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is an important medicinal plant and a spice in Asia. Curcumin (diferuloylmethane) is a hydrophobic bioactive ingredient found in a rhizome of the . It has drawn immense attention in recent years for its variety of biological and pharmacological action. However, its low water solubility, poor bioavailability, and rapid metabolism represent major drawbacks for its successful therapeutic applications. Hence, researchers have attempted to enhance the biological and pharmacological activity of curcumin and overcome its drawbacks by efficient delivery systems, particularly nanoencapsulation. Research efforts so far and data from the available literature have shown a satisfactory potential of nanorange formulations of curcumin (Nanocurcumin), it increases all the biological and pharmacological benefits of curcumin, which was not significantly possible earlier. For the synthesis of nanocurcumin, an array of techniques has been developed and each technique has its own advantages and individual characteristics. The two most popular and effective techniques are ionic gelation and antisolvent precipitation. So far, many curcumin nanoformulations have been developed to enhance curcumin delivery, thereby overcoming the low therapeutic effects. However, most of the nanoformulation of curcumin remained at the concept level evidence, thus, several questions and challenges still exist to recommend the nanocurcumin as a promising candidate for therapeutic applications. In this review, we discuss the different curcumin nanoformulation and nanocurcumin implications for different therapeutic applications as well as the status of ongoing clinical trials and patents. We also discuss the research gap and future research directions needed to propose curcumin as a promising therapeutic candidate.

Integrins are components of cell-matrix adhesions, and function as scaffolds for various signal transduction pathways. So far no lipid ligand for integrin has been reported. Here we show that a lipid, oxysterol 25-hydroxycholesterol (25HC), directly binds to α5β1 and αvβ3 integrins to activate integrin-focal adhesion kinase (FAK) signaling. Treatment of macrophages and epithelial cells with 25HC results in an increase in activated αvβ3 integrin in podosome and focal adhesion matrix adhesion sites. Moreover, activation of pattern recognition receptor on macrophages induces secretion of 25HC, triggering integrin signaling and the production of proinflammatory cytokines such as TNF and IL-6. Thus, the lipid molecule 25HC is a physiologically relevant activator of integrins and is involved in positively regulating proinflammatory responses. Our data suggest that extracellular 25HC links innate immune inflammatory response with integrin signaling. Integrins are key modulators of cell adhesion and signaling. Here the authors show, unexpectedly, that a complex of integrins and the lipid 25-hydroxycholesterol induces FAK activation and proinflammatory cytokine production, thereby serving as an integral part of innate immunity regulation.

Mung bean, a legume, is sensitive to abiotic stresses at different growth stages, and its yield potential is affected by drought and high-temperature stress at the sensitive stage. Melatonin is a multifunctional hormone that plays a vital role in plant stress defense mechanisms. This study aimed to evaluate the efficiency of melatonin under individual and combined drought and high-temperature stress in mung bean. An experiment was laid out with five treatments, including an exogenous application of 100 µM melatonin as a seed treatment, foliar spray, and a combination of both seed treatment and foliar spray, as well as absolute control (ambient condition) and control (stress without melatonin treatment). Stresses were imposed during the mung bean’s reproductive stage (31–40 DAS) for ten days. Results revealed that drought and high-temperature stress significantly decreased chlorophyll index, Fv/Fm ratio, photosynthetic rate, stomatal conductance, and transpiration rate through increased reactive oxygen species (ROS) production. Foliar application of melatonin at 100 µM concentration enhanced the activity of antioxidant enzymes such as superoxide dismutase, catalase, and ascorbate peroxidase and the concentration of metabolites involved in osmoregulation and ion homeostasis; thereby, it improves physiological and yield-related traits in mung bean under individual and combined stress at the reproductive stage.

The genus Vigna (Fabaceae) consists of five subgenera, and includes more than 100 wild species. In Vigna, 10 crops have been domesticated from three subgenera, Vigna, Plectrotropis, and Ceratotropis. The habitats of wild Vigna species are so diverse that their genomes could harbor various genes responsible for environmental stress adaptation, which could lead to innovations in agriculture. Since some of the gene bank Vigna accessions were unidentified and they seemed to be novel genetic resources, these accessions were identified based on morphological traits. The phylogenetic positions were estimated based on the DNA sequences of nuclear rDNA-ITS and chloroplast atpB-rbcL spacer regions. Based on the results, the potential usefulness of the recently described species V. indica and V. sahyadriana, and some wild Vigna species, i.e., V. aconitifolia, V. dalzelliana, V. khandalensis, V. marina var. oblonga, and V. vexillata, was discussed.

