Introduction: Cancer disease is known due to its unregulated proliferation of cells that have evolved from the body's regular cells. The disease develops as a result of epigenetic and genetic ...modifications, tumor suppressor gene inactivation, and oncogene activation. The present work describes an environmentally benign approach for the synthesis of manganese oxide nanoparticles (MnO.sub.2 NPs) using Gmelina arborea fruit extract (GAE) in an aqueous medium. Methods: The study evaluated the formation of MnO.sub.2 NPs and their anticancer efficacy against MCF-7 breast cancer cell line. Results: The formation of MnO.sub.2 NPs was confirmed through powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM). The crystalline nature of as-prepared MnO.sub.2 NPs was evident from XRD pattern. The morphology of the material was studied using SEM analysis, which suggested a rod-like nature with an average diameter of 50 nm. Further, the TEM and HR-TEM images confirmed the rod shape of the as-prepared MnO.sub.2 NPs with an interplanar distance of 0.271 nm. In addition, the concentric rings from selected area electron diffraction (SAED) analysis show the crystalline nature of the as-prepared material, which further supports the obtained XRD pattern. The anticancer efficacy of MnO.sub.2 NPs was evaluated against MCF-7 breast cancer cell line, which showed up to 96% inhibition of the cells at 400 microg/mL concentration. Conclusion: Bio-conjugation of MnO.sub.2 NPs can provide enough scope for the therapeutic use of Gmelina arborea, assuming appropriate mechanistic evaluations are conducted. Keywords: Gmelina arborea, MnO.sub.2 NPs, HR-TEM, MCF-7
The tumor microenvironment is highly complex, and immune escape is currently considered an important hallmark of cancer, largely contributing to tumor progression and metastasis. Named for their ...capability of killing target cells autonomously, natural killer (NK) cells serve as the main effector cells toward cancer in innate immunity and are highly heterogeneous in the microenvironment. Most current treatment options harnessing the tumor microenvironment focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. The limited success achieved by T cell immunotherapy highlights the importance of developing new-generation immunotherapeutics, for example utilizing previously ignored NK cells. Although tumors also evolve to resist NK cell-induced cytotoxicity, cytokine supplement, blockade of suppressive molecules and genetic engineering of NK cells may overcome such resistance with great promise in both solid and hematological malignancies. In this review, we summarized the fundamental characteristics and recent advances of NK cells within tumor immunometabolic microenvironment, and discussed potential application and limitations of emerging NK cell-based therapeutic strategies in the era of presicion medicine.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Ultrafast DES pretreatment was developed for deconstructing the compact cell wall.•Transgenic poplars have low “biomass recalcitrance” as compared to control group.•Structural ...changes of lignin during the DES pretreatment were fully investigated.•The regenerated DES lignin fractions exhibited excellent antioxidant properties.•Enzymatic saccharification of the pretreated substrates was observably elevated.
Reducing the “biomass recalcitrance” and simultaneously improving the efficiency of deconstruction and conversion is vitally important in a biorefinery process. Herein, a microwave-assisted deep eutectic solvents (DES) pretreatment was developed to deconstruct the control and transgenic (C3H, HCT and C3H + HCT co-inhibition) poplars, and improve the lignin extractability and valorization. NMR and GPC results showed that native lignin (Double Enzymatic Lignin, DEL) in different poplars exhibited slightly different structural characteristics, affecting the subsequent lignin extractability and value-added applications. After two kinds of DES (ethylene glycol-based and glycerol-based DES) pretreatments, the yield of DES lignin was obviously increased to 45.38–53.09 % and 46.38–54.30 % in transgenic poplar woods as compared to control poplar wood (37.25 and 38.86 %). In addition, molecular weight, and abundances of different linkages (β-O-4, β-β, β-5, etc.) in the DES lignin fractions were significantly decreased, suggesting the microwave-assisted DES pretreatment has a strong deconstruction ability towards to poplar wood. Moreover, the rapid and efficient pretreatment facilitated the isolation of the lignin fractions from transgenic poplars, and the regenerated DES lignin fractions exhibited excellent antioxidant properties, which will lay the foundation for the lignin valorization. Furthermore, the enzymatic saccharification ratios of the DES pretreated substrates were significantly increased to 87.36–96.55 % in control and transgenic poplar woods, indicating that microwave-assisted DES pretreatment indeed boosted cellulose bioconversion. In short, the combination of genetic modification and DES pretreatment can significantly reduce the “biomass recalcitrance” and promote the biomass valorization.
•People tend to rely on intuitive reasoning to make a judgment on GMOs.•This intuitive reasoning includes folk biology, teleological and intentional intuitions and disgust.•Anti-GMO activists have ...exploited intuitions successfully to promote their cause.•Intuitive judgments steer people away from sustainable solutions.
Public opposition to genetically modified organisms (GMOs) remains strong. By contrast, studies demonstrate again and again that GM crops make a valuable contribution to the development of a sustainable type of agriculture. The discrepancy between public opinion and the scientific evidence requires an explanation. We argue that intuitive expectations about the world render the human mind vulnerable to particular misrepresentations of GMOs. We explain how the involvement of particular intuitions accounts for the popularity, persistence, and typical features of GM opposition and tackle possible objections to our approach. To conclude, we discuss the implications for science education, science communication, and the environmental movement.
