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Arrhythmia is an important cause of death after myocardial infarction (MI). Different substances have been evaluated for their anti-arrhythmic effect in MI. This study was performed to evaluate the anti-arrhythmic impacts of crocin in an MI animal model (rat) by estimation of the expression of connexin 43 (Cx43). Fifty male Sprague-Dawley rats were grouped into 5 groups, each composed of 10 rats. The first group was regarded as the normal control group and the second one was considered as the MI group, which was caused by ligation of the left anterior descending artery. The other three groups received crocin 50 or 10 mg/kg/day or metoprolol 100 mg/kg/day for 1 week, following ligation of the left anterior descending artery. Evaluated outcomes were cardiac Cx43 expression, arrhythmia incidence, histological findings, and myocyte resting potential. Crocin-treated MI groups showed a significantly lower arrhythmia score than the non-treated MI group, 10 mg/kg/day (1.85 ± 0.55

Pathogenic bacterial strains can alter the normal function of cells and induce different levels of inflammatory responses that are connected to the development of different diseases, such as tuberculosis, diarrhea, cancer etc. Chlamydia trachomatis (C. trachomatis) is an intracellular obligate gram-negative bacterium which has been connected with the cervical cancer etiology. Nevertheless, establishment of causality and the underlying mechanisms of carcinogenesis of cervical cancer associated with C. trachomatis remain unclear. Studies reveal the existence of C. trachomatis in cervical cancer patients. The DNA repair pathways including mismatch repair, nucleotide excision, and base excision are vital in the abatement of accumulated mutations that can direct to the process of carcinogenesis. C. trachomatis recruits DDR proteins away from sites of DNA damage and, in this way, impedes the DDR. Therefore, by disturbing host cell-cycle control, chromatin and DDR repair, C. trachomatis makes a situation favorable for malignant transformation. Inflammation originated due to infection directs over production of reactive oxygen species (ROS) and consequent oxidative DNA damage. This review may aid our current understanding of the etiology of cervical cancer in C. trachomatis-infected patients.

Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials.

Gallbladder cancer (GBC) is one of the leading causes of cancer-related mortality worldwide. Researchers have investigated that specific strains of bacteria are connected with growth of different types of cancers in human. Some reports show possible implication of Helicobacter pylori (H. pylori) in the etiology of gallbladder cancer (GBC). Their enigmatic mechanisms, nevertheless, are not still well clear. We sought to predict whether various proteins of H. pylori targeted to nucleus of host cells and their implication in growth of gallbladder cancer. GBC is one of the leading causes of cancer mortality worldwide. We applied bioinformatics approach to analyze the H. pylori proteins targeting into the nucleus of host cells using different bioinformatics predictors including nuclear localization signal (NLS) mapper Balanced Subcellular Localization (BaCelLo) and Hum-mPLoc 2.0. Various nuclear targeting proteins may have a potential role in GBC etiology during intracellular infection. We identified 46 H. pylori proteins targeted into nucleus of host cell through bioinformatics tools. These H. pylori nucleus-targeting proteins might alter the normal function of host cells by disturbing the different pathways including replication, transcription, translation etc. Various nucleus-targeted proteins can affect the normal growth and development of infected cells. We propose that H. pylori proteins targeting into the nucleus of host cells regulate GBC growth using different strategies. These integrative bioinformatics research demonstrated several H. pylori proteins that may serve as possible targets or biomarkers for early cure and treatment or diagnosis GBC.

