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Objectives The aim of this study was to investigate the potential of poly(amido amine) (PAMAM) dendrimer decorated graphene oxide (GO) based nanocarrier for targeted delivery of a hydrophobic anticancer drug, quercetin (QSR). Methods GO-PAMAM was successfully synthesized by covalent bonding between GO and NH2-terminated PAMAM dendrimer (zero generation). To investigate drug loading performance, QSR was loaded on the surface of GO as well as GO-PAMAM. Further, the release behaviour of QSR-loaded GO-PAMAM was studied. Finally, an in-vitro sulforhodamine B assay was performed in HEK 293T epithelial cells and MDA MB 231 breast cancer cells. Key findings It was observed that GO-PAMAM shows higher QSR loading capacity compared to GO. Also, synthesized nanocarrier exhibits controlled as well as pH-responsive release of QSR and the amount of QSR released at pH 4 was approximately two times higher than the release at pH 7.4. Furthermore, GO-PAMAM was found to be biocompatible for HEK 293T cells, and a high cytotoxic effect was observed for QSR-loaded GO-PAMAM on MDA MB 231 cells. Conclusions The present investigation highlights the potential application of synthesized hybrid materials as a nanocarrier with excellent loading and controlled releasing efficiency for the delivery of the hydrophobic anticancer drug.

Polymer grafted magnetic graphene oxide (GO–PVP–Fe3O4) as an efficient nanocarrier for the delivery of anticancer drug quercetin.

Isocoumarin is a lactone, a type of natural organic compound that is used as synthetic intermediates of several natural products and pharmaceutical compounds explored for their potential therapeutic applications like antifungal, antimicrobial, anti-inflammatory, and anticancer activities. In our previous work, we were the first group to report the use of amide C-N bond of isatins as the oxidizing directing group for the synthesis of 8-amido isocoumarin derivatives. Whereas in our present work, we have screened the cytotoxic effects of novel 8-amido isocoumarin derivatives (S1-S10) in human breast cancer MCF-7 and MDA-MB-231 cells. Our novel results revealed that N-(3-(4-methoxyphenyl)-1-oxo-4-(4-propylphenyl)-1H-isochromen-8yl)acetamide (S1) and N-(4-(3,5-difluorophenyl)-1-oxo-3-(p-tolyl)-1H-isochromen-8-yl) acetamide (S2) are the two potent compounds among the rest synthesized isocoumarin derivatives that are cytotoxic against MCF-7 and MDA-MB-231 cells, whereas less toxic to the non-tumorigenic IOSE-364 cells. Flow cytometry studies have confirmed the induction of apoptotic effects of compounds by Annexin V/PI double staining. We also observed the cytotoxic effects of S1 and S2, as evaluated by DAPI-PI immunostaining and H&E staining. The morphological alterations consistent with apoptotic blebs were observed in both cancer cells treated with compounds assessed by scanning electron microscopy. Overall, this present study strongly demonstrates that 8-amido isocoumarin derivatives have potent cytotoxic and apoptotic effects in breast cancer cells.

Background:Isothiocyanates (ITCs) are small molecules that are important in synthetic organic chemistry, but their actual importance lies in their potential as anti-carcinogens. Through this piece of work, an effort was made to assess the anti-cancer activity of some simple ITCs which can be synthesized through easy greener pathways.Methods:Cell proliferation assay was performed on ovarian cancer cells (PA-1) and non-tumorigenic ovarian epithelial cells (IOSE-364). Furthermore, qRT-PCR for transcript expression levels of Spindlin1 and caspases in ovarian cancer cells and cell cycle analysis was performed. In silico studies were incorporated to understand the mode of ligand-protein interaction, ADME/Toxicity and drug-likeliness parameters. Density functional theory studies have been also been employed on the ITCs to assess their efficiency in anticancer activity.Results:An inexpensive, environmentally benign pathway has been developed for synthesizing a series of ITCs. Among the synthesized ITCs, NC6 showed better cytotoxic effects as compared to its counterparts. Novel findings revealed that NC6 had 5-folds lower transcript expression levels of Spindlin1 and induced caspases 3 and 7 expressions assessed by qRT-PCR in ovarian cancer cells. Furthermore, flow cytometry assay showed the cell cycle arrest at G1/S phase of cell cycle. The molecular docking studies revealed favorable binding affinities and the physiochemical parameters were predicted to be compatible with drug-likeliness.Conclusion:The results demonstrated the possibility that small isothiocyanate molecules which can be synthesized by a simple green methodology, can pose as promising candidates for their application as anticancer agents.

