Investigation on structure and photoluminescence properties of Ho3+ doped Ca3(VO4)2 phosphors for luminescent devices.

This study focuses on the synthesis and characterization of Ho3+ doped Ca3(VO4)2 phosphor for potential application in solid-state lighting technology. A citrate-based sol-gel process is optimized to achieve sheet-like morphologies in the phosphor material. The investigation reveals UV absorption at 371 nm, indicating a band gap of 3.28 eV. Emission transitions at (506, 541, and 651) nm are observed when excited at 451 nm, with an optimal Ho3+ concentration of 0.05 mol resulting in robust green emission at 541 nm. The concentration quenching in Ca3(VO4)2:xHo3+ phosphors is discussed in detail with Blesse's and Dexter's models. The concentration quenching effect found in the studied samples is due to the dipole-dipole interactions. Judd-Ofelt intensity parameters were calculated from the excitation bands, and for Ω 2, Ω 4, and Ω 6 are (0.16, 0.17, and 0.36) × 10-20 cm2, respectively. The emission properties for the (5S2 + 5F4) → 5I8 and 5F5 → 5I8 transitions are also estimated with J-O parameters. The higher magnitude of branching ratios (83%) and emission cross-sections (1.6 × 10-21 cm2) suggest that the Ca3(VO4)2:0.05Ho3+ phosphor materials may be suitable for efficient green-emitting device applications. The CIE coordinates confirm the potential of Ho3+-doped phosphors for green emissions, making them suitable for solid-state lighting and display technology.

Identification of a novel GSK3ß inhibitor involved in abrogating KRas dependent pancreatic tumors in Wnt/beta-catenin and NF-kB dependent manner.

Pancreatic cancer is an aggressive malignancy with a poor survival rate because it is difficult to diagnose the disease during its early stages. The currently available treatments, which include surgery, chemotherapy and radiation therapy, offer only limited survival benefit. Pharmacological interventions to inhibit Glycogen Synthase Kinase-3beta (GSK3ß) activity is an important therapeutic strategy for the treatment of pancreatic cancer because GSK3ß is one of the key factors involved in the onset, progression as well as in the acquisition of chemoresistance in pancreatic cancer. Here, we report the identification of MJ34 as a potent GSK3ß inhibitor that significantly reduced growth and survival of human mutant KRas dependent pancreatic tumors. MJ34 mediated GSK3ß inhibition was seen to induce apoptosis in a ß-catenin dependent manner and downregulate NF-kB activity in MiaPaCa-2 cells thereby impeding cell survival and anti-apoptotic processes in these cells as well as in the xenograft model of pancreatic cancer. In vivo acute toxicity and in vitro cardiotoxicity studies indicate that MJ34 is well tolerated without any adverse effects. Taken together, we report the discovery of MJ34 as a potential drug candidate for the therapeutic treatment of mutant KRas-dependent human cancers through pharmacological inhibition of GSK3ß.

Discovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter.

JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.

Hydrothermal Synthesis and Characterization of WSe2 Nanosheets: A Promising Approach for Wearable Photodetector Applications.

The two-dimensional (2D) WSe2 nanostructure was successfully synthesized via the hydrothermal method and subjected to comprehensive characterization using various spectroscopic techniques. X-ray diffraction (XRD) analysis confirmed the formation of nanosheets with a hexagonal crystal structure having a space symmetry of P63/mmc. Scanning electron microscopy (SEM) images showed irregular and nonuniform morphology. The size of the 2D nanosheets was determined using transmission electron microscopy (TEM) providing insights intotheir physical characteristics. The optical spectrum analysis yielded a discernible band gap value of 2.1 eV, as determined by the Tauc equation. Photoluminescence (PL) spectra display an emission at a wavelength of 610 nm, showing a broad emission associated with self-trapped excitons. Under excitation at λexc = 360 nm, PL emission spectra displayed a distinct peak at 610 nm, demonstrating the ability of the nanostructure to emit vivid red light. Photometric analysis underscored the potential of this nanostructure as a prominent red-light source for diverse display applications. The optimized photodetection performance of a device showcases a photoresponsivity of approximately 1.25 × 10-3 AW-1 and a detectivity of around 5.19 × 108 Jones at a wavelength of 390 nm. Additionally, the quantum efficiency is reported to be approximately 6.99 × 10-3 at a wavelength of 635 nm. These findings highlight the capability of the device for efficient photoconversion at specified wavelengths, indicating potential applications in sensing, imaging, and optical communication. The combination of structural, morphological, and optical characterizations highlights the suitability of 2D WSe2 nanostructure for practical optoelectronic applications, particularly in display technologies.

