Dynamic Virtual Machine Migration using Network Aware Topology

Clients of the applications communicate with the services hosted in the VMs. Many applications have clients all over the world. An application is expected to provide faster access and transmission of data to its clients if it is geographically close to its clients, as some of the research work suggests that geographical distance has impact on quality of service (QoS) [1,2,3]. In order to provide a faster access and data transfer, applications which have clients all over the world should be hosted in a data center, which is on average close to its clients geographically

Basal cell carcinoma in oculo-cutaneous albinism

The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition and diagnosis of suspected lesions by performing histopathological examination in unusual circumstances

Nebulization based Inhalation Nanomedicine for Lung Cancer Treatments

Background: Lung cancer is reported to have a high incidence rate and first leading cause of cancer-related morbidity and mortality across the world including in the United States. Noninvasive nebulized inhalation is a promising delivery strategy for lung, which can enhance the targeting efficiency and detention time interval of nanoparticles in the lung tissue, thus elevating the therapeutic index of therapeutic agent(s) at lower dosages. The aim of this study is to develop inhalable nanoparticles (INPs) for effective delivery of therapeutic agents in lung cancer cell lines and ex vivo models. Methods: The inhalation nanoparticles (INPs) were prepared by solvent evaporation and self-assembly approach. The INPs formulations were characterized by particle size, chemical composition, and drug loading efficiency using various analytical methods including FT-IR, DSC, SEM, and DSC/TGA. Cellular uptake of INPs was evaluated in 2D and 3D models of lung cancer cell lines (A549 and NCI-H1299) using fluorescence microscopy and flow cytometry analysis. Additionally, the therapeutic evaluation of gambogic acid and gemcitabine encapsulated INPs was performed by basic in vitro biological assays using proliferation (CCK-8), mucoadhesion Boyden chamber, and apoptosis assays using lung cancer (A549 and NCI-H1299) monolayers, spheroids, and xenograft tumors. Results: The developed INPs exhibited an average size of ~110 nm in dynamic light scattering measurements. INPs formulation showed a remarkable mucoadhesion and mucopenetration potential in-vitro model(s). Cellular uptake studies demonstrated that INPs formulation facilitates an effective endosomal release into the cytosol. The in vitro study confirms that INPs release the drugs in a sustained manner. Additionally, the INPs formulation showed superior in vitro anti-cancer activity in lung cancer cell lines, spheroids and xenograft tumor. Conclusions: Altogether this study confirms that INPs formulation demonstrates an improved therapeutic benefit over free drug against lung cancer cell lines, spheroids and xenograft tumor. This study could lead as an innovative therapeutic modality for the treatment of lung cancer

Role of Terpenoids Active Ingredients Targeting for Neuroprotective Agents

Neuroinflammation is a characteristic sign of a wide variety of neurodegenerative diseases, including Alzheimer\u27s and Parkinson\u27s, amongst others. Microglia, which are native immune cells found in the brain, become activated very quickly in response to a brain infection or injury. When microglia become overactivated, their production of pro-inflammatory and cytotoxic chemicals can become unregulated and uncontrolled, which is the primary cause of neuroinflammation. Microglia are principally responsible for neuroinflammation. As a result, the investigation of novel approaches to reduce neuroinflammatory reactions is an essential component of neurodegenerative disease treatment. In the research of brain inflammation, bacterial lipopolysaccharide is frequently used. This compound is responsible for the initiation of a number of significant cellular processes that significantly contribute to the pathophysiology of neuroinflammation

Antibacterial finish of textile using papaya peels derived silver nanoparticles

The present study is aimed at the extracellular synthesis of highly stable silver nanoparticles for the development of nanosafe textile using the extracts of yellow papaya peel. Fabric is treated with nanoparticles using dip and dry method to observe the effect of antibacterial activity. The synthesized nanoparticles are also characterized and quantified. Due to their potent antibacterial activity, papaya peels derived silver nanoparticles can be incorporated into fabrics and the manufacturers can make textiles free from spoilage by microorganisms

In Vitro Propagation and Conservation of Inula Racemosa Hook. F. an Endangered Medicinal Plant of Temperate Origin