Background: In particular, combinatorial use of anticancer drugs, dual or multiple, onto a specific nanocarrier is one of the most hopeful attempts in the field of drug delivery. The current work reports potassium contained graphene oxide (K-GO) as a nanocarrier in the drug delivery system of two anticancer drugs, gefitinib (GEF) and camptothecin (CPT), simultaneously. Methods: To characterize K-GO, K-GO-related single and combined drug systems, different techniques has been performed and studied using spectroscopic tools (Thermo gravimetric Analysis (TGA 4000), UV–visible spectroscopy, Raman spectroscopy, Transmission electron microscopy (TEM)). The in vitro cytotoxicity tests of K-GO, single drug system and the combined drug system were also performed in the human breast cancer MDA-MB-231 cells. Results: The release profile of the dual drug conjugates grafted on to the surface of K-GO was found up to 38% in PBS solution over 72hr. The percentage of MDA-MB-231 cell viability were about 18% when treated with K-GO-GEF-CPT combined system, for K-GO, K-GO-GEF, and K-GO-CPT that were only 79 %, 31% and 32 % respectively. Conclusion: We studied the loading, release, and delivery of two anticancer drugs onto the fluorescent nanocarrier i.e. K-GO. Due to superb aqueous solubility, excellent biocompatibility and richness of potassium in it make them a promising nanocarrier for single or multiple drug delivery. With this, our novel findings revealed that the loading capacity and cytotoxicity of combined drug loaded system superior then that of individual drug system towards human breast cancer cells.

Solid cancers are one of the leading causes of cancer related deaths, characterized by rapid growth of tumour, and local and distant metastases. Current advances on multimodality care have substantially improved local control and metastasis-free survival of patients by resection of primary tumour. The major concern in disease prognosis is the timely detection of resectable or metastatic tumour, thus reinforcing the need for identification of biomarkers for premalignant lesions of solid cancer. This ultimately improves the outcome for the patients. Therefore, the purpose of this review is to update the recent advancements on prognostic and diagnostic biomarkers to enhance early detection of common solid cancers including, breast, lung, colorectal, prostate and stomach cancer. We also provide an insight into Food and Drug Administration (FDA)-approved solid cancers biomarkers; various conventional techniques used for detection of prognostic and diagnostic biomarkers and discuss approaches to turn challenges in this field into opportunities.

Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D) in-vitro culture models of tumorigenesis are inadequate to replicate the complexity of in-vivo microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis.

In this work, the preparation of new composite from layered double hydroxide (LDH) and surface modified carbon (AC) was elaborated. The basic carbon was obtained by carbonizing Ipomoea carnea stems at 500 °C. The LDH compound was furthermore intercalated with antibiotic molecule norfloxacin (NOR). The chemically activated functionalized carbon particles had surface negative charge which helped in intense interaction with LDH basal positive charges. The prepared nanocomposites were characterized by powder XRD, FT−IR, FE−SEM with EDS, TGA, Zeta potential and BET surface specific area. Powder XRD and SEM studies proved that LDH was deposited over the AC surface homogeneously. The increase of the basal spacing from 0.78 nm to 1.33 nm indicated that not all LDH sheets were intercalated by NOR. Additionally, the water dispersional stability test has shown remarkable advantage compared to simple LDH. The thermal analysis results further showed a good improvement of NOR stability after intercalation into AC−LDH nanocomposite. The release behavior of NOR from the nanocomposite and its antibacterial activity were also investigated. The gradual release of NOR from AC−LDH−NOR nanocomposite suggests its prospective application as an effective delivery system for prolonged drug release.

