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AbstractFisetin, a natural flavonoid molecule, has been shown to have anticancer properties against various malignancies. In this investigation, we discovered that Fisetin decreased cell viability of both the treated skin cancer cell lines A375 and A431 in a dose and time-dependent manner. The IC50values ranging from 57.60 µM ± 6.59 to 41.70 µM ± 1.25 in A375 and 48.70 µM ± 5.49 to 33.67 µM ± 1.03 for A431 at the observed time ranging between 24 h to 72 h of treatment remained quite enthusiastic when compared with the normal HEK 293 cells. Fisetin significantly decreased colony formation and migratory ability of the cancer cells. Flow cytometry analysis revealed that Fisetin significantly restricted the progression of skin cancer cells in the G0/G1phase of the cell cycle and induced cells to undergo apoptosis by increasing reactive oxygen species, decreasing mitochondrial membrane potential, and elevating the count of early and late apoptotic cells. Our in silicostudies of molecular docking followed by molecular dynamics simulation found that the interactions and stability of MTH1 protein with Fisetin further showed a considerable binding affinity for MTH1 (–11.4 kcal/mol) and developed stable complexes maintained throughout 100 ns trajectories. Our western blot analysis endorsed this. We found that Fisetin downregulated the expression levels of MTH1 also in addition, it played a crucial role in regulation of apoptotic events in cancer cells. We therefore, conclude that Fisetin anticancer properties against skin cancer cells are mediated through MTH1 inhibition followed by ATM and P53 upregulation.Communicated by Ramaswamy H. Sarma

AbstractA new pyrazole-tethered thiazolidine-2,4-dione derivative (8) has been synthesized by the Knoevenagel condensation of 3-(4-nitrophenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (4) and 3-(2,4-dioxothiazolidin-3-yl)propanenitrile (7). The structure of the final compound was confirmed by standard spectroscopic techniques including IR spectroscopy, 1H-NMR spectroscopy, and ESI-MS mass spectrometry. Molecular features including frontier molecular orbital (HOMO-LUMO) energies, reactivity descriptors and molecular electrostatic potential (ESP) of the title molecule were determined using density functional theory (DFT) calculation. The in vitrocytotoxicity of both the intermediate (4) and final (8) compounds were investigated against cancerous (SW-480 and MCF-7) and normal (HEK-293) cell lines by MTT assay. Compound (8) displayed higher activity than (4) with higher sensitivity against breast cancer cell line and lesser toxicity. The experimental data were further complemented by docking and absorption, distribution, metabolism, and excretion (ADME) studies.Communicated by Ramaswamy H. Sarma

Herein, we have shown the eco-friendly and low-cost synthesis of biogenic copper oxide nanoparticles (CuONPs) from Delonix regia(D. regia) leaf extract in aqueous medium. The formation of biogenic CuONPs was characterized by ultraviolet (UV)-visible, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) as well as transmission electron microscopy (TEM). Characterization of green synthesized nanoparticles demonstrated a UV–visible peak at 273 nm. Particle size was analysed from TEM monograph in the range of 69–108 nm which validates formation of nanoparticles. The in-vitroanticancer activity was done against A549 (IC50 = 4.70 μg/mL) and MCF7 (IC50 = 3.77 μg/mL) cell line. The biocompatibility assay of these nanoparticles was done on HEK–293 cell line (normal non-cancerous cells). Moreover, the effect of CuONPs on the lytic activity of HEWL was evaluated against Micrococcus lysodeikticus. Further, the interaction of CuONPs with hen egg white lysozyme (HEWL) at different temperature was investigated by steady state fluorescence spectroscopy. UV–visible and far ultra violet-circular dichroism (far UV-CD) spectroscopies were also employed to study the interaction of CuONPs with HEWL. All the results supported each other and show efficient binding between HEWL and CuONPs. The fluorescence emission study revealed that CuONPs quenches the fluorescence of HEWL involving dynamic quenching. The various binding parameters and structural disparity of HEWL in the presence of synthesised CuONPs were also calculated.