Background Infections of Salmonella typhimurium (S. typhimurium) are major threats to health, threats include diarrhoea, fever, acute intestinal inflammation, and cancer. Nevertheless, little information is available about the involvement of S. typhimurium in colon cancer etiology. Methods The present study was designed to predict nuclear targeting of S. typhimurium proteins in the host cell through computational tools, including nuclear localization signal (NLS) mapper, Balanced Subcellular Localization predictor (BaCeILo), and Hum-mPLoc using next-generation sequencing data. Results Several gene expression-associated proteins of S. typhimurium have been predicted to target the host nucleus during intracellular infections. Nuclear targeting of S. typhimurium proteins can lead to competitive interactions between the host and pathogen proteins with similar cellular substrates, and it may have a possible involvement in colon cancer growth. Our results suggested that S. typhimurium releases its proteins within compartments of the host cell, where they act as a component of the host cell proteome. Protein targeting is possibly involved in colon cancer etiology during intracellular bacterial infection. Conclusion The results of current in-silico study showed the potential involvement of S. typhimurium infection with alteration in normal functioning of host cell which act as possible factor to connect with the growth and development of colon cancer.

A coprecipitation process was utilized for the preparation of terbium fluoride nanocrystals by cerium fluoride. Silica was used to modify the surface of these core/shell nanocrystals. The synthesized CeF3:Tb@LaF3 and CeF3:Tb@LaF3@SiO2 nanoparticles (NPs) were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV/vis spectrophotometry, and photoluminescence spectrophotometry. XRD patterns showed resolved reflection planes with broad widths, confirming the nanocrystalline nature of the CeF3:Tb@LaF3@SiO2 NPs. Fourier transform infrared spectra clearly revealed a uniform, smooth silica layer encapsulating the luminescent seed core and confirmed the polycrystalline nature of the CeF3:Tb@LaF3@SiO2 NPs. The TEM result showed an average crystalline size of 18 nm, which illustrated good agreement with the XRD results. The results of photoluminescence spectrophotometry confirmed the doping of terbium ions in the CeF3 crystal lattice. The cytotoxicity results of the MTT assay showed that CeF3:Tb@LaF3@SiO2 NPs have minimum toxicity with respect to CeF3:Tb@LaF3 NPs and the control drug dasatinib on HT-29 and HepG2 cell lines. Moreover, results of inverted microscopy confirmed the nontoxic and biocompatible nature of CeF3:Tb@LaF3@SiO2 NPs. These findings show that CeF3:Tb@LaF3@SiO2 NPs are promising candidates for applications in biomedical science in the future, such as bioimaging, biolabeling, biodetection or bio-probing, labeling of cells and tissue, drug delivery, cancer therapy, and multiplexed analysis.

BackgroundThe epidemic of 2019 novel coronavirus (SARS-CoV-2) is challenge to the world which was at first confirmed in the Wuhan city of China in December 2019. It was declared a pandemic by the World Health Organization (WHO) in March 2020. In the current work we evaluated effect of health policy of Saudi Arabia for the management of COVID-19 pandemic in early phase and compared to other four countries. MethodBased on the Ministry of Health, Kingdom of Saudi Arabia (KSA) data, the summary of daily report of COVID-19 was prepared from 02 March to 30 April 2020. Further, the daily report of enhancement in cases and recovery of the patients was also summarized. Moreover, the incidence, death and recoveries of COVID-19 cases in KSA were compared with major infected country including China, Italy, Spain and United State of America (USA). The important role of artificial intelligence was shown for the development of drug targets against to infectious diseases Results In KSA, the first case of COVID-19 was reported on 02 March 2020. Since then, it has affected 22,753 persons till the end of the April 2020. Also, the results showed that the infection rate of COVID-19 increased continuously during the current period of study in KSA. Nevertheless, the rate of death due to COVID-19 is much less with comparison to China, Italy, Spain, and USA due to good medical facilities along with quick action by the government of KSA after the emergence of first case. There is a dire need to develop new platforms and approaches to combat new and old diseases including COVID-19 at warp speed when compared to traditional approaches. DeepDrug’s approach to drug discovery and development showed brighter future towards the discovery of novel drugs against infectious diseases including COVID-19.ConclusionCurrently, there is higher probability of COVID-19 spread at any place. Therefore good health policy, precautionary measures and medical facility of whole nations should be excellent to combat against the COVID-19 pandemic until the reliable vaccine or antiviral drug developed for the proper treatment of virus. The artificial intelligence (AI) based available process might be very helpful for the drug discovery and development against of old and newly discovered diseases including COVID-19.

