Marker-assisted introgression to improve the oleic acid content in the TMV 7 groundnut (Arachis hypogaea L.) variety suitable for the oil industry.

BACKGROUND: Improving the quality and shelf life of groundnut oil is one of the foremost objectives of groundnut breeding programmes. This can be achieved by marker-assisted introgression, a technique that efficiently and precisely enables breeders to develop plants with enhanced qualities. This study focused on improving the oleic acid content of an elite groundnut variety, TMV 7, by introgressing a recessive mutation responsible for the increase in oleic acid from ICG 15419. Hybridization was performed between the donor and recurrent parents to develop the F1, BC1F1, BC2F1 and BC2F2 populations. Introgressed lines with increased oleic acid in the genetic background of TMV 7 were identified using allele-specific marker, F435-F, F435SUB-R and a set of SSR markers were employed to recover the genome of the recurrent parent. RESULTS: With two backcrosses, a total of ten homozygous plants in the BC2F2 population were identified with oleic acid content ranging from 54.23 to 57.72% causing an increase of 36% over the recurrent parent. Among the ten lines, the line IL-23 exhibited the highest level of recurrent parent genome recovery of 91.12%. CONCLUSIONS: The phenotypic evaluation of 10 homozygous introgressed lines indicated fewer differences for all other traits under study compared to the recurrent parent, except for oleic acid and linoleic acid content confirming the genetic background of the recurrent parent. The identified lines will be subjected to multilocation trials before their commercial release.

Computational and Mathematical Methods in Medicine Glioma Brain Tumor Detection and Classification Using Convolutional Neural Network.

The classification of the brain tumor image is playing a vital role in the medical image domain, and it directly assists the clinicians to understand the severity and to take an appropriate solution. The magnetic resonance imaging tool is used to analyze the brain tissues and to examine the different portion of brain circumstance. We propose the convolutional neural network database learning along with neighboring network limitation (CDBLNL) technique for brain tumor image classification in medical image processing domain. The proposed system architecture is constructed with multilayer-based metadata learning, and they have integrated with CNN layer to deliver the accurate information. The metadata-based vector encoding is used, and the type of coding estimation for extra dimension is known as sparse. In order to maintain the supervised data in terms of geometric format, the atoms of neighboring limitation are built based on a well-structured k-neighbored network. The resultant of the proposed system is considerably strong and subjective for classification. The proposed system used two different datasets, such as BRATS and REMBRANDT, and the proposed brain MRI classification technique outcome is more efficient than the other existing techniques.

Degradation of Toxic Dye and Antimicrobial and Free Radical Potential of Environmental Benign Zinc Oxide Nanoparticles.

Several industries have become major contributors to waterbody contamination due to the improper removal of dyes and effluents into water bodies. Due to their carcinogenic properties and low biodegradability, dye degradation is a considerable danger to people, animals, and the oceanic environment. As part of this study, Andrographis paniculata leaf extract was used as a reducing and stabilizing agent to synthesize zinc nanoparticles and degrade dyes such as methyl red and eosin. Zinc oxide nanoparticles (ZnONPs) showed a surface plasmon resonance peak at 430 nm in the UV spectrum. The FTIR result showed a band at 597.93 cm-1 that confirmed the formation of zinc nanoparticles. AFM results revealed spherical ZnONPs. The SEM results predicted an average particle size of 60 nm for crystalline particles. Biologically synthesized zinc nanoparticles exhibited greater antibacterial activity against Pseudomonas spp. and Proteus spp. but lesser activity against Klebsiella spp. and S. aureus. At 1000 µg/ml concentration, ZnONPs had the highest antioxidant activity of 45.34%. An ultraviolet-visible spectrophotometer measured dye degradation progress between 300 and 800 nm. For methyl red, the maximum absorption peak was measured at 415 nm, and for eosin, the maximum peak value was measured between 500 and 515 nm.

Hemin-Induced Death Models Hemorrhagic Stroke and Is a Variant of Classical Neuronal Ferroptosis.

