both in vitro and in vivo experiments. The 2 isolated compounds viz.; 4hydroxyacetophenone, a phenol and picein, a phenolic glycoside were reported for the first time from the genus Morina. Conclusion: The findings of the present investigation clearly show that the plant M. coulteriana Royle has a strong antimutagenic potential. Its administration decreased the mutagenic load on the cells both in vitro and in vivo experiments Thus the present study provides a platform for the exploration of new plants with potential antimutagenic properties.

Artemisinin-based combinational therapies (ACTs) constitute the first line of malaria treatment. However, due to its trichome-specific biosynthesis, low concentration, and poor understanding of regulatory mechanisms involved in artemisinin biosynthesis and trichome development, it becomes very difficult to meet the increased demand for ACTs. Here, we have reported that a bHLH transcription factor, AaMYC2-type, plays an important role in regulating GST development and artemisinin biosynthesis in Artemisia annua. AaMYC2-type encodes a protein that is transcriptionally active and localised to the nucleus. It is prominently expressed in aerial parts like leaves, stems, inflorescence and least expressed in roots. AaMYC2-type expression is significantly increased under different hormonal treatments. In transgenic overexpression lines, AaMYC2-type OE, a significant increase in the expression of trichome development and artemisinin biosynthesis genes was observed. While in knockdown lines, Aamyc2-type, expression of trichome development and artemisinin biosynthesis genes were significantly reduced. Yeast one-hybrid assay clearly shows that the AaMYC2-type directly binds to the E-boxes in the promoter regions of ADS and CYP71AVI. The SEM microscopy depicted the number of trichomes elevated from 11 mm-2 in AaMYC2-type OE lines to 6.1 mm-2 in Aamyc2-type. The final effect of the alteration in biosynthetic and trichome developmental genes was observed in the accumulation of artemisinin. In the AaMYC2-type OE, the artemisinin content was 12 mg g-1DW, which was reduced to 3.2 mg g-1DW in the Aamyc2-type. Altogether, the above findings suggest that the AaMYC2-type play a dual regulating role in controlling both trichome developmental and artemisinin biosynthetic genes.

The leaves of Artemisia annua contain GSTs (Glandular secretory trichomes) that can secrete and store artemisinin, the drug most effective for treating uncomplicated malaria. Therefore, increasing the density of GSTs in A. annua is an efficient way to enhance artemisinin content. However, our understanding of how GSTs develop still needs to be improved. Here, we isolated an A. annua homolog of AtGL3 (GLABRA3), known as AaGL3-like, that positively regulates trichome density in A. annua. AaGL3-like is nuclear-localized and transcriptionally active. It is least expressed in roots and most prominently in aerial components like leaves, stems, and inflorescence. Under JA and GA hormonal treatments, AaGL3-like expression is significantly increased. In transgenic over-expression AaGL3-like lines, trichome developmental genes such as AaHD1 and AaGSW2 showed much increased expression. The AaGL3RNAi line exhibited considerably lower levels of AaHD1 and AaGSW2 transcripts. As a result, the AaGL3-RNAi lines showed reduced levels of artemisinin content and trichome density compared to wild-type and overexpression lines. Additionally, we have found that when co-expressed with AaJAZ8, the induction of trichome developmental genes was reduced as compared to individual OEAaGL3-like lines. Further, AaJAZ8 directly binds to AaGL3-like in the Y2H assay. These findings suggest that AaGL3-like is a jasmonate-induced bHLH transcription factor that drastically increases the final accumulation of artemisinin content by regulating trichome density in A. annua.

Cancer is a fatal condition brought on by unchecked cellular growth. One of the gravest dangers to people worldwide is this. Both the incidence and mortality of cancer are rising. With their great benefits, particularly in the treatment of cancer, nanoparticles have revolutionized the globe. Conventional chemotherapy used to be the main treatment option for patients. Chemotherapeutics, however, also have several pharmacological drawbacks, including drug resistance, drug-drug interactions, water solubility, and stability. Reciprocally, dose-limiting toxicity is important, with non-specific toxicity to healthy cells, appetite loss, hair loss, peripheral neuropathy, vomiting, fatigued muscles, and diarrheal being the usual side effects. Drug delivery systems employ nanocarriers such as gold nanoparticles, high-density lipoprotein nanostructures, polymer nanoparticles, dendrimers, quantum dots, and nanodiamonds. Keywords: Nanotechnology, Cancer, Drug delivery