The adoption of genetically modified organisms (GMOs) in Ghana has raised a lot of public concerns and mixed feelings among some Ghanaians. Our present study, therefore, explored the current ...knowledge of the general public on GMOs, their perceptions, and factors that influence their understanding of GMOs. A total of 200 Ghanaians were interviewed using an online semi-structured questionnaire to solicit information on their knowledge of GMOs. The findings of the study showed that most Ghanaians (183 out of 200) are aware of GMOs. Age and level of education significantly influenced consumers’ awareness of GMOs. The results also revealed that most of the participants have a medium to a high level of knowledge of GMOs; however, limited information about GMOs is available to the public. About 61% of the respondents are willing to consume GMOs when made available in Ghana. Also, the findings of the study showed that the respondents would prefer GM-labelled products. The educational level of the respondents significantly influenced their knowledge and understanding of GMOs. The study recommends that scientists and various media platforms provide a platform to address the concerns of the public on GMOs and occasionally engage them in GMO-related issues and their role in addressing food insecurity and malnutrition.
Nature uses 64 codons to encode the synthesis of proteins from the genome, and chooses 1 sense codon-out of up to 6 synonyms-to encode each amino acid. Synonymous codon choice has diverse and ...important roles, and many synonymous substitutions are detrimental. Here we demonstrate that the number of codons used to encode the canonical amino acids can be reduced, through the genome-wide substitution of target codons by defined synonyms. We create a variant of Escherichia coli with a four-megabase synthetic genome through a high-fidelity convergent total synthesis. Our synthetic genome implements a defined recoding and refactoring scheme-with simple corrections at just seven positions-to replace every known occurrence of two sense codons and a stop codon in the genome. Thus, we recode 18,214 codons to create an organism with a 61-codon genome; this organism uses 59 codons to encode the 20 amino acids, and enables the deletion of a previously essential transfer RNA.
POU Class 1 Homeobox1 (POU1F1/Pou1f1) is a well-established pituitary-specific transcription factor, and causes, when mutated, combined pituitary hormone deficiency in humans and mice. POU1F1/Pou1f1 ...has 2 isoforms: the alpha and beta isoforms. Recently, pathogenic variants in the unique coding region of the beta isoform (beta domain) and the intron near the exon-intron boundary for the beta domain were reported, although their functional consequences remain obscure. In this study, we generated mice carrying the Pou1f1 c.143-83A>G substitution that recapitulates the human intronic variant near the exon-intron boundary for the beta domain. Homozygous mice showed postnatal growth failure, with an average body weight that was 35% of wild-type littermates at 12 weeks, which was accompanied by anterior pituitary hypoplasia and deficiency of circulating insulin-like growth factor 1 and thyroxine. The results of RNA-seq analysis of the pituitary gland were consistent with reduction of somatotrophs, and this was confirmed immunohistochemically. Reverse transcription polymerase chain reaction of pituitary Pou1f1 mRNA showed abnormal splicing in homozygous mice, with a decrease in the alpha isoform, an increase in the beta isoform, and the emergence of the exon-skipped transcript. We further characterized artificial variants in or near the beta domain, which were candidate positions of the branch site in pre-mRNA, using cultured cell-basis analysis and found that only c.143-83A>G produced transcripts similar to the mice model. Our report is the first to show that the c.143-83A>G variant leads to splicing disruption and causes morphological and functional abnormalities in the pituitary gland. Furthermore, our mice will contribute understanding the role of POU1F1/Pou1f1 transcripts in pituitary development. Key Words: POU1F1/Pou1f1, pituitary, splicing, branch site Abbreviations: ACTH, adrenocorticotropin; CPHD, combined pituitary hormone deficiency; ELISA, enzyme-linked immunosorbent assay; GE, genetically engineered; GH, growth hormone; gRNA, guide RNA; IGF, insulin-like growth factor; POU1F1, POU class 1 homeobox1; PRL, prolactin; RT-PCR, reverse transcription polymerase chain reaction; TSH, thyroid-stimulating hormone; WT, wild type.
Immune-checkpoint inhibitors and chimeric antigen receptor (CAR) T cells are revolutionizing oncology and haematology practice. With these and other immunotherapies, however, systemic biodistribution ...raises safety issues, potentially requiring the use of suboptimal doses or even precluding their clinical development. Delivering or attracting immune cells or immunomodulatory factors directly to the tumour and/or draining lymph nodes might overcome these problems. Hence, intratumoural delivery and tumour tissue-targeted compounds are attractive options to increase the in situ bioavailability and, thus, the efficacy of immunotherapies. In mouse models, intratumoural administration of immunostimulatory monoclonal antibodies, pattern recognition receptor agonists, genetically engineered viruses, bacteria, cytokines or immune cells can exert powerful effects not only against the injected tumours but also often against uninjected lesions (abscopal or anenestic effects). Alternatively, or additionally, biotechnology strategies are being used to achieve higher functional concentrations of immune mediators in tumour tissues, either by targeting locally overexpressed moieties or engineering 'unmaskable' agents to be activated by elements enriched within tumour tissues. Clinical trials evaluating these strategies are ongoing, but their development faces issues relating to the administration methodology, pharmacokinetic parameters, pharmacodynamic end points, and immunobiological and clinical response assessments. Herein, we discuss these approaches in the context of their historical development and describe the current landscape of intratumoural or tumour tissue-targeted immunotherapies.
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