A straightforward and efficient synthesis of tryptanthrin derivatives has been accomplished by the addition reaction of isatoic anhydrides and isatins under microwave irradiation. This decarboxylative and dehydrative addition reaction proceeded under solvent free conditions. In vitro cell based bioassay results revealed that 3ab and 3bb had unique cytotoxicity and selectivity with IC50 values of 5.90 �� 3.65 ��M and 1.96 �� 0.83 ��M, respectively in DU145 cells and they were found to be nontoxic to normal prostate epithelial RWPE-1 cells up to 25 ��M.

The incidence of nonmelanoma skin cancer (NMSC) has been increasing worldwide. Most studies have highlighted the importance of cancer-associated fibroblasts (CAFs) in NMSC progression. However much less is known about the communication between normal fibroblasts and epithelia; disruption of this communication affects tumor initiation and the latency period in the emergence of tumors. Delineating the mechanism that mediates this epithelial-mesenchymal communication in NMSC could identify more effective targeted therapies. The nuclear receptor PPARβ/δ in fibroblasts has been shown to modulate adjacent epithelial cell behavior, however, its role in skin tumorigenesis remains unknown. Using chemically induced skin carcinogenesis, we showed that FSPCre-Pparb/dex4 mice, whose Pparb/d gene was selectively deleted in fibroblasts, had delayed emergence and reduced tumor burden compared with control mice (Pparb/dfl/fl). However, FSPCre-Pparb/dex4-derived tumors showed increased proliferation, with no difference in differentiation, suggesting delayed tumor initiation. Network analysis revealed a link between dermal Pparb/d and TGF-β1 with epidermal NRF2 and Nox4. In vitro investigations showed that PPARβ/δ deficiency in fibroblasts increased epidermal Nox4-derived H2O2 production, which triggered an NRF2-mediated antioxidant response. We further showed that H2O2 upregulated NRF2 mRNA via the B-Raf-MEK1/2 pathway. The enhanced NRF2 response altered the activities of PTEN, Src, and AKT. In vivo, we detected the differential phosphorylation profiles of B-Raf, MEK1/2, PTEN, Src, and AKT in the vehicle-treated and chemically treated epidermis of FSPCre-Pparb/dex4 mice compared with that in Pparb/dfl/fl mice, prior to the first appearance of tumors in Pparb/dfl/fl. Our study revealed a role for fibroblast PPARβ/δ in the epithelial-mesenchymal communication involved in cellular redox homeostasis. Ministry of Education (MOE) Accepted version This research/project is supported by Start-Up Grant (M4082040) and Ministry of Education, Singapore, under Academic Research Fund Tier 1 (2017-T1-002-103) to NST, (2015-T1-001-034) to WW and Start-Up Grant from the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore to WW and XW; the Région Midi-Pyrénées through the Chaire d’Excellence Pierre de Fermat and the Bonizzi-Theler-Stiftung to WW; SERB-DST, Govt. of India funded Ramanujan Fellowship Grant (SB/S2/RJN-087/2014) to MP

Herein, we report the synthesis of a novel class of substituted androst[17,16- b]pyridines (pyridosteroids) from the reaction of β-formyl enamides with alkynes in high yields. The optimized reaction protocol was extended to acyclic and cyclic β-formyl enamides to afford nonsteroidal pyridines. Cell survival assay of all compounds were carried against prostate cancer PC-3 cells wherein 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine showed the highest cytotoxic activity. Phase contrast microscopy and flow cytometry studies exhibited marked morphological features characteristic of apoptosis in 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine and abiraterone treated PC-3 cells. The treatment of 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine induces G2/M phase cell cycle arrest in prostate cancer PC-3 cells. Enhancement of apoptotic inductions of PC-3 cells by 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine and abiraterone through the activation of caspases-6, -7, and -8 pathways were supported by qRT-PCR. In silico study of the compound 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine showed stable and promising interaction with the key caspase proteins. Our studies revealed that the pyridosteroid 3-hydroxy-5-en-2',3'-dicarbethoxy-androst[17,16- b]pyridine, bearing pyridine-2,3-dicarbethoxy pharmacophore, facilitated initiation of caspase-8 and activates downstream effectors caspase-6 and caspase-7 and thereby triggering apoptosis of PC-3 cancer cells.

