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  • Article
    Parkins KM, Dubois VP, Kelly JJ, Chen Y, Knier NN, Foster PJ, Ronald JA.
    Theranostics. 2020;10(17):7925-7937.
    New ways to target and treat metastatic disease are urgently needed. Tumor "self-homing" describes the recruitment of circulating tumor cells (CTCs) back to a previously excised primary tumor location, contributing to tumor recurrence, as well as their migration to established metastatic lesions. Recently, self-homing CTCs have been exploited as delivery vehicles for anti-cancer therapeutics in preclinical primary tumor models. However, the ability of CTCs to self-home and treat metastatic disease is largely unknown. Methods: Here, we used bioluminescence imaging (BLI) to explore whether systemically administered CTCs home to metastatic lesions and if CTCs armed with both a reporter gene and a cytotoxic prodrug gene therapy can be used to visualize and treat metastatic disease. Results: BLI performed over time revealed a remarkable ability of CTCs to home to and treat tumors throughout the body. Excitingly, metastatic tumor burden in mice that received therapeutic CTCs was lower compared to mice receiving control CTCs. Conclusion: This study demonstrates the noteworthy ability of experimental CTCs to home to disseminated breast cancer lesions. Moreover, by incorporating a prodrug gene therapy system into our self-homing CTCs, we show exciting progress towards effective and targeted delivery of gene-based therapeutics to treat both primary and metastatic lesions.
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  • Article
    Hudson JE, Frith JE, Donose BC, Rondeau E, Mills RJ, Wolvetang EJ, Brooke GP, Cooper-White JJ.
    Biomaterials. 2010 Nov;31(31):7937-47.
    As strategies for manipulating cellular behaviour in vitro and in vivo become more sophisticated, synthetic biomaterial substrates capable of reproducing critical biochemical and biophysical properties (or cues) of tissue micro-environments will be required. Cytoskeletal tension has been shown to be highly deterministic of cell fate decisions, yet few synthetic biomaterials are capable of modulating cytoskeletal tension of adhered cells through variations in stiffness, at least in the ranges applicable to tissue properties (e.g., 1-100 kPa), whilst also possessing other required properties, such as biodegradability, biocompatibility and processability. In this paper we describe a non-cytotoxic polymer system based on acrylated polypropylene glycol triol (aPPGT). This new elastomer system has tunable elastic moduli, is degradable, can be easily surface modified and can be manufactured into porous three dimensional scaffolds or micropatterned substrates. We demonstrate that the PPGT substrates can modulate hMSC morphology, growth, and differentiation, and that they can produce similar outcomes as observed for a non-degradable polyacrylamide substrate, confirming their utility as a degradable elastomer for tissue engineering and other biomedical applications.
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  • Article
    Yu PH, Hsiao YT.
    PeerJ. 2019;7:e7937.
    Avian animals are visually inclined, which has caused them to attract increasing attention for visual neurophysiology or electrophysiology studies, including the study of the visual evoked potential (VEP). VEP has developed into an investigative tool for understanding the physiology and the pathology of the visual pathway. Chemical restraint is a common method to minimize motion artifacts in animals when acquiring VEP data, but little is known about its influence on the signal in an avian animal. In addition, it is difficult to make comparisons between conscious state data when the animals are ultimately under anesthesia. Therefore, finding drugs and developing protocols that have an acceptable effect is valuable. We compared the local field potentials of physically and chemically restrained zebra finches (Taeniopygia guttata), a small avian species, to simulate a relatively challenging recording condition. Finches were sedated with midazolam-butorphanol, and anesthesia was maintained by isoflurane. Electrodes were implanted into the left nucleus rotundus, which is a visual nucleus in birds. The VEPs of the control group (N = 3) were recorded after they fully recovered and were restrained by towels. The other birds (N = 3) were recorded under anesthesia. The results show that without the visual stimuli, anesthesia generally suppressed the overall power of field potentials. However, by focusing on the spectra during VEPs, visual stimuli still triggered significant VEPs in frequencies below 30.8 Hz, which were even stronger than towel-restrained birds. The drugs also prolonged the latency of the VEP, increased the duration of the VEP when compared to towel-restrained birds. As regard to towel-restrained zebra finches, the field potentials were less synchronized and may need data preprocessing to have clear VEPs. In conclusion, the current study presents evidence of basic VEP for zebra finch under midazolam-butorphanol-isoflurane anesthesia with a protocol that is a safe and feasible anesthetic combination for chemical restraint, which is particularly useful for small animals when obtaining evoked potentials.