Ferroptosis is a caspase-independent, iron-dependent form of regulated necrosis extant in traumatic brain injury, Huntington disease, and hemorrhagic stroke. It can be activated by cystine deprivation leading to glutathione depletion, the insufficiency of the antioxidant glutathione peroxidase-4, and the hemolysis products hemoglobin and hemin. A cardinal feature of ferroptosis is extracellular signal-regulated kinase (ERK)1/2 activation culminating in its translocation to the nucleus. We have previously confirmed that the mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor U0126 inhibits persistent ERK1/2 phosphorylation and ferroptosis. Here, we show that hemin exposure, a model of secondary injury in brain hemorrhage and ferroptosis, activated ERK1/2 in mouse neurons. Accordingly, MEK inhibitor U0126 protected against hemin-induced ferroptosis. Unexpectedly, U0126 prevented hemin-induced ferroptosis independent of its ability to inhibit ERK1/2 signaling. In contrast to classical ferroptosis in neurons or cancer cells, chemically diverse inhibitors of MEK did not block hemin-induced ferroptosis, nor did the forced expression of the ERK-selective MAP kinase phosphatase (MKP)3. We conclude that hemin or hemoglobin-induced ferroptosis, unlike glutathione depletion, is ERK1/2-independent. Together with recent studies, our findings suggest the existence of a novel subtype of neuronal ferroptosis relevant to bleeding in the brain that is 5-lipoxygenase-dependent, ERK-independent, and transcription-independent. Remarkably, our unbiased phosphoproteome analysis revealed dramatic differences in phosphorylation induced by two ferroptosis subtypes. As U0126 also reduced cell death and improved functional recovery after hemorrhagic stroke in male mice, our analysis also provides a template on which to build a search for U0126's effects in a variant of neuronal ferroptosis.SIGNIFICANCE STATEMENT Ferroptosis is an iron-dependent mechanism of regulated necrosis that has been linked to hemorrhagic stroke. Common features of ferroptotic death induced by diverse stimuli are the depletion of the antioxidant glutathione, production of lipoxygenase-dependent reactive lipids, sensitivity to iron chelation, and persistent activation of extracellular signal-regulated kinase (ERK) signaling. Unlike classical ferroptosis induced in neurons or cancer cells, here we show that ferroptosis induced by hemin is ERK-independent. Paradoxically, the canonical MAP kinase kinase (MEK) inhibitor U0126 blocks brain hemorrhage-induced death. Altogether, these data suggest that a variant of ferroptosis is unleashed in hemorrhagic stroke. We present the first, unbiased phosphoproteomic analysis of ferroptosis as a template on which to understand distinct paths to cell death that meet the definition of ferroptosis.

Excellent photocatalytic performances of Co3O4-AC nanocomposites for H2 production via wastewater splitting.

Natural sunlight-driven photocatalytic hydrogen production from wastewater is one of the most desirable techniques that can realize future green energy technology. Herein, we report the synthesis and the characterization of the biomass activated carbon (AC)-decorated cobalt oxide (Co3O4) nanocomposites for solar-stimulated photocatalytic hydrogen production from sulphide wastewater. The Co3O4-AC nanocomposites were ultrasonically synthesized by using hydrothermally-grown spinel Co3O4 nanoflakes and biomass-derived AC nanoflakes. Co3O4-AC showed a nanobundle-like aggregated morphology, and exhibited a large specific surface area (~133 m2/g). Through utilizing Co3O4-AC as a photocatalyst for photocatalytic splitting of sulphide wastewater (0.2 M) under solar irradiance with 730 W/m2, an enhanced H2 production efficiency (~70 mL/h) was achieved owing to the synergic effects from 2-dimentionally configured Co3O4 and AC microstructures; i.e., large surface area of Co3O4 and high electrical conductivity of AC. These findings suggest the nanocomposites of Co3O4-AC to hold great promise for the green approach of photocatalytic wastewater splitting.