Physico-chemical and antifungal studies of spun cotton thread reinforced cellulose film.

This study examines cellulose films reinforced with spun cotton thread and their antifungal properties. The morphology and structure of the cellulose film are analyzed using various techniques, including X-ray Diffraction (XRD), Fourier Transform Infrared (FT-IR) Spectroscopy, Field Emission Scanning Electron Microscope (FE-SEM), Atomic Force Microscope (AFM), UV-Visible Spectroscopy (UV-Vis), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). The XRD pattern confirms the crystalline nature of the spun cotton-reinforced cellulose film. UV absorption analysis shows activity in the UV region of the optical spectrum. The reinforced cellulose film shows a band gap of 4.7 eV by employing the Wood and Tauc equation. FTIR spectroscopy confirms the film's structural formation. Morphological analysis reveals a random distribution of numerous pore structures on the material's surface. Thermalgravimetric Analysis indicates the material's stability at elevated temperatures, suggesting versatile applications. The film also exhibits antifungal activity against Candida albicans. This research highlights the potential of reinforced cellulose film in various applications, such as food and non-food packaging, offering enhanced UV protection and strength for heavy goods transport. The study emphasizes the multifunctional properties of the material, showcasing its promising role as a polymer in various practical applications.

Photoluminescence Emission Studies on a Lanthanum-Doped Lead Free Double Halide Perovskite, La:Cs2SnCl6.

Recent advances in bandgap engineering have increased the possibility of vacancy ordered double halide perovskites (VO-DHPs), Cs2SnX6 where X = Cl, Br, I with designable optoelectronic features. Doping with La3+ ions modulates the band gap from 3.8 to 2.7 eV, allowing a steady room temperature dual emission (PL) centered at 440 and 705 nm in Cs2SnCl6. Pristine Cs2SnCl6 and La:Cs2SnCl6 both have a crystalline cubic structure with a space symmetry of Fm3m. The cubic phase correlates well with the Rietveld refinement. SEM analysis confirms anisotropic development with huge micrometer-sized (>10 µm) truncated octahedral structures. DFT investigations show that the insertion of La3+ ions into the crystal lattice leads to the band splitting. The present study elaborates the experimental understanding of the dual PL emission properties of La:Cs2SnCl6 leaving a scope for detailed theoretical study on the origin of the complex electronic transitions involving f-orbital electrons.

Clinical relevance of biomarkers, new therapeutic approaches, and role of post-translational modifications in the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive loss of cognitive functions like thinking, memory, reasoning, behavioral abilities, and social skills thus affecting the ability of a person to perform normal daily functions independently. There is no definitive cure for this disease, and treatment options available for the management of the disease are not very effective as well. Based on histopathology, AD is characterized by the accumulation of insoluble deposits of amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs). Although several molecular events contribute to the formation of these insoluble deposits, the aberrant post-translational modifications (PTMs) of AD-related proteins (like APP, Aß, tau, and BACE1) are also known to be involved in the onset and progression of this disease. However, early diagnosis of the disease as well as the development of effective therapeutic approaches is impeded by lack of proper clinical biomarkers. In this review, we summarized the current status and clinical relevance of biomarkers from cerebrospinal fluid (CSF), blood and extracellular vesicles involved in onset and progression of AD. Moreover, we highlight the effects of several PTMs on the AD-related proteins, and provide an insight how these modifications impact the structure and function of proteins leading to AD pathology. Finally, for disease-modifying therapeutics, novel approaches, and targets are discussed for the successful treatment and management of AD.

Genetic Determinants of Hydrogen Sulfide Biosynthesis in Fusobacterium nucleatum Are Required for Bacterial Fitness, Antibiotic Sensitivity, and Virulence.

