In-vivo Analysis Research Articles

Inside the decentralised casino: A longitudinal study of actual cryptocurrency gambling transactions.

Decentralised gambling applications are a new way for people to gamble online. Decentralised gambling applications are distinguished from traditional online casinos in that players use cryptocurrency as a stake. Also, rather than being stored on a single centralised server, decentralised gambling applications are stored on a cryptocurrency's blockchain. Previous work in the player behaviour tracking literature has examined the spending profiles of gamblers on traditional online casinos. However, similar work has not taken place in the decentralised gambling domain. The profile of gamblers on decentralised gambling applications are therefore unknown. This paper explores 2,232,741 transactions from 24,234 unique addresses to three such applications operating atop the Ethereum cryptocurrency network over 583 days. We present spending profiles across these applications, providing the first detailed summary of spending behaviours in this technologically advanced domain. We find that the typical player spends approximately $110 equivalent across a median of 6 bets in a single day, although heavily involved bettors spend approximately $100,000 equivalent over a median of 644 bets across 35 days. Our findings suggest that the average decentralised gambling application player spends less than in other online casinos overall, but that the most heavily involved players in this new domain spend substantially more. This study also demonstrates the use of these applications as a research platform, specifically for large scale longitudinal in-vivo data analysis.

Antioxidant and antiproliferative properties of Moringa oleifera Lam. leaf aqueous extract

Moringa oleifera Lam. is a highly valued medicinal plant in India, especially Kerala. In the present study, antioxidant activity of aqueous extract of leaves of M. oleifera was determined both in-vitro and in-vivo. Male Wistar rats of 3 age groups- 6, 12, and 18 months old were used for in-vivo analysis. In vitro anti-proliferative effect of the extract was carried out in Dalton’s Lymphoma Ascites (DLA) Cells. LCMS-QTOF analysis of the extract was also done to determine the bioactive components present in the extract. Antioxidant activity of M. oleifera leaf showed an IC 50 value of 10.47 ?g/ml and whereas for standard drug, ascorbic acid, it was 19.52 ?g/ml. In-vivo analysis of lipid peroxidation showed a significant reduction of lipid peroxidation in the brains of 12 and 18-months old treated groups. Up to 75% mortality of DLA cancerous cells was observed in-vitro in different concentrations of M. oleifera leaf water extract in a dose-dependent manner, demonstrating its anti-proliferative property. LCMS-QTOF analysis revealed the presence of emodin-8-glucoside in the extract. Molecular docking analysis (Auto Dock Vina) of emodin-8-glucoside with six cancer related proteins showed highest binding affinity with AKT-1 with a binding score of -10.4 kcal/mol, also showed good affinity with NF-kB (p65), Stat-3, Bcl-2, Bcl-xl and c-FLIP. This study helps to choose healthy diet practices to overcome free radical onslaught and cancerous cell proliferation especially in the later stages of life. This can also pave way for the emergence of diet based therapeutic cure for cancer.

CT, US and MRI of xanthine urinary stones: in-vitro and in-vivo analyses

BackgroundXanthine urinary stones are a rare entity that may occur in patients with Lesch–Nyhan syndrome receiving allopurinol. There is little literature describing imaging characteristics of these stones, and the most appropriate approach to imaging these stones is therefore unclear. We performed in-vitro and in-vivo analyses of xanthine stones using computed tomography (CT) at different energy levels, ultrasound (US), and magnetic resonance imaging (MRI).MethodsFive pure xanthine stones from a child with Lesch-Nyhan were imaged in-vitro and in-vivo. CT of the stones was performed at 80 kVp, 100 kVp, 120 kVp and 140 kVp and CT numbers of the stones were recorded in Hounsfield units (HU). US of the stones was performed and echogenicity, acoustic shadowing and twinkle artifact were assessed. MRI of the stones was performed and included T2-weighted, ultrashort echo-time-weighted and T2/T1-weighted 3D bFFE sequences and signal was assessed.ResultsIn-vitro analysis on CT demonstrated that xanthine stones were radiodense and the average attenuation coefficient did not differ with varying kVp, measuring 331.0 ± 51.7 HU at 80 kVp, 321.4 ± 63.4 HU at 100 kVp, 329.7 ± 54.2 HU at 120 kVp and 328.4 ± 61.1 HU at 140 kVp. In-vivo analysis on CT resulted in an average attenuation of 354 ± 35 HU. On US, xanthine stones where echogenic with acoustic shadowing and twinkle artifact. On MRI, stones lacked signal on all tested sequences.ConclusionXanthine stone analyses, both in-vitro and in-vivo, demonstrate imaging characteristics typical of most urinary stones: dense on CT, echogenic on US, and lacking signal on MRI. Therefore, the approach to imaging xanthine stones should be comparable to that of other urinary stones.