The major hallmarks of Epithelial-Mesenchymal Transition (EMT) is the loss of epithelial cell polarity and loss of expression of the cell- cell adhesion molecule like E-cadherin and acquired mesenchymal cells marker called N-Cadherin. This phenotypical changes of E-M plasticity of cells is extensively considered to be a crucial factor for tumor cells invasion and cancer metastasis; landmark events for transforming a locally growing tumor (benign tumor) into a systemic and live-threatening disease (malignant tumor). Cadherin molecules are adherens junction proteins and expressed as multiple isoforms. Cadherin switching occurs during normal tissue developmental processes; also recapitulates the increasing aggressive behavior and metastatic nature of cancer cells when E-Cadherin converts to N-Cadherin, in particular. There are several mechanisms established that cadherin switching and some of the underlying pathways involves multiple steps associated with migration and invasion of cancer cells, and finally colonization of micro metastatic lesions to form macro-metastasis. Inhibition of metastasis is complicated by the plasticity of cancer cells behaviors and the evolving nature of microenvironment. Although there is no clear evidence how that dynamic structural switching of cadherin family member occurs, stabilized and eventually influence cell behavior, phenotypic transformations and initiate tumorigenesis. Therefore, we emphasize here the major functions of over 20 existing human cadherins in tissue integrity and stability as well as mechanistic understanding on recent work of cadherin ectodomain-mediated adhesion, functional studies of the cell-cell adhesion through key signaling intermediates interacting with other binding partners. We hope understanding on how the dynamic all existing cadherins influence the cell behavior can be targeted to design possible therapeutic interventions to combat its activity and prevent tumor cell growth, invasion and metastasis.

Ovarian carcinomas relate to highest death rate in gynecologic malignancies as absence of symptoms shield the disease in the early stage. Current evidences have been devoted to discovering early effective screening mechanism prior to the onset of clinical symptoms. Therefore, biomarkers are the crucial tools that are capable of predicting progression, risk stratification and overall therapeutic benefit to fight against this deadly disease. Although recent studies have revealed serum protein markers, CA-125, HE4, mesothelin etc. have higher sensitivity and specificity at the early stages of the cancer; the critical questions arise regarding the applicability and reproducibility of genomic profiling across different patient groups. Hence, our hypothesis is that the panels of signature biomarkers will be much more effective to improve the diagnosis and prediction of patient survival outcome with high sensitivity and specificity. Ovarian cancer is heterogeneous in nature and contain a sub-population of stem cell-like characteristics that has the ability to grow as anchorage-independent manner and subsequently is able to metastasize. Highly tumorigenic and chemotherapy-resistant cancer stem cells (CSCs)-specific biomarkers therefore reflects the interesting possibilities to be targeted to minimize the high frequency of relapse and resistance to drugs. Several putative ovarian CSC markers such as CD24, CD44, CD133, SSEA have already been proposed in recent studies, yet, a large panel of updated biomarkers have high clinical relevance to define the prospective isolation of viable circulating CSCs. Therefore, this review highlights current evidence based updated ovarian cancer specific prognostic and diagnostic biomarkers and potential importance of CSCs in context of tumorigenicity and metastatic activity for fundamental biological and clinical implications.

Breast cancer is found to be the most prevalent neoplasm in women worldwide. Despite the function of physically tethering cells to the matrix, transmembrane protein integrins are crucially involved in diverse cellular functions such as cell differentiation, proliferation, invasion, migration, and metastasis. Dysregulation of integrins and their interactions with the cells and their microenvironment can trigger several signaling cues that determine the cell fate decision. In this review, we spotlight all pre-existing integrin molecules, their structure, molecular interactions motifs, and function through several cross talks with kinase receptors. We also discuss the role of these integrins as potential prognostic and therapeutic targets and also in the regulation of breast cancer cells differentiation. Understanding of integrin structure and their motifs for ligand interactions in this context will enable the development of new therapeutic approaches to sensitize the tumors and their microenvironment to conventional therapy and overall suppress their metastatic phenotype.