Inula racemosa is an endangered medicinal plant. It is commonly known as Pushkarmool, Pushkar and Manu. The great sage Charaka has characterized it as Hikka magrahana (stops hiccups) and Savasahara (helpful in asthma). Also, he has cited it as the best medicament for pleurisy along with cough and asthma (http://enwikipedia.org/wiki/charaka-samhita). Due to the fragile nature of its habitat and exploitation due to its commercial medicinal properties, the species are facing the onslaught of indiscriminate over-exploitation. So far, this plant has not got the required attention from researchers, hence, except for a few efforts, not much work has been done for its cultivation and conservation. Plant tissue culture offers an attractive and quick method for its multiplication and further conservation. In the present investigation, effective procedures for micropropagation and in vitro conservation by vitrification were developed. In vitro propagation using aseptically grown seedlings and in vitro conservation via vitrification were standardized. The in vitro conserved material could be retrieved and multiplied normally on MS (Murashige and Skoog, 1962) medium fortified with 1.00 mg l-1BA (benzyl adenine) which has been recorded as the best performing medium for in vitro shoot multiplication. The conserved shoots showed normal in vitro propagation and after retrieval from vitrification, platelets were hardened and successfully established in the experimental fields under Nauni (Solan, HP) conditions at an elevation of around 1275 meters above mean sea level

Piperlongumine nanoformulation attenuates pancreatic tumor desmoplasia and alter tumor immune responses

Pancreatic cancer (PanCa) is characterized by lack of early diagnosis, poor response to available therapeutic modalities and chemoresistance. Gemcitabine (GEM) is currently considered the most effective therapy for PanCa; however, it shows only a marginal survival benefit of 6 months. This poor drug response has been attributed to desmoplasia, causes suboptimal drug delivery, alters tumor microenvironment (TME), which includes tumor surrounding blood vessels, fibroblasts, immune cells, extracellular matrix, and other signaling molecules and induces chemo-resistance in tumors. To overcome these existing issues associated with chemotherapy, identification and development of novel therapeutic modalities are a pressing need. Piperlongumine (PL) is a natural alkaloid isolated from the long pepper, Piper longum L., and has shown substantial cancer-preventive and therapeutic efficacy against a variety of cancers. However, delivering its effective concentration in pancreatic tumors has been challenging. We have recently engineered a multi-layered Pluronic F127 and polyvinyl alcohol stabilized, and poly-L-lysine coated piperlongumine loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PLGA-PL), which effectively inhibits the growth of PanCa cells. In this study, we demonstrate that PLGA-PL effectively sensitizes tumor cells to GEM via decreased desmoplasia, altered TME, SHH/CXCL12/CXCR4 and immune surveillance. Our finding show that PLGA-PL synergizes with GEM in inhibiting PanCa cell (HPAF-II and Panc-1) growth, migration, and invasion compared to free PL. Mechanistically, PLGA-PL targets the TME via inhibition of sonic hedgehog (SHH) pathway and oncogenic CXCR4/CXCL12 signaling axis that inhibits bidirectional tumor-stromal cells interaction. We have also found that PLGA-PL alone and in combination with GEM targets cancer stem cells by inhibiting pluripotency maintaining stemness factors (Nanog, Sox2, c-Myc, CD133, and Oct-4) as determined by qRT-PCR, Western blotting, and immunofluorescence analysis, and further confirmed by restricting tumor sphere formation. Furthermore, PLGA-PL also effectively targets tumor-associated macrophages (TAM) by repolarizing M2 into M1 phenotype via inhibiting expression of M2 markers and an increase in M1 markers in mouse macrophage cell line RAW264.7. M2 polarization of RAW264.7 cells were induced by culture with IL-4 (20 ng/mL) in presence of PLGA-PL or vehicle control. In addition, PLGA-PL effectively increases phagocytic capacity in murine macrophages as determined by phagocytosis assay (Vybrant Phagocytosis Assay Kit). In conclusion, we observed that PLGA-PL effectively targets TME, facilitates GEM uptake by inhibiting the activation of CXCR4/CXCL12/SHH signaling, and reprograming the tumor immune surveillance. This study suggests that PLGA-PL has great potential for future clinical use in management of PanCa