Lanthanide nanocrystals (NCs) are the most promising luminescent materials for bioapplications, but their use is hindered by difficulties in obtaining biocompatible and photoluminescence lanthanide NCs. To solve this problem, a simple and versatile strategy was developed for improving the luminescence efficiency with the hydrophilicity of the lanthanide NCs. In this study, the effects of shell formation on structural, morphological, and optical properties (optical absorption, band-gap energy, excitation, emission, and luminescent decay time) were evaluated. To improve the luminescence efficiency and aqueous dispersion, luminescent core-NCs were encapsulated with inert NaGdF4 and amorphous silica layers. These surface coating layers significantly improved the luminescence efficiency and dispersion of the core/shell NCs in which the silica surface provides a negatively charged surface to the NCs at physiological pH. Optical properties of these NCs strongly depend on the external change of NCs, demonstrating the impact of coating in improving the luminescence efficiency. The outcomes can be ascribed to the development of surface chemical bonds between core/shell and noncrystalline SiO2 shell via GdOSi bridges, activating the ‘dormant’ Ce3+ and Tb3+ ions on the surface of NCs. An intensive emission and good hydrophilic property from the active functional groups in solutions show a great potential for applications such as multi-analyte fluorescent biolabeling, optical biosensing, staining, display, and other optical technologies. The core/shell/SiO2 NCs showed higher nontoxicity and biocompatibility with respect to the core NCs because of biocompatible silica surface modification, facilitating entry into the living cells. Therefore, this developed synthesis approach might advance the field of biomolecule-based nanotechnology in near future. Keywords: Core/shell/SiO2NCs, Toxicity, Absorption spectra, Optical band gap, Luminescent property

Despite the extensive implication of nickel oxide nanoparticles (NiO-NPs) in different fields such as biomedical science and industrial manufacturing, their effect on human cancer cells has not been elucidated. In this study, we report a simple process for the preparation of NiO-NPs. X-ray diffraction and transmission electron microscopy were used to characterize the surface architecture and dimension of the synthesized NiO-NPs. The average diameter of the NiO-NPs was approximately 20–25 nm. We used two human colon cancer cell lines, HT-29 and SW620, to assess the nanoparticles’ cytotoxicity. The MTT assay showed that the NiO-NPs reduced cell viability of HT-29 and SW620 cell lines. The results of inverted microscopy showed the highest cytotoxic activity with 600 μg/ml concentration of NiO-NPs on HT-29 cells. Western blot assay showed the downregulation of anti-apoptotic Bcl2 and Bcl-xL proteins in HT-29 cells treated with NiO-NPs. Moreover the results demonstrated the induction of PARP (Cleaved) in NiO-NPs treated HT-29 cells which are considered the marker of apoptosis. The NiO-NPs were not demonstrated bactericidal effect on six different bacterial strains tested, implying that the NiO-NPs may not perturb the human normal gut microbiome. The results have showed the promising application of the NiO-NPs in management of cancer in near future.

Gallbladder cancer (GBC) is one of the leading causes of cancer-related mortality worldwide. Researchers have investigated that specific strains of bacteria are connected with growth of different types of cancers in human. Some reports show possible implication of Helicobacter pylori (H. pylori) in the etiology of gallbladder cancer (GBC). Their enigmatic mechanisms, nevertheless, are not still well clear. We sought to predict whether various proteins of H. pylori targeted to nucleus of host cells and their implication in growth of gallbladder cancer. GBC is one of the leading causes of cancer mortality worldwide. We applied bioinformatics approach to analyze the H. pylori proteins targeting into the nucleus of host cells using different bioinformatics predictors including nuclear localization signal (NLS) mapper Balanced Subcellular Localization (BaCelLo) and Hum-mPLoc 2.0. Various nuclear targeting proteins may have a potential role in GBC etiology during intracellular infection. We identified 46 H. pylori proteins targeted into nucleus of host cell through bioinformatics tools. These H. pylori nucleus-targeting proteins might alter the normal function of host cells by disturbing the different pathways including replication, transcription, translation etc. Various nucleus-targeted proteins can affect the normal growth and development of infected cells. We propose that H. pylori proteins targeting into the nucleus of host cells regulate GBC growth using different strategies. These integrative bioinformatics research demonstrated several H. pylori proteins that may serve as possible targets or biomarkers for early cure and treatment or diagnosis GBC.

