Polyester nanomedicines for visceral leishmaniasis treatment.

Tweetable abstract Unveiling the power of polyester nanomedicines in revolutionizing visceral leishmaniasis treatment with enhanced drug loading and precise targeting.

Current Trends on the Effects of Metal-Based Nanoparticles on Microbial Ecology.

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.

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

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.

Nanotechnology-based therapeutic formulations in the battle against animal coronaviruses: an update.

Outbreak of infectious diseases imposes a serious threat to human population and also causes a catastrophic impact on global economy. Animal coronaviruses remain as one of the intriguing problems, known to cause deadly viral diseases on economically important animal population, and also these infections may spread to other animals and humans. Through isolation of the infected animals from others and providing appropriate treatment using antiviral drugs, it is possible to prevent the virus transmission from animals to other species. In recent times, antiviral drug-resistant strains are being emerged as a deadly virus which are known to cause pandemic. To overcome this, nanoparticles-based formulations are developed as antiviral agent which attacks the animal coronaviruses at multiple sites in the virus replication cycle. Nanovaccines are also being formulated to protect the animals from coronaviruses. Nanoformulations contain particles of one or more dimensions in nano-scale (few nanometers to 1000 nm), which could be inorganic or organic in nature. This review presents the comprehensive outline of the nanotechnology-based therapeutics formulated against animal coronaviruses, which includes the nanoparticles-based antiviral formulations and nanoparticles-based adjuvant vaccines. The mechanism of action of these nanoparticles-based antivirals against animal coronavirus is also discussed using relevant examples. In addition, the scope of repurposing the existing nano-enabled antivirals and vaccines to combat the coronavirus infections in animals is elaborated.

Recent trends in biodegradable polyester nanomaterials for cancer therapy.

Biodegradable polyester nanomaterials-based drug delivery vehicles (DDVs) have been largely used in most of the cancer treatments due to its high biological performance and wider applications. In several previous studies, various biodegradable and biocompatible polyester backbones were used which are poly(lactic acid) (PLA), poly(ε-caprolactone) (PCL), poly(propylene fumarate) (PPF), poly(lactic-co-glycolic acid) (PLGA), poly(propylene carbonate) (PPC), polyhydroxyalkanoates (PHA), and poly(butylene succinate) (PBS). These polyesters were fabricated into therapeutic nanoparticles that carry drug molecules to the target site during the cancer disease treatment. In this review, we elaborately discussed the chemical synthesis of different synthetic polyesters and their use as nanodrug carriers (NCs) in cancer treatment. Further, we highlighted in brief the recent developments of metal-free semi-aromatic polyester nanomaterials along with its role as cancer drug delivery vehicles.

Bracing NK cell based therapy to relegate pulmonary inflammation in COVID-19.

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.

A novel lincRNA identified in buffalo oocytes with protein binding characteristics could hold the key for oocyte competence.

Studying the maternal oocyte-specific genes, in farm animals is a significant step towards delineating the underlying mechanisms that regulate oocyte quality, early embryonic development and survival. With the creation of buffalo oocyte-specific subtracted cDNA library, it has raised new questions which need to be answered. The present study has characterized one of the ESTs selected from the library and highlighted its importance in the oocyte quality. The selected EST was made full length by RLM-RACE and four transcript variants were identified. Bioinformatics analysis indicated the novelty of full-length transcript along with conserved intergenic nature. The largest transcript was identified as long intergenic noncoding RNA based upon coding potential calculator output. The expression analysis at different hours of oocyte maturation showed a significant variation in developmentally competent oocytes to that of incompetent ones. Along with this, the transcript was also found to have protein binding ability which was confirmed by RNA electrophoretic mobility shift assay. The protein used in the experiment was isolated from oocyte and cumulus cells via sonication. A novel lincRNA has been reported here that might have an important role in maturation of oocytes, inferred from its relative gene expression study and protein binding characteristics.

The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues.

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 ßTrcP1 and ßTrcP2, 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.

Nanoparticulate RNA delivery systems in cancer.

BACKGROUND: Drug delivery system is a common practice in cancer treatment. RNA interference-mediated post-transcriptional gene silencing holds promise as an approach to knockdown in the expression of target genes responsible for cancer cell growth and metastasis. RNA interference (RNAi) can be achieved by delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) to target cells. Since neither interfering RNAs can be delivered in naked form due to poor stability, an efficient delivery system is required that protects, guides, and delivers the siRNA and shRNA to target cells as part of cancer therapy (chemotherapy). RECENT FINDINGS: In this review, a discussion is presented about the different types of drug delivery system used to deliver siRNA and shRNA, together with an overview of the potential benefits associated with this sophisticated biomolecular therapy. Improved understanding of the different approaches used in nanoparticle (NP) fabrication, along with an enhanced appreciation of the biochemical properties of siRNA/shRNA, will assist in developing improved drug delivery strategies in basic and clinical research. CONCLUSION: These novel delivery techniques are able to solve the problems that form an inevitable part of delivering genes in more efficient manner and as part of more effective treatment protocols. The present review concludes that the nanoparticulate RNA delivery system has great possibility for cancer treatment along with several other proposed methods. Several NPs or nanocarriers are already in use, but the methods proposed here could fulfill the missing gap in cancer research. It is the future technology, which unravels the mystery of resolving genomic diseases that is, especially genomic instability and its signaling cascades.