Maize ( Zea mays L.) is the leading cereal crop and staple food in many parts of the world. This study aims to develop nutrient-rich maize genotypes by incorporating crtRB1 and o2 genes associated with increased β-carotene, lysine, and tryptophan levels. UMI1200 and UMI1230, high quality maize inbreds, are well-adapted to tropical and semi-arid regions in India. However, they are deficient in β-carotene, lysine, and tryptophan. We used the concurrent stepwise transfer of genes by marker-assisted backcross breeding (MABB) scheme to introgress crtRB1 and o2 genes. In each generation (from F 1 , BC 1 F 1 –BC 3 F 1 , and ICF 1 –ICF 3 ), foreground and background selections were carried out using gene-linked ( crtRB1 3′TE and umc1066) and genome-wide simple sequence repeats (SSR) markers. Four independent BC 3 F 1 lines of UMI1200 × CE477 (Cross-1), UMI1200 × VQL1 (Cross-2), UMI1230 × CE477 (Cross-3), and UMI1230 × VQL1 (Cross-4) having crtRB1 and o2 genes and 87.45–88.41% of recurrent parent genome recovery (RPGR) were intercrossed to generate the ICF 1 -ICF 3 generations. Further, these gene pyramided lines were examined for agronomic performance and the β-carotene, lysine, and tryptophan contents. Six ICF 3 lines (DBT-IC-β 1 σ 4 -4-8-8, DBT-IC-β 1 σ 4 -9-21-21, DBT-IC-β 1 σ 4 -10-1-1, DBT-IC-β 2 σ 5 -9-51-51, DBT-IC-β 2 σ 5 -9-52-52 and DBT-IC-β 2 σ 5 -9-53-53) possessing crtRB1 and o2 genes showed better agronomic performance (77.78–99.31% for DBT-IC-β 1 σ 4 population and 85.71–99.51% for DBT-IC-β 2 σ 5 population) like the recurrent parents and β-carotene (14.21–14.35 μg/g for DBT-IC-β 1 σ 4 and 13.28–13.62 μg/g for DBT-IC-β 2 σ 5 ), lysine (0.31–0.33% for DBT-IC-β 1 σ 4 and 0.31–0.34% for DBT-IC-β 2 σ 5 ), and tryptophan (0.079–0.082% for DBT-IC-β 1 σ 4 and 0.078–0.083% for DBT-IC-β 2 σ 5 ) levels on par with that of the donor parents. In the future, these improved lines could be developed as a cultivar for various agro-climatic zones and also as good genetic materials for maize nutritional breeding programs.

The African trypanosome Trypanosoma brucei, which persists within the bloodstream of the mammalian host, has evolved potent mechanisms for immune evasion. Specifically, antigenic variation of the variant-specific surface glycoprotein (VSG) and a highly active endocytosis and recycling of the surface coat efficiently delay killing mediated by anti-VSG antibodies. Consequently, conventional VSG-specific intact immunoglobulins are non-trypanocidal in the absence of complement. In sharp contrast, monovalent antigen-binding fragments, including 15 kDa nanobodies (Nb) derived from camelid heavy-chain antibodies (HCAbs) recognizing variant-specific VSG epitopes, efficiently lyse trypanosomes both in vitro and in vivo. This Nb-mediated lysis is preceded by very rapid immobilisation of the parasites, massive enlargement of the flagellar pocket and major blockade of endocytosis. This is accompanied by severe metabolic perturbations reflected by reduced intracellular ATP-levels and loss of mitochondrial membrane potential, culminating in cell death. Modification of anti-VSG Nbs through site-directed mutagenesis and by reconstitution into HCAbs, combined with unveiling of trypanolytic activity from intact immunoglobulins by papain proteolysis, demonstrates that the trypanolytic activity of Nbs and Fabs requires low molecular weight, monovalency and high affinity. We propose that the generation of low molecular weight VSG-specific trypanolytic nanobodies that impede endocytosis offers a new opportunity for developing novel trypanosomiasis therapeutics. In addition, these data suggest that the antigen-binding domain of an anti-microbial antibody harbours biological functionality that is latent in the intact immunoglobulin and is revealed only upon release of the antigen-binding fragment.

Cowpea ( Vigna unguiculata (L.) Walp) is one of the major food legume crops grown extensively in arid and semi-arid regions of the world. The determinate habit of cowpea has many advantages over the indeterminate and is well adapted to modern farming systems. Mutation breeding is an active research area to develop the determinate habit of cowpea. The present study aimed to develop new determinate habit mutants with terminal flowering (TFL) in locally well-adapted genetic backgrounds. Consequently, the seeds of popular cowpea cv P152 were irradiated with doses of gamma rays (200, 250, and, 300 Gy), and the M 1 populations were grown. The M 2 populations were produced from the M 1 progenies and selected determinate mutants (TFLCM-1 and TFLCM-2) from the M 2 generation (200 Gy) were forwarded up to the M 5 generation to characterize the mutants and simultaneously they were crossed with P152 to develop a MutMap population. In the M5 generation, determinate mutants (80–81 days) were characterized by evaluating the TFL growth habit, longer peduncles (30.75–31.45 cm), erect pods (160°- 200°), number of pods per cluster (4–5 nos.), and early maturity. Further, sequencing analysis of the VuTFL1 gene in the determinate mutants and MutMap population revealed a single nucleotide transversion (A-T at 1196 bp) in the fourth exon and asparagine (N) to tyrosine (Y) amino acid change at the 143 rd position of phosphatidylethanolamine-binding protein (PEBP). Notably, the loss of function PEPB with a higher confidence level modification of anti-parallel beta-sheets and destabilization of the protein secondary structure was observed in the mutant lines. Quantitative real-time PCR (qRT-PCR) analysis showed that the VuTFL1 gene was downregulated at the flowering stage in TFL mutants. Collectively, the insights garnered from this study affirm the effectiveness of induced mutation in modifying the plant’s ideotype. The TFL mutants developed during this investigation have the potential to serve as a valuable resource for fostering determinate traits in future cowpea breeding programs and pave the way for mechanical harvesting.