Green, eco-friendly method for synthesis of Au-Ag-In-rGO nanocomposite was developed using leaf extract of Piper pedicellatum C.DC. Its characterization was done by UV–Visible, FT-IR, XRD, XPS, EDX and TEM analysis. The α-glucosidase inhibitory assay revealed that the Au-Ag-In-rGO has excellent inhibitory potency compared to GO where Acarbose was used as positive control. The IC 50 value was found 0.178 ± 0.01 and 1.330 ± 0.28 µg/ml for Au-Ag-In-rGO and GO respectively. Cytotoxicity assay indicated that Au-Ag-In-rGO is more toxic than GO nanoparticles against PC3 prostate cancer cells compared to non-tumorigenic prostate epithelial cells, RWPE-1.

2D carbon nanomaterials such as graphene and its oxide counterpart have sought good research attention for their application as well as fundamental interest. Especially the versatility of graphene oxide establishes its elite candidature in every field because of diverse application potential. Here we are reporting a greener, eco-friendly and cost effective one step hydrothermal route for the synthesis of potassium doped graphene oxide (K-doped GO) from agricultural waste i.e. Quercus ilex Fruit. The elemental analysis and XPS study showed the high percentage (6.81%) of natural doping of potassium. The K-doped GO is specific and demonstrates bright blue photoluminescence (PL) under UV-light (λex = 365 nm). Low toxicity, intracellular localization, good biocompatibility and strong PL properties of the synthesized K-doped GOs portray it as an excellent bio-imaging agent holding great promise in analytical and biological fields.

In the present study, seven axenic fresh water microchlorophytes were isolated and identified as Tetradesmus dimorphus (NEIST BT-1), Chlorella sorokiniana (NEIST BT-2), Desmodesmus sp. (NEIST BT-10), Selenastrum sp. (NEIST BT-A6), Tetradesmus obliquus (NEIST BT-A1), Tetradesmus sp. (NEIST BT-A10), and Asterarcys sp. (NEIST BT-A15) based on morphological and molecular characterization. Their potential to be used as biodiesel feedstock was evaluated depending on their growth characteristics and lipid profiles. Among the seven isolates, NEIST BT-2 was found to be the most promising candidate owing to its high biomass yield (2.09 ± 0.037 g L(−1)) and lipid productivity (107.60 ± 10.175 mg L(−1) day(−1)). The gas chromatography analysis confirmed the presence of significant amounts of palmitic acid, linoleic acid, linolenic acid, and oleic acid in the isolate which are some of the major constituents of any biodiesel. The predictive models showed that the biodiesel from this isolate has ideal fuel properties which comply with the ASTM D6751 and EN 14214 specifications. These findings demonstrate that NEIST BT-2 can be used as a prospective candidate for consideration of large-scale biodiesel production. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13205-019-1664-1) contains supplementary material, which is available to authorized users.

Aptamers are promising alternative binders and single-stranded DNA or RNA sequences. They are of 20–60 bases long which have the skill to fold into secondary and tertiary structures. They have the ability to bind with the specific target including amino acids, drugs, proteins and entire cells with high affinity and specificity. Due to the advances in aptamer selection technologies and nanomedicine, aptamer-functionalized nanoparticles are being explored as promising platforms for targeted therapeutic and diagnostic applications with their high affinity, specificity, and stability in cancer therapy. It has been reported that aptamers can bind to different cancer cell types with high affinity and also have gained attraction in numerous application together with their use on nanostructured materials. Although it is very complex, low drug loading capability and requires costly preparation procedures, it is considered as an alternative to antibodies in many biological applications because of its higher affinity and stability for binding with some ligands. In this chapter, we have highlighted the importance of aptamer-conjugated functionalized nano-biomaterials for diagnostic and targeted drug delivery applications in cancer therapies. In addition, we have also emphasized recent progress on the advantages, disadvantages, current challenges, and future perspectives in current drug delivery systems.

