Department of Bioscience & Bioengineering

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IIT Jodhpur

In humans, trophoblast hypoxia during placental development can be a cause of serious pregnancy complications, such as preeclampsia and fetal growth restriction. The pathogenesis of these conditions is not fully clear and may be associated with changed expression of some genes and regulatory molecules, including miRNA, in trophoblast cells. The aim of this study was to analyze miRNA profiles and measure the expression of their target genes in a model of trophoblast hypoxia. Human choriocarcinoma BeWo b30 cells were used as a trophoblast model. Hypoxia was induced by cobalt chloride (CoCl2) and an oxyquinoline derivative. MRNA and miRNA expression profiles were evaluated by means of next generation sequencing (NGS); the expression of individual genes was analyzed by PCR. We studied the secondary structure of mRNAs of target genes for those miRNAs whose expression had changed significantly and analyzed potential competition between these miRNAs for the binding site. The observed changes in the expression of the key genes involved in the response to hypoxia confirmed the feasibility of using CoCl2 and the oxyquinoline derivative as hypoxia inducers. The analysis revealed an increase in miR-374 levels following the activation of the hypoxia pathway in our trophoblast model. The changes were accompanied by a reduction in FOXM1 mRNA expression; this mRNA is a target for hsa-miR-374a-5p and hsa-miR-374b-5p, which can compete with hsa-miR-21-5p for the binding sites on FOXM1 mRNA. The involvement of FOXM1 in the regulation of the invasive cell potential suggests the role of miR-374 and FOXM1 in the pathogenesis of disrupted trophoblast invasion during placental development as predisposing for fetal growth restriction and preeclampsia. © 2021 Pirogov Russian National Research Medical University. All rights reserved.

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Bulletin of Russian State Medical University

Levels of MIR-374 increase in BEWO B30 cells exposed to hypoxia [УРОВЕНЬ микроРНК MIR-374 ПОВЫШАЕТСЯ В КЛЕТКАХ BEWO B30 ПРИ ГИПОКСИИ]

A healthy physiological environment of cells represents the dynamic homeostasis of crowded molecules. A subset of cellular proteome forms protein quality control (PQC) machinery to maintain an uninterrupted synthesis of new polypeptides and targeted elimination of old or defective proteins. The process of PQC may get overwhelmed under specific genetic mutations, environmental stress conditions, and aging-associated perturbances. Many of these conditions may lead to the generation of various types of aberrant protein species that may or may not accumulate as large cellular inclusions. These proteinaceous formations, referred to as inclusion bodies (IBs), could be membrane-bound or membrane-less, cytoplasmic, or nuclear. Most importantly, they could either be toxic or protective. Under acute stress conditions, the formation of aggregates may cause proteostasis failure, leading to large-scale changes in the cellular proteome compositions. However, the large insoluble IBs may act as reservoirs for many soluble proteins with high aggregation propensities, which can overwhelm the cellular chaperoning capacity and protein degradation machinery. The kinetic equilibrium between folding and unfolding, misfolding, and refolding; aggregation and degradation is perturbed in one or many neurodegenerative disorders (NDDs) associated with dementia, cognitive impairments, movement, and behavioural losses. However, a detailed interplay of IBs into the manifestation of the NDDs is unknown, and a very primitive knowledge of structural compositions of amyloid inclusions is present. The present article presents a brief evolutionary background of IBs; their functional relevance for prokaryotes, plants, and animals; and associated involvement in neuronal proteostasis. © The Author(s) 2021.