Etodolac loaded solid lipid nanoparticle based topical gel for enhanced skin delivery

Abstract The main purpose of this study was to manufacture & evaluate a topical formulation of etodolac, based on solid lipid nanoparticles (SLNs), to improve its percutaneous permeation rate. Topical Nanolipidic gel of etodolac was manufactured and its various evaluation parameter were checked. The objective of research also included that how much amount of drug retained in skin and skin retention study was performed in Wister rat. Central composite design (CCD) has been utilized to optimize the current work. Factors studied are stearic acid concentration & lecithin effect, and the responses studied included mean particle size, trap efficiency. Etodolac encapsulated stable lipid nanoparticles are prepared by slight modification of the technique of microemulsion (method of melt emulsification at low temperature). Size distribution d90, drug entrapping capacity, in-vitro study and kinetics, differential calorimetry scanning (DSC), analyzes of permeation parameters, stability tests, studies of skin conservation by tape stripping process are conducted to evaluate the SLN. For in vivo anti-inflammatory tests of etodolac based SLN hydrogel, the tailored batches were evaluated. The solid lipid nanoparticles were prepared from 402 to 684 nm in different size ranges. The efficacy of drug trapping and the zeta potential of prepared SLN were found to be 74.18 to 80.30 percent and-19.0 to-24.0 mV respectively. Etodolac encapsulated nano gel showed more skin permeation of the drug over normal etodolac gel, and also lecithin concentration plays a major role in increasing permeation rates. In-vivo analysis of etodolac nano gel with excellent compared to normal, which is capable of decreasing the edema starting from 3rd hour and throughout the period and suggesting the preservation of etodolac SLN gel anti-inflammatory function.

Evaluation of automated pre-treatment and transit in-vivo dosimetry in radiotherapy using empirically determined parameters.

First reports on clinical use of commercially automated systems for Electronic Portal Imaging Device (EPID)-based dosimetry in radiotherapy showed the capability to detect important changes in patient setup, anatomy and external device position. For this study, results for more than 3000 patients, for both pre-treatment verification and in-vivo transit dosimetry were analyzed. For all Volumetric Modulated Arc Therapy (VMAT) plans, pre-treatment quality assurance (QA) with EPID images was performed. In-vivo dosimetry using transit EPID images was analyzed, including causes and actions for failed fractions for all patients receiving photon treatment (2018-2019). In total 3136 and 32,632 fractions were analyzed with pre-treatment and transit images respectively. Parameters for gamma analysis were empirically determined, balancing the rate between detection of clinically relevant problems and the number of false positive results. Pre-treatment and in-vivo results depended on machine type. Causes for failed in-vivo analysis included deviations in patient positioning (32%) and anatomy change (28%). In addition, errors in planning, imaging, treatment delivery, simulation, breath hold and with immobilization devices were detected. Actions for failed fractions were mostly to repeat the measurement while taking extra care in positioning (54%) and to intensify imaging procedures (14%). Four percent initiated plan adjustments, showing the potential of the system as a basis for adaptive planning. EPID-based pre-treatment and in-vivo transit dosimetry using a commercially available automated system efficiently revealed a wide variety of deviations and showed potential to serve as a basis for adaptive planning.

SIX1 ve Kanser Kök Hücre Belirteçlerinin Hepatoselluler Karsinomada Kapsamlı Analizi