Hosts and microbes have co-evolved over millions of years. Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated diseases. Although the etiology of IBD remains an enigma, various studies have proposed the involvement of mucosa-associated Escherichia coli (E. coli) strains in the pathogenesis of IBD. E. coli, a usual inhabitant of the intestine, causes disease after acquiring virulence factors; however, the mechanisms underlying this phenomenon are not well understood. In the present review, we will discuss recent findings on how gut E. coli regulates and controls gut homeostasis and the pathogenesis of IBD. We will also summarize current knowledge regarding the cause, mechanism, genetics, and environmental factors involved in the regulation of IBD. Furthermore, we will discuss the possibility of alterations in innate and acquired immunity during the course of disease as well as possible treatment.

Collecting evidence suggests that the intercellular infection of Chlamydia pneumoniae in lungs contributes to the etiology of lung cancer. Many proteins of Chlamydia pneumoniae outmanoeuvre the various system of the host. The infection may regulate various factors, which can influence the growth of lung cancer in affected persons. In this in-silico study, we predict potential targeting of Chlamydia pneumoniae proteins in mitochondrial and cytoplasmic comportments of host cell and their possible involvement in growth and development of lung cancer. Various cellular activities are controlled in mitochondria and cytoplasm, where the localization of Chlamydia pneumoniae proteins may alter the normal functioning of host cells. The rationale of this study is to find out and explain the connection between Chlamydia pneumoniae infection and lung cancer. A sum of 183 and 513 proteins were predicted to target in mitochondria and cytoplasm of host cell out of total 1112 proteins of Chlamydia pneumoniae. In particular, many targeted proteins may interfere with normal growth behaviour of host cells, thereby altering the decision of program cell death. Present article provides a potential connection of Chlamydia pneumoniae protein targeting and proposed that various targeted proteins may play crucial role in lung cancer etiology through diverse mechanisms. Keywords: Lung cancer, Chlamydia pneumoniae, Etiology, Systems biology, Protein targeting

Copper oxide nanoparticles (CuO-NPs) were synthesized using a urea-based thermal decomposition technique, and characterized using different techniques. X-ray diffraction (XRD) and Raman spectroscopy confirmed the phase purity and crystalline structure of CuO-NPs. The size of CuO-NPs was investigated using XRD and was confirmed via dynamic light scattering analysis. CuO-NPs showed an average diameter of ∼20nm. The possible cytotoxicity of CuO-NPs was evaluated in HT-29 and SW620 cancer cell lines. The median inhibitory concentration of CuO-NPs in HT-29 and SW-620 cells was 4.99 and 3.75μg/mL, respectively. The underlying mechanism responsible for apoptosis in colon cancer cells after CuO-NP exposure has not been well understood. In this study, we investigated the possible mechanisms of induction of apoptosis via analysis of the expression of Bcl-2 and Bcl-xL proteins in HT-29 human colon cancer cells after CuO-NP exposure. Western blot assay showed downregulation of Bcl-2 and Bcl-xL protein expression after CuO-NP exposure. Our findings may aid in the understanding of the potential mechanisms responsible for induction of apoptosis owing to inhibition of Bcl-2 and Bcl-xL protein expression. Furthermore, the antibacterial activity assay showed that the synthesized CuO-NPs did not exert significant inhibitory effects against different gram-positive and gram-negative bacteria in vitro.