Neuroscientist

Complex Inclusion Bodies and Defective Proteome Hubs in Neurodegenerative Disease: New Clues, New Challenges

Major cause of proteopathies is the accumulation of unwanted mutant and aberrant proteins. We know that imperfect ageing is one of chief risk factor for most neurodegenerative diseases. Neurodegenerative diseases are characterized by mutant misfolded protein aggregates developing neural stress and debilitating several neuronal processes. Reducing the levels of these abnormal proteins using various natural compounds can be a promising possible therapeutic strategy. But the advancement of natural compound-based therapies in neurodegeneration and imperfect ageing treatment has been impeded by different challenges and unknown molecular patho-mechansim. The complexity in the causative factors generating protein aggregates in neurons and their respective path towards cell death is high, making it a difficult to treat disorder. Several plant based compounds have proven to promote different neuronal homeostasis mechanisms. However, there is a pressing necessity to screen, find and develop cost-effective natural compound-based new therapeutic interventions which can be useful for clinical purposes in treating neurodegenerative ailments. It is critical to discuss and elaborate the applications of few important natural compounds and their connections with following mechanisms: protein disposal machineries, apoptosis, neuroinflammation, neuronal development, synaptogenesis and neural homeostasis. This article summarizes the current knowledge and discusses the unanswered questions linked with the natural compounds and their promising therapeutic avenues primarily focusing on neurodegenerative diseases and defective neurobiological mechanisms. © 2021 The Author(s)

Cellular Physiology and Biochemistry

Proteome linked biochemical targets: Can repair defective cellular physiological mechanisms?

The aim of this work was to compare the performance of the two types of photosynthetic microbial fuel cells (MFCs) fed with real wastewater- one having plant Canna indica (PMFC) and the other having alga Chlorella vulgaris (AMFC) at the cathode. The chemical oxygen demand (COD), phosphate, and nitrate removal stood at 57.16% 88.81%, 59.82% for PMFC and 65.27%, 95.59%, 66.61% for the AMFC. While AMFC was slightly superior in water treatment, the power output was 6 times higher in PMFC (22.76 mW m−2) than the AMFC (3.64 mW m−2). The biomass growth was good in both systems, with biomass productivity of 0.031 Kg m−3 day−1 in AMFC and a leaf area index of 0.006 in PMFC. The study's findings suggest that PMFCs are equally good or even better than AMFCs when the goal is simultaneous water treatment and power generation. © 2021 Elsevier Ltd

Bioresource Technology

Effect of cathodic culture on wastewater treatment and power generation in a photosynthetic sediment microbial fuel cell (SMFC): Canna indica v/s Chlorella vulgaris

This study reports the use of Chlamydomonas reinhardtii at the cathode in a photosynthetic microbial fuel cell (PMFC). The PMFC produced power and current density of 15.21 W m(3) and 39 A m(3), respectively. The specific growth rate of algae culture at the cathode was 0.284 day(-1). The system achieved COD removal at 73.30\% with a Coulombic efficiency of 9.068\%. The usability of algae biomass was assessed in terms of its total phenol content (157.69 mg GAE/g algae DW), antioxidant activity (IC50 = 67.07 mu g/ml), total Chlorophyll (18.95 mg/g), total Carotenoids (2.40 mg/g), and antibacterial properties against known pathogens. Overall, the study's findings suggested that C. reinhardtii supports high power output from a PMFC and is highly resourceful in terms of valueadded products.

School of Liberal Arts (SoLA)

BIORESOURCE TECHNOLOGY

Performance evaluation of a photosynthetic microbial fuel cell (PMFC) using Chlamydomonas reinhardtii at cathode

There has been a recent increase in the development of delivery systems based on red blood cells (RBCs) for light-mediated imaging and therapeutic applications. These constructs are able to take advantage of the immune evasion properties of the RBC, while the addition of an optical cargo allows the particles to be activated by light for a number of promising applications. Here, we review some of the common fabrication methods to engineer these constructs. We also present some of the current light-based applications with potential for clinical translation, and offer some insight into future directions in this exciting field. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Biomolecules

