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Fulltext In Vivo Toxicological Analysis of MnFe2O4@poly(tBGE-alt-PA) Composite as a Hybrid Nanomaterial for Possible Biomedical Use

Kumar R, Bauri S, Sahu S, Chauhan S, Dholpuria S, Ruokolainen J, et al.

ACS Appl Bio Mater, 2023 Mar 20;6(3):1122-1132.
PMID: 36757355 DOI: 10.1021/acsabm.2c00983

Nanocomposites have significantly contributed to biomedical science due to less aggregation behavior and enhanced physicochemical properties. This study synthesized a MnFe2O4@poly(tBGE-alt-PA) nanocomposite for the first time and physicochemically characterized it. The obtained hybrid nanomaterial was tested in vivo for its toxicological properties before use in drug delivery, tissue engineering fields, and environmental applications. The composite was biocompatible with mouse fibroblast cells and hemocompatible with 2% RBC suspension. This nanocomposite was tested on Drosophila melanogaster due to its small size, well-sequenced genome, and low cost of testing. The larvae's crawling speed and direction were measured after feeding. No abnormal path and altered crawling pattern indicated the nonappearance of abnormal neurological disorder in the larva. The gut organ toxicity was further analyzed using DAPI and DCFH-DA dye to examine the structural anomalies. No apoptosis and necrosis were observed in the gut of the fruit fly. Next, adult flies were examined for phenotypic anomalies after their pupal phases emerged. No defects in the phenotypes, including the eye, wings, abdomen, and bristles, were found in our study. Based on these observations, the MnFe2O4@poly(tBGE-alt-PA) composite may be used for various biomedical and environmental applications.
Current Trends on the Effects of Metal-Based Nanoparticles on Microbial Ecology

Rawat J, Kumar V, Ahlawat P, Tripathi LK, Tomar R, Kumar R, et al.

Appl Biochem Biotechnol, 2023 Oct;195(10):6168-6182.
PMID: 36847986 DOI: 10.1007/s12010-023-04386-0

The growing field of nanotechnology and its many applications have led to the irregular release of nanoparticles (NPs), with unintended effects on the environment and continued contamination of water bodies. Metallic NPs are used more frequently in extreme environmental conditions due to their higher efficiency, which attracts more attention in various applications. Due to improper pre-treatment of biosolids, inefficient wastewater treatment practices, and other unregulated agricultural practices continue to contaminate the environment. In particular, the uncontrolled use of NPs in various industrial applications has led to damage to the microbial flora and caused irreplaceable damage to animals and plants. This study focuses on the effect of different doses, types, and compositions of NP on the ecosystem. The review also mentions the impact of various metallic NPs on microbial ecology, their interactions with microorganisms, ecotoxicity studies, and dosage evaluation of the NPs, mainly focused on the review article. However, further research is still needed to understand the complexity of interactions between NPs and microbes in soil and aquatic ecosystems.
Fulltext Bracing NK cell based therapy to relegate pulmonary inflammation in COVID-19

Jeyaraman M, Muthu S, Bapat A, Jain R, Sushmitha ES, Gulati A, et al.

Heliyon, 2021 Jul;7(7):e07635.
PMID: 34312598 DOI: 10.1016/j.heliyon.2021.e07635

The contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same.
Fulltext The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues

Kar R, Jha SK, Ojha S, Sharma A, Dholpuria S, Raju VSR, et al.

Cancer Rep (Hoboken), 2021 08;4(4):e1369.
PMID: 33822486 DOI: 10.1002/cnr2.1369

BACKGROUND: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer.
RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like βTrcP1 and βTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis.
CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.