Zipper phosphorene as sensing element towards formaldehyde and acetaldehyde - A first-principles insight.

We ascertained the structural stability of zipper phosphorene nanosheet (zP-NS) and studied the adsorption behaviour of toxic aldehyde compounds including formaldehyde (FD) and acetaldehyde (AD) on zP-NS based on first-principles calculation. Considerably, zP-NS reveal a semiconducting character with band gap of 1.35 eV. Especially, four distinct favourable adsorption positions including bridge-, hollow-, top- and valley-site of FD and AD vapours on zP-NS were investigated. Furthermore, the calculated binding-energy of prominent adsorption sites are observed to be in the scope of -0.143 eV to -0.411 eV advocating physisorption nature of the interaction of chief aldehydes on zP-NS. The overall outcomes recommend that zP-NS can be persuasively utilised as a chemical sensor for monitoring FD and AD molecules in indoor air environment.

N,N-Ru(II)-p-cymene-poly(N-vinylpyrrolidone) surface functionalized gold nanoparticles: from organoruthenium complex to nanomaterial for antiproliferative activity.

Organometallic Ru-arene complexes are promising as anticancer agents, but the lack of tumor uptake and poor solubility in the physiological medium impede their development. In order to deal with these challenges, we developed gold nanoparticles coated with Ru(arene)-functionalized PNVP-Py, where PNVP-Py is pyridine end-functionalized poly(N-vinylpyrrolidone). It is demonstrated that these particles exhibit higher anti-proliferative activity than the individual organometallic ruthenium(ii) complex of the type [Ru(η6-p-cymene)(NN)Cl]PF6, where NN is bis(4-methoxyphenylimino)acenaphthene, against colorectal adenocarcinoma cell lines. More specifically, a RuII(η6-p-cymene) complex containing a NN bidentate ligand has been prepared and characterized by spectral studies and X-ray crystallography. To tether the isolated complex onto the surface of the AuNPs, PNVP-Py, which contains a pyridine group at one end to coordinate to the Ru-complex and a suitable functional group at the other end to bind on the surface of the AuNPs, has been prepared and utilized to obtain the macromolecular complex [Ru(η6-p-cymene)(NN)(PNVP-Py)]Cl2. Next, stable Ru(p-cym)(NN)(PNVP-Py)@AuNPs were obtained via a ligand exchange reaction of citrate-stabilized AuNPs with a macromolecular complex by a direct 'grafting to' approach and characterized well. Despite the lower DNA cleavage activity, the nanoconjugate exhibits better cytotoxicity than the individual complex against HT-29 colorectal adenocarcinoma cells on account of its enhanced permeability across the cell membrane. The AO/EB staining assay revealed that the nanoconjugate is able to induce an apoptotic mode of cell death, which was further quantitatively evaluated by Annexin V-FITC/PI double assay. An immunofluorescence assay indicated the higher potency of the nanoconjugate to inhibit cyclin D1 gene expression that is required for cancer cell growth. To the best of our knowledge, this is the first report of the modification of an organometallic Ru(arene) complex into a Ru(arene)metallopolymer-gold nanoconjugate for the development of ruthenium-based nanomedicine for cancer treatment.

Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage.

Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14+ monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort. Initially, hematoma myeloid cells expressed a robust anabolic proinflammatory profile characterized by activation of hypoxia-inducible factors (HIFs) and expression of genes encoding immune factors and glycolysis. Subsequently, inflammatory gene expression decreased over time, whereas anti-inflammatory circuits were maintained and phagocytic and antioxidative pathways up-regulated. During this transition to immune resolution, glycolysis gene expression and levels of the potent proresolution lipid mediator prostaglandin E2 remained elevated in the hematoma, and unexpectedly, these elevations correlated with positive patient outcomes. Ex vivo activation of human macrophages by ICH-associated stimuli highlighted an important role for HIFs in production of both inflammatory and anti-inflammatory factors, including PGE2, which, in turn, augmented VEGF production. Our findings define the time course of myeloid activation in the human brain after ICH, revealing a conserved progression of immune responses from proinflammatory to proresolution states in humans after brain injury and identifying transcriptional programs associated with neurological recovery.

Preparation and characterization of Pectin/Polypyrrole based multifunctional coatings on TiNbZr alloy for orthopaedic applications.

Being a natural and renewable polysaccharide, pectin (PC) is considered a polymer with promising potential for many applications. In the present investigation, novel multifunctional pectin/polypyrrole (PC/PPy) composite coatings loaded with gentamicin (GM) were electrochemically deposited on TiNbZr alloy to enhance its biocompatibility, antibacterial performance and corrosion resistance in physiological environment. Various surface and structural characterization techniques were deployed to examine the composite coatings. in vitro corrosion analysis confirmed that the composite coated TiNbZr specimen exhibited higher corrosion resistant performance in simulated body fluid (SBF). The drug release kinetics was estimated and the results corroborated the sustained release of GM from the controlled degradation of the composite matrix. The pectin composite coatings exhibited effective antibacterial performance; due to the sustained release of GM. In-vitro cell culture studies validated the improved biocompatibility of the composite coatings. Among the developed coatings, composite coatings loaded with 10 wt. % of GM exhibited the lowest corrosion rate, enhanced biocompatibility, and antibacterial performance.

The drug adaptaquin blocks ATF4/CHOP-dependent pro-death Trib3 induction and protects in cellular and mouse models of Parkinson's disease.

Identifying disease-causing pathways and drugs that target them in Parkinson's disease (PD) has remained challenging. We uncovered a PD-relevant pathway in which the stress-regulated heterodimeric transcription complex CHOP/ATF4 induces the neuron prodeath protein Trib3 that in turn depletes the neuronal survival protein Parkin. Here we sought to determine whether the drug adaptaquin, which inhibits ATF4-dependent transcription, could suppress Trib3 induction and neuronal death in cellular and animal models of PD. Neuronal PC12 cells and ventral midbrain dopaminergic neurons were assessed in vitro for survival, transcription factor levels and Trib3 or Parkin expression after exposure to 6-hydroxydopamine or 1-methyl-4-phenylpyridinium with or without adaptaquin co-treatment. 6-hydroxydopamine injection into the medial forebrain bundle was used to examine the effects of systemic adaptaquin on signaling, substantia nigra dopaminergic neuron survival and striatal projections as well as motor behavior. In both culture and animal models, adaptaquin suppressed elevation of ATF4 and/or CHOP and induction of Trib3 in response to 1-methyl-4-phenylpyridinium and/or 6-hydroxydopamine. In culture, adaptaquin preserved Parkin levels, provided neuroprotection and preserved morphology. In the mouse model, adaptaquin treatment enhanced survival of dopaminergic neurons and substantially protected their striatal projections. It also significantly enhanced retention of nigrostriatal function. These findings define a novel pharmacological approach involving the drug adaptaquin, a selective modulator of hypoxic adaptation, for suppressing Parkin loss and neurodegeneration in toxin models of PD. As adaptaquin possesses an oxyquinoline backbone with known safety in humans, these findings provide a firm rationale for advancing it towards clinical evaluation in PD.

In vitro anticancer activity of fucoidan extracted from Sargassum cinereum against Caco-2 cells.

Fucoidan is a marine sulfated polysaccharide, which is extracted from brown seaweed that has a wide range of bioactivities including anti-cancer properties. However, the underlying mechanism of fucoidan on its anti-cancer and apoptotic activity against colon cancer cell line Caco-2 remains to be elucidated. Hence, the present study evaluated the cytotoxicity, apoptotic and anti-cancer activity of fucoidan extracted from brown seaweed Sargassum cinereum against Caco-2 cell line. Cytotoxicity, morphological examination of nuclei, mitochondrial membrane potential, flow cytometry, reactive oxygen species (ROS) formation and detection of apoptotic efficacy of fucoidan were assessed by different assay protocols. Fucoidan inhibited growth of Caco-2 cells in a dose-dependent manner. IC50 concentration of fucoidan was found to be 250 µg/ml. AO/EB, Hoechst and Annexin V/PI staining confirmed the apoptosis induced by fucoidan in Caco-2 cells. Fucoidan was also found to increase ROS production and augment mitochondrial membrane permeability. The findings of the study suggest that fucoidan exerts potent anti-cancer and apoptotic effect on Caco-2 cells by enhancing ROS production. Thus, fucoidan may be used as a promising therapeutic regimen against various cancer cell types.

Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke.

Ferroptosis, a non-apoptotic form of programmed cell death, is triggered by oxidative stress in cancer, heat stress in plants, and hemorrhagic stroke. A homeostatic transcriptional response to ferroptotic stimuli is unknown. We show that neurons respond to ferroptotic stimuli by induction of selenoproteins, including antioxidant glutathione peroxidase 4 (GPX4). Pharmacological selenium (Se) augments GPX4 and other genes in this transcriptional program, the selenome, via coordinated activation of the transcription factors TFAP2c and Sp1 to protect neurons. Remarkably, a single dose of Se delivered into the brain drives antioxidant GPX4 expression, protects neurons, and improves behavior in a hemorrhagic stroke model. Altogether, we show that pharmacological Se supplementation effectively inhibits GPX4-dependent ferroptotic death as well as cell death induced by excitotoxicity or ER stress, which are GPX4 independent. Systemic administration of a brain-penetrant selenopeptide activates homeostatic transcription to inhibit cell death and improves function when delivered after hemorrhagic or ischemic stroke.

PEDOT/FHA nanocomposite coatings on newly developed Ti-Nb-Zr implants: Biocompatibility and surface protection against corrosion and bacterial infections.

The fabrication of bioactive polymer nanocomposite coatings with enhanced biocompatibility and surface protection has been a topic of abundant concern in orthopaedic implant applications. Herein, we electrochemically prepared a novel poly (3,4-ethylenedioxythiophene) (PEDOT) based nanocomposite coatings with different contents of fluoro hydroxyapatite (FHA) nanoparticles on a newly developed Ti-Nb-Zr (TNZ) alloy; an appropriate approach to advance the surface features of TNZ implants. FTIR, XRD, and Raman analyses of the coating confirm the successful preparation of PEDOT/FHA nanocomposite, and XPS validate the chemical interaction between FHA and PEDOT matrix. SEM and TEM examination show the uniform distribution of spherical FHA nanoparticles inside the PEDOT matrix. Hardness and contact angle measurement results showed improving in the hardness and surface wettability of the coated samples respectively. Electrochemical corrosion tests specified that the PEDOT/FHA coatings exhibit higher corrosion protection than the pure PEDOT coatings. The fabricated nanocomposite coating supports the cell adsorption and proliferation of MG-63 cells. Moreover, antibacterial studies against Gram positive and negative bacteria reveal the enhanced antibacterial performance of the coated TNZ substrates. Our results show the potential applications of PEDOT/FHA nanocomposite as a most viable coating for the orthopaedic implants.

An Enhancement of Deep Learning Algorithm for Brain Tumor Segmentation Using Kernel Based CNN with M-SVM.

The brain tumor can be created by uncontrollable increase of abnormal cells in tissue of brain and it has two kinds of tumors: one is benign and another one is malignant tumor. The benign brain tumor does not affect the adjacent normal and healthy tissue but the malignant tumor can affect the neighboring tissues of brain that can lead to the death of person. An early detection of brain tumor can be required to protect the survival of patients. Usually, the brain tumor is detected using MRI scanning method. However, the radiologists are not providing the effective tumor segmentation in MRI image due to the irregular shape of tumors and position of tumor in the brain. Accurate brain tumor segmentation is needed to locate the tumor and it is used to give the correct treatment for a patient and it provides the key to the doctor who must execute the surgery for patient. In this paper, a novel deep learning algorithm (kernel based CNN) with M-SVM is presented to segment the tumor automatically and efficiently. This presented work contains several steps that are preprocessing, feature extraction, image classification and tumor segmentation of brain. The MRI image is smoothed and enhanced by Laplacian of Gaussian filtering method (LoG) with Contrast Limited Adaptive Histrogram Equalization (CLAHE) and feature can be extracted from it based on tumor shape position, shape and surface features in brain. Consequently, the image classification is done using M-SVM depending on the selected features. From MRI image, the tumor is segmented with help of kernel based CNN method.. Experimental results of proposed method can show that this presented technique can executes brain tumor segmentation accurately reaching almost 84% in evaluation with existing algorithms.

Ferroptosis in Neurons and Cancer Cells Is Similar But Differentially Regulated by Histone Deacetylase Inhibitors.

Ferroptotic death is a mechanism for tumor suppression by pharmacological inhibitors that target the Xc- transporter (cystine/glutamate antiporter) in a host of non-CNS and CNS tumors. Inhibition of this transporter leads to reduction of cystine uptake, cyst(e)ine deprivation, subsequent depletion of the versatile antioxidant glutathione, and reactive lipid species-dependent death. Accordingly, pharmacological inhibitors of the Xc- transporter can also induce neuronal cell death raising concerns about toxicity in the CNS and PNS if these agents are used for chemotherapy. Here, we show that ferroptotic death induced by the canonical ferroptosis inducer erastin is similar in HT1080 fibrosarcoma cells and primary cortical neurons although cell death is mediated more potently in cancer cells. Reducing the toxicity of ferroptosis inducers will require, among other things, the identification of agents that protect neurons from ferroptosis but exacerbate it in tumor cells. Although we show that a number of agents known to block ferroptosis in primary mouse neurons also inhibit ferroptosis in fibrosarcoma cells, class I histone deacetylase (HDAC) inhibitors selectively protect neurons while augmenting ferroptosis in cancer cells. Our results further suggest that cell death pathways induced by erastin in these two cell types are statistically identical to each other and identical to oxidative glutamate toxicity in neurons, where death is also mediated via inhibition of Xc- cystine transport. Together, these studies identify HDACs inhibitors as a novel class of agents to augment tumor suppression by ferroptosis induction and to minimize neuronal toxicity that could manifest as peripheral neuropathy or chemo brain.

N-acetylcysteine targets 5 lipoxygenase-derived, toxic lipids and can synergize with prostaglandin E2 to inhibit ferroptosis and improve outcomes following hemorrhagic stroke in mice.

OBJECTIVES: N-acetylcysteine (NAC) is a clinically approved thiol-containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled as an "antioxidant," poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke. METHODS: Hemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5-lipoxygenase (ALOX5) knockout mice, and viral-gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC. RESULTS: NAC prevented hemin-induced ferroptosis by neutralizing toxic lipids generated by arachidonate-dependent ALOX5 activity. NAC efficacy required increases in glutathione and is correlated with suppression of reactive lipids by glutathione-dependent enzymes such as glutathione S-transferase. Accordingly, its protective effects were mimicked by chemical or molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced neuronal death and improved functional recovery at least 7 days following ICH in mice and can synergize with clinically approved prostaglandin E2 (PGE2 ). INTERPRETATION: NAC is a promising, protective therapy for ICH, which acted to inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with exogenously delivered protective PGE2 in vitro and in vivo. The findings provide novel insight into a target for NAC, beyond the generic characterization as an antioxidant, resulting in neuroprotection and offer a feasible combinatorial strategy to optimize efficacy and safety in dosing of NAC for treatment of neurological disorders involving ferroptosis such as ICH. Ann Neurol 2018;84:854-872.

A review of natural polysaccharides for drug delivery applications: Special focus on cellulose, starch and glycogen.

Natural polysaccharides are renewable with a high degree of biocompatibility, biodegradability, and ability to mimic the natural extracellular matrix (ECM) microenvironment. Comprehensive investigations of polysaccharides are essential for our fundamental understanding of exploiting its potential as bio-composite, nano-conjugate and in pharmaceutical sectors. Polysaccharides are considered to be superior to other polymers, for its ease in tailoring, bio-compatibility, bio-activity, homogeneity and bio-adhesive properties. The main focus of this review is to spotlight the new advancements and challenges concerned with surface modification, binding domains, biological interaction with the conjugate including stability, polydispersity, and biodegradability. In this review, we have limited our survey to three essential polysaccharides including cellulose, starch, and glycogen that are sourced from plants, microbes, and animals respectively are reviewed. We also present the polysaccharides which have been extensively modified with the various types of conjugates for combating last-ditch pharmaceutical challenges.

Chitosan/nano-hydroxyapatite/nano-zirconium dioxide scaffolds with miR-590-5p for bone regeneration.

Bone tissue engineering (BTE) relies on biocomposite scaffolds and bioactive molecules for bone regeneration. The present study was aimed to synthesize and characterize biocomposite scaffolds containing chitosan (CS), nano-hydroxyapatite (nHAp) and nano­zirconium dioxide (nZrO2) along with microRNA (miRNA) for BTE applications. miRNAs act as post-transcriptional regulator of gene expression. The fabricated biocomposite scaffolds were characterized using SEM, FT-IR and XRD analyses. The effect of a bioactive molecule (miR-590-5p) with scaffolds was tested for osteoblast differentiation at the cellular and molecular levels using mouse mesenchymal stem cells (C3H10T1/2). The results showed that CS/nHAp/nZrO2 scaffolds promoted osteoblast differentiation, and this effect was further increased in the presence of miR-590-5p in C3H10T1/2 cells. Thus, we suggested that CS/nHAp/nZrO2 scaffolds with miR-590-5p would have potential towards the treatment of bone defects.

Swertiamarin, a natural steroid, prevent bone erosion by modulating RANKL/RANK/OPG signaling.

Bone erosion is a central feature of rheumatoid arthritis (RA) that is characterized by the infiltration of the synovial lining by osteoclasts and lymphocytes. In the present study, swertiamarin a major secoiridoid glycoside was evaluated for anti-osteoclastogenic property to prevent bone erosion in Freund's complete adjuvant (FCA) induced in-vivo model, in-vitro osteoblast and osteoclasts as well as in co-culture system and in-silico molecular docking analysis. The swertiamarin treatment decreased the expression of TRAP, RANKL, and RANK levels and increased the levels of OPG levels significantly in both in vitro and in vivo models. In in vitro, the compound treatment significantly increased the cell proliferation and ALP levels in osteoblast cells; the high proliferation (153.8600±5.23%) and ALP release (165.6033±4.13%) were observed at 50µg/ml concentration of swertiamarin treatment. At the same time the treatment decreased the TRAP positive cells in osteoclast cells; the high reductions of TRAP positive cells (39.32±3.19%) were observed at 50µg/ml of swertiamarin treatment. The treatment modulated the levels of pro-inflammatory cytokines, MMPs and NF-κB levels in osteoblast and osteoclast co-culture system. In in silico analysis swertiamarin had affinity towards the proteins RANK, RANKL and OPG residues with low binding energy -4.5, -3.92 and -5.77kcal/mol respectively. Thus, the results of this study revealed the anti-osteoclastogenic activity of swertiamarin on the prevention of bone destruction.

Occurrence of double primary malignancies in an African renal transplant recipient.

A 63-year-old African male with end stage renal disease who received a renal transplantation from his daughter after successful treatment of hepatitis C virus, type 1 genotype developed metastatic Kaposi's sarcoma and subsequently adenocarcinoma of the prostate. He was successfully treated with chemotherapy and reduction of immunosuppression and switch over to rapamycin.