Background Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs) that downregulated in the mucosal epithelia of large intestine shigellosis. Oral treatment Shigella infected rabbits with sodium butyrate (NaB) reduces clinical severity counteracts downregulation cathelicidin (CAP-18) intestinal epithelia. Aims To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected 4-phenylbutyrate (PB), a registered drug metabolic disorder as...

Journal of Cancer Metastasis and Treatment is an open access journal, focusing on basic clinical studies related to cancer cell, cell biology, oncology, radiation therapy radiology, obstetrics gynecology, pediatrics, surgery, hematology, neuro-oncology, etc.

The malaria parasite Plasmodium falciparum traffics the virulence protein P. erythrocyte membrane 1 (PfEMP1) to surface of infected red blood cells (RBCs) via membranous organelles, known as Maurer's clefts. We developed a method for efficient enrichment clefts and profiled composition this trafficking organelle. identified 13 previously uncharacterized or poorly characterized cleft proteins. generated transfectants expressing green fluorescent (GFP) fusions 7 proteins confirmed their...

The remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity plasma membrane and cell contents surface area to volume (SA:V) ratio; however, it remains unclear which these factors is key determinant for passage through small capillaries. We used a microfluidic device examine traversal normal, stiffened, swollen, parasitised immature RBCs. show that dramatic stiffening RBCs had no measurable effect their ability traverse channels. By contrast, moderate decrease in...

Presentation of the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (EMP1), at knob-like protrusions on surface infected red blood cells, underpins parasite’s pathogenicity. Here we describe a PF3D7_0301700 (PTP7), that functions nexus between intermediate trafficking organelle, Maurer’s cleft, and cell surface. Genetic disruption PTP7 leads to accumulation vesicles clefts, grossly aberrant knob morphology, failure deliver EMP1 We show an expanded low complexity...

Breast cancer, the second leading cause of female deaths worldwide, is usually treated with cytotoxic drugs, accompanied by adverse side-effects, development chemoresistance and relapse disease condition. Survival proliferation cancer cells are greatly empowered over-expression or over-activation growth factor receptors anti-apoptotic factors. Identification these key players that cross-talk to each other, subsequently, knockdown their respective siRNAs in a synchronous manner could be...

The simian parasite Plasmodium knowlesi causes severe and fatal malaria infections in humans, but the process of host cell remodelling that underpins pathology this zoonotic is only poorly understood. We have used serial block-face scanning electron microscopy to explore topography P. knowlesi-infected red blood cells (RBCs) at different stages asexual development. elaborates large flattened cisternae (Sinton Mulligan's clefts) tubular vesicles cytoplasm, as well parasitophorous vacuole...

Cancer cells lose their control on cell cycle by numerous genetic and epigenetic alterations. In a tumor, these highly express growth factor receptors (GFRs), eliciting growth, division. Among the GFRs, epidermal receptor-1 (EGFR1) (Her1/ERBB1) receptor-2 (EGFR2) (Her2/ERBB2) from (EGF) family insulin-like factor-1 receptor (IGF1R) are expressed breast cancer cells, thus contributing to aggressive invasiveness, have been focused in this study. Moreover, overexpression of is related...

Most of the classical drugs used today to destroy cancer cells lead development acquired resistance in those by limiting cellular entry or exporting them out efflux pumps. As a result, higher doses are usually required kill affecting normal and causing numerous side effects. Accumulation therapeutic level inside is thus for an adequate period time get drugs' complete efficacy minimizing effects on cells. In order improve chemotherapeutic drugs, nanoparticles carbonate apatite its strontium...

RNA interference (RNAi) is a powerful approach in functional genomics to selectively silence messenger mRNA (mRNA) expression and can be employed rapidly develop potential novel drugs against complex disease like cancer. However, naked siRNA being anionic unable cross the cell membrane through passive diffusion therefore, delivery of remains major hurdle overcome before technology fully exploited pH-sensitive carbonate apatite has recently been developed as an efficient tool deliver into...

in the presence of anti-cancer drugs to MCF-7 cells whereas 3-(4, 5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide assay and Western blot were performed assess cell viability detect phosphorylation levels mitogenactivated protein kinase AKT1, respectively. Results Intracellular delivery siRNA targeting c-ROS1 gene transcript MCF which constitutively express gene, dose-dependently enhanced chemosensitivity cisplain paclitaxel, while demonstrating no significant enhancement death with...