Cardiovascular disease is one of the major threats to global health with an increasing mortality rate over the past few years, giving utmost importance to the early diagnosis and prevention of cardiovascular disorder (CVD). Current studies reported that the most important validated biomarkers used for the detection of cardiac infarction include troponin T (cTn), troponin I (cTnI), C-reactive protein (CRP), creatine kinase MB (CK-MB), myeloperoxidase (MPO), and myoglobin (cMb). But the major concern is the detection of those biomarkers at very low concentrations during onset of disease. Therefore, a highly efficient, rapid, and sensitive detection method is urgently needed. Currently, chemiluminescent, fluoro-and radioimmunoassay, colorimetric, conventional ELISA-based approaches are being used for the detection of biomarkers, although these approaches are not very reliable in many cases. Biosensors play a crucial role in point-of-care diagnostics due to their simplicity, rapidness, low cost, and analysis in real time. Most importantly, the electrochemical biosensor approach is one of the efficient methods for the early detection of biomarkers. It is noteworthy to mention that a single biomarker is not sufficient for early detection of CVD in an efficient way. Instead, a panel of biomarkers’ detection approach in a single platform will improve the quality of life for CVD individuals and reduce the financial burden to health care providers. In this book chapter, we summarize the current advances on various strategies and methods with their analytical performances used for detecting transcriptome and protein-based emerging CVD biomarkers in biological samples. We also propose a multiplex diagnosis approach that may significantly improve the early, fast, accurate diagnosis and point-of-care application.

Cancer is a major burden of disease worldwide and requires an effective therapeutic approach. Several strategies have been developed to formulate a safer anti-cancer drug. Despite the significant advances in the development of new drug delivery systems, it remains a challenge for most of the chemotherapeutic drugs with its narrow therapeutic index, poor water solubility, and slow drug delivery systems. Nanotechnology has emerged as a potential alternative for strategic cancer therapy through the formulation of polymeric nanoparticles for drug delivery systems in overcoming the inherent limitations of the physicochemical properties of poorly soluble anticancer drugs. Among the polymeric nanoparticles, polysaccharide-based nanoparticles have gained huge attention due to their safety, biodegradability, biocompatibility, low immunogenicity, and the low cost of the biopolymers. Most importantly, polysaccharides are of a wide range of molecular weights and contain several chemical functional groups suitable for bio-conjugate modifications. The conjugation of a hydrophobic drug with hydrophilic polysaccharide nanoparticles surpasses the barrier of solubilization and regulates the control release of hydrophobic moieties; thereby it promotes the therapeutic benefit by extending the half-life of drugs and potential pharmacological responses. Such nanoconjugate formulations eliminate the local adverse effects and instability drawbacks of many existing delivery systems. Considering the recent advances on several delivery systems for clinical use in therapeutic applications, in this chapter we highlight the current advances in characteristics and applications of various polysaccharide-based nanoparticles for improving cancer therapy. We hope that once the major concerns are addressed, polysaccharide-based nanoconjugate drug delivery strategy will improve the diagnosis, treatment, and prognosis of cancer.

We report the construction and characterization of a novel, level free impedimetric immunosensor for rapid, sensitive and selective detection of myoglobin (Mb). Monoclonal anti-myoglobin (anti-Mb-IgG) antibody was immobilized on screen-printed multiwalled carbon nanotubes electrode for signal amplification without the need of natural enzymes. The fabrication of resulting immunosensor was extensively characterized by using scanning electron microscopy (SEM), fourier transform infrared (FT-IR) spectroscopy, cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Electrochemical impedance spectroscopy (EIS) technique offered a linear detection range (0.1-90ngmL(-1)) of myoglobin with sensitivity of 0.74kΩngmL(-1) (correlation coefficient, R(2)=0.97) and detection limit of 0.08ngmL(-1) (S/N=3). The mean percentage recovery of Mb in serum samples using this working biosensor is 97.33%. Furthermore, the proposed strategy can be a promising alternative for detection of Mb related cardiovascular disorders.

