Somatic hypermutation in B cells is initiated by activation-induced cytidine deaminase-catalyzed C→U deamination at immunoglobulin variable regions. Here we investigate the role of the germinal centre-associated nuclear protein (GANP) in enhancing the access of activation-induced cytidine deaminase (AID) to immunoglobulin variable regions. We show that the nuclear export factor GANP is involved in chromatin modification at rearranged immunoglobulin variable loci, and its activity requires a histone acetyltransferase domain. GANP interacts with the transcription stalling protein Spt5 and facilitates RNA Pol-II recruitment to immunoglobulin variable regions. Germinal centre B cells from ganp-transgenic mice showed a higher AID occupancy at the immunoglobulin variable region, whereas B cells from conditional ganp-knockout mice exhibit a lower AID accessibility. These findings suggest that GANP-mediated chromatin modification promotes transcription complex recruitment and positioning at immunoglobulin variable loci to favour AID targeting.
Poly (methyl methacrylate) (PMMA) is basically biocompatible polyester with high resistance to chemical hydrolysis, and high drug permeability and the most important characteristics of PMMA is that it does not produce any toxicity. There is not much information about PMMA action on the colon cancer cells. In the present study, we have synthesized PMMA nanoparticles. The distribution pattern of PMMA particles was analysed by Zeta sizer and the size of the particles was calculated by using quasi elastic light scattering (QELS). The surface structure and the morphology of PMMA were characterized by transmission electron microscope (TEM) and scanning electron microscope (SEM), respectively. We have also analysed their effects on cancerous cells (human colorectal carcinoma cells, HCT-116) and normal, healthy cells (human embryonic kidney cells, HEK-293) by using morphometric, MTT, DAPI and wound healing methods. We report that PMMA particles inhibited the cancer cell viability in a dose-dependent manner. The lower dose (1.0 lg/ml) showed a moderate decrease in cancer cell viability, whereas higher dosages (2.5 lg/ml, 5.0 lg/mL and 7.5 lg/mL) showed steadily decrease in the cancer cell viability. We also report that PMMA is highly selective to cancerous cells (HCT-116), as we did not find any action on the normal healthy cells (HEK-293). In conclusion, our results suggest PMMA particles are potential biomaterials to be used in the treatment of colon cancer.
Nanoparticles have enormous applications in textiles, cosmetics, electronics, and pharmaceuticals. But due to their exceptional physical and chemical properties, particularly antimicrobial, anticancer, antibacterial, anti-inflammatory properties, nanoparticles have many potential applications in diagnosis as well as in the treatment of various diseases. Over the past few years, nanoparticles have been extensively used to investigate their response on the neuronal cells. These nanoparticles cause stem cells to differentiate into neuronal cells and promote neuronal cell survivability and neuronal cell growth and expansion. The nanoparticles have been tested both in in vitro and in vivo models. The nanoparticles with various shapes, sizes, and chemical compositions mostly produced stimulatory effects on neuronal cells, but there are few that can cause inhibitory effects on the neuronal cells. In this review, we discuss stimulatory and inhibitory effects of various nanoparticles on the neuronal cells. The aim of this review was to summarize different effects of nanoparticles on the neuronal cells and try to understand the differential response of various nanoparticles. This review provides a bird’s eye view approach on the effects of various nanoparticles on neuronal differentiation, neuronal survivability, neuronal growth, neuronal cell adhesion, and functional and behavioral recovery. Finally, this review helps the researchers to understand the different roles of nanoparticles (stimulatory and inhibitory) in neuronal cells to develop effective therapeutic and diagnostic strategies for neurodegenerative diseases.
Nanoparticles have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. The aim of the present study is to examine whether fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) have any impact on human colorectal cancer cells. In the present study, we have tested FMSP-nanoparticles with an average size of 100-200 nm on human colorectal carcinoma cells (HCT-116) to check their cytotoxic and anti-cancer capabilities. The effects of FMSP-nanoparticles on cancer cells were observed after 6 h, 24 h and 48 h intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4lue-diamidino-2-phenylindole (DAPI) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Our MTT analysis results revealed that FMSP-nanoparticles produced dose-dependent effects on cancer cells, FMSP-nanoparticles with dose of 1.25 µg/mL did not decrease cell survivability, whereas dosages of 12.5 µg/mL and 50 µg/mL respectively showed 23.59% and 59.47% decrease in the cancer cell survivability. In conclusion, our results demonstrate FMSP-nanoparticles have a potential anti-cancer capability and hold a great promise for colon cancer treatments.
Currently, breast cancer treatment mostly revolves around radiation therapy and surgical interventions, but often these treatments do not provide satisfactory relief to the patients and cause unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we tested the effect of FMSP-nanoparticles on human breast cancer cells (MCF-7). We tested different concentrations (1.25, 12.5 and 50 µg/mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, a dose of 1.25 µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5 and 50 µg/mL resulted in significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate that FMSP-nanoparticles induce cell death in MCF-7 cells and may be a potential anti-cancer agent for breast cancer treatment.
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