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 μg/ml) showed a moderate decrease in cancer cell viability, whereas higher dosages (2.5 μg/ml, 5.0 μg/mL and 7.5 μg/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.

Human embryonic stem cells (hESCs) hold great potential for the treatment of various degenerative diseases. Pluripotent hESCs have a great ability to undergo unlimited self-renewal in culture and to differentiate into all cell types in the body. The journey of hESC research is not that smooth, as it has faced several challenges which are limited to not only tumor formation and immunorejection but also social, ethical, and political aspects. The isolation of hESCs from the human embryo is considered highly objectionable as it requires the destruction of the human embryo. The issue was debated and discussed in both public and government platforms, which led to banning of hESC research in many countries around the world. The banning has negatively affected the progress of hESC research as many federal governments around the world stopped research funding. Afterward, some countries lifted the ban and allowed the funding in hESC research, but the damage has already been done on the progress of research. Under these unfavorable conditions, still some progress was made to isolate, culture, and characterize hESCs using different strategies. In this review, we have summarized various strategies used to successfully isolate, culture, and characterize hESCs. Finally, hESCs hold a great promise for clinical applications with proper strategies to minimize the teratoma formation and immunorejection and better cell transplantation strategies.

Nanoformulation involving biocompatible MOFs and magnetic nanocarriers is an emerging multifunctional platform for drug delivery and tumor imaging in targeted cancer therapeutics. In this study, a nanocomposite has been developed comprising Fe/SBA-16 and ZIF-8 (Fe/S-16/ZIF-8) through ultrasonication. The drug delivery of cisplatin was studied using an automated diffusion cell system equipped with a flow type Franz cell. The anticancer activity of Fe/S-16/ZIF-8 was studied in vitro in MCF-7, HeLa cells and Human Foreskin Fibroblast (HFF-1) cells. XRD and d-spacing measurements of Fe/S-16/ZIF-8 using TEM revealed the presence of cubic-structured Fe₃O₄, γ-Fe₂O₄ (magnetite), and α-FeOOH (goethite) over an SBA-16/ZIF-8 nanocomposite. The composite showed a surface area of 365 m² g⁻¹, a pore size of 8.3 nm and a pore volume of 0.33 cm³ g⁻¹. VSM analysis of Fe/S-16/ZIF-8 showed that it possessed paramagnetic behavior with a saturated magnetization value of 2.39 emu g⁻¹. The Fe²⁺/Fe³⁺ coordination environment was characterized using diffuse reflectance spectroscopy. The cisplatin drug delivery study clearly showed the synergistic effects present in Fe/S-16/ZIF-8 with over 75% of cisplatin release as compared to that of Fe/S-16 and ZIF-8, which showed 56% and 7.5%, respectively. The morphology analysis of CP/Fe/SBA-16/ZIF-8 using TEM showed an effective transit of nanoparticles into MCF-7 cells. The lethal concentration (LC₅₀) of Fe/SBA-16/ZIF-8 for MCF-7 and HeLa cells is 0.119 mg mL⁻¹ and 0.028 mg mL⁻¹ at 24 h, respectively. For HFF-1 cells, the LC₅₀ is 0.016 mg mL⁻¹. The antibiofilm activity of Fe/SBA-16/ZIF-8 was investigated against biofilm-forming strains of drug resistant P. aeruginosa and MRSA by a microtiter tissue culture plate assay. Overall, nanosized ZIF-8 with a bioactive alkaloid imidazole inside the 3D cage type of SBA-16 pores is found to exhibit both anticancer and antibacterial properties. A Fe/S-16/ZIF-8 composite could be effectively used as a drug and drug delivery system against cancer and promote antibacterial activity.

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.