The Gram-negative anaerobe Fusobacterium nucleatum is a major producer of hydrogen sulfide (H2S), a volatile sulfur compound that causes halitosis. Here, we dissected the genetic determinants of H2S production and its role in bacterial fitness and virulence in this important member of the oral microbiome. F. nucleatum possesses four enzymes, CysK1, CysK2, Hly, and MegL, that presumably metabolize l-cysteine to H2S, and CysK1 was previously shown to account for most H2S production in vitro, based on correlations of enzymatic activities with gene expression at mid-log phase. Our molecular studies showed that cysK1 and megL were highly expressed at the late exponential growth phase, concomitant with high-level H2S production, while the expression levels of the other genes remained substantially lower during all growth phases. Although the genetic deletion of cysK1 without supplementation with a CysK1-catalyzed product, lanthionine, caused cell death, the conditional ΔcysK1 mutant and a mutant lacking hly were highly proficient in H2S production. In contrast, a mutant devoid of megL showed drastically reduced H2S production, and a cysK2 mutant showed only minor deficiencies. Intriguingly, the exposure of these mutants to various antibiotics revealed that only the megL mutant displayed altered susceptibility compared to the parental strain: partial sensitivity to nalidixic acid and resistance to kanamycin. Most significantly, the megL mutant was attenuated in virulence in a mouse model of preterm birth, with considerable defects in the spread to amniotic fluid and the colonization of the placenta and fetus. Evidently, the l-methionine γ-lyase MegL is a major H2S-producing enzyme in fusobacterial cells that significantly contributes to fusobacterial virulence and antibiotic susceptibility. IMPORTANCE Fusobacterium nucleatum is a key commensal anaerobe of the human oral cavity that plays a significant role in oral biofilm development and contributes to additional pathologies at extraoral sites, such as promoting preterm birth and colorectal cancer. Although F. nucleatum is known as a major producer of hydrogen sulfide (H2S), its genetic determinants and physiological functions are not well understood. By a combination of bacterial genetics, biochemical methods, and in vivo models of infection, here, we demonstrate that the l-methionine γ-lyase MegL not only is a major H2S-producing enzyme of F. nucleatum but also significantly contributes to the antibiotic susceptibility and virulence of this organism.

Identification of a stretch of four discontinuous amino acids involved in regulating kinase activity of IGF1R.

IGF1R is pursued as a therapeutic target because of its abnormal expression in various cancers. Recently, we reported the presence of a putative allosteric inhibitor binding pocket in IGF1R that could be exploited for developing novel anti-cancer agents. In this study, we examined the role of nine highly conserved residues surrounding this binding pocket, with the aim of screening compound libraries in order to develop small-molecule allosteric inhibitors of IGF1R. We generated GFP fusion constructs of these mutants to analyze their impact on subcellular localization, kinase activity and downstream signaling of IGF1R. K1055H and E1056G were seen to completely abrogate the kinase activity of IGF1R, whereas R1064K and L1065A were seen to significantly reduce IGF1R kinase activity. During molecular dynamics analysis, various structural and conformational changes were observed in different conserved regions of mutant proteins, particularly in the activation loop, compromising the kinase activity of IGF1R. These results show that a stretch of four discontinuous residues within this newly identified binding pocket is critical for the kinase activity and structural integrity of IGF1R. This article has an associated First Person interview with the first author of the paper.

Interactive effect of Meloidogyne incognita and fly ash on the growth, physiology, and antioxidant properties of carrot (Daucus carota L.).

Alternative methods are needed to replace chemical nematicides because they have the potential to damage beneficial soil microbial diversity. Therefore, the present work was done to elucidate the soil ameliorative, plant-growth-promoting, and nematicidal properties of fly ash. A random block-designed pot experiment was conducted during the period, December 2018-February 2019. Seeds of carrot (Daucus carota L.) were sown under natural conditions in clay pots containing a growth medium comprising of field soil amended with different levels of fly ash. Plants were inoculated with Meloidogyne incognita that were molecularly characterized using 18S and D2/D3 fragments of 28S rDNA and morphologically through perineal pattern arrangement. The results revealed that fly ash application improved the soil's important physicochemical characteristics. The inoculation of M. incognita significantly reduced the plant growth, yield, and pigment content of carrot compared to the untreated uninoculated plants. Carrot grown in 15% fly ash (85:15 w/w field soil:fly ash) growth substrate had significantly (P ≤ 0.05) improved plant growth, yield, and pigment content as compared to the untreated inoculated plants. Moreover, the proline content and the activity of superoxide dismutase (SOD) and catalase (CAT) were enhanced by applying 15% fly ash. Fly ash amendment to the soil not only improved plant growth and yield but also reduced the gall index and egg mass index per root system of the carrot as well. Our results, therefore, suggest that 15% fly ash can be used in a sustainable way to improve the growth, yield, and resistance of carrot against the infection of M. incognita.