Phototheranostics using erythrocyte-based particles

Ovarian cancer is the deadliest gynecological cancer. Cytoreductive surgery to remove primary and intraperitoneal tumor deposits remains as the standard therapeutic approach. However, lack of an intraoperative image-guided approach to enable the visualization of all tumors can result in incomplete cytoreduction and recurrence. We engineered nano-sized particles derived from erythrocytes that encapsulate the near infrared (NIR) fluorochrome, indocyanine green, as potential imaging probes for tumor visualization during cytoreductive surgery. Herein, we present the first demonstra-tion of the use of these nanoparticles in conjunction with spatially-modulated illumination (SMI), at spatial frequencies in the range of 0–0.5 mm−1, to fluorescently image intraperitoneal ovarian tumors in mice. Results of our animal studies suggest that the nanoparticles accumulated at higher levels within tumors 24 h post-intraperitoneal injection as compared to various other organs. We demon-strate that, under the imaging specifications reported here, use of these nanoparticles in conjunction with SMI enhances the fluorescence image contrast between intraperitoneal tumors and liver, and between intraperitoneal tumors and spleen by nearly 2.1, and 3.0 times, respectively, at the spatial frequency of 0.2 mm−1 as compared to the contrast values at spatially-uniform (non-modulated) illumination. These results suggest that the combination of erythrocyte-derived NIR nanoparticles and structured illumination provides a promising approach for intraoperative fluorescence imaging of ovarian tumor nodules at enhanced contrast. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Cancers

Near infrared fluorescence imaging of intraperitoneal ovarian tumors in mice using erythrocyte-derived optical nanoparticles and spatially-modulated illumination

We have engineered nano-sized constructs from erythrocytes doped with the FDA-approved near infrared (NIR) chromophore, indocyanine green (ICG). Herein, we present results that demonstrate membrane cholesterol enrichment is associated with reduced uptake of these nanoparticles by macrophages in vitro, and greater accumulation of the nanoparticles in intraperitoneal implants in immunodeficient mice. These preliminary findings suggest that cholesterol-enrichment of erythrocyte-derived optical nanoparticles can provide a potential capability for enhanced NIR imaging of tumors. © 2021 SPIE. All rights reserved.

Progress in Biomedical Optics and Imaging - Proceedings of SPIE

Cholesterol-enriched erythrocyte-derived optical nanoparticles for nir fluorescence imaging of intraperitoneal ovarian tumors in mice

We propose a granular architecture as a potential impact protector and signal filter. The system consists of monodispersed granular chains decorated with side beads fixed (welded) on sidewalls. Numerical results from usual monodispersed chains and simple tapered chains are employed as reference. An appropriate material combination and an optimal radii ratio between the side and axial granules show that more than 90% of the momentum amplitude of solitary pulses can be attenuated using a small and scalable system composed of five axial granules. Considering sinusoidal signals, the findings suggest that regular chains (monodispersed and tapered) are low-pass filters with cutoff frequencies as functions of the driven amplitude, restitutional losses, and tapering. The granular chain with fixed decoration filters all the input signals. © 2021 American Physical Society.

Physical Review E

Granular chains with fixed side decoration as impact protector and signals filter

Recent studies revealed that ethnic differences in mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK-1/2) signaling pathways might be associated with the development and progression of different human malignancies. The African American (AA) population has an increased rate of cancer incidence and mortality compared to the Caucasian American (CA) population. Although the socioeconomic differences across different ethnic groups contribute to the disparity in developing different cancers, recent scientific evidence indicates the association of molecular and genetic variations in racial disparities of different human malignancies. The mTOR and ERK-1/2 signaling pathways are one of the well-known oncogenic signaling mechanisms that regulate diverse molecular and phenotypic aspects of normal as well as cancer cells in response to different external or internal stimuli. To date, very few studies have been carried out to explore the significance of racial disparity with abnormal mTOR and ERK-1/2 kinase signaling pathways, which may contribute to the development of aggressive human cancers. In this review, we discuss the differential regulation of mTOR and ERK-1/2 kinase signaling pathways across different ethnic groups, especially between AA and CA populations. Notably, we observed that key signaling proteins associated with mTOR and ERK-1/2 pathway including transforming growth factor-beta (TGF-β), Akt, and VEGFR showed racially disparate expression in cancer patients. Overall, this review article encompasses the significance of racially disparate signaling molecules related to mTOR/ERK1/2 and their potential in developing tailor-made anti-cancer therapies. © Copyright © 2021 Mishra, Charan, Verma, Ramaswamy, Ahirwar and Ganju.