Indomethacin chitosan nanoparticles (NPs) were developed by ionotropic gelation and optimized by concentrations of chitosan and tripolyphosphate (TPP) and stirring time by 3-factor 3-level Box-Behnken experimental design. Optimal concentration of chitosan (A) and TPP (B) were found 0.6mg/mL and 0.4mg/mL with 120min stirring time (C), with applied constraints of minimizing particle size (R1) and maximizing encapsulation efficiency (R2) and drug release (R3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R1, while factor A has a negative impact on R2 and R3. Interaction of AB was negative on R1 and R2 but positive on R3. The factor AC was having synergistic effect on R1 and on R3, while the same combination had a negative effect on R2. The interaction BC was positive on the all responses. NPs were found in the size range of 321-675nm with zeta potentials (+25 to +32mV) after 6 months storage. Encapsulation, drug release, and content were in the range of 56-79%, 48-73% and 98-99%, respectively. In vitro drug release data were fitted in different kinetic models and pattern of drug release followed Higuchi-matrix type.

Cancer has long been assumed to be a genetic disease. However, recent evidence supports the enigmatic connection of bacterial infection with the growth and development of various types of cancers. The cause and mechanism of the growth and development of prostate cancer due to Mycoplasma hominis remain unclear. Prostate cancer cells are infected and colonized by enteroinvasive M. hominis, which controls several factors that can affect prostate cancer growth in susceptible persons. We investigated M. hominis proteins targeting the nucleus of host cells and their implications in prostate cancer etiology. Many vital processes are controlled in the nucleus, where the proteins targeting M. hominis may have various potential implications. A total of 29/563 M. hominis proteins were predicted to target the nucleus of host cells. These include numerous proteins with the capability to alter normal growth activities. In conclusion, our results emphasize that various proteins of M. hominis targeted the nucleus of host cells and were involved in prostate cancer etiology through different mechanisms and strategies.

Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are released into the extracellular milieu or body fluids; this process was reported for mesenchymal, epithelial, endothelial, and different immune cells (B-cells and dendritic cells), and was reported to be correlated with normal physiological processes. The compositions and abundances of exosomes depend on their tissue origins and cell types. Exosomes range in size between 30 and 100 nm, and shuttle nucleic acids (DNA, messenger RNAs (mRNAs), microRNAs), proteins, and lipids between donor and target cells. Pathogenic microorganisms also secrete exosomes that modulate the host immune system and influence the fate of infections. Such immune-modulatory effect of exosomes can serve as a diagnostic biomarker of disease. On the other hand, the antigen-presenting and immune-stimulatory properties of exosomes enable them to trigger anti-tumor responses, and exosome release from cancerous cells suggests they contribute to the recruitment and reconstitution of components of tumor microenvironments. Furthermore, their modulation of physiological and pathological processes suggests they contribute to the developmental program, infections, and human diseases. Despite significant advances, our understanding of exosomes is far from complete, particularly regarding our understanding of the molecular mechanisms that subserve exosome formation, cargo packaging, and exosome release in different cellular backgrounds. The present study presents diverse biological aspects of exosomes, and highlights their diagnostic and therapeutic potentials.

Cancer was initially considered a genetic disease. However, recent studies have revealed the connection between bacterial infections and growth of different types of cancer. The enteroinvasive strain of Mycoplasma hominis alters the normal behavior of host cells that may result in the growth of prostate cancer. The role of M. hominis in the growth and development of prostate cancer still remains unclear. The infection may regulate several factors that influence prostate cancer growth in susceptible individuals. The aim of this study was to predict M. hominis proteins targeted into the endoplasmic reticulum (ER) of the host cell, and their potential role in the induction of prostate cancer. From the whole proteome of M. hominis, 19 proteins were predicted to be targeted into the ER of host cells. The results of our study predict that several proteins of M. hominis may be targeted to the host cell ER, and possibly alter the normal pattern of protein folding. These predicted proteins can modify the normal function of the host cell. Thus, the intercellular infection of M. hominis in host cells may serve as a potential factor in prostate cancer etiology.