An eco-friendly, very simple method for synthesis of gold-reduced graphene oxide (Au-rGO) nanocomposite was developed using fruit of Piper pedicellatum C.DC. Its characterization was done by UV–visible, FT-IR, XRD, XPS, Raman, SEM-EDX, TEM analysis. The antibacterial activity of Au-rGO nanoparticles was investigated against the Gram negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and Gram positive bacteria Staphylococcus aureus and Bacillus cereus . In addition, in-vitro cell based cytotoxicity study was performed for Au-rGO and GO against PC3 (aggressive human prostate carcinoma cell line) and RWPE-1(non-malignant human prostate epithelial cells). Cytotoxicity assay revealed that Au-rGO is more toxic than GO nanoparticles against PC3 cancer cells compared to RWPE-1

Isothiocyanates (ITCs) are small molecules that are important in synthetic organic chemistry, but their actual importance lies in their potential as anti-carcinogens. Through this piece of work, an effort was made to assess the anti-cancer activity of some simple ITCs which can be synthesized through easy greener pathways.Cell proliferation assay was performed on ovarian cancer cells (PA-1) and non-tumorigenic ovarian epithelial cells (IOSE-364). Furthermore, qRT-PCR for transcript expression levels of Spindlin1 and caspases in ovarian cancer cells and cell cycle analysis was performed. In silico studies were incorporated to understand the mode of ligand-protein interaction, ADME/Toxicity and drug-likeliness parameters. Density functional theory studies have been also been employed on the ITCs to assess their efficiency in anticancer activity.An inexpensive, environmentally benign pathway has been developed for synthesizing a series of ITCs. Among the synthesized ITCs, NC6 showed better cytotoxic effects as compared to its counterparts. Novel findings revealed that NC6 had 5-folds lower transcript expression levels of Spindlin1 and induced caspases 3 and 7 expressions assessed by qRT-PCR in ovarian cancer cells. Furthermore, flow cytometry assay showed the cell cycle arrest at G1/S phase of cell cycle. The molecular docking studies revealed favorable binding affinities and the physiochemical parameters were predicted to be compatible with drug-likeliness.The results demonstrated the possibility that small isothiocyanate molecules which can be synthesized by a simple green methodology, can pose as promising candidates for their application as anticancer agents.

Graphene Oxide (GO) has been extensively studied in the field of biomedical sciences as one of the most promising biomaterials due to its exceptional physiochemical properties. Experts have long favored anticancer drug cocktails over single drugs, given that the former may provide a more balanced molecular basis for novel chemotherapeutic strategies. Here, we investigated a combinatorial anticancer drug treatment involving the well-proven anticancer drugs quercetin and gefitinib and compared it with gefitinib and quercetin loaded separately onto polyvinylpyrrolidone (PVP)-functionalized graphene oxide (GO-PVP). The loading and cancer cell cytotoxicity of the individual drug systems and their combined loading onto GO-PVP nanovehicles were investigated in PA-1 ovarian cancer cells and compared to their effects on IOSE-364 ovarian epithelial cells. In this report, the combined drug system loaded on the GO-PVP nanovehicle was found to be significantly more toxic than the individual drug loaded systems, as well as the free drugs, toward PA-1 cells compared to the toxicity toward IOSE-364 cells. The combined drug system loaded on the GO-PVP nanovehicle is likely to be more successful than individual drug therapy, given the stronger impact of the combinatorial approach and the efficiency of chemotherapeutic delivery.

Epithelial-mesenchymal transition (EMT) is a key step in transdifferentiation process in solid cancer development. Forthcoming evidence suggest that the stratified program transforms polarized, immotile epithelial cells to migratory mesenchymal cells associated with enhancement of breast cancer stemness, metastasis, and drug resistance. It involves primarily several signaling pathways, such as transforming growth factor-β (TGF-β), cadherin, notch, plasminogen activator protein inhibitor, urokinase plasminogen activator, and WNT/beta catenin pathways. However, current understanding on the crosstalk of multisignaling pathways and assemblies of key transcription factors remain to be explored. In this review, we focus on the crosstalk of signal transduction pathways linked to the current therapeutic and drug development strategies. We have also performed the computational modeling on indepth the structure and conformational dynamic studies of regulatory proteins and analyze molecular interactions with their associate factors to understand the complicated process of EMT in breast cancer progression and metastasis. Electrostatic potential surfaces have been analyzed that help in optimization of electrostatic interactions between the protein and its ligand. Therefore, understanding the biological implications underlying the EMT process through molecular biology with biocomputation and structural biology approaches will enable the development of new therapeutic strategies to sensitize tumors to conventional therapy and suppress their metastatic phenotype.