Sol–gel as a chemical solution deposition technique is compatible with functional device fabrication technology. Single-phase bismuth ferrite (BiFeO3) mutiferroic with its multi-functionality has extensively been studied for a variety of prospective novel device applications. However, the synthesis of BiFeO3is confronted with a challenge to produce pure state without any secondary phase. Scarcity of unified process parameters impede justification of best synthesis techniques. In this work, sol–gel methods with and without auto-combustion reactions were used to synthesize bismuth ferrite (BiFeO3) nanoparticles. Different techniques UV–Vis–NIR spectroscopy, XRD, EDS, and SEM were used to investigate the effect of preparation routes on the crystal purity and properties of prepared samples. Synthesized nanoparticles were calcined at temperature between 400 and 800∘C and an optimal calcination temperature was found to be 600∘C. Band-gap was determined by UV–Vis–NIR spectroscopy and found to vary from 1.93 to 2.07 eV. X-ray diffraction (XRD) has confirmed single phase rhombohedral crystal structure with R3c symmetry. Avg crystallite size was found to be higher (40–68 nm) in auto-combustion reaction compared to that of 23–42 nm obtained in sol–gel method without auto-combustion reaction. The band-gap energy was found to reduce with decreasing crystallite size (above the critical size of 10 nm) following Brus’s effective mass model. Induced strain was found to exhibit an inverse relation with crystallite size and displayed substantial reduction in auto-combustion reaction route. The microstructural features were investigated by field emission scanning electronic microscopy and avg particle size was shown to vary from 107 to 197 nm depending on adopted synthesis route. A low reaction temperature (70∘C–80∘C) without auto-combustion and calcination temperature at 600∘C were found to be optimal conditions for the preparation of low impurity un-doped bismuth ferrite nanaoparticles.

Cancer poses a significant global health challenge, contributing to substantial mortality rates and driving the urgent need for exploration into bioactive compounds with potent anticancer properties. Polydatin (PD), a stilbenoid compound abundant in various fruits and vegetables, has emerged as a promising candidate in cancer research. Renowned in traditional Chinese medicine for its multifaceted biological activities encompassing antioxidant, anti-inflammatory, anticancer, hepatoprotective, neuroprotective, and immunostimulatory effects, PD stands out as a versatile therapeutic agent. This review paper meticulously compiles the diverse anticancer attributes of polydatin across a spectrum of cancer types, elucidating its impact on pivotal cancer hallmarks such as proliferation, migration, metastasis, apoptosis, modulation of the tumour microenvironment, autophagy, and more. Furthermore, the review intricately explores the intricate pathways influenced by polydatin within cancer cells, unveiling its mechanisms of action and identifying potential therapeutic targets. By providing a comprehensive analysis of how polydatin affects various facets of cancer progression and addresses treatment resistance, this paper aims to enhance our understanding of its pivotal role in cancer therapy. Moreover, the synergistic potential of polydatin in combination with other drugs is investigated to underscore its amplified efficacy in combating cancer through innovative mechanism-based strategies. The synthesis of these insights underscores polydatin's significance as a valuable component in the advancement of novel approaches to cancer prevention and treatment.

Noscapine is effective to inhibit cellular proliferation and induced apoptosis in nonsmall cell, lung, breast, lymphoma, and prostate cancer. It also shows good efficiency to skin cancer cells. In the current work, we studied the mechanism of interaction between the anticancer drug noscapine (NOS) and carrier protein human serum albumin (HSA) by using a variety of spectroscopic techniques (fluorescence spectroscopy, time-resolved fluorescence, UV–visible, fluorescence resonance energy transfer (FRET), Fourier transform infrared (FTIR), and circular dichroism (CD) spectroscopy), electrochemistry (cyclic voltammetry), and computational methods (molecular docking and molecular dynamic simulation). The steady-state fluorescence results showed that fluorescence intensity of HSA decreased in the presence of NOS via a static quenching mechanism, which involves ground state complex formation between NOS and HSA. UV–visible and FRET results also supported the fluorescence result. The corresponding thermodynamic result shows that binding of NOS with HSA is exothermic in nature, involving electrostatic interactions as major binding forces. The binding results were further confirmed through a cyclic voltammetry approach. The FRET result signifies the energy transfer from Trp214 of HSA to the NOS. Molecular site marker, molecular docking, and MD simulation results indicated that the principal binding site of HSA for NOS is site I. Synchronous fluorescence spectra, FTIR, 3D fluorescence, CD spectra, and MD simulation results reveal that NOS induced the structural change in HSA. In addition, the MTT assay study on a human skin cancer cell line (A-431) was also performed for NOS, which shows that NOS induced 80% cell death of the population at a 320 μM concentration. Moreover, the esterase-like activity of HSA with NOS was also done to determine the variation in protein functionality after binding with NOS.