Chemotherapy, the commonly favoured approach to treat cancer is frequently associated with treatment failure and recurrence of disease as a result development multidrug resistance (MDR) concomitant over-expression drug efflux proteins on cells. One most widely used drugs, doxorubicin (Dox) substrate three different ATP-binding cassette (ABC) transporters, namely, ABCB1, ABCG2 ABCC1, predominantly contributing MDR phenotype in cancer. To silence these transporter-coding genes thus enhance...

The malaria parasite uses actin-based mechanisms throughout its lifecycle to control a range of biological processes including intracellular trafficking, gene regulation, motility and invasion. In this work we assign functions the Plasmodium falciparum formins 1 2 (FRM1 FRM2) proteins in asexual sexual blood stage development. We show that FRM1 is essential for merozoite invasion FRM2 required efficient cell division. also observed divergent gametocyte Conditional deletion leads delay...

Treatment of breast cancer, the second leading cause female deaths worldwide, with classical drugs is often accompanied by treatment failure and relapse disease condition. Development chemoresistance drug toxicity compels compromising concentration below threshold level consequence therapeutic inefficacy. Moreover, amplification over-activation proto-oncogenes in tumor cells make more challenging. The oncogene, ROS1 which highly expressed diverse types cancers including carcinoma, functions...

Despite being widely used for treating cancer, chemotherapy is accompanied by numerous adverse effects as a result of systemic distribution and nonspecific interactions the drugs with healthy tissues, eventually leading to therapeutic inefficacy chemoresistance. Cyclophosphamide (Cyp) one chemotherapeutic pro-drugs activated in liver treat breast cancer high dose combination other drugs. In an attempt reduce off-target enhance efficacy, pH-sensitive carbonate apatite nanoparticles that had...

Giardia duodenalis is the causative agent of neglected diarrhoeal disease giardiasis. While often self-limiting, giardiasis ubiquitous and impacts hundreds millions people annually. It also a common gastro-intestinal domestic pets, wildlife, livestock animals. However, despite this impact, there no vaccine for currently available. In addition, treatment relies on chemotherapies that are associated with increasing failure rates. To identify new options we recently screened Compounds Australia...

Giardia duodenalis, the most prevalent human intestinal parasite causes disease, giardiasis. On an annual basis G. duodenalis infects ~1 billion people, of which ~280 million develop symptomatic disease. Giardiasis can be severe and chronic, causing malnutrition, stunted growth poor cognitive development in children. Current treatment options rely on drugs with declining efficacy side-effects. To improve health well-being millions people world-wide, new anti-Giardia different modes action to...

Cervical cancer is the second most common and fourth leading cause of cancer-related deaths among women. Advanced stage disease treated with radiation therapy chemotherapy poor therapeutic outcome adverse side effects. NFκB, a well-known transcription factor in control immunity inflammation, has recently emerged as key regulator cell survival through induction antiapoptotic genes. Many human cancers, including cervical carcinoma, constitutively express NF-κB blockade expression its subunit...

A screen for compounds with antigiardial activity in the Compounds Australia Scaffolds library identified SN00797640 (supplied structure being 8-acylaminodibenzoxazepinone 1) as a hit compound potent anti-parasitic (concentration 50% growth inhibition of Giardia duodenalis, IC50 0.18 μM). To further explore structure–activity relationships this series, 1 and analogues, including its 7-acylaminodibenzoxazepinone regioisomer (2), were synthesized assessed anti-Giardia activity. While 2...

On an annual basis the flagellate protozoan, Giardia duodenalis, is responsible for estimated one billion human infections of which approximately two hundred million cause disease. However, treatment reliant on a small group chemotherapeutic classes that have broad spectrum antimicrobial activity and increasing failure rates. To improve this situation, we need new drugs. In study screened Compounds Australia Scaffolds Library compounds with potent selective against these parasites. Unlike...

Abstract Presentation of the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (EMP1), at knob-like protrusions on surface infected red blood cells, underpins P. malaria pathogenicity. Here we describe a PF3D7_0301700 (PTP7), that functions nexus between intermediate trafficking organelle, Maurer’s cleft, and cell surface. Genetic disruption PTP7 leads to accumulation vesicles clefts, grossly aberrant knob morphology, failure deliver EMP1 We show an expanded low...