Search

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G′, 2.3–2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Introduction: Haematogenous spread of tumours to bone marrow is a common phenomenon and implies advanced stage of disease with poor prognosis. In most instances, the site of primary malignancies is known and is demonstrated in the bone marrow, when the procedure is carried out as a part of the staging process. However In some cases, detection is incidental and bone marrow involvement may be the first clue to these unsuspected non haematopoietic malignancies. Objective: In this study, we aim to analyse the clinico-pathological spectrum of non-hematopoietic neoplasms detected in bone marrow biopsies carried out in our setting. Methods: This is a descriptive cross-sectional study, where the Laboratory Information System (LIS) was used to screen all the bone marrow trephine biopsies done over the last 7 years, from January 2014 to December 2020. Out of total 4370 bone marrow trephine biopsies performed, 53 cases of bone marrow metastases by nonhematopoeitic malignancies were detected. All the stained slides and the tissue blocks of metastases were retrieved for observation and their laboratory parameters were retrieved from the Laboratory Information System (LIS). Results: Out of these 53 cases, primary was known in 16 (30.2%) cases prior to performing marrow biopsies. 15 (28.3%) cases presented with severe backache and/or presence of lytic lesions on radiological examination and underwent marrow examination with a clinical suspicion of multiple myeloma verses metastases. 16 (30.2%) cases were incidentally detected while evaluating for causes of cytopenias and leucoerythroblastic blood picture. Adenocarcinoma prostate was the most common tumour with first presentation as bone marrow metastases followed by adenocarcinomatous deposits from gastrointestinal tract. Conclusion: Bone marrow metastases by non-hematopoietic neoplasms can be the first presenting feature in many cases as seen in our study. So, performing a trephine biopsy routinely along with aspiration for any unexplained cytopenias is of paramount importance in clinching the primary diagnosis. [ABSTRACT FROM AUTHOR]

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly( N -acryloylglycine)- co -(acrylamide)- co -( N -acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability ( G ', 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.

In this work, the glycine-based acryloyl monomer is polymerized to obtain a neurogenic polymeric hydrogel for regenerative applications. The synthesized poly( N -acryloylglycine-acrylamide) [poly(NAG- b -A)] nanohydrogel exhibits high swelling (∼1500%) and is mechanically very stable, biocompatible, and proliferative in nature. The poly(NAG- b -A) nanohydrogel provides a stable 3D extracellular mimetic environment and promotes healthy neurite growth for primary cortical neurons by facilitating cellular adhesion, proliferation, actin filament stabilization, and neuronal differentiation. Furthermore, the protective role of the poly(NAG- b -A) hydrogel for the neurons in oxidative stress conditions is revealed and it is found that it is a clinically relevant material for neuronal regenerative applications, such as for promoting nerve regeneration via GSK3β inhibition. This hydrogel additionally plays an important role in modulating the biological microenvironment, either as an agonist and antagonist or as an antioxidant. Furthermore, it favors the physiological responses and eases the neurite growth efficiency. Additionally, we found out that the conversion of glycine-based acryloyl monomers into their corresponding polymer modulates the mechanical performance, mimics the cellular microenvironment, and accelerates the self-healing capability due to the responsive behavior towards reactive oxygen species (ROS). Thus, the p(NAG- b -A) hydrogel could be a potential candidate to induce neuronal regeneration since it provides a physical cue and significantly boosts neurite outgrowth and also maintains the microtubule integrity in neuronal cells.

Invasive bacterial and fungal infections have notably increased the burden on the health care system and especially in immune compromised patients. These invasive bacterial and fungal species mimic and interact with the host extracellular matrix and increase the adhesion and internalization into the host system. Further, increased resistance of traditional antibiotics/antifungal drugs led to the demand for other therapeutics and preventive measures. Presently, metallic nanoparticles have wide applications in health care sectors. The present study has been designed to evaluate the advantage of Ag/Sn-SnO 2 composite nanoparticles over the single oxide/metallic nanoparticles. By using in silico molecular docking approaches, herein we have evaluated the effects of Ag/Sn-SnO 2 nanoparticles on adhesion and invasion responsible molecular targets such as LpfD ( E. coli ), Als3 ( C. albicans ) and on virulence/resistance causing PqsR ( P. aeruginosa ), RstA (Bmfr) ( A. baumannii ), FoxA ( K. pneumonia ), Hsp90 and Cyp51 ( C. albicans ). These Ag/Sn-SnO 2 nanoparticles exhibited higher antimicrobial activities, especially against the C. albicans , which are the highest ever reported results. Further, Ag/Sn-SnO 2 NPs exhibited interaction with the heme proionate residues such as Lys143, His468, Tyr132, Arg381, Phe105, Gly465, Gly464, Ile471 and Ile304 by forming hydrogen bonds with the Arg 381 residue of lanosterol 1 4α-demethylase and increased the inhibition of the Candida strains. Additionally, the Ag/Sn-SnO 2 nanoparticles exhibited extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species followed by several molecular pathways which indicated that it can be used to eliminate the resistance to traditional antibiotics., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

In this work, mesoporous (pore size below 4 nm) composite nanoparticles of ZnO-Ag 2 O/Ag, ZnO-CuO, and ZnO-SnO 2 of size d ≤ 10 nm (dia.) have been synthesized through the in situ solvochemical reduction method using NaBH 4 . These composite nanoparticles exhibited excellent killing efficacy against Gram-positive/negative bacterial and fungal strains even at a very low dose of 0.010 μg/mL. Additionally, by applying the in silico docking approach, the nanoparticles and microorganism-specific targeted proteins and their interactions have been identified to explain the best anti-bacterial/anti-fungal activities of these composites. For this purpose, the virulence and resistance causing target proteins such as PqsR , RstA , FosA , and Hsp90 of Pseudomonas aeruginosa , Acinetobacter baumannii , Klebsiella pneumoniae , and Candida albicans have been identified to find out the best inhibitory action mechanisms involved. From the in vitro study, it is revealed that all the composite nanoparticle types used here can act as potent antimicrobial components. All the composite nanoparticles have exhibited excellent inhibition against the microorganisms compared to their constituent single metal or metal oxide nanoparticles. Among the nanoparticle types, the ZnO-Ag 2 O/Ag composite nanoparticles exhibited the best inhibition activity compared to the other reported nanoparticles. The microorganisms which are associated with severe infections lead to the multidrug resistance and have become a huge concern in the healthcare sector. Conventional organic antibiotics are less stable at a higher temperature. Therefore, based on the current demands, this work has been focused on designing inorganic antibiotics which possess stability even under harsh conditions. In this direction, our developed composite nanoparticles were explored for potential uses in the healthcare technology, and they may solve many problems in global emergency and epidemics caused by the microorganisms., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)