Background: Cyanobacteria are rich source of secondary metabolites being studied for their potential pharmaceutical applications. Objective: We studied methanolic extracts of two cyanobacteria- Nostoc muscorum NCCU-442 and Calothrix brevissima NCCU-65 for their bioactivities. Method: The phenolic content was estimated by Follin-Ciocalteu method. FRAP assay, DPPH, ABTS and SOR scavenging assays were performed to evaluate the antioxidant activity of extracts. Antimicrobial effect was studied against Staphylococcus aureus, Escherichia coli and Candida albicans by agar well diffusion assay. MTT assay was performed on cancerous HepG2 cells and Noncancerous HEK-293 cell lines to determine the anti-proliferative activity. Apoptosis was studied through DNA fragmentation assay and fluorescent microscopy. The composition of the test extracts was determined using Gas Chromatography Mass Spectroscopy (GC-MS). Results: Methanolic extract of N. muscorum NCCU-442 showed slightly higher phenolic content (55.67±0.85 mg GAE/g) than the extract of C. brevissima NCCU-65 (55.38±2.28 mg GAE/g). N. muscorum extract was observed to be the best for scavenging DPPH, ABTS radical and superoxide radicals, whereas, C. brevissima extract was better for FRAP assay. Both the extracts showed promising antimicrobial activities against given microbes. As compared to N. muscorum extract, C. brevissima extract was found to be more effective against HepG2 cell lines with IC50 value = 210.5 µg/ml. At IC50 values the extracts showed evident morphological characteristics of apoptosis. Various probable bioactive constituents were identified in the GC-MS analysis. Conclusion: The test extracts revealed that the given cyanobacterial strains have promising bioactive potential and could be developed in future as the pharmaceutical sources.

The paper discusses a performance feedback model for an effective performance appraisal system in organisations. Most organisations today lack an effective performance appraisal system primarily because the way performance feedback is given and received promotes a culture that discourages an effective performance appraisal (PA) system. An effective performance feedback model can play a key role in an organisation by enhancing employee engagement, motivation and job satisfaction. Keeping in view the problems that organisations face owing to poor feedback culture, the paper proposes and outlines a new performance feedback model that involves a positive quality-centred feedback approach relying on employee assertion and reinforcement. Unlike the conventional limitation-centred performance feedback model that highlights the gap areas and shortcomings of the employees, the new model takes its sustenance from a positive feedback culture.

AbstractWe evaluated the loss of heterozygosity (LOH) at 10q23.3locus of microsatellite markers; D10S198, D10S192, and D10S541 of PTENgene in 223 North Indian colorectal cancer (CRC) specimens. DNA was isolated and microsatellite-specific markers polymerase chain reaction was performed. Out of total 223 cases 102 showed LOH for at least one of the locus. In addition, thereto a significant association was found with the clinicopathologic features like grade of differentiation, clinical stage, invasion, lymph node invasion, and the clinical outcome (p < 0.05). These data argue that the given markers to check the possible LOH of PTENgene at locus 10q23.3could be considered as one of the diagnostic markers in CRC.

Genetic and epigenetic alterations of Parkin(PRKN gene) have been identified in colorectal cancer (CRC), but its correlation with P53(TP53 gene) status and progression of CRC is not well established. This study investigates the association of Parkinexpression with P53, clinical features, and prognosis in the north Indian population.

Proper Karush–Kuhn–Tucker (PKKT) conditions are said to hold when all the multipliers of the objective functions are positive. In 2012, Burachik and Rizvi introduced a new regularity condition under which PKKT conditions hold at every Geoffrion-properly efficient point. In general, the set of Borwein properly-efficient points is larger than the set of Geoffrion-properly efficient points. Our aim is to extend the PKKT conditions to the larger set of Borwein-properly efficient points.