Objective: Transcription factor SIX1 aberrant expression has been shown in various mammalian tumors, and also recent studies indicated that SIX1 has a role in cancer stem cell properties. However, its roles in HCC cancer stem cell characteristics remain unclear. The aim of the study, to evaluate the EMT-inducer SIX1 and cancer stem cell markers expression profile in-vitro and in-vivo analyses.
 Material and Methods: SIX1 expression was suppressed by short hairpin RNA transduction in the SNU398 HCC cell line. Tumorsphere formation assay is a golden useful assay for cancer stem cell analysis. SIX1-dependent cancer stem cell markers PROM1, EPCAM, and OCT4 differential gene expression profiles were assessed in tumorsphere formation assay by RT-qPCR. Differential expression and correlation analyses were performed in transcriptome data in cirrhosis and HCC tissue samples.
 Results: Assessment of SIX1-knockdown expression of target genes in tumorsphere formation assay revealed PROM1, EPCAM expressions were significantly up-regulated but OCT4 gene expression was significantly down-regulated. Conformably, PROM1 and EPCAM expressions were inversely but OCT4 expression was positively correlated in transcriptome arrays in HCC tissues. Interestingly, to the evaluation of the same gene expressions were shown different patterns except, OCT4 in cirrhosis samples. The mRNA expression profiles did not change between cirrhosis and HCC samples in the SIX1, EPCAM, PROM1, and OCT4 gene expression profiles.
 Conclusion: Cancer stem cells are self‐renewable cell types and are responsible for cancer progression. Findings from this study highlight the SIX1 and cancer stemness-related genes expression correlations to improve our knowledge for HCC molecular signatures.

Epidemiological and pathogenic characteristics of Haitian variant V. cholerae circulating in India over a decade (2000–2018)

Vibrio cholerae, causative agent of the water-borne disease cholera still threatens a large proportion of world's population. The major biotypes of the pathogen are classical and El Tor. There have been recent reports of variant V. cholerae strains circulating around the world. In the present study, the epidemiological status of V. cholerae strains circulating in the country over a decade was assessed. Also, a comprehensive analysis of the difference in pathogenicity between the different biotypes of V. cholerae strains was evaluated both in-vitro and in-vivo. The amount of CT produced by different biotypes of V. cholerae strains were analyzed by GM1 ELISA and the probable reasons for the difference in toxin production was discussed. MLST analysis grouped the isolates into a single Sequence Type (ST 69) whereas PFGE analysis clustered the isolates into ten different pulsotypes revealing molecular diversity. The circulating strains were identified to produce cholera toxin and CT mRNA intermediate to the classical and prototype El Tor strains. Also, the circulating strains were identified to possess four ToxR binding sequences. In-vivo pathogenicity analysis by rabbit ileal loop fluid accumulation assay revealed the Haitian variant strains to be more hyperemic than the prototype strains.

Central Vestibular Tuning Arises from Patterned Convergence of Otolith Afferents

As sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict that complexity arises via convergent inputs from neurons with diverse response properties, in most vertebrate systems, convergence has only been inferred rather than tested directly. Here, we measure sensory computations in zebrafish vestibular neurons across multiple axes invivo. We establish that whole-cell physiological recordings reveal tuning of individual vestibular afferent inputs and their postsynaptic targets. Strong, sparse synaptic inputs can be distinguished by their amplitudes, permitting analysis of afferent convergence invivo. An independent approach, serial-section electron microscopy, supports the inferred connectivity. We find that afferents with similar or differing preferred directions converge on central vestibular neurons, conferring more simple or complex tuning, respectively. Together, these results provide a direct, quantifiable demonstration of feedforward input convergence invivo.

The relationship between alignment, function and loading in total knee replacement: In-vivo analysis of a unique patient population

The purpose of this study was to quantify the effect of total knee replacement (TKR) alignment on in-vivo knee function and loading in a unique patient cohort who have been identified as having a high rate of component mal-alignment. Post-TKR (82.4 ± 6.7 months), gait analysis was performed on 25 patients (27 knees), to calculate knee kinematics and kinetics. For a step activity, video fluoroscopic analysis quantified in-vivo implant kinematics. Frontal plane lower-limb alignment was defined by the Hip-Knee-Ankle angle (HKA) measured on long leg static X-rays. Transverse plane component rotation was calculated from computed tomography scans. Sagittal plane alignment was defined by measuring the flexion angle of the femoral component and the posterior tibial slope angle (PTSA). For gait analysis, a more varus HKA correlated with increased peak and dynamic joint kinetics, predicting 47.6% of Knee Adduction Angular Impulse variance. For the step activity, during step-up and single leg loaded, higher PTSA correlated with a posterior shift in medial compartment Anterior-Posterior (AP) translation. During step-down, higher PTSA correlated with reduced lateral compartment AP translation with a posterior shift in AP translation in both compartments. A more varus HKA correlated with a more posterior medial AP translation and inter-component rotation was related to transverse plan range of motion. This in-vivo study found that frontal plane lower-limb alignment had a significant effect on joint forces during gait but had minimal influence on in-vivo implant kinematics for step activity. PTSA was found to influence in-vivo TKR translations and is therefore an important surgical factor.

