Strengthening microbial cell factories for efficient production of bioactive molecules.

High demand of bioactive molecules (food additives, antibiotics, plant growth enhancers, cosmetics, pigments and other commercial products) is the prime need for the betterment of human life where the applicability of the synthetic chemical product is on the saturation due to associated toxicity and ornamentations. It has been noticed that the discovery and productivity of such molecules in natural scenarios are limited due to low cellular yields as well as less optimized conventional methods. In this respect, microbial cell factories timely fulfilling the requirement of synthesizing bioactive molecules by improving production yield and screening more promising structural homologues of the native molecule. Where the robustness of the microbial host can be potentially achieved by taking advantage of cell engineering approaches such as tuning functional and adjustable factors, metabolic balancing, adapting cellular transcription machinery, applying high throughput OMICs tools, stability of genotype/phenotype, organelle optimizations, genome editing (CRISPER/Cas mediated system) and also by developing accurate model systems via machine-learning tools. In this article, we provide an overview from traditional to recent trends and the application of newly developed technologies, for strengthening the systemic approaches and providing future directions for enhancing the robustness of microbial cell factories to speed up the production of biomolecules for commercial purposes.

Immunomodulation-mediated anticancer activity of a novel compound from Brugmansia suaveolens leaves.

Immunomodulation activity-guided fractionation of ethanol extract of Brugmansia suaveolens leaves was carried out to isolate a novel compound SUPH036-022A (1) by co-culturing the test fraction/compound activated PBMC with MCF7 and A549 cancer cell lines. Assessment of immune markers in PBMC, and analysis of apoptosis markers and cell cycle was carried out for cancer cells. The structure of the isolated compound was elucidated by spectral analysis. Compound 1 enhanced the secretion of immune markers, IL-2 and IFN-γ, from PBMC. Further, compound 1 treated PBMC increased cell death in MCF7 and A549 cell lines and induced ROS production and mitochondrial membrane perturbation, leading to apoptosis. Flow cytometry analysis revealed; compound 1 stimulated PBMC to cause a five-fold increase in cell cycle perturbations in the sub-G1 stage of cancer cells as compared to the negative control. The compound, in the absence of PBMC, only had a weak cytotoxic activity against these cell lines. Thus, compound 1 is a novel lead for immunomodulation-mediated anticancer activity.

Recent advances in cancer immunology and immunology-based anticancer therapies.

Cancer immunotherapies offer promise for cure of cancer with specificity and minimal toxicity. Recent developments in cancer immunology have led to the better understanding of role of immune regulatory mechanisms in cancer. There is rapid progress in this field in the last few years. Several clinical studies report the efficacy of immunotherapies for treating cancer. The immunology-based anticancer therapies have shown better safety profiles in clinic as compared to other chemotherapeutic agents, thus increasing interest in this area. This review summarizes recent advances in cancer immunology and discusses tumor microenvironment and immunology-based anticancer therapies, including vaccines and therapies targeting immune checkpoints.