Overexpression of Artemisia annua jasmonic acid carboxyl methyltransferase (AaJMT) leads to enhanced artemisinin content in Artemisia annua. Artemisinin-based combination therapies remain the sole deterrent against deadly disease malaria and Artemisia annua remains the only natural producer of artemisinin. In this study, the 1101 bp gene S-adenosyl-l-methionine (SAM): Artemisia annua jasmonic acid carboxyl methyltransferase (AaJMT), was characterised from A. annua, which converts jasmonic acid (JA) to methyl jasmonate (MeJA). From phylogenetic analysis, we confirmed that AaJMT shares a common ancestor with Arabidopsis thaliana, Eutrema japonica and has a close homology with JMT of Camellia sinensis. Further, the Clustal Omega depicted that the conserved motif I, motif III and motif SSSS (serine) required to bind SAM and JA, respectively, are present in AaJMT. The relative expression of AaJMT was induced by wounding, MeJA and salicylic acid (SA) treatments. Additionally, we found that the recombinant AaJMT protein catalyses the synthesis of MeJA from JA with a Km value of 37.16 µM. Moreover, site-directed mutagenesis of serine-151 in motif SSSS to tyrosine, asparagine-10 to threonine and glutamine-25 to histidine abolished the enzyme activity of AaJMT, thus indicating their determining role in JA substrate binding. The GC–MS analysis validated that mutant proteins of AaJMT were unable to convert JA into MeJA. Finally, the artemisinin biosynthetic and trichome developmental genes were upregulated in AaJMT overexpression transgenic lines, which in turn increased the artemisinin content.

A spike in the emergence of several viruses is observed in the modern era, including the present SARS-CoV2 virus. The continuous emergence of new viral strains and growing resistance to the existing antiviral drugs urge new drug targets and novel antiviral candidates against them. Host genes utilized by the viruses for their proliferation, also known as host factors, have surfaced as a new antiviral strategy. If affordable to the host cells, targeting the host factors may prove beneficial in controlling viral infection. Host factors play an essential function in the viral life cycle, and modulating their functions would thus impact viral replication. Often, the interacting interfaces between the host and the viral proteins aim at antiviral interventions. This aspect of antiviral drug development is in its inception phase. However, with the advancement in molecular techniques identifying various viral host factors, this field is believed to have immense potential as an antiviral drug targeting strategy. This chapter briefly describes the host proteins' implication in viral biology and how they can be exploited to treat viral diseases.<br>

The concept of nation cannot be described merely on empirical or subjective grounds. However, nations are trapped in a temporal paradox. Nation as an abstract concept has captured people's imagination and awareness to such an extent that it has become reified in modern times. In transitional cultures such as India, it has become an identity identifier, a cause of exclusion, a forum for the spread of prejudice, distrust, and justification for violence. So, what exactly is a nation? Is it just a marriage of persons of the same race, religion, and language? The primary topic of this article is whether the nation as a notion is essentially universal and a force of integration, or if it is parochial and resulting in schism! This study seeks solutions by exploring the viewpoints of two thinkers: Ernest Renan and Emile Durkheim.

This study aimed to determine the potential of quercetin and Zingiber officinale (ZO) Roscoe extract to alleviate the renal damage induced by dimethoate (DM) and fluoride (F-) alone and by their combined exposure in rats. A total of 54 adult Wistar rats were randomly allocated to nine groups (n = 6). A sub-lethal dose of DM (1/10th of the median lethal dose) was administered by oral gavage alone and along with F- (4.5 ppm, three-fold the permissible limit) in their drinking water continuously for 28 days. Chromatographical analysis revealed the presence of quercetin, curcumin, and other phytochemicals with strong antioxidant properties in ZO-rhizome extract. Severe changes were observed in the levels of the renal biomarkers and histoarchitecture after co-administration of the toxicants, indicating greater kidney damage. The administration of ZO extract (300 mg/kg) along with either or both toxicants led to a significant restoration of the biochemical markers and renal antioxidant profile and histology.