This paper presents the results from a systematic study into the characterization and anticancer and biological activity of synthesized super-paramagnetic manganese oxide nanoparticles (Mn3O4-NPs). The Mn3O4-NPs showed an IC50 value of 666.44 μg mL−1 on the HT29 human colorectal cell line. Furthermore, we investigated the molecular mechanism of Mn3O4-NPs for the inhibition of Bcl-2 and Bcl-xL through an in vitro study. Bcl-2 and Bcl-xL are key signaling regulators of the programmed cell death pathway and ensure proper apoptosis and have been proposed as a novel target for anticancer therapy. The down-regulation of Bcl-2 and Bcl-xL on the HT29 cancer cell line showed that the NPs under study could be useful in the treatment of cancer. The down-regulation of the anti-apoptotic regulators Bcl-2 and Bcl-xL enhances cytotoxicity in colon carcinoma cells connected with the induction of apoptosis. Moreover, the in vitro haemolysis study antibacterial tests showed that Mn3O4-NPs have no significant toxicity and antibacterial activity, thereby exhibiting their biocompatibility and reliability in biomedical sciences.

In the current study, we modified the surface of Tb(OH)3 nanoparticles with a silica layer to enhance their solubility and biocompatibility. Transmission electron microscopy confirmed the improvements in these properties. Tb(OH)3@SiO2 core–shell nanoparticles (TS-CSNPs) exhibited a strong green emission peak upon irradiation with ultraviolet light, which originates from the electric-dipole transition 5D4 → 7F5 (543 nm) of the Tb3+ ion. In vitro anticancer and antimicrobial activities of the synthesized TS-CSNPs has been evaluated through their potential cytotoxicity and antibacterial activity. TS-CSNPs were shown to have more cytotoxicity against HT29 human colorectal cancer cells with a value of IC50 420.33 in an MTT assay. The alteration of the morphological features of HT29 cells was analysed using various concentrations of TS-CSNPs by inverted microscopy. Western blot analysis results of the apoptotic pathway showed that TS-CSNPs inhibited the growth of HT29 cancer cells through the induction of apoptosis, as evidenced by the down regulation of the expression of anti-apoptotic Bcl-2 and Bcl-xL gene products. Furthermore, the results of the in vitro hemolysis assay with human erythrocytes demonstrated the excellent blood biocompatibility of TS-CSNPs. Our silica coated TS-CSNPs exhibited a non-significant effect on the viability of both Gram negative and Gram positive bacterial strains up to 18 hours of exposure. These results highlight that modified TS-CSNPs can be functionalized to enhance the efficacy of cancer therapeutics due to the significant potential against cancerous cells and antibacterial activity.

The epithelium of gastrointestinal tract organizes many innate defense systems against microbial intruders such as integrity of epithelial, rapid eviction of infected cells, quick turnover of epithelial cell, intrinsic immune responses and autophagy. However, Enteropathogenic Escherichia coli (EPEC) are equipped with well developed infectious tricks that evade the host defense systems and utilize the gastrointestinal epithelium as a multiplicative foothold. During multiplication on and within the epithelium, EPEC secrete various toxins that can weaken, usurp, and use many host cellular systems. However, the possible mechanisms of pathogenesis are still poorly elusive. Recent study reveals the existence of EPEC in colorectal cancer patients and their potential role in depletion of DNA mismatch repair (MMR) proteins of host cell in colonic cell lines. The EPEC colonised intracellularly in colon mucosa of colorectal carcinoma whereas extracellular strain was detected in mucosa of normal colon cells. Interestingly, alteration in MutS, MutL complexes and MUTYH of mammalian cells may be involved in development of CRC. These data propose that MMR of E. coli may be potential therapeutic targets and early detection biomarkers for CRC. This article reviews the potential role of E. coli MutS, MutL and MutY protein in CRC aetiology.

