Myeloid‐derived suppressor cells (MDSC) are negative regulators of the immune response and are in part responsible for the inhibition of the T cell–mediated immune responses. While MDSC have been demonstrated to participate in the induction of prolonged allograft survival in animal models of transplantation, little is known about their immune regulatory function in human transplant recipients. Here, we report that two subsets of human MDSC expressing CD11b+, CD33+ and HLA‐DR− develop in renal patients posttransplantation. We found that CD14+ expressing monocytic MDSC isolated from transplant recipients were highly efficient in suppressing the proliferation of CD4+ T cells in mixed leukocyte reactions. In addition, we observed that CD11b+CD33+HLA‐DR− MDSC are capable of expanding Treg in vitro, and their accumulation overtime after transplantation linearly correlated with an increase in Treg in vivo. This is the first study to link the presence of MDSC with the emergence of Treg in vivo in transplant recipients, and to define the subpopulation of MDSC derived from transplant recipients responsible for generation of Treg. Further studies are necessary to determine the alloimmune regulatory function of MDSC in human transplant recipients.
In the ever-changing classroom dynamics of the twenty-first century, teaching needs to be innovative in order to be effective. The youth of the present age are members of virtual societies communicating mostly through the digital medium. This digital communication has its effects on the traditional classroom lectures. There has been a marked decline in basic language skills. Learners are less attentive and need more motivation. Interactive method of teaching is the best method of teaching language. But for this, the learners have to participate in the classroom and contribute something of their own. Learners have to be taught in a method that interests them and makes the language taught to them relevant in context. There is a need to incorporate digital communicative medium inside the language classroom in an enterprising and novel way while maintaining a low affective filter. For this, teachers have to adopt a systematic approach to digital technology. They need to be more versatile and integrate digital information in their daily lesson plans and the classroom activities. This research proposes one such digital age teaching procedure wherein internet memes are used to teach English. Internet memes provide humour and reduce anxiety. They can make the learners attentive and relate to the language learning process.
The molecular targeted drug ATRA demands a suitable carrier that delivers to the cancer site due to its poor bioavailability and drug resistance. ATRA, being a lipid with carboxylic acid, has been nano-formulated as a cationic lipo-ATRA with DOTAP:cholesterol:ATRA (5:4:1) and its pH-responsive release, intracellular drug accumulation, and anticancer effect on human lung cancer (A549) cell line analysed. The analysis of the physicochemical characteristics of the developed lipo-ATRA (0.8 µmol) revealed that the size of 231 ± 2.35 d.nm had a zeta potential of 6.4 ± 1.19 and an encapsulation efficiency of 93.7 ± 3.6%. The ATRA release from lipo-ATRA in vitro was significantly (p ≤ 0.05) higher at acidic pH 6 compared to pH 7.5. The intracellular uptake of ATRA into lipo-ATRA-treated A549 cells was seven-fold higher (0.007 ± 0.001 mg/ml) while only threefold uptake was observed in free ATRA treatment (0.003 ± 0.002 mg/ml). The lipo-ATRA treatment caused a highly significant (p ≤ 0.001) decrease in percent cell viability at 48 h when compared with the free ATRA treatment. Overall, the results proved that the developed lipo-ATRA has suitable physicochemical properties with enhanced ATRA release at acidic pH, while maintaining stability at physiologic pH and temperature. This resulted in an increased ATRA uptake by lung cancer cells with enhanced treatment efficiency. Hence, it is concluded that DOTAP lipo-ATRA is a suitable carrier for ATRA delivery to solid cancer cells.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
This study focused on evaluating the potency of Methyl Palmitate in reducing in vivo toxicity with enhancement of anti‐cancer effects of Sorafenib. In vitro anti‐cancer effects on human Hep‐G2 cell line were analysed by MTT, Trypan blue, clonogenic, wound scratch migration and TUNEL assays. An in vivo study for anti‐angiogenesis effect, toxicity and teratogenicity was analysed in Zebrafish embryos. The combination of Sorafenib (4.5 µmol/L) with Methyl Palmitate (3 mmol/L) significantly enhanced anti‐cancer effects on Hep‐G2 cell line by increasing cytotoxicity (P ≤ .05 in MTT assay; P ≤ .01 in Trypan blue assay), apoptosis (P ≤ .05) and decreasing the metastatic migration (P ≤ .01) than Sorafenib alone treatment. A prominent inhibition of angiogenesis in vivo was observed for combination treatment. At 5 dpf, only <20% toxicity was observed for 3 mmol/L Methyl palmitate while it was 65.75% for Sorafenib treatment which implies that it is a safer dose for in vivo treatments. A highly significant (P ≤ .001) reduction (43.20%) in toxicity was observed in combination treatment. Thus, the Sorafenib‐Methyl Palmitate combination showed a promising treatment effect with significantly reduced in vivo toxicity when compared with Sorafenib alone treatment, and hence the Methyl Palmitate may serve as a good adjuvant for Sorafenib therapy.
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