The unique physiology of tumors limits the efficacy ofchemotherapeutics.In efforts to improve the effectiveness of the existing chemotherapydrugs, nanomedicine emerged as a new hope but proved inadequate dueto the transport barriers present within the tumor tissues, whichlimits the potential of nanomedicine. Dense collagen networks in fibrotictissues contribute to hindering the penetration of molecular- or nano-scalemedicine through tumor interstitium. In the present study, human serumalbumin (HSA)-based nanoparticles (NPs) were developed for gemcitabine(GEM) and losartan (LST), which could offer secreted protein acidsrich in cysteine (SPARC) and enhanced permeability and retention effect(EPR)-mediated drug accumulation in tumors. Also, the tumor microenvironment(TME) modulation approach using LST was coupled to investigate theimpact on antitumor efficacy. GEM-HSA NPs and LST-HSA NPs were preparedby the desolvation-cross-linking method and characterized for size,potential, morphology, drug loading, drug-polymer interactions,and hemocompatibility. For investigating the efficacy of preparedNPs, cytotoxicity and mechanisms of cell death were elucidated invitro by using various assays. Intracellular uptake studies of preparedHSA NPs indicated their uptake and cytoplasmic localization. Furthermore,in vivo studies demonstrated significantly improved anticancer efficacyof GEM-HSA NPs in combination with LST pretreatment. Extended LSTtreatment further improved the anticancer potential. It was shownthat the improved efficacy of the nanomedicine was correlated withthe reduced thrombospondin-1 (TSP-1) and collagen level in tumor tissueupon LST pretreatment. Moreover, this approach exhibited augmentednanomedicine accumulation in the tumor, and hematological, biochemical,and tissue histology indicated the safety profile of this combinationregimen. Concisely, the undertaken study demonstrated the potentialof the triple targeting (SPARC, EPR, TME modulation) approach foraugmented efficacy of chemotherapeutics.

The wonder drug artemisinin, a sesquiterpene lactone endoperoxide from Artemisia annua is the million-dollar molecule required to curb the deadliest disease, Malaria. One of the major challenges even today is to increase the concentration of artemisinin within plants. The transcription factors are important regulators of plant secondary metabolites and have the potential to regulate key steps or the whole biosynthetic pathway. In this study, we have identified and characterised two bHLH transcription factors (Aa6119 and Aa7162) from A. annua. Both the transcription factors turned out to be transcriptionally active and nuclear-localised typical bHLH proteins. In our study, we found that Aa6119 specifically binds to the E-box element present on the promoter of artemisinin biosynthetic gene, AMORPHA-4,11-DIENE SYNTHASE (ADS). The protein-DNA interaction confirmed by Yeast one-hybrid assay was specific as Aa6119 was unable to bind to the mutated E-boxes of ADS. Further, Aa6119 interacted physically with Aa7162, which was confirmed in vitro by Yeast two-hybrid assay and in vivo by Bimolecular Fluorescent complementation assay. Our quantitative expression studies have confirmed that Aa6119 and Aa7162 act synergistically in the regulation of artemisinin biosynthetic and trichome developmental genes. The higher accumulation of artemisinin content in the transient co-transformed transgenic plants than in the individual over-expression transgenic plants has further validated that Aa6119 and Aa7162 act positively and synergistically to regulate artemisinin accumulation.

This study makes an attempt to queer Indian sociology. Queering encompasses the viewpoints of individuals who do not conform or do not desire to adhere to the heterosexual or hetero-gender thinking, or both. Non-conformity to established gender and sexual norms in a particular culture has significant implications for non-conforming individuals, which can range from physical assault to various exclusions, stigma, and marginalisation. Since the early 1990s, activists in India have been mobilising against unfairness, stigma, and abuses suffered by the sexually marginalised. Popularly termed as the LGBTQI movement or movements of "sexual minorities," these mobilizations across South Asia have brought to light numerous unpleasant and hazardous trajectories that comprise the very existence of these sexually marginalised people.

A fast and efficient method for synthesising ipomone (4), a bicyclo[3.2.1]octanone containing aromatised derivative, from gibberellic acid (1) has been developed using molecular iodine as a mild and effective mediator under heating conditions in a single step. Evidence was obtained that the reaction simultaneously proceeds through aromatisation and pinacol-pinacolone type 1,2-alkyl shift. Use of excess iodine afforded iodomethyl derivative (5) that could serve as starting material for the synthesis of additional analogs.

