Disulfiram/copper induces BAK-mediated caspase-independent apoptosis in MCF-7 cells.

Disulfiram (DSF) and copper (Cu) in combination exhibit powerful anti-cancer effect on a variety of cancer cell lines. Here, we found that DSF/Cu facilitated the accumulation of intracellular reactive oxygen species (ROS), and induced ROS-dependent apoptosis accompanied by chromatin condensation and phosphatidylserine externalization in MCF-7 cells. DSF/Cu caused caspase-independent apoptosis by promoting the AIF translocation from mitochondria to nucleus.

Hdm2 disrupts HdmX-mediated nuclear export of p53 by sequestering it in nucleus.

Dysfunction of the tumor suppressor p53 occurs in most human cancers, Hdm2 and HdmX play critical roles in p53 inactivation and degradation. Under unstressed conditions, HdmX binds to p53 like Hdm2, but HdmX cannot directly induce p53 degradation. Moreover, HdmX has been reported to stimulate Hdm2-mediated ubiquitination and degradation of p53.

YAP upregulates AMPKα1 to induce cancer cell senescence.

Yes-associated protein (YAP)-a major effector protein of the Hippo pathway- regulates cell proliferation, differentiation, apoptosis, and senescence. Amp-activated protein kinase (AMPK) is a key sensor that monitors cellular nutrient supply and energy status. Although YAP and AMPK are considered to regulate cellular senescence, it is still unclear whether AMPK is involved in YAP-regulated cellular senescence.

Dependence of ghost on the incident light angle into dichroic mirror.

The dichroic mirror (DM) is a key component in microscope. We found a ghost in the reflection channel of a dual-channel fluorescence microscope and studied the relationship between the ghost and the incidence angle into the DM. The DM emission surface reflection generated ghost if the is not .

Regorafenib induces Bim-mediated intrinsic apoptosis by blocking AKT-mediated FOXO3a nuclear export.

Regorafenib (REGO) is a synthetic oral multi-kinase inhibitor with potent antitumor activity. In this study, we investigate the molecular mechanisms by which REGO induces apoptosis. REGO induced cytotoxicity, inhibited the proliferation and migration ability of cells, and induced nuclear condensation, and reactive oxygen species (ROS)-dependent apoptosis in cancer cells.

Bad is essential for Bcl-xL-enhanced Bax shuttling between mitochondria and cytosol.

Although Bcl-xL has been shown to retrotranslocate Bax from mitochondria to cytosol, other studies have found that Bcl-xL also stabilizes the mitochondrial localization of Bax. It is still unclear what causes the difference in Bcl-xL-regulated Bax localization. Bad, a BH3-only protein with a high affinity for Bcl-xL, may play an important role in Bcl-xL-regulated Bax shuttling.

Enhanced Immune Responses to Mucosa by Functionalized Chitosan-Based Composite Nanoparticles as a Vaccine Adjuvant for Intranasal Delivery.

Nasal administration for vaccine delivery is a novel non-invasive vaccine administration approach that can induce local or systemic immune responses and overcome the disadvantages caused by traditional injectable administration. However, mucosal vaccine and adjuvant delivery systems with sustained-release ability and enhanced immune effects at mucosal sites have still been highly demanded. In this work, -2-hydroxypropyl trimethyl ammonium chloride chitosan/,-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) with excellent mucosal absorption, high drug loading capacity, and enhanced immune responses were prepared by the ionic cross-linking method.

BAK plays a key role in A-1331852-induced apoptosis in senescent chondrocytes.

Osteoarthritis occurs when the number of senescent chondrocytes in the joints reaches an intolerable level. The purpose of our study was to explore the therapeutic effect and mechanism of action of A-1331852 in osteoarthritis. Doxorubicin and etoposide were used to induce cell senescence as determined by the cessation of cell proliferation, augmented senescence-associated beta-galactosidase (SA-β-Gal) staining, and increased p53 expression levels.

Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells.

Metformin (Met) exhibits anticancer ability in various cancer cell lines. This report aims to explore the exact molecular mechanism of Met-induced apoptosis in HCT116 cells, a human colorectal cancer cell line. Met-induced reactive oxygen species (ROS) increase and ROS-dependent cell death accompanied by plasma membrane blistering, mitochondrial swelling, loss of mitochondrial membrane potential, and release of cytochrome c.