Phylogeny and Optimization of Trichoderma harzianum for Chitinase Production: Evaluation of Their Antifungal Behaviour against the Prominent Soil Borne Phyto-Pathogens of Temperate India.

Trichoderma is the most commonly used fungal biocontrol agent throughout the world. In the present study, various Trichoderma isolates were isolated from different vegetable fields. In the isolated microflora, the colony edges varied from wavy to smooth. The mycelial forms were predominantly floccose with hyaline color and conidiophores among all the strains were highly branched. Based on morphological attributes, all the isolates were identified as Trichoderma harzianum. The molecular identification using multilocus sequencing ITS, rpb2 and tef1α, genes further confirmed the morphological identification. The average chitinase activity varied from 1.13 units/mL to 3.38 units/mL among the various isolates, which increased linearly with temperature from 15 to 30 °C. There was an amplified production in the chitinase production in the presence of Mg+ and Ca2+ and Na+ metal ions, but the presence of certain ions was found to cause the down-regulated chitinase activity, i.e., Zn2+, Hg2+, Fe2+, Ag+ and K+. All the chitinase producing Trichoderma isolates inhibited the growth of tested pathogens viz., Dematophora necatrix, Fusarium solani, Fusarium oxysporum and Pythium aphanidermatum at 25% culture-free filtrate concentration under in vitro conditions. Also, under in vivo conditions, the lowest wilt incidence and highest disease control on Fusarium oxysporum was observed in isolate BT4 with mean wilt incidence and disease control of 21% and 48%, respectively. The Trichoderma harzianum identified in this study will be further used in formulation development for the management of diseases under field conditions.

Optical, electrochemical and photocatalytic properties of cobalt doped CsPbCl3 nanostructures: a one-pot synthesis approach.

The present manuscript aims at the synthesis of cesium based halide perovskite nanostructures and the effect of cobalt doping on the structural, optical, lumnisent, charge storage and photocatalytic properties. In a very first attempt, we report the solvothermal synthesis of Co doped CsPbCl3 nanostructures under subcritical conditions. The structural features were demonstrated by X-ray diffraction (XRD) Surface morphology determined cubic shape of the synthesized particles. Doping is an excellent way to modify the properties of host material in particular to the electronic structure or optical properties. Incorporation of Co2+ ions in the perovskite structure tunes the optical properties of the nanostructures making this perovskite a visible light active material (Eg = 1.6 eV). This modification in the optical behaviour is the result of size effect, the crystallite size of the doped nanostructures increases with cobalt doping concentration. Photolumniscance (PL) study indicated that CsPbCl3 exhibited Blue emission. Thermogravametric analysis (TGA) revealed that the nanostructures are quite stable at elavated temperatures. The electrochemical performance depicts the pseudocapacative nature of the synthesized nanostructures and can used for charge storage devices. The charge storage capability showed direct proportionality with cobalt ion concentration. And Finally the photocatalytic performance of synthesized material shows superior catalytic ability degrading 90% of methylene blue (MB) dye in 180 min under visible light conditions.

Facile Way of Making Hydrothermally Synthesized Crystalline SrSnO3 Perovskite Nanorods Suitable for Blue LEDs and Spintronic Applications.