Background: Cryptosporidiosis caused by Cryptosporidium spp. is a zoonotic disease and is the most prevalent pathogens worldwide and leads to severe diarrhoeal diseases and affects the immunological status of the individual. Thus, the study was undertaken to examine the anti-cryptosporidial efficacy of curcumin in comparison with ethanolic extract of curcuma longa in immunocompromised mice infected with oocysts isolated from cattle calves of Jammu region and identified as Cryptosporidium parvum using nested PCR on small subunit ribosomal ribonucleic acid (SSU rRNA) gene. Methods: Two hundred female Swiss albino mice were equally divided into ten groups. Group I were kept as a healthy control, group II were immunocompromised, group III were immunocompromised and infected, group IV animals were immunocompromised, infected and treated orally with nitazoxanide. Animals in groups V to VII were immunocompromised, infected and treated with ethanolic extract of C. longa @ 4, 6 and 8 mg/kg/day/os respectively whereas groups VIII to X were immunocompromised, infected and treated with pure salt of curcumin @ 4, 6 and 8 mg/kg/day/os respectively for 5 successive days. Thus, mean oocysts per gram faeces, body weight gain and histopathological changes were measured in different groups. Result: Administration of curcumin as a therapeutic agent @ 8 mg/kg body weight for five days resulted in higher percent mean oocyst reduction of 74.03% and improved body weight gain in experimentally infected mice. Histopathological changes showed that treatment with oral curcumin (group X) in animals had minimal and improved intestinal lesions as compared to animals treated with C. longa (group VII). Altogether, curcumin showed promising anticryptosporidial effects under in vivo conditions and deserves further exploration.

One of the biggest global causes of death is cancer. The side effects of currently available therapies have triggered the search for new drugs. The marine environment, with its vast biodiversity, including sponges, is a rich source of natural products with immense pharmaceutical potential. The aim of the study was to analyze the microbes associated with the marine sponge, Lamellodysidea herbacea, and explore them as resources for anticancer ability. This study includes the isolation of fungi from L. herbacea, and their evaluation for cytotoxic potential against human cancer cell lines such as A-549 (lung), HCT-116 (colorectal carcinoma), HT-1080 (Fibrosarcoma), and PC-3 (prostate) using MTT assay. This revealed that fifteen extracts showed significant anticancer ability (IC50 ≤ 20 µg/mL), at least against one of the cell lines. Three extracts, SPG12, SPG19, and SDHY 01/02, were found significant in terms of anticancer activity, at least against three to four cell lines (IC50 values ≤ 20 µg/mL). The fungus SDHY01/02 was identified by sequencing the internal transcribed spacer (ITS) region as Alternaria alternata. Its extract showed IC50 values < 10 µg/mL against all the tested cell lines and was further analysed through light and fluorescence microscopy. The extract of SDHY01/02 was active (lowest IC50 4.27 µg/mL) against A549 cells in a dose-dependent manner and caused apoptotic cell death. Further, the extract was fractionated and analyzed the constituents by GC-MS (Gas Chromatography-Mass Spectrometry). Di-ethyl ether fraction revealed the constituents (having anticancer activity) such pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl); 4,5,6,7-tetrahydro-benzo[C]rhiophene-1-carboxylic acid cyclopropylamide; 17-pentatriacontene; 9,12-octadecadienoic acid (Z, Z)-, methyl ester; while DCM fraction contained Oleic acid, eicosyl ester. This is the first report of A. alternata with anticancer potential that has been isolated from the sponge L. herbacea, as far as we are aware.This A. alternata can be exploited to get anticancer molecule(s) in the future.

Coleus barbatus is a medicinal herb belonging to Lamiaceae. It is the only living organism known to produce forskolin, which is a labdane diterpene and is reported to activate adenylate cyclase. Microbes associated with plants play an important role in maintaining plant health. Recently, the targeted application of beneficial plant-associated microbes and their combinations in abiotic and biotic stress tolerance has gained momentum. In this work, we carried out the rhizosphere metagenome sequencing of C. barbatus at different developmental stages to understand how rhizosphere microflora are affected by and affect the metabolite content in plants. We found that the Kaistobacter genus was abundantly present in the rhizosphere of C. barbatus and its accumulation pattern appears to correlate with the quantities of forskolin in the roots at different developmental stages. Members of the Phoma genus, known for several pathogenic species, were in lower numbers in the C. barbatus rhizosphere in comparison with C. blumei. To our knowledge, this is the first metagenomic study of the rhizospheric microbiome of C. barbatus, which may help to explore and exploit the culturable and non-culturable microbial diversity present in the rhizosphere.