Remdesivir for COVID-19: A review of pharmacology, mechanism of action, in-vitro activity and clinical use based on available case studies

Remdesivir as a drug attracted a very serious consideration of whole Globe in treatment of the pandemic disease COVID-19. More recently published in-vitro inhibition activity and in-vivo case studies were showing promising clinical results and outcome of effective inhibition of SARS-CoV-2 virus by the use of remdesivir. However at the same time, use of the remdesivir showed substantial detrimental adverse events in patients which needs a special attention during treatment course of COVID-19. Thus, the use of remdesivir in treatment of COVID-19 is having current international interest although some more clinical evidences are still necessary in order to understand the actual efficiency and mechanism of remdesivir against COVID-19. In view of this, the present literature study spotlight the current ongoing research related to use of remdesivir which includes (i) pharmacology of remdesivir, (ii) mechanism of action of remdesivir (iii) in-vitro inhibition of remdesivir against SARS-CoV-2 virus, (iv) in-vivo analysis and clinical use of remdesivir against COVID-19. Finally possible adverse events (of use of remdesivir) are also discussed considering the pharmacovigilance concern.
 Keywords: Remdesivir; COVID-19; Remdesivir side effects, Remdesivir pharmacology; SARS-CoV-2 virus

Hsa_circ_0000515 is a novel circular RNA implicated in the development of breast cancer through its regulation of the microRNA-296-5p/CXCL10 axis.

Cancer metastasis is a major cause of death among women afflicted with breast cancer (BC) and understanding the molecular processes involved is a major focus in BC research. Circular RNAs (circRNAs) have emerged as genomic regulatory molecules in carcinogenesis and metastasis; however, their role in BC is unclear. We characterized a novel circRNA, hsa_circ_0000515, in context of BC. We collected 340 cancerous tissues surgically resected from BC patients and found hsa_circ_0000515 was upregulated in BC tissues and associated with poor prognosis of BC. Silencing of hsa_circ_0000515 impaired cell cycle progression, cell proliferation, and invasion, attenuated inflammatory response, and reduced the proangiogenetic potential of BC cells. RNA pull-down and dual-luciferase reporter gene assays showed that hsa_circ_0000515 binds miR-296-5p, preventing it from repressing CXCL10 expression. We also observed that miR-296-5p inhibition or CXCL10 overexpression promoted cell cycle progression, restored proliferative, invasive and proangiogenetic abilities, and increased inflammatory response in MCF-7 cells in the absence of hsa_circ_0000515. Invivo analyses showed that partial loss of hsa_circ_0000515 reduced the tumor growth of MCF-7 cells in nude mice. The key findings from this study revealed that targeting hsa_circ_0000515 might be an effective strategy to combat BC.

2021 – TRANSCRIPTIONAL REGULATION OF MITOCHONDRIAL METABOLISM BY TIF1GAMMA DRIVES ERYTHROID PROGENITOR DIFFERENTIATION

Understanding in-vivo mechanisms of erythropoiesis is critical for directed differentiation approaches to treat blood disorders. Zebrafish moonshine (mon) mutant embryos defective for the conserved transcriptional intermediary factor 1 gamma (tif1γ) do not specify enough erythroid progenitors. To elucidate the TIF1γ-mediated mechanisms in erythroid differentiation, we performed a chemical suppressor screen using 3,100 compounds and identified inhibitors of the essential mitochondrial pyrimidine synthesis enzyme dihydroorotate dehydrogenase (DHODH). Leflunomide as well as the structurally unrelated DHODH inhibitor brequinar rescue the formation of erythroid progenitors in 61% (38/62) and 68% (50/74) of mon embryos, respectively. Beyond changes in nucleotide metabolism, in-vivo metabolic analyses revealed low levels of TCA cycle metabolites which were functionally linked to a reduced oxygen consumption rate. In addition, an increased 2HG/αKG ratio was associated with higher histone methylation states at H3K27, H3K36 and H4K20 as assessed by quantitative targeted mass spectrometry, which may contribute to the erythroid differentiation block upon tif1γ loss. DHODH is the only pyrimidine de novo synthesis enzyme located in mitochondria and its activity is coupled to that of the electron transport chain (ETC) via coenzyme Q (CoQ). Rotenone, a potent ETC complex I inhibitor reversed the rescue by DHODH inhibition in mon embryos. Through parallel genome-wide transcriptome and chromatin immunoprecipitation analyses, we found that genes encoding CoQ metabolic enzymes are direct TIF1γ targets. Treatment with the CoQ analog decylubiquinone rescued erythroid progenitors in 26% (33/126) of mon embryos. Our work highlights the importance of transcription regulatory processes for tuning metabolism during lineage differentiation and could have therapeutic implications.