Mn doping in SrSnO3 perovskite material via hydrothermal process under subcritical conditions is reported for the very first time. The present article aims to carry this perovskite suitable for blue light-emitting diodes (LEDs) and spintronic applications. The influence of various Mn doping percentages on structural, morphological, compositional, optical, photoluminescent, and magnetic properties of SrSnO3 is demonstrated. The perovskite material is grown in an orthorhombic crystal structure having a space symmetry of Pnma along with point group of mmm as determined from the Rietveld refinement. Doping is an excellent way to modify the properties of wide-band-gap perovskite nanostructures. Incorporation of Mn is the result of exact substitution. Morphological studies indicate formation of rodlike structures with thickness in nanoscale dimensions (180-280 nm), and the thickness is a function of doping concentration. The higher doping concentration resulted in enhanced growth of the nanorods. Selected area electron diffraction (SAED) results showed the single-crystal nature of the nanorods. Thermogravimetric analysis (TGA) confirmed the high stability of the material at elevated temperatures. Also, the doped perovskite material is transparent in the visible light, active in the ultraviolet region having a band gap of ∼2.78 eV, and is tuned up to 2.25 eV as the Mn doping concentration reaches 10%. The transfer of excitonic energy from the host material to the dopant Mn2+ ion leads to the formation of spin-forbidden [4T1-6A1] emission. Later on, photoluminescence study indicates an enhancement in luminescence behavior of Mn doped perovskite nanostructures. The Commission Internationale de l'éclairage (CIE) diagram drawn to find the color coordinates of the nanorods determines their suitability for blue LEDs. In addition, Mn doping results the conversion of diamagnetic SrSnO3 into a ferromagnetic material, making the nanorods suitable for spintronic applications.

Anchoring surface proteins to the bacterial cell wall by sortase enzymes: how it started and what we know now.

In Gram-positive bacteria, the peptidoglycan serves as a placeholder for surface display of a unique class of monomeric and polymeric proteins, or pili - the precursors of which harbor a cell wall sorting signal with LPXTG motif that is recognized by a conserved transpeptidase enzyme called sortase. Since this original discovery over two decades ago, extensive genetic, biochemical and structural studies have illuminated the basic mechanisms of sortase-mediated cell wall anchoring of surface proteins and pili. We now know how LPXTG-containing surface proteins are folded post-translocationally, how sortase enzymes recognize substrates, and how a remnant of the cell wall sorting signal modulates intramembrane signaling. In this review, we will highlight new findings from a few model experimental paradigms and present future prospects for the field.

Identification of a cross-talk between EGFR and Wnt/beta-catenin signaling pathways in HepG2 liver cancer cells.

EGFRis a transmembrane receptor tyrosine kinase involved in regulating cell proliferation, differentiation and survival. EGFR is actively pursued as a therapeutic target because its aberrant expression or activity has been reported in several cancers. Several studies have reported the nuclear localization of the EGFR in various cell types, however, its exact nuclear functions are not clear yet. In this study, we have generated GFP fusion constructs of EGFR and its mutants to analyze their subcellular localizationin normal and cancer cells and impact of its sub-cellular location on its various activities using immunoblotting, confocal microscopy, reporter assays, loss-of-function EGFR mutants, and EGFR specific small molecule inhibitors. We show that EGFR is involved in modulating TCF dependent ß-catenin transcriptional activity in HepG2 cells in a similar fashion as IGF1R tyrosine kinase. Moreover, we show that cytoplasmic and nuclear functions are two independent activities of EGFR.

Growth and properties of hydrothermally derived crystalline ZnSe quantum dots.

Chalcogenide nanostructures are the materials with diverse applications. Here, we report rapid hydrothermal synthesis of crystalline ZnSe quantum dots (QDs), avoiding the use of toxic chemicals. To the best of our knowledge, this is the first report on very rapid (5 h) hydrothermal synthesis of pristine ZnSe QDs. Elemental selenium is used as a source for selenium. Structural, morphological, compositional, and optical properties of the semiconductor were studied. Structural properties (X-ray diffraction) demonstrate that the particles have grown in a single cubic phase. Morphological studies show formation of agglomerated QDs (4 nm). The material possess stoichiometric ratio of the constituent elements that are uniformly distributed. Selected area electron diffraction (SAED) study indicated the material is polycrystalline in nature. Optical properties demonstrated that the QDs are suitable for optoelectronic devices exhibiting room temperature photoluminescence. Commission Internationale de l'Éclairage (CIE) chromaticity diagram shows the material exhibits violet emission and hence suitable for violet LEDs that have potential ability in clinical applications.

Analyzing structural differences between insulin receptor (IR) and IGF1R for designing small molecule allosteric inhibitors of IGF1R as novel anti-cancer agents.