AbstractCassia fistulaLinn. (Fabaceae) fruit has been used in folk medicine and reported for various pharmacological properties. We evaluated the anticancer activity of C. fistulafruit extracts [ethyl acetate extract of pulp (EEP), n-butanol extract of pulp (BEP), ethyl acetate extract of seeds (EES), n-butanol extract of seeds (BES)] against human cervical cancer (SiHa) and breast cancer (MCF-7) cell lines. Phytochemicals analysis revealed that the EEP and EES contained anticancer compounds like 2(3H)-furanone, rhein, thymoland oleic acid. BES contained inositol and palmitic acid, whereas BEP contained inositol and 2-pyrrolidone. IC50of EEP, EES, BEP and BES against SiHa cells were 415.5±0.19, 435.7±0.11, 535.3±0.32 and 580.2±0.41 µg/mL, whereas against MCF-7 cells were 422.2±0.32, 451.4±0.27, 564.5±0.21 and 575.6±0.47 µg/mL respectively (p ≤ 0.01). At IC50, EEP, EES, BEP and BES treated MCF-7 cells formed colonies of 17.5, 16.3, 22.5 and 18.8 % whereas treated SiHa cells formed colonies of 11.5, 12.8, 19.2 and 16.7 % (p≤0.03). Seeds and pulp treated both cell lines showed up-regulation of p53 and Bax genes, down-regulation of Bcl-2 gene and increased caspase-3, 7 & 10 and -9 enzymes activities. Also, the fragmented genomic DNA in pulp and seeds extracts treated SiHa and MCF-7 cells showed sign of apoptosis.We concluded that the fruit pulp and seeds extracts inhibited MCF-7 and SiHa cells growth and induced cells death by modulating the expression of apoptosis-regulatory genes and caspase enzymes.

Abstract: Cervical cancer is one of the most common malignant diseases affecting women worldwide. Studies on loss of heterozygosity have been made for PTEN gene specific microsatellite markers in malignancies like breast, ovary and lungs and the results have shown a significant association. However the role of this gene is not clearly understood in cervical cancer from Indian population. A total of 135 cervical carcinoma tissues samples were analyzed for loss of heterozygosity. DNA was isolated from the samples and their matched control specimens. Polymerase chain reaction was performed using primer specific for two intragenic markers (D10S198 & D10S192) and one marker (D10S541) in flanking region and further electrophoresed on 8% denaturing polyacrylamide gel. Overall, 31 out of 133(23%) informative cases showed loss of heterozygosity in at least one locus in the region examined. The percentage of loss of heterozygosity for these markers ranged from 8% (D10S192) to 13% (D10S198). Loss of heterozygosity was more frequently detected in intragenic region (D10S198 & D10S192) than in flanking region, D10S541 (21% versus 9%). These data argue that PTEN is a tumor suppressor gene whose inactivation may play an important role in the carcinoma of uterine cervix.

Abstract: Parkin, a tumor suppressor gene located on chromosome 6q25-27, has been identified as a target for mutation in many human malignancies like breast, ovaries, cervical and lungs etc. After a preliminary report on the loss of heterozygosity and altered Parkin expression in breast and ovarian tumors, we aimed to study loss of heterozygosity in the Parkin gene associated microsatellite markers and its expression in human ovarian cancer patients from Indian population. We examined 102 paired normal and ovarian cancer samples for allelic loss in Parkin gene locus using Parkin gene associated microsatellite markers through loss of heterozygosity and changes in its expression through semiquantitative RT-PCR. Loss of heterozygosity identified common region of loss in Parkin locus with highest frequency for the intragenic marker D6S1599 (53%) whereas, 49 of 102 (48%) specimens showed decreased or no expression of Parkin in ovarian tumors. The study revealed that presence of loss of heterozygosity was significantly higher in both the intragenic markers (D6S1599 and D6S305) as compared with the locus of flanking region (D6S1008) with their p value 0.000001 and 0.00008, respectively. It also revealed that Parkin inactivation is probably a combination of loss of heterozygosity coupled with downregulation of Parkin gene through an alternative means like epigenetic mechanism. These data strongly supports the previous study and argue that Parkin is a tumor suppressor gene whose inactivation may play an important role in ovarian carcinoma.

Abstract: New Schiff bases, salicylidene- and pyridoxylidene-thyroxine have been prepared and characterized. They were labeled with99mTc. The labeling yield of the Schiff bases was over 95%. About 60% of the activity was bound to gamma-globulin and albumin fractions when the labled compounds were incubated with a serum sample. The labeled compounds, after i.v. administration to rats, rapidly cleared from blood and excreted into the small intestine. They appeared to behave as hepatobiliary agents.

Abstract: Superoxide dismutase, containing copper and zinc, has been labeled with copper-64 by incubating the prepared apoenzyme with cupric(65) chloride at room temperature. No significant loss in the enzymatic activity was observed after labeling. The incorporation of copper-64 was ascertained by starch gel electrophoresis and high performance liquid chromatography. The labeling efficiency was found to be >95%.