Yellow Mosaic Disease (YMD) caused by mungbean yellow mosaic virus (MYMV, begomovirus) is one of the main causes of low mungbean (Vigna radiata L.) productivity, primarily in South Asia. Agroinoculation screening for MYMV resistance in mungbean cultivar VGGRU 1, an interspecific derivative of mungbean × rice bean and VRM (Gg)1 across replications, revealed VGGRU1 as highly resistant to MYMV infection. Gas chromatography mass spectrometry analysis was performed on the methanolic leaf extracts of susceptible and resistant genotypes, along with necessary controls. The metabolite profiling of the susceptible and resistant genotypes, along with controls, identified 121 discriminant metabolites belonging to 24 different classes of metabolites. A maximum number of 27 metabolites were accumulated in agroinoculated VGGRU1 alone. Metabolite profiles of VGGRU1 and VRM1 were clustered hierarchically and revealed substantial variations between the genotypes. Fold change revealed the upregulation of amino acids and phenol in the resistant genotype. The resistant genotype, VGGRU1, showed significantly higher levels of key defense-related metabolites, such as amino acids and phenolics. In this study, 18 significant VIP metabolites were identified, differentiating the resistant VGGRU1 and susceptible VRM (Gg)1 genotypes.

A growing body of evidence suggests that oxysterols such as 25-hydroxycholesterol (25HC) are biologically active and involved in many physiological and pathological processes. Our previous study demonstrated that 25HC induces an innate immune response during viral infections by activating the integrin-focal adhesion kinase (FAK) pathway. 25HC produced the proinflammatory response by binding directly to integrins at a novel binding site (site II) and triggering the production of proinflammatory mediators such as tumor necrosis factor-α (TNF) and interleukin-6 (IL-6). 24-(S)-hydroxycholesterol (24HC), a structural isomer of 25HC, plays a critical role in cholesterol homeostasis in the human brain and is implicated in multiple inflammatory conditions, including Alzheimer’s disease. However, whether 24HC can induce a proinflammatory response like 25HC in non-neuronal cells has not been studied and remains unknown. The aim of this study was to examine whether 24HC produces such an immune response using in silico and in vitro experiments. Our results indicate that despite being a structural isomer of 25HC, 24HC binds at site II in a distinct binding mode, engages in varied residue interactions, and produces significant conformational changes in the specificity-determining loop (SDL). In addition, our surface plasmon resonance (SPR) study reveals that 24HC could directly bind to integrin αvβ3, with a binding affinity three-fold lower than 25HC. Furthermore, our in vitro studies with macrophages support the involvement of FAK and NFκB signaling pathways in triggering 24HC-mediated production of TNF. Thus, we have identified 24HC as another oxysterol that binds to integrin αvβ3 and promotes a proinflammatory response via the integrin-FAK-NFκB pathway.

Turmeric is an important commercial crop widely grown in Asia due to its pharmacological and nutritional value. India is the centre of turmeric diversity and many turmeric accessions have good rhizome yield, varying curcuminoids content and are well-adapted to various agro-climatic zones. In the present study, we unravel the diversity among 200 Indian turmeric accessions based on rhizome yield traits and curcuminoids content. Clustering and correlation studies were also performed to group the turmeric accessions and to observe the relationship between the traits. Results revealed the presence of large variability among turmeric accessions including the major traits such as yield (24.77 g p -1 to 667.63 g p -1 ), dry recovery percentage (13.42% to 29.18%), curcumin (0.41% to 2.17%), demethoxycurcumin (0.38% to 1.45%), bisdemethoxycurcumin (0.37% to 1.24%) and total curcuminoid content (1.26% to 4.55%). The superior germplasm identified for curcuminoids content were as follows; curcumin (CL 157 – 2.17% and CL 272 – 2.13%), demethoxycurcumin (CL 253 – 1.45% and CL 157 – 1.31%), bisdemethoxycurcumin (CL 216 – 1.24% and CL 57 – 1.11%) and total curcuminoid content (CL 157 – 4.55% and CL 272 – 4.37%). Clustering based on dendrogram, grouped 200 accessions into seven clusters. Among seven clusters, the maximum number of accessions were grouped into cluster II while cluster VII showed maximum mean value for majority of the traits. Correlation analysis revealed a significant relationship between the traits where the total curcuminoid content is significantly and positively correlated with the primary rhizome core diameter and length of the secondary rhizome. The selection of these particular traits may result in the identification of germplasm with high total curcuminoid content. Taken together, it is the first report on the large screening of turmeric accessions for variation in the rhizome yield traits and curcuminoids content. The genetic diversity revealed in this study could be useful for further crop improvement programs in turmeric to develop new varieties with high rhizome yield coupled with high curcuminoids content.