Intranasal immunization with O-2'-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles loaded with Newcastle disease virus DNA vaccine enhances mucosal immune response in chickens.

Background: There has been a great interest in developing strategies for enhancing antigen delivery to the mucosal immune system as well as identifying mucosal active immunostimulating agents. To elevate the potential of O-2'-Hydroxypropyl trimethyl ammonium chloride chitosan (O-2'-HACC) as an adjuvant and mucosal immune delivery carrier for DNA vaccine, we prepared the O-2'-HACC loaded with Newcastle disease virus (NDV) F gene plasmid DNA and C3d6 molecular adjuvant (O-2'-HACC/pFDNA microparticles).

Results: The O-2'-HACC/pFDNA exhibited a regular spherical morphology with a particle size of 202.

Inhibitory effects of brusatol delivered using glycosaminoglycan‑placental chondroitin sulfate A‑modified nanoparticles on the proliferation, migration and invasion of cancer cells.

Breakthroughs in cancer management result from the development of drugs that can be used for early diagnosis and effective treatment. Surgery, chemotherapy, radiotherapy and hormone therapy are the main anticancer therapies. However, traditional cancer chemotherapy is associated with serious systemic side effects.

Screening and surveillance of multiple solid tumours using plasma placental-like chondroitin sulfate A (pl-CSA).

Placental-like chondroitin sulfate A (pl-CSA) is known to be exclusively synthesized in multiple cancer tissues and associated with disease severity. Here, we aimed to assess whether pl-CSA is released into bio-fluids and can serve as a cancer biomarker. A novel ELISA was developed to analyse pl-CSA content in bio-fluids using pl-CSA binding protein and an anti-pl-CSA antibody.

R-spondin3 promotes the tumor growth of choriocarcinoma JEG-3 cells.

R-spondin3 (RSPO3), an activator of Wnt/β-catenin signaling, plays a key role in tumorigenesis of various cancers, but its role in choriocarcinoma remains unknown. To investigate the effect of RSPO3 on the tumor growth of choriocarcinoma JEG-3 cells, the expression of RSPO3 in human term placenta was detected, and a stable RSPO3-overexpressing JEG-3 cell line was established via lentivirus-mediated transduction. The expression of biomarkers involved in tumorigenicity was detected in the RSPO3-overexpressing JEG-3 cells, and cell proliferation, invasion, migration, and apoptosis were investigated.

Targeting delivery of partial VAR2CSA peptide guided N-2-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles for multiple cancer types.

To developing a multiple cancer types targeting drug delivery carrier system, a 28 amino acids from the VAR2CSA was synthesized as the placental CSA-binding peptide (plCSA-BP). Its specific binding ability to cancer cells was tested on cancer tissue array, and the results showed that plCSA-BP could bind to multiple cancer types. Then, the plCSA-BP was used as a guiding peptide to coat nanoparticles synthesized from N-2-HACC (CSA/HACC-NPs) which were loaded with prodigiosin (CSA/HACC-PNPs) or indocyanine green (CSA/HACC-INPs).

Biomedical Applications of Chitosan and Its Derivative Nanoparticles.

Chitosan is a biodegradable natural polymer with many advantages such as nontoxicity, biocompatibility, and biodegradability. It can be applied in many fields, especially in medicine. As a delivery carrier, it has great potential and cannot be compared with other polymers.

Quaternized Chitosan Nanoparticles in Vaccine Applications.

Different natural and synthetic biodegradable polymers have been used in vaccine formulations as adjuvant and delivery system but have faced various limitations. Chitosan is a new delivery system with the potential to improve development of nano vaccines and drugs. However, chitosan is only soluble in acidic solutions of low concentration inorganic acids such as dilute acetic acid and dilute hydrochloric acid and in pure organic solvents, which greatly limits its application.

Polysaccharides as vaccine adjuvants.

Adjuvant is a substance added to vaccine to improve the immunogenicity of antigens, and it can induce stronger immune responses and reduce the dosage and production cost of vaccine in populations responding poorly to vaccination. Adjuvants in development or in use mainly include aluminum salts, oil emulsions, saponins, immune-stimulating complexes, liposomes, microparticles, nonionic block copolymers, polysaccharides, cytokines and bacterial derivatives. Polysaccharide adjuvants have attracted much attention in the preparation of nano vaccines and nano drugs because natural polysaccharides have the characteristics of intrinsic immunomodulating, biocompatibility, biodegradability, low toxicity and safety.