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics

Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and the potential of Withania somnifera (WS) as an anticancer and immunomodulatory molecule. Several preclinical studies have shown the potential of WS to prevent or slow the progression of cancer originating from various organs such as the liver, cervix, breast, brain, colon, skin, lung, and prostate. WS extracts act via various pathways and provide optimum effectiveness against drug resistance in cancer. However, stability, bioavailability, and target specificity are major obstacles in combination therapy and have limited their application. The novel nanotechnology approaches enable solubility, stability, absorption, protection from premature degradation in the body, and increased circulation time and invariably results in a high differential uptake efficiency in the phytochemical\u27s target cells. The present review primarily emphasizes the insights of WS source, chemistry, and the molecular pathways involved in tumor regression, as well as developments achieved in the delivery of WS for cancer therapy using nanotechnology. This review substantiates WS as a potential immunomodulatory, anticancer, and chemopreventive agent and highlights its potential use in cancer treatment

Antibody-Drug Conjugates for Cancer Therapy: Chemistry to Clinical Implications

Chemotherapy is one of themajor therapeutic options for cancer treatment. Chemotherapy is often associated with a low therapeutic window due to its poor specificity towards tumor cells/tissues. Antibody-drug conjugate (ADC) technology may provide a potentially new therapeutic solution for cancer treatment. ADC technology uses an antibody-mediated delivery of cytotoxic drugs to the tumors in a targeted manner, while sparing normal cells. Such a targeted approach can improve the tumor-to-normal tissue selectivity and specificity in chemotherapy. Considering its importance in cancer treatment, we aim to review recent efforts for the design and development of ADCs. ADCs are mainly composed of an antibody, a cytotoxic payload, and a linker, which can offer selectivity against tumors, anti-cancer activity, and stability in systemic circulation. Therefore, we have reviewed recent updates and principal considerations behind ADC designs, which are not only based on the identification of target antigen, cytotoxic drug, and linker, but also on the drug-linker chemistry and conjugation site at the antibody. Our review focuses on site-specific conjugation methods for producing homogenous ADCs with constant drug-antibody ratio (DAR) in order to tackle several drawbacks that exists in conventional conjugation methods

Integrative transcriptomics data analysis of TRPV1 in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective Ca2+ channel protein that is widely expressed and plays a significant role in cancer initiation and progression. However, the biological significance of TRPV1 in HCC has not been systematically and comprehensively investigated. Using deep data mining and transcriptomics analyses, in this study, we described the significance of TRPV1 expression and its association with HCC prognosis. Methods: TRPV1 mRNA expression in HCC was examined using the Cancer Genome Atlas (TCGA), the Genotype Tissue Expression Atlas (GTEx), the Tumor Immune Estimation Resource (TIMER), and the UALCAN databases to examine the relationship between the expression of TRPV1 and the clinicopathological characteristics of HCC. The genetic alterations and frequency of TRPV1 were analyzed using the cBioPortal and COSMIC databases. The correlations between TRPV1 and tumor-infiltrating immune cells were examined using the TIMER 2.0, TISIDB, and GEPIA databases. The data processing analysis is based on the R language. LinkedOmics was used for TRPV1 co-expression network analysis. Results: TRPV1 mRNA expression was upregulated in HCC samples as compared to normal liver tissues. Kaplan-Meier analysis demonstrated that high expression of TRPV1 is associated with better prognostic significance for overall survival (OS) and disease-free survival (DFS) in HCC patients. The mutation landscape analysis confirms that TRPV1 genetic alterations reached 6%, of which missense substitutions accounted for the highest proportion of 16.16%. The findings of the TIMER analysis indicated a correlation between immune cell infiltration and TRPV1 copy number alterations (CNA). The expression level of TRPV1 was positively correlated with the infiltration level of CD4+ T cells but negatively correlated with CD8+ T cells, B cells, macrophages, and dendritic cell infiltration. Additionally, TRPV1 expression was also found to be associated with certain immunosuppressive cells, chemokines, and receptors. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, TRPV1 expression was found to be closely related to some immune pathways, including drug metabolism, PPAR signaling pathway, and chemical carcinogenesis. Conclusion: Our observation demonstrates that TRPV1 was highly expressed in HCC tissues and is linked to prognosis of HCC patients and tumor immune responses