Efficient extraction of proteins is a great challenge for numerous downstream proteomic analyses. During the protein extraction procedure, it is critical to maintain the conformational stability, integrity, as well as higher yield of the protein. To do so, 5-different lysis buffers of Tris and HEPES have been used as the primary buffering reagents with variable compositions at different concentrations and pH using human cancer cells. In this study, different protein lysates of human breast cancer cells T47D and MDA-MB-231 and ovarian cancer cell PA-1 were subjected to run SDS-PAGE for separation of proteins based on their molecular size, followed by Coomassie blue, silver staining, and immunoblot assays to compare the extraction yield of total cytoplasmic proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the integral membrane protein, integrin β-1. Our results revealed that Tris-based lysis buffer with 50 mM concentration, pH 7.5, is relatively the efficient and reliable protein extraction method for a wide range of MW subcellular markers, cytoplasmic GAPDH and transmembrane integrin β-1 proteins. We anticipate that this simple and cost-effective protein extraction protocol might be extremely useful across a broad range of subcellular proteins in different biologic samples.

Prostate-derived Ets transcription factor (PDEF) is a member of the Ets transcription factor family originally identified in prostate tissue. PDEF functions like a tumor metastasis suppressor. Although the underlying mechanism is not very clear. In this study, a significantly higher expression level of integrin β3 was observed in aggressive prostate cancer (PCa) cells; PC3, that lack the expression of PDEF, was confirmed by quantitative real-time polymerase chain reaction and the immunoblot analysis. Dual immunofluorescence studies have confirmed the lower expression of PDEF and higher expression level of integrin β3 in PCa cells compared with non-tumorigenic prostate epithelial RWPE-1 cells. Then, it was attempted to identify integrin β3-mediated downstream signaling pathways that modulate actin cytoskeleton remodeling in PCa cells. Inhibition of PDEF by RNA interference (PDEFKD ) in DU145 cells confirmed by transcript and western blot analysis, exhibited significantly higher expression level of integrin β3 and its downstream signaling molecules talin and paxillin, associated with promoting migration and invasion of cells. Given the involvement of integrin-mediated invasion of cells, PDEFKD DU145 cells were treated with Echistatin, a potent integrin β3-specific antagonist and found that the cells significantly reduced the transcript and protein expression levels of talin and paxillin; and reduced the invasion of cells. Overall, the cytoskeleton remodeling by integrin β3, modulated by PDEF, may represent a novel molecular link with cell adhesion and migration leading to the suppression of metastasis in PCa cells.

Ovarian cancer is the most lethal of all common gynaecological malignancies in women worldwide. Ovarian cancer comprises of >15 distinct tumor types and subtypes characterized by histopathological features, environmental and genetic risk factors, precursor lesions and molecular events during oncogenesis. Recent studies on gene signature profiling of different subtypes of ovarian cancer have revealed significant genetic heterogeneity between and within each ovarian cancer histological subtype. Thus, an immense interest have shown towards a more personalized medicine for understanding the clinical and molecular complexities of four major types of epithelial ovarian cancer (serous, endometrioid, clear cell, and mucinous). As such, further in depth studies are needed for identification of molecular signalling network complexities associated with effective prognostication and targeted therapies to prevent or treat metastasis. Therefore, understanding the metastatic potential of primary ovarian cancer and therapeutic interventions against lethal ovarian cancer for the development of personalized therapies is very much indispensable. Consequently, in this review we have updated the key dysregulated genes of four major subtypes of epithelial carcinomas. We have also highlighted the recent advances and current challenges in unravelling the complexities of the origin of tumor as well as genetic heterogeneity of ovarian cancer.

Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre-Pparb/d−/−) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 (Lrg1), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of Lrg1 by PPARβ/δ in fibroblasts is an important signaling conduit integrating PPARβ/δ and TGFβ1-signaling networks in skin health and disease. Thus, the FSPCre-Pparb/d−/− mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis.