A hybrid thyroid tumor type classification system using feature fusion, multilayer perceptron and bonobo optimization.

BACKGROUND: Thyroid tumor is considered to be a very rare form of cancer. But recent researches and surveys highlight the fact that it is becoming prevalent these days because of various factors. OBJECTIVES: This paper proposes a novel hybrid classification system that is able to identify and classify the above said four different types of thyroid tumors using high end artificial intelligence techniques. The input data set is obtained from Digital Database of Thyroid Ultrasound Images through Kaggle repository and augmented for achieving a better classification performance using data warping mechanisms like flipping, rotation, cropping, scaling, and shifting. METHODS: The input data after augmentation goes through preprocessing with the help of bilateral filter and is contrast enhanced using dynamic histogram equalization. The ultrasound images are then segmented using SegNet algorithm of convolutional neural network. The features needed for thyroid tumor classification are obtained from two different algorithms called CapsuleNet and EfficientNetB2 and both the features are fused together. This process of feature fusion is carried out to heighten the accuracy of classification. RESULTS: A Multilayer Perceptron Classifier is used for classification and Bonobo optimizer is employed for optimizing the results produced. The classification performance of the proposed model is weighted using metrics like accuracy, sensitivity, specificity, F1-score, and Matthew's correlation coefficient. CONCLUSION: It can be observed from the results that the proposed multilayer perceptron based thyroid tumor type classification system works in an efficient manner than the existing classifiers like CANFES, Spatial Fuzzy C means, Deep Belief Networks, Thynet and Generative adversarial network and Long Short-Term memory.

Bio inspired growth factor loaded self assembling peptide nano hydrogel for chronic wound healing.

Self assembling peptidebased hydrogel has been explored for delivering growth factors, anticancer drugs, antibiotics etc. Here, RADA 16-I (RADARADARADARADA), an ionic self complementary peptide that forms a well defined nanohydrogel has been studied for its ability to deliver PDGF-BB in a sustained manner and to destruct biofilm formed by wound specific pathogens. Results of the structural analysis of the nanohydrogel studied through AFM, FeSEM, CD, FT-IR and Rheometry, revealed the hydrogel forming ability of RADA 16-I with stable ß-sheet structure at room temperature. The nanohydrogel was also found to destruct the biofilm formed under in vitro condition using S. aureus, E. coli and P. aeruginosa. The growth factor incorporated in the nanohydrogel followed first order release kinetics and showed sustained release up to 48 h. Angiogenic potential and wound healing ability of PDGF-BB incorporated nanohydrogel was confirmed in both in vitro and in vivo conditions. The animals treated with PDGF-BB incorporated nanohydrogel exhibited 99.5% wound closure at day 21. The content of hydroxyproline and ascorbic acid was significantly high in the treated animals when compared to control and untreated animals. Overall, the study provides the essential information and data for using RADA 16-I for treating chronic wounds.

Molecular identification and evolutionary relationships between the subspecies of Musa by DNA barcodes.

BACKGROUND: The banana (Musa sp., AAA) genome is constantly increasing due to high-frequency of somaclonal variations. Due to its large diversity, a conventional numerical and morphological based taxonomic identification of banana cultivars is laborious, difficult and often leads to subject of disagreements. RESULTS: Hence, in the present study, we used universal DNA barcode ITS2 region to identify and to find the genetic relationship between the cultivars and varieties of banana. Herein, a total of 16 banana cultivars were PCR amplified using ITS2 primer pair. In addition, 321 sequences which were retrieved from GenBank, USA, were used in this study. The sequences were then aligned using Clustal W and genetic distances were computed using MEGA V5.1. The study showed significant divergence between the intra- and inter-specific genetic distances in ITS2 region. BLAST1 and Distance methods proved that ITS2 DNA barcode region successfully identified and distinguished the cultivar and varieties of banana. CONCLUSION: Thus, from the results of the present study, it is clear that ITS2 is not only an efficient DNA barcode to identify the banana species but also a potential candidate for enumerating the phylogenetic relationships between the subspecies and cultivars. This is the first comprehensive study to categorically distinguish the economically important banana subspecies and varieties using DNA barcodes and to understand its evolutionary relationship.