Computational and Pharmacological Evaluation of Carveol for Antidiabetic Potential.

BackgroundCarveol is a natural drug product present in the essential oils of orange peel, dill, and caraway seeds. The seed oil of Carum Carvi has been reported to be antioxidant, anti-inflammatory, anti-hyperlipidemic, antidiabetic, and hepatoprotective.MethodsThe antidiabetic potential of carveol was investigated by employing in-vitro, in-vivo, and in-silico approaches. Moreover, alpha-amylase inhibitory assay and an alloxan-induced diabetes model were used for in-vitro and in-vivo analysis, respectively.ResultsCarveol showed its maximum energy values (≥ -7 Kcal/mol) against sodium-glucose co-transporter, aldose reductase, and sucrose-isomaltase intestinal, whereas it exhibited intermediate energy values (≥ -6 Kcal/mol) against C-alpha glucosidase, glycogen synthase kinases-3β, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and other targets according to in-silico analysis. Similarly, carveol showed lower energy values (≥ 6.4 Kcal/mol) against phosphoenolpyruvate carboxykinase and glycogen synthase kinase-3β. The in-vitro assay demonstrated that carveol inhibits alpha-amylase activity concentration-dependently. Carveol attenuated the in-vivo alloxan-induced (1055.8 µMol/Kg) blood glucose level in a dose- and time-dependent manner (days 1, 3, 6, 9, and 12), compared to the diabetic control group, and further, these results are comparable with the metformin positive control group. Carveol at 394.1 µMol/Kg improved oral glucose tolerance overload in rats compared to the hyperglycemic diabetic control group. Moreover, carveol also attenuated the glycosylated hemoglobin level along with mediating anti-hyperlipidemic and hepatoprotective effects in alloxan-induced diabetic animals.ConclusionsThis study reveals that carveol exhibited binding affinity against different targets involved in diabetes and has antidiabetic, anti-hyperlipidemic, and hepatoprotective actions.

In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases.

COVID-19 is a life-threatening novel corona viral infection to our civilization and spreading rapidly. Tremendousefforts have been made by the researchers to search for a drug to control SARS-CoV-2. Here, a series of arsenical derivatives were optimized and analyzed with in silico study to search the inhibitor of RNA dependent RNA polymerase (RdRp), the major replication factor of SARS-CoV-2. All the optimized derivatives were blindly docked with RdRp of SARS-CoV-2 using iGEMDOCK v2.1. Based on the lower idock score in the catalytic pocket of RdRp, darinaparsin (-82.52 kcal/- mol) was revealed to be the most effective among them. Darinaparsin strongly binds with both Nsp9 replicase protein (-8.77 kcal/mol) and Nsp15 endoribonuclease (-8.3 kcal/mol) of SARS-- CoV-2 as confirmed from the AutoDock analysis. During infection, the ssRNA of SARS-CoV-2 is translated into large polyproteins forming viral replication complex by specific proteases like 3CL protease and papain protease. This is also another target to control the virus infection where darinaparsin also performs the inhibitory role to proteases of 3CL protease (-7.69 kcal/mol) and papain protease (-8.43 kcal/mol). In the host cell, the furin protease serves as a gateway to the viral entry and darinaparsin docked with furin protease, which revealed a strong binding affinity. Thus, screening of potential arsenic drugs would help in providing the fast in-vitro to in-vivo analysis towards the development of therapeutics against SARS-CoV-2.