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  • Article
    Sui T, Sandholzer MA, Baimpas N, Dolbnya IP, Walmsley A, Lumley PJ, Landini G, Korsunsky AM.
    Acta Biomater. 2013 Aug;9(8):7937-47.
    Human dentine is a hierarchical mineralized tissue with a two-level composite structure, with tubules being the prominent structural feature at a microlevel, and collagen fibres decorated with hydroxyapatite (HAp) crystallite platelets dominating the nanoscale. Few studies have focused on this two-level structure of human dentine, where the response to mechanical loading is thought to be affected not only by the tubule volume fraction at the microscale, but also by the shape and orientation distribution of mineral crystallites, and their nanoscale spatial arrangement and alignment. In this paper, in situ elastic strain evolution within HAp in dentine subjected to uniaxial compressive loading along both longitudinal and transverse directions was characterized simultaneously by two synchrotron X-ray scattering techniques: small- and wide-angle X-ray scattering (SAXS and WAXS, respectively). WAXS allows the evaluation of the apparent modulus linking the external load to the internal HAp crystallite strain, while the nanoscale HAp distribution and arrangement can be quantified by SAXS. We proposed an improved multiscale Eshelby inclusion model that takes into account the two-level hierarchical structure, and validated it with a multidirectional experimental strain evaluation. The agreement between the simulation and measurement indicates that the multiscale hierarchical model developed here accurately reflects the structural arrangement and mechanical response of human dentine. This study benefits the comprehensive understanding of the mechanical behaviour of hierarchical biomaterials. The knowledge of the mechanical properties related to the hierarchical structure is essential for the understanding and predicting the effects of structural alterations that may occur due to disease or treatment on the performance of dental tissues and their artificial replacements.
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  • Article
    Tareen SA, Rodriguez J, Bolos D.
    Cureus. 2020 May 02;12(5):e7937.
    INTRODUCTION: Landmark trials repeatedly demonstrate that pertuzumab and trastuzumab plus standard chemotherapy have the best outcomes in human epidermal growth factor receptor 2 (HER2) positive breast cancer in the neoadjuvant, adjuvant, and metastatic setting. However, many of these multicenter landmark trials lack diversity and studied largely Caucasian populations. Our goal is to address this under-representation of minorities, and compare pathologic complete response (pCR) rates in our predominantly Hispanic population with HER2 positive breast cancer receiving the same neoadjuvant chemotherapy (NACT) at Olive View-UCLA Medical Center (OVMC) to that of pCR rates observed in the TRYPHAENA trial.
    METHODS: For this retrospective cohort study, we compiled a list of 53 patients aged 18 and older, 52 female and 1 male, with HER2 positive breast cancer identified by fluorescence in situ hybridization treated at OVMC from December 2015 to May 2018. Our population was 57% Hispanic, 13% white, 13% Filipino, 11% Asian, 2% black, and 4% other. The complete list included patients receiving standard neoadjuvant, adjuvant, and metastatic chemotherapy regimens. We analyzed 23 female patients with HER2 positive breast cancer staged I to IIIC, receiving standard NACT (docetaxel, carboplatin, trastuzumab, and pertuzumab). Metastatic HER2 positive breast cancer patients were excluded. The primary outcome studied was pCR rates after receiving NACT. pCR was defined as the absence of invasive cancer cells from tissue samples removed after surgery. Secondary outcomes measured were side effects of chemotherapy. pCR rates and side effects were compared to TRYPHAENA. Data regarding insurance status, breast cancer detection modality, and time to seek medical attention were recorded.