IR and insulin-like growth factor-1 receptor (IGF-1R) share high degree of sequence and structural similarity that hinders the development of anticancer drugs targeting IGF1R, which is dysregulated in many cancers. Although IR and IGF1R mediate their activities through similar signalling pathways, yet they show different physiological effects. The exact molecular mechanism(s) how IR and IGF1R exert their distinct functions remain largely unknown. Here, we performed in silico analysis and generated GFP-fusion proteins of wild type IR and its K1079R mutant to analyze their subcellular localization, cytoplasmic and nuclear activities in comparison to IGF1R and its K1055R mutant. We showed that, like K1055R mutation in IGF1R, K1079R mutation does not impede the subcellular localization and nuclear activities of IR. Although K1079R mutation significantly decreases the kinase activity of IR but not as much as K1055R mutation, which was seen to drastically reduce the kinase activity of IGF1R. Moreover, K1079 residue in IR is seen to be sitting in a pocket which is different than the allosteric inhibitor binding pocket present in its homologue (IGF1R). This is for the first time such a study has been conducted to identify structural differences between these receptors that could be exploited for designing small molecule allosteric inhibitor(s) of IGF1R as novel anti-cancer drugs.

BoMiProt: A database of bovine milk proteins.

Bovine milk has become an important biological fluid for proteomic research due to its nutritional and immunological benefits. To date, over 300 publications have reported changes in bovine milk protein composition based on seasons, lactation stages, breeds, health status and milk fractions while there are no reports on consolidation or overlap of data between studies. Thus, we have developed a literature-based, manually curated open online database of bovine milk proteome, BoMiProt (http://bomiprot.org), with over 3100 proteins from whey, fat globule membranes and exosomes. Each entry in the database is thoroughly cross-referenced including 397 proteins with well-defined information on protein function, biochemical properties, post-translational modifications and significance in milk from different publications. Of 397 proteins, over 199 have been reported with a structural gallery of homology models and crystal structures in the database. The proteome data can be retrieved using several search parameters such as protein name, accession IDs, FASTA sequence. Furthermore, the proteome data can be filtered based on milk fractions, post-translational modifications and/or structures. Taken together, BoMiProt represents an extensive compilation of bovine milk proteins from literature, providing a foundation for future studies to identify specific milk proteins which may be linked to mammary gland pathophysiology. BIOLOGICAL SIGNIFICANCE: Protein data identified from different previously published proteomic studies on bovine milk samples (21 publications) were gathered in the BoMiProt database. Unification of the identified proteins will give researchers an initial reference database on bovine milk proteome to understand the complexities of milk as a biological fluid. BoMiProt has a user-friendly interface with several useful features, including different search criteria for primary and secondary information of proteins along with cross-references to external databases. The database will provide insights into the existing literature and possible future directions to investigate further and improve the beneficial effects of bovine milk components and dairy products on human health.

Identification of dinactin, a macrolide antibiotic, as a natural product-based small molecule targeting Wnt/ß-catenin signaling pathway in cancer cells.

PURPOSE: Despite the fact that hyper-activation of Wnt/ß-catenin signaling pathway has been seen in many cancers, including liver, colorectal and lung carcinoma, no small molecule inhibitors are available that specifically target this pathway. In this study, we analyzed the impact of dinactin (DA), an antibiotic ionophore produced by Streptomyces species, as an effective small molecule targeting Wnt/ß-catenin signaling pathway in cancer cells. METHODS: We performed MTT assays to investigate cell viability and proliferation after exposure to small molecules. Protein expression analysis was carried out by western blotting. Top-Flash reporter assays were used to score for ß-catenin signaling and cell cycle analysis was carried out by flow cytometry. RESULTS: In the first set of experiments, DA was seen to selectively inhibit the proliferation of HCT-116 and HepG2 cancer cells, unlike HEK-293 cells (a low tumorigenic cell line), in apoptosis-independent manner. Further, DA was seen to block the G1/S progression and decrease the expression of cyclin D1 in cancer cells. Since cyclin D1 is the downstream target gene of Wnt/ß-catenin signaling, we examined the impact of DA on TCF-dependent ß-catenin activity using Top-Flash reporter assay. Interestingly, DA significantly decreased Top-Flash activity at lower nano-molar concentrations when compared with salinomycin in HCT-116 and HepG2 cells. CONCLUSION: We report the identification of dinactin as a natural product-based small molecule that effectively blocks the Wnt/ß-catenin signaling pathway in cancer cells at nano-molar concentration. We anticipate that DA could be developed as a novel drug for anti-cancer therapy and for the management of neuropathic pain.