[EN] Tumor-derived extracellular vesicles (EVs) have a pleiotropic role in cancer, interacting with target cells of the tumor microenvironment, such as fibroblasts, immune and endothelial cells. EVs can modulate tumor progression, angiogenic switch, metastasis, and immune escape. These vesicles are nano-shuttles containing a wide spectrum of miRNAs that contribute to tumor progression. MiRNAs contained in extracellular vesicles (EV-miRNAs) are disseminated in the extracellular space and are able to influence the expression of target genes with either tumor suppressor or oncogenic functions, depending on both parental and target cells. Metastatic cancer cells can balance their oncogenic potential by expressing miRNAs with oncogenic function, whilst exporting miRNAs with tumor suppressor roles out of the cells. Importantly, treatment of cancer cells with specific natural and chemical compounds could induce the elimination of miRNAs with oncogenic function, thereby reducing their aggressiveness. In this review, we discuss the mechanisms by which EV-miRNAs, acting as miRNAs with oncogenic or tumor suppressor functions, could contribute to cancer progression., Elena Durendez has a predoctoral fellowship by Asociacion Espanola Contra el Cancer (AECC, Valencia, Spain).

Cryptococcus neoformans is one of the most lethal fungi causing mortality across the globe. Immuno-competent patients and patients taking immuno-suppressive medications are extremely susceptible to its infection. For effective removal of cryptococcal burden, there is an urgent need for new forms of therapy. In the present study, we have explored the potential effects of amphotericin B (AMB) and fluconazole (FLC) in combination, against cryptococcosis in Swiss albino mice. To enhance the therapeutic potential of the tested drugs, they were entrapped into fibrin microspheres; a dual delivery vehicle comprising of poly-lactide co-glycolide (PLGA) microsphere that was additionally encapsulated into the fibrin cross-linked plasma bead. Dynamics of fibrin microspheres included survival and fungal burden in lung, liver and spleen of treated mice. While each drug was effective in combination or alone, prominent additive potential of AMB and FLC were clearly observed when used in fibrin microsphere. Significant reduction in fungal burden and increase in survival rate of AMB + FLC-fibrin microspheres treated mice shows an extensive accessibility of both tested drugs without any side-effects. A full potential of two-drug combination encapsulated in fibrin microspheres proposes an effective approach of safe delivery to the target site in their intact form and decrease the drug associated toxicities.

Eighteen N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide derivatives were synthesized, evaluated against ten clinical isolates of Candida spp. and compared with itraconazole. Introduction of p-chloro (2c), p-iodo (2q), m-chloro (2l) and o-nitro (2r) substitution at phenyl ring of thiosemicarbazide enhanced the anti-Candida activity. Compound (2c) bearing p-cholorophenyl ring was found to be the most effective against Candida albicans ATCC 66027, Candida spp. 12810 (blood) and Candida spp. 178 (HVS) with MIC value of 0.09–0.78 μg/mL, whereas itraconazole exhibits the inhibitory activity with MIC value of 0.04–1.56 μg/mL against all tested strains. There is a correlation between anti-Candidal activity and p-chloro substitution at phenyl ring of thiosemicarbazide. All synthesized compounds were investigated for their potential cytotoxicity against non cancer cell line MCF-10A. The active compounds 2c, 2r and 2a were further investigated for their cytotoxic effects on three cancer cell lines; HT1080 (skin), HepG2 (liver) and A549 (lung). The active compounds showed minimal cytotoxic activity against non cancer cell line and all three cancer cell lines. Moreover, compound 2c displaying better activity against C. albicans ATCC66027 and Candida spp. [blood] compared to reference drug (itraconazole), represents a good lead for the development of newer, potent and broad spectrum anti-Candidal agents.