    RESULTS: 50% of our patients who received NACT achieved pCR. Our pCR rates mirrored those observed in the TRYPHAENA trial (51.9%). The most common side effect observed in our population was diarrhea. A higher proportion (37.5%) of our patients had liver function test (LFT) elevation compared to the TRYPHAENA trial (3.9%). Baseline LFTs were normal prior to treatment in 96% of patients. In terms of modality of detection, 70% were self-palpated, 26% were detected through routine mammography, and 4% were found incidentally. Average time from mass discovery to seeking medical attention was 3.4 months. Only 26% had medical insurance at diagnosis. Although not included in our study, 28% of our patients were initially diagnosed with stage IV metastatic disease.  Conclusion: Our study found that pCR rates in our primarily Hispanic population compared well to the response rates observed in landmark trials with largely Caucasian populations. Genetic variations in chemo-sensitivity may have a minimal influence on cancer care outcomes in this population.
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  • Article
    Pellegrino RM, Di Veroli A, Valeri A, Goracci L, Cruciani G.
    Anal Bioanal Chem. 2014 Dec;406(30):7937-48.
    Over the last decade, technological advances have improved the sensitivity and selectivity of LC/MS analyzers, providing very efficient tools for lipidomics research. In particular, the nine lipid classes that constitute 99 % of the human serum lipidome (sterols, cholesteryl esters, phosphocholines, phosphoethanolamines, sphingomyelins, triacylglycerols, fatty acids, lysophosphocholines, and diacylglycerols) can be easily detected. However, until today there has not been a unique technique for sample preparation that provides a satisfactory recovery for all of these nine classes together. In this work, we have developed and validated a new one-phase extraction (OPE) method that overcomes this limitation. This method was also compared with the gold standard lipid extraction methods such as Folch, Bligh & Dyer, and recently developed methods with methanol and methyl-tert-butyl ether. Results demonstrate that the mixture of methanol/chloroform/MTBE (MMC) provides a recovery very close to 100 % for all nine lipid classes of the human serum investigated. For this extraction method, 100 μL of human serum is incubated with 2 mL of the solvents mixture, then vortexed and centrifuged. For its simplicity of execution, rapidity, reproducibility, and the reduced volume of sample required, this method opens the door to the use of human serum lipid profiling for large-scale applications in scientific research and clinical trials.
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  • Article
    Yuasa J, Mukai R, Hasegawa Y, Kawai T.
    Chem Commun (Camb). 2014 Jul 28;50(59):7937-40.
    A dinuclear europium(III) complex with a structure of [BP-(Eu(III))2-(ODA)3] (BP = 2,2'-bipyridine-6,6'-dicarboxylic acid bis(N-hydroxy-succinimide) ester, ODA = diglycolic acid) shows a fully reversible emission spectral change at the extremely narrow (5)D0 → (7)F2 transition band in response to temperature changes ranging from 283 K to 333 K.
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  • Article
    Pandey S, Gupta R.
    Sci Rep. 2023 May 16;13(1):7937.
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  • Article
    Xu ST, Ding X, Ni QF, Jin SJ.
    Int J Clin Exp Pathol. 2015;8(7):7937-44.
    The purpose of this article is to research on whether MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma (BUC). In this study, the expression of MACC1 gene was knocked down by RNA interference (RNAi) in the T24 cell (human BUC cell). The transcription level of MACC1 was detected by RT-PCR. Activities of MACC1, caspase-3, caspase-8, Bax and Met (mesenchymal-epithelial transition factor) protein were measured by Western blot. The cell proliferation and apoptosis were detected by MTT and flow cytometry. The cell's invasion ability was performed on Matrigel transwell assay. We also detect MMP2 (metalloproteinase-2) proteins by ELISA. The results showed that the level of MACC1 mRNA and protein was significantly reduced after RNAi. MTT assay showed that the proliferation of T24 cell was decreased due to RNA interference. Apoptosis studies also showed that MACC1 gene interference in T24 loses its anti-apoptotic effects. The expression of apoptosis proteins (Caspase-3, Caspase-8 and Bax) increased significantly due to the MACC1 RNAi. The level of Met protein was down-regulated obviously due to RNAi. Transwell assay showed that invasion abilities of T24 cells were reduced obviously due to MACC1 RNAi. Further studies showed that the secretion of MMP-2 was reduced by RNAi