Radiomics in diffusion data: a test–retest, inter- and intra-reader DWI phantom study

The aim of this study was to evaluate the robustness of radiomics features of a MRI (magnetic resonance imaging) phantom in quantitative diffusion-weighted imaging (DWI) and depending on the image resolution. Scanning of an in-house developed DWI phantom was performed at a 1.5 T MRI scanner (Magnetom AERA, Siemens, Erlangen, Germany) using an echo planar imaging (EPI) DWI sequence (b=0,500,1,000 s/mm2) with low (3×3 mm2) and high (2×2 mm2) image resolutions. Scans were repeated after phantom repositioning to evaluate retest reliability. Radiomics features were extracted after semi-automatic segmentation and standardised pre-processing. Intra-/interobserver reproducibility and test-retest robustness were assessed using intraclass correlation coefficients (ICC). Differences were tested with non-parametric Wilcoxon's signed-rank and Friedman's test (p<0.05) with Dunn's post-hoc analysis. Test-retest ICC was overall high with >0.90 for 39/46 radiomics features in all sequences/resolutions. Decreased test-retest ICCs were pronounced for conventional Min-value (overall ICC=0.817), and grey-level zone length matrix (GLZLM) features Short-Zone Emphasis (SZE) and Short-Zone Low Grey-level Emphasis (SZLGE) (for both overall ICC=0.927). Test-retest reproducibility was significantly different between b=500, 1,000 and apparent diffusion coefficient (ADC) (mean 0.975±0.050, 0.974±0.051 and 0.966±0.063), which remained significant after post-hoc analysis between b=1,000 and ADC (p = 0.022). ICCs were not significantly different between resolutions of 2×2 and 3×3 mm2 regarding b=500 (mean: 0.977±0.052 and 0.974±0.049, p = 0.612), b=1,000 (mean: 0.973±0.059 and 0.974±0.054, p = 0.516), and ADC (mean: 0.972±0.049 and 0.955±0.101, p = 0.851). Inter- and intra-observer reliability was consistently high for all sequences (overall mean 0.992±0.021 and 0.990±0.028). Under ex-vivo conditions, DWI provided robust radiomics features with those from ADC being slightly less robust than from raw DWI (b=500, 1,000 s/mm2). No significant difference was detected for different resolutions. Although, ex-vivo reliability of DWI radiomics features was high, no implications can be made regarding in-vivo analyses.

Dysplastic hip anatomy alters muscle moment arm lengths, lines of action, and contributions to joint reaction forces during gait

Developmental dysplasia of the hip (DDH) is characterized by abnormal bony anatomy, which causes detrimental hip joint loading and leads to secondary osteoarthritis. Hip joint loading depends, in part, on muscle-induced joint reaction forces (JRFs), and therefore, is influenced by hip muscle moment arm lengths (MALs) and lines of action (LoAs). The current study used subject-specific musculoskeletal models and in-vivo motion analysis to quantify the effects of DDH bony anatomy on dynamic muscle MALs, LoAs, and their contributions to JRF peaks during early (~17%) and late-stance (~52%) of gait. Compared to healthy hips (N = 15, 16–39 y/o), the abductor muscles in patients with untreated DDH (N = 15, 16–39 y/o) had smaller abduction MALs (e.g. anterior gluteus medius, 35.3 vs. 41.6 mm in early stance, 45.4 vs. 52.6 mm late stance, p ≤ 0.01) and more medially-directed LoAs. Abduction-adduction and rotation MALs also differed for major hip flexors such as rectus femoris and iliacus. The altered MALs in DDH corresponded to higher hip abductor forces, medial JRFs (1.26 vs. 0.87 × BW early stance, p = 0.03), and resultant JRFs (5.71 vs. 4.97 × BW late stance, p = 0.05). DDH anatomy not only affected hip muscle force generation in the primary plane of function, but also their out-of-plane mechanics, which collectively elevated JRFs. Overall, hip muscle MALs and their contributions to JRFs were significantly altered by DDH bony anatomy. Therefore, to better understand the mechanisms of joint degeneration and improve the efficacy of treatments for DDH, the dynamic anatomy-force relationships and multi-planar functions of the whole hip musculature must be collectively considered.

Polysaccharide-Based Controlled Release Systems for Antipsychotic Therapeutics Delivery

Researches in pharmaceutical fields are now focusing on biopolymer-based drug delivery systems for treatment of mild to severe diseases. Amongst all biopolymers, pectin is one of the frequently available and eco-friendly bio-polymer extracted from different fruit peels and abundantly available in nature. This study focuses to extract the pectin from two different fruits using different methods namely hot water-based extraction and cold maceration, involving two different fruit peels. Post extraction and isolation of polymer, study was performed for characterization of pectin powder by particle shape, particle size distribution, surface area angle of repose, flowability and tapped density. The obtained pectin was used for anti-psychotic drug delivery when incorporated into microspheres by solvent evaporation method. It’s surface morphology and release kinetics was analyzed using in vitro methods and in vivo models and kinetics of drug release (goodness of fit) was assessed. The result revealed that the pectin extracted from mango peel using soxhlation method showed good flow rate, minimum particle size and shape distribution, porosity etc. Moreover, it showed the better drug release data in both invitro and in-vivo analysis. The study concludes that in future the natural biopolymer like pectin stands as a potential candidate for formulation of drug release system for efficient delivery of drug

In-vivo analysis of iron-gold composite nanoparticles as potential exogenous contrast agents for magnetomotive optical coherence tomography (MMOCT)

Magnetomotive optical coherence tomography (MMOCT) is a functional modification of conventional optical coherence tomography (OCT). It utilizes the nano-scale displacement embedded magnetic nanoparticles (MNPs) and subsequent amplitude and phase changes in OCT interferogram scattered from samples. We report a new robust method for ‘phase-lock-in’ detection of MMOCT signals and subsequent imaging. We validated this method utilizing iron-gold (Fe-Au) composite nanoparticles as an exogenous contrast agent for MMOCT. High contrast and specific background-subtracted images was generated for Fe-Au MNPs targeted samples. MMOCT with MNPs imaging systems was corroborated with tissue phantoms and in-vivo swiss albino mice model with modulating external magnetic field (resonant frequency of 30 Hz). A time-dependent dynamics study of diffusion for MNPs inside the tissue of mice as a function of time and depth is also reported.

Multifunctional ZnO/SiO2 Core/Shell Nanoparticles for Bioimaging and Drug Delivery Application.

Semiconducting nanoparticles with luminescent properties are used as detection probes and drug carriers in in-vitro and in-vivo analysis. ZnO nanoparticles, due to its biocompatibility and low cost, have shown potential application in bioimaging and drug delivery. Thus, ZnO/SiO2 core/shell nanoparticle was synthesised by wet chemical method for fluorescent probing and drug delivery application. The synthesised core/shell nanomaterial was characterized using XRD, FTIR, UV-VIS spectroscopy, Raman spectroscopy, TEM and PL analysis. The silicon shell enhances the photoluminescence and aqueous stability of the pure ZnO nanoparticles. The porous surface of the shell acts as a carrier for sustained release of curcumin. The synthesized core/shell particle shows high cell viability, hemocompatibility and promising florescent property. Graphical Abstract.

Epitope based peptide vaccine against SARS-COV2: an immune-informatics approach

World is witnessing exponential growth of SARS-CoV2 and fatal outcomes of COVID 19 has proved its pandemic potential already by claiming more than 3 lakhs deaths globally. If not controlled, this ongoing pandemic can cause irreparable socio-economic and psychological impact worldwide. Therefore a safe and effective vaccine against COVID 19 is exigent. Recent advances in immunoinformatics approaches could potentially decline the attrition rate and accelerate the process of vaccine development in these unprecedented times. In the present study, a multivalent subunit vaccine targeting S2 subunit of the SARS-CoV2 S glycoprotein has been designed using open source, immunoinformatics tools. Designed construct comprises of epitopes capable of inducing T cell, B cell (Linear and discontinuous) and Interferon γ. physiologically, vaccine construct is predicted to be thermostable, antigenic, immunogenic, non allergen and non toxic in nature. According to population coverage analysis, designed multiepitope vaccine covers 99.26% population globally. 3D structure of vaccine construct was designed, validated and refined to obtain high quality structure. Refined structure was docked against Toll like receptors to confirm the interactions between them. Vaccine peptide sequence was reverse transcribed, codon optimized and cloned in pET vector. Our in-silico study suggests that proposed vaccine against fusion domain of virus has the potential to elicit an innate as well as humoral immune response in human and restrict the entry of virus inside the cell. Results of the study offer a framework for in-vivo analysis that may hasten the process of development of therapeutic tools against COVID 19. Communicated by Ramaswamy H. Sarma