Rational Design, Synthesis, and In Vitro Neuroprotective Evaluation of Novel Glitazones for PGC-1α Activation via PPAR-γ: a New Therapeutic Strategy for Neurodegenerative Disorders.

In the present study, two structurally diverse novel glitazones were designed and synthesized for activation of central PGC-1α signaling through stimulation of PPAR-γ receptor. The functional interaction between PGC-1α and PPAR-γ is a key interaction in the normal physiology of neuroprotective mechanism. Therefore, activation of PPAR-γ-dependent PGC-1α co-activator signaling could be an effective strategy to exhibit neuroprotection in several neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and cerebral ischemia. As part of rational design, analogs were designed manually based on principles of bioisosterism, followed by virtually screened using docking to predict the mode of interaction of compound towards the binding site and molecular dynamic simulation to observe the structural changes that occur during compound interaction with active site. The designed two glitazones (G1, G2) were synthesized and structurally analyzed. As part of evaluation, synthesized glitazones were subjected for preliminary neuroprotective evaluation in Lipopolysaccharide (LPS) intoxicated SH-SY5Y neuroblastoma cells. The results indicate that pre-treatment with synthesized glitazones have increased the percentage cell viability, protected the cell morphology, and decreased the release of pro-inflammatory cytokines (IL-1ß, TNF-α), lipid peroxide (LPO), and nitric oxide (NO) level in LPS intoxicated SH-SY5Y cells. Interestingly, among the two glitazones, G2 has shown significant neuroprotection in comparison to G1 and neuroprotective effect exerted by G2 was similar and comparable with the standard pioglitazone. Altogether, neuroprotection exhibited by this non-thiazolidione-based glitazones during neuroinflammatory conditions may be attributed to the activation of central PGC-1α signaling via PPAR-γ receptor.

In silico characterisation and functional validation of chilling tolerant divergence 1 (COLD1) gene in monocots during abiotic stress.

The G protein-coupled receptor is one of the major transmembrane proteins in plants. It consists of an α subunit, a ß subunit and three γ subunits. Chilling tolerant divergence 1 (COLD1) includes a Golgi pH receptor (GPHR) domain, which maintains cell membrane organisation and dynamics, along with abscisic acid linked G protein-coupled receptor (ABA_GPCR) that regulates the signalling pathways during cold stress. In the present study, we performed characterisation of a homologous COLD1 from the economically important monocot species Oryza sativa L., Zea mays L., Sorghum bicolor (L.)Moench and Erianthus arundinaceus (L.) Beauv. IK 76-81, a wild relative of Saccharum. COLD1 was isolated from E. arundinaceus IK 76-81, analysed for its evolution, domain, membrane topology, followed by prediction of secondary, tertiary structures and functionally validated in all four different monocots. Gene expression studies of COLD1 revealed differential expression under heat, drought, salinity and cold stresses in selected monocots. This is the first study on regulation of native COLD1 during abiotic stress in monocots, which has opened up new leads for trait improvement strategies in this economically important crop species.

Corrigendum to: In silico characterisation and functional validation of chilling tolerant divergence 1 (COLD1) gene in monocots during abiotic stress.

The G protein-coupled receptor is one of the major transmembrane proteins in plants. It consists of an α subunit, a ß subunit and three γ subunits. Chilling tolerant divergence 1 (COLD1) includes a Golgi pH receptor (GPHR) domain, which maintains cell membrane organisation and dynamics, along with abscisic acid linked G protein-coupled receptor (ABA_GPCR) that regulates the signalling pathways during cold stress. In the present study, we performed characterisation of a homologous COLD1 from the economically important monocot species Oryza sativa L., Zea mays L., Sorghum bicolor (L.)Moench and Erianthus arundinaceus (L.) Beauv. IK 76-81, a wild relative of Saccharum. COLD1 was isolated from E. arundinaceus IK 76-81, analysed for its evolution, domain, membrane topology, followed by prediction of secondary, tertiary structures and functionally validated in all four different monocots. Gene expression studies of COLD1 revealed differential expression under heat, drought, salinity and cold stresses in selected monocots. This is the first study on regulation of native COLD1 during abiotic stress in monocots, which has opened up new leads for trait improvement strategies in this economically important crop species.