Abstract: Homopolymers of chlorotrifluoroethylene (CTFE), vinylidene fluoride (VDF) and methyl methacrylate (MMA) and their copolymers were studied by PGC/IR with regard to the separation and identification of the degraded products and clarification of the degradation mechanism. Besides monomers, HCl CO2, C2H2, HF, C5H10O2, C3F5Cl and dimers are the observed pyrolysis products. Mechanisms for different degradation reactions have also been studied.

Several procedures for ranking populations according to the quantile of a given order have been discussed in the literature. These procedures deal with continuous distributions. This paper deals with the problem of selecting a population with the largest α-quantile from k ≥ 2 finite populatins, where the size of each population is known. A selection rule is given based on the sample quantiles, where he samples are drawn without replacement. A formula for the minimum probability of a correct selection for the given rule, for a certain configuration of the population α-quantiles, is given in terms of the sample numbers.

A procedure for selecting the t largest of k multivariate normal populations on the basis of distance is reviewed. Computation of integrals of products of non-central Beta distribution and density functions, required for implementing the procedure, is described. A table of minimum sample sizes needed to guarantee a specified probability of correct selection is given (Table 1).

This paper is concerned with the problems of selection and ranking of non-central chi-squared and non-centralFpopulations, defined in terms of their non-centrality parameters. We are interested in selecting thetlargest of the populations and a subset containing thetlargest for which two procedures, namedR2andR2are given. It is required that the probability of a correct selection using these procedures should be at least as large as any given number P*< 1. We call this the “P* condition”. The main part of the problem is to determine the least favorable configurations of the parameter space for which the probability of a correct selection is minimum. The expression for the minimum value determines the smallest sample size needed to satisfy theP*condition. The least favorable configurations and the corresponding expressions for the minimum of the probability of a correct selection are obtained forR1andR2.

Local delivery of anticancer agents via injectable hydrogels could be a promising method for achieving spatiotemporal control on drug release as well as minimizing the disadvantages related to the systemic mode of drug delivery. Keeping this in mind, we report the development of N,O-carboxymethyl chitosan (N,O-CMCS)–guar gum-based injectable hydrogels for the sustained delivery of anticancer drugs. The hydrogels were synthesized by chemical crosslinking of multialdehyde guar gum (MAGG) and N,O-CMCS through dynamic Schiff base linkages, without requiring any external crosslinker. Fabrication of injectable hydrogels, involving N,O-CMCS and MAGG via Schiff base crosslinking, is being reported for the first time. The hydrogels exhibited pH-responsive swelling behavior and good mechanical properties with a storage modulus of about 1625 Pa. Due to the reversible nature of Schiff base linkages, hydrogels displayed excellent self-healing and thixotropic properties. Doxorubicin (Dox), an anticancer agent, was loaded onto these hydrogels and its release studies were conducted at pH 7.4 (physiological) and pH 5.5 (tumoral). A sustained release of about 67.06% Dox was observed from the hydrogel after 5 days at pH 5.5 and about 32.13% at pH 7.4. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on the human embryonic kidney cell line (HEK-293) and the hemolytic assay demonstrated the biocompatible nature of the hydrogels. The Dox-loaded hydrogel exhibited a significant killing effect against breast cancer cells (MCF-7) with a cytotoxicity of about 72.13%. All the data presented support the efficiency of the synthesized N,O-CMCS/MAGG hydrogel as a biomaterial that may find promising applications in anticancer drug delivery.

Cassia fistulaoil was investigated for antifungal activities against standard and clinical isolates of Candidaspecies. Gas chromatography coupled with mass spectrometric (GC-MS) analysis of C. fistulaoil revealed the presence of antimicrobial compounds like β-sitosterol, stigmasterol, ergosterol, betulinic acid, lupeol, fucosterol, α-amyrin and friedelin. The minimum inhibitory concentration (MIC) of the pulp and seed oils ranged between 250-300 and 350-500 μg/mL respectively. Both oils also inhibited by ≥63.8% ergosterol bio-synthesis in Candidacell wall {fluconazole (standard) ≥89.1%)}. The MICs were significantly correlated with the ergosterol content decrease in the cell wall (Student's ttest p ≤0.005). We can, therefore, conclude that active compounds are present in Cassia fistulaoil that primarily target ergosterol biosynthesis in Candidacell wall.