A "NOTCH" Deeper into the Epithelial-To-Mesenchymal Transition (EMT) Program in Breast Cancer.

Notch signaling is a primitive signaling pathway having various roles in the normal origin and development of each multicellular organisms. Therefore, any aberration in the pathway will inevitably lead to deadly outcomes such as cancer. It has now been more than two decades since Notch was acknowledged as an oncogene in mouse mammary tumor virus-infected mice. Since that discovery, activated Notch signaling and consequent up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. Moreover, consistent over-expression of Notch ligands and receptors has been shown to correlate with poor prognosis in human breast cancer. Notch regulates a number of key processes during breast carcinogenesis, of which, one key phenomenon is epithelial-mesenchymal transition (EMT). EMT is a key process for large-scale cell movement during morphogenesis at the time of embryonic development. Cancer cells aided by transcription factors usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. In this review, we recapitulate recent progress in breast cancer research that has provided new perceptions into the molecular mechanisms behind Notch-mediated EMT regulation during breast tumorigenesis.

Transient Arrest of Germinal Vesicle Breakdown Improved In Vitro Development Potential of Buffalo (Bubalus Bubalis) Oocytes.

Germinal vesicle breakdown (GVBD) is the first milestone that an oocyte needs to achieve toward completing the maturation and gaining potential to fertilize. Significantly lower in vitro embryo production rate in buffaloes can be attributed to heterogeneity of GVBD occurrence among oocytes obtained from abattoir derived ovaries. Evidence from our earlier work had suggested that different qualities of buffalo oocytes differ significantly in their timing of GVBD. Besides, these oocytes also differ in terms of volume of Akt phosphorylation, which initiates the process of GVBD. With objective of synchronizing the oocytes for GVBD, immature buffalo oocytes were subjected to a two-step culture protocol, initially in the presence of GVBD inhibitors and subsequently, in vitro maturation (IVM) with added SC79 (activates Akt). Expression of developmentally important genes was assessed along with embryo development rate and blastocyst health to interpret the consequences. Oocytes subjected to a short GVBD inhibition period of 6 h followed by IVM with SC79 resulted in improved cleavage and blastocyst rates. Resultant blastocysts also possessed higher ICM: TE ratio. Further, GVBD inhibited oocytes displayed a sustained cytoplasmic maturation status in terms of reorganization of cortical granules (CGs), mitochondrial membrane potential, and glutathione levels during the period of inhibition. We conclude that a temporary GVBD arrest of buffalo oocytes and modulation of Akt improves the in vitro embryo development rate as well as quality of resultant embryos. Besides, our meiotic arrest protocol does not affect the cytoplasmic maturation. J. Cell. Biochem. 119: 278-289, 2018. © 2017 Wiley Periodicals, Inc.

An immunological approach of sperm sexing and different methods for identification of X- and Y-chromosome bearing sperm.

Separation of X- and Y-chromosome bearing sperm has been practiced for selection of desired sex of offspring to increase the profit in livestock industries. At present, fluorescence-activated cell sorter is the only successful method for separation of X- and Y-chromosome bearing sperm. This technology is based on the differences in DNA content between these two types of sperm and has been commercialized for bovine sperm. However, this technology still has problems in terms of high economic cost, sperm damage, and lower pregnancy rates compared to unsorted semen. Therefore, an inexpensive, convenient, and non-invasive approach for sperm sexing would be of benefit to agricultural sector. Within this perspective, immunological sperm sexing method is one of the attractive choices to separate X- and Y-chromosome bearing sperm. This article reviews the current knowledge about immunological approaches, viz., H-Y antigen, sex-specific antigens, and differentially expressed proteins for sperm sexing. Moreover, this review also highlighted the different methods for identification of X- and Y-sperm.

Differential Expression of Newly Identified Long Intergenic Non-Coding RNAs in Buffalo Oocytes Indicating Their Possible Role in Maturation and Embryonic Development.

Female germ cell and its intricate milieu regulate key processes of folliculogenesis and early embryonic development. However, the composition and dynamics of the oocyte transcriptome defines its future fertilizing ability which in turn depends on a number of oocyte specific genes whose identities are still unknown. In this context, the construction of buffalo oocyte specific subtracted cDNA library has raised fresh challenges of defining the importance of a battery of oocyte expressed transcripts in oocyte maturation. The present study tried to characterize these hitherto unknown transcripts and further to assess their expression dynamics in buffalo oocytes of different quality. For this purpose, three ESTs were selected from the library and subjected to 5' and 3' RACE for generating their full length sequences. These constructed full length sequences were validated by amplifying them in oocytes. Further these sequences were extensively analyzed for their coding potential and possible role using coding potential calculator and miRNA database. Besides, their expression was monitored during in vitro maturation in good (BCB+) and poor quality (BCB-) oocytes which was interestingly found to be differing significantly. All the three sequences under study were interpreted as long intergenic non-coding RNAs with the possibility of two of them acting as a miRNA precursors. Also, their differential expression trends in competitively diverse oocytes hints at their possible involvement in oocyte maturation and future embryonic development which needs to be explored further. J. Cell. Biochem. 118: 1712-1721, 2017. © 2016 Wiley Periodicals, Inc.