Proliferation and differentiation of mesenchymal stem cells on scaffolds containing chitosan, calcium polyphosphate and pigeonite for bone tissue engineering.

OBJECTIVES: Treatment of critical-sized bone defects with cells and biomaterials offers an efficient alternative to traditional bone grafts. Chitosan (CS) is a natural biopolymer that acts as a scaffold in bone tissue engineering (BTE). Polyphosphate (PolyP), recently identified as an inorganic polymer, acts as a potential bone morphogenetic material, whereas pigeonite (Pg) is a novel iron-containing ceramic. In this study, we prepared and characterized scaffolds containing CS, calcium polyphosphate (CaPP) and Pg particles for bone formation in vitro and in vivo. MATERIALS AND METHODS: Chitosan/CaPP scaffolds and CS/CaPP scaffolds containing varied concentrations of Pg particles (0.25%, 0.5%, 0.75% and 1%) were prepared and characterized by SEM, XRD, EDAX, FT-IR, degradation, protein adsorption, mechanical strength and biomineralization studies. The cytocompatibility of these scaffolds with mouse mesenchymal stem cells (mMSCs, C3H10T1/2) was determined by MTT assay and fluorescence staining. Cell proliferation on scaffolds was assessed using MUSE™ (Merck-Millipore, Germany) cell analyser. The effect of scaffolds on osteoblast differentiation at the cellular level was evaluated by Alizarin red (AR) and alkaline phosphatase (ALP) staining. At the molecular level, the expression of osteoblast differentiation marker genes such as Runt-related transcription factor-2 (Runx2), ALP, type I collagen-1 (Col-I) and osteocalcin (OC) was determined by real-time reverse transcriptase (RT-PCR) analysis. Bone regeneration was assessed by X-ray radiographs, SEM and EDAX analyses, and histological staining such as haematoxylin and eosin staining and Masson's trichrome staining (MTS) in a rat critical-sized tibial defect model system. RESULTS: The inclusion of iron-containing Pg particles at 0.25% concentration in CS/CaPP scaffolds showed enhanced bioactivity by protein adsorption and biomineralization, compared with that shown by CS/CaPP scaffolds alone. Increased proliferation of mMSCs was observed with CS/CaPP/Pg scaffolds compared with control and CS/CaPP scaffolds. Increase in cell proliferation was accompanied by G0/G1 to G2/M phase transition with increased levels of cyclin(s) A, B and C. Pg particles in CS/CaPP scaffolds enhanced osteoblast differentiation at the cellular and molecular levels, as evidenced by increased calcium deposits, ALP activity and expression of osteoblast marker genes. In vivo implantation of scaffolds in rat critical-sized tibial defects displayed accelerated bone formation after 8 weeks. CONCLUSION: The current findings indicate that CS/CaPP scaffolds containing iron-containing Pg particles serve as an appropriate template to support proliferation and differentiation of MSCs to osteoblasts in vitro and bone formation in vivo and thus support their candidature for BTE applications.

An immunoinformatics approach to define T cell epitopes from polyketide and non-ribosomal peptide synthesis proteins of Mycobacterium tuberculosis as potential vaccine candidates.

The role of polyketide and non-ribosomal proteins from the class of small molecule metabolism of Mycobacterium tuberculosis is well documented in envelope organization, virulence, and pathogenesis. Consequently, the identification of T cell epitopes from these proteins could serve to define potential antigens for the development of vaccines. Fourty-one proteins from polyketide and non-ribosomal peptide synthesis of small molecule metabolism proteins of M tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nanomeric peptides. All possible overlapping nanomeric peptide sequences from 41 small molecule metabolic proteins were generated through in silico and analyzed for their ability to bind to 33 alleles belonging to A, B, and C loci of HLA class I molecule. Polyketide and non-ribosomal protein analyses revealed that 20% of generated peptides were predicted to bind HLA with halftime of dissociation T1/2  ≥ 100 minutes, and 77% of them were mono-allelic in their binding. The structural bases for recognition of nanomers by different HLA molecules were studied by structural modeling of HLA class I-peptide complexes. Pathogen peptides that could mimic as self-peptides or partially self-peptides in the host were excluded using a comparative study with the human proteome; thus, subunit or DNA vaccines will have more chance of success.

Effects of flavonoids incorporated biological macromolecules based scaffolds in bone tissue engineering.

Skeletal tissue damage caused by trauma, injury, or disease can often result in considerable morbidity and the need for new, more reliable strategies for skeletal regeneration. So, to address the unmet need for bone augmentation, bone tissue engineering and regenerative medicine have evolved in the recent years. Bone tissue engineering harnesses novel scaffolds, stem cells and biological factors that promise enhanced and more reliable bone formation. Increasingly phytochemicals, particularly flavonoids are gaining renowned interest lately for their therapeutic potential on bone. Intake of flavonoids has shown to improve bone health due to their antioxidant and anti-inflammatory properties. Inclusion of biomaterials for flavonoids delivery has potential towards bone tissue engineering. Hence, this review was aimed to provide an overview of recent developments in bone tissue engineering focusing on flavonoids and their potent biological properties that enhance bone health.

Pharmacognostic Assesment of the Endemic and Vulnerable Medicinal Climber-Cayratia pedata (Lam.) Gagnep. var. glabra Gamble and Its Antibacterial Activity.

OBJECTIVE: The objective of this study is to evaluate a meticulous pharmacognostic cram is to supplement constructive information with regard to its identification, characterization, and standardization of endemic and endangered medicinal climber Cayratia pedata var. glabra and also screening the antibacterial activity of this climber. MATERIALS AND METHODS: The morphological characters of study plant, microscopic examination of leaf powder, anatomy of young stem, physicochemical analysis of plant powder, extractive values, phytochemical analysis, powder with different chemical reagents, fluorescence analysis of plant powder, and other World Health Organization (WHO) recommended for standardization were analyzed. The antibacterial activity of this study plant is also analyzed. RESULTS: C. pedata var. glabra belongs to the family Vitaceae, commonly known as "Kattuppirandai" is one such endemic and endangered species in Thaisholai, Nilgiris South Division, Western Ghats. With the patronage of veteran ethnic group traditional knowledge of this region, the species C. pedata var. glabra was selected for the pharmacognostical examination and antibacterial screening. There were no pharmacognostical reports of this plant, specifically to determine the anatomical and other physicochemical standards required for its quality control. The current study deals with pharmacognostical parameters for the aerial parts of study plant, which mainly consists of macromorphological and microanatomical characters, physicochemical constants (ash values and extractive values), fluorescence analysis, and phytochemical screening, one of the WHO accepted parameter for the identification of medicinal plants. The pharmacognostical exploration was undertaken for this species with the purpose of sketch the pharmacopeial standards. The antibacterial activity of this plant confirms the therapeutic power. CONCLUSION: The information obtained from pharmacognostical studies will be of used for supplementary pharmacological and therapeutical evaluation of the species and will assist in standardization for quality, purity, and authentication with the help, of which adulteration and substitution can be prevented. The antibacterial activity of this plant confirm the traditional knowledge of local healers on the wound healing property of this species and also suggest this plant species can be used as a promising source for the development of new pharmaceuticals that address the therapeutic needs to cure infectious diseases. SUMMARY: The species C. pedata var. glabra was selected for present research work, since this species is listed in Red data book and has a wider use for different ailments among the tribal population of Thiashola due to its high medicinal value. Pharmacognostical profile was generated from macroscopical analysis, microscopical studies, powder analysis, physico-chemical constituent values, fluorescence analysis and preliminary phytochemical evaluation. The antibacterial activity of this plant confirms the therapeutic power. Abbreviations Used: WHO: World Health Organization; IUCN: International Union for the Conservation of Nature.

Chitosan based nanofibers in bone tissue engineering.

Bone tissue engineering involves biomaterials, cells and regulatory factors to make biosynthetic bone grafts with efficient mineralization for regeneration of fractured or damaged bones. Out of all the techniques available for scaffold preparation, electrospinning is given priority as it can fabricate nanostructures. Also, electrospun nanofibers possess unique properties such as the high surface area to volume ratio, porosity, stability, permeability and morphological similarity to that of extra cellular matrix. Chitosan (CS) has a significant edge over other materials and as a graft material, CS can be used alone or in combination with other materials in the form of nanofibers to provide the structural and biochemical cues for acceleration of bone regeneration. Hence, this review was aimed to provide a detailed study available on CS and its composites prepared as nanofibers, and their associated properties found suitable for bone tissue engineering.

A review of chitosan and its derivatives in bone tissue engineering.

Critical-sized bone defects treated with biomaterials offer an efficient alternative to traditional methods involving surgical reconstruction, allografts, and metal implants. Chitosan, a natural biopolymer is widely studied for bone regeneration applications owing to its tunable chemical and biological properties. However, the potential of chitosan to repair bone defects is limited due to its water insolubility, faster in vivo depolymerization, hemo-incompatibility, and weak antimicrobial property. Functionalization of chitosan structure through various chemical modifications provides a solution to these limitations. In this review, current trends of using chitosan as a composite with other polymers and ceramics, and its modifications such as quaternization, carboxyalkylation, hydroxylation, phosphorylation, sulfation and copolymerization in bone tissue engineering are elaborated.

Guar gum succinate-sodium alginate beads as a pH-sensitive carrier for colon-specific drug delivery.

Guar gum succinate - sodium alginate (GGS-SA) beads cross-linked with barium ions were prepared and characterized as a pH sensitive carrier for colon-specific drug delivery. The structure of GGS-SA beads was confirmed by FT-IR spectroscopy. Scanning Electron Microscope (SEM) studies revealed that the drug loaded GGS-SA beads prepared using 2:2 (w/v) weight percent of GGS and SA had a diameter about 1.4mm and roughly spherical in shape. X-ray diffraction (XRD) studies showed that the peaks corresponding to GGS and SA at 13.5°, 17.5°, 20.2° and 13.5°, 22°, 24.1°, respectively were destroyed in GGS-SA beads which show that these beads are more amorphous in nature. Swelling studies demonstrated the pH-dependent swelling behavior of GGS-SA beads. The beads showed higher swelling degrees in pH 7.4 than that in pH 1.2 due to the existence of anionic groups in the polymer chains. The drug release study showed that the amount of model drug, ibuprofen, released from the GGS-SA beads was higher in pH 7.4 than that in pH 1.2 due to the pH-dependent swelling behavior of the beads. MTT assay revealed that GGS-SA beads at a concentration range of 0-30µg/ml had no cytotoxic effect on the cultured mouse mesenchymal stem cells (C3H10T1/2). These results suggest that GGS-SA beads can be used as effective colon-specific drug delivery system with pH-dependent drug release ability.

Metallic Nanomaterials for Bone Tissue Engineering.

Conventional grafting techniques for bone regeneration are currently being replaced by tissue engineering approaches of using 3D biomimetic materials. Of these biomaterials, metals have the highest mechanical strength; moreover, they play a major role in accelerating bone formation and promoting bone regeneration. They act as cofactors for enzymes, serving as a structural component of bone forming enzymes and proteins, stimulating angiogenesis, increasing extra-cellular matrix synthesis, promoting bone formation, and inhibiting bone resorption. Metals have the inherent ability to promote osseointegration and osteoconductivity and possess antimicrobial activity. The current developments in bone tissue engineering focus on metal surface modifications by physical and chemical treatments to improve their bioactivity. Based on the recent literature available, this review aims at discussing the biological role of metals, namely Zn, Ti, Zr, B, Sr, Mg, Ag, and Cu along with their surface modifications for significantly enhanced bone regeneration.

Scaffolds containing chitosan/carboxymethyl cellulose/mesoporous wollastonite for bone tissue engineering.

Scaffold based bone tissue engineering utilizes a variety of biopolymers in different combinations aiming to deliver optimal properties required for bone regeneration. In the current study, we fabricated bio-composite scaffolds containing chitosan (CS), carboxymethylcellulose (CMC) with varied concentrations of mesoporous wollastonite (m-WS) particles by the freeze drying method. The CS/CMC/m-WS scaffolds were characterized by the SEM, EDS and FT-IR studies. Addition of m-WS particles had no effect on altering the porosity of the scaffolds. m-WS particles at 0.5% concentration in the CS/CMC scaffolds showed significant improvement in the bio-mineralization and protein adsorption properties. Addition of m-WS particles in the CS/CMC scaffolds significantly reduced their swelling and degradation properties. The CS/CMC/m-WS scaffolds also showed cyto-friendly nature to human osteoblastic cells. The osteogenic potential of CS/CMC/m-WS scaffolds was confirmed by calcium deposition and expression of an osteoblast specific microRNA, pre-mir-15b. Thus, the current investigations support the use of CS/CMC/m-WS scaffolds for bone tissue engineering applications.

Nanohydroxyapatite-reinforced chitosan composite hydrogel for bone tissue repair in vitro and in vivo.

BACKGROUND: Bone loss during trauma, surgeries, and tumor resection often results in critical-sized bone defects that need to be filled with substitutionary materials. Complications associated with conventional grafting techniques have led to the development of bioactive tissue-engineered bone scaffolds. The potential application of hydrogels as three-dimensional (3D) matrices in tissue engineering has gained attention in recent years because of the superior sensitivity, injectability, and minimal invasive properties of hydrogels. Improvements in the bioactivity and mechanical strength of hydrogels can be achieved with the addition of ceramics. Based on the features required for bone regeneration, an injectable thermosensitive hydrogel containing zinc-doped chitosan/nanohydroxyapatite/beta-glycerophosphate (Zn-CS/nHAp/ß-GP) was prepared and characterized, and the effect of nHAp on the hydrogel was examined. METHODS: Hydrogels (Zn-CS/ß-GP, Zn-CS/nHAp/ß-GP) were prepared using the sol-gel method. Characterization was carried out by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) as well as swelling, protein adsorption, and exogenous biomineralization studies. Expression of osteoblast marker genes was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analyses. In vivo bone formation was studied using a rat bone defect model system. RESULTS: The hydrogels exhibited sol-gel transition at 37°C. The presence of nHAp in the Zn-CS/nHAp/ß-GP hydrogel enhanced swelling, protein adsorption, and exogenous biomineralization. The hydrogel was found to be non-toxic to mesenchymal stem cells. The addition of nHAp to the hydrogel also enhanced osteoblast differentiation under osteogenic conditions in vitro and accelerated bone formation in vivo as seen from the depositions of apatite and collagen. CONCLUSIONS: The synthesized injectable hydrogel (Zn-CS/nHAp/ß-GP) showed its potential toward bone formation at molecular and cellular levels in vitro and in vivo. The current findings demonstrate the importance of adding nHAp to the hydrogel, thereby accelerating potential clinical application toward bone regeneration.

Biomaterials mediated microRNA delivery for bone tissue engineering.

Bone tissue engineering is an alternative strategy to overcome the problems associated with traditional treatments for bone defects. A number of bioactive materials along with new techniques like porous scaffold implantation, gene delivery, 3D organ printing are now-a-days emerging for traditional bone grafts and metal implants. Studying the molecular mechanisms through which these biomaterials induce osteogenesis is an equally hot field. Biomaterials could determine the fate of a cell via microRNAs (miRNAs). miRNAs are short non-coding RNAs that act as post-transcriptional regulators of gene expression and play an essential role for regulation of cell specific lineages including osteogenesis. Thus, this review focuses the recent trends on establishing a link of biomaterials with miRNAs and their delivery for bone tissue engineering applications.