The microbiome is a collection of all microbial species that coexist with an individual.These organisms influence several aspects of individual body functions. Probiotic organisms are generally beneficial components of microflora and confer normal health status. Usually, probiotics should be provided from the outside in the diet for maintaining proper health status. Probiotics can also have a significant impact on cancer management. While the results toward cancer management with probiotics are promising, careful risk assessment of probiotics use in cancer patients, who are usually immunocompromised due to radical therapy, comes as a great demand. This article provides an overview of the current research status of probiotics use in cancer patients and discusses the role of probiotics in cancer management. Drug Dev Res •• : ••-••, 2013. © 2013 Wiley Periodicals, Inc.

Collecting evidence suggests that the intercellular infection of Chlamydia pneumoniae in lungs contributes to the etiology of lung cancer. Many proteins of Chlamydia pneumoniae outmanoeuvre the various system of the host. The infection may regulate various factors, which can influence the growth of lung cancer in affected persons. In this in-silico study, we predict potential targeting of Chlamydia pneumoniae proteins in mitochondrial and cytoplasmic comportments of host cell and their possible involvement in growth and development of lung cancer. Various cellular activities are controlled in mitochondria and cytoplasm, where the localization of Chlamydia pneumoniae proteins may alter the normal functioning of host cells. The rationale of this study is to find out and explain the connection between Chlamydia pneumoniae infection and lung cancer. A sum of 183 and 513 proteins were predicted to target in mitochondria and cytoplasm of host cell out of total 1112 proteins of Chlamydia pneumoniae. In particular, many targeted proteins may interfere with normal growth behaviour of host cells, thereby altering the decision of program cell death. Present article provides a potential connection of Chlamydia pneumoniae protein targeting and proposed that various targeted proteins may play crucial role in lung cancer etiology through diverse mechanisms.

Cerium oxide nanocrystals (CeO2-NCs) exhibit superoxide dismutase and catalase mimetic activities. Based on these catalytic activities, CeO2-NCs have been suggested to have the potential to treat various diseases. The crystalline size of these materials is an important factor that influences the performance of CeO2-NCs. Previous reports have shown that several metal-based nanocrystals, including CeO2-NCs, can induce cytotoxicity in cancer cells. However, the underlying mechanisms have remained unclear. To characterize the anticancer activities of CeO2-NCs, several assays related to the mechanism of cytotoxicity and induction of apoptosis has been performed. Here, we have carried out a systematic study to characterize CeO2-NCs phase purity (X-ray diffraction), morphology (electron microscopy), and optical features (optical absorption, Raman scattering, and photoluminescence) to better establish their potential as anticancer drugs. Our study revealed anticancer effects of CeO2-NCs in HT29 and SW620 colorectal cancer cell lines with half-maximal inhibitory concentration (IC50) values of 2.26 and 121.18 μg ml–1, respectively. Reductions in cell viability indicated the cytotoxic potential of CeO2-NCs in HT29 cells based on inverted and florescence microscopy assessments. The mechanism of cytotoxicity confirmed by estimating possible changes in the expression levels of Bcl2, BclxL, Bax, PARP, cytochrome c, and β-actin (control) proteins in HT29 cells. Down-regulation of Bcl2 and BclxL and up-regulation of Bax, PARP, and cytochrome c proteins suggested the significant involvement of CeO2-NCs exposure in the induction of apoptosis. Furthermore, biocompatibility assay showed minimum effect of CeO2-NCs on human red blood cells.

Introduction: The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered: This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion: Most of the TKR share intracellular signaling pathways; therefore, cancer cells tend to overcome the inhibition of one tyrosine kinase receptor by activating another. The future of TIC (Tyrosine Kinase Inhibitor) therapy will potentially come from multi-targeted TKIs that target different TKR simultaneously. It is crucial to understand the interaction of the FGF-FGFR axis with other known driver TKRs. Based on this, it is possible to develop therapeutic strategies targeting multiple connected TKRs at once. One correct step in this direction is the reassessment of multi target inhibitors considering the FGFR status of the tumor. Another opportunity arises from assessing the use of FGFR TKI on patients harboring FGFR alterations. (C) 2017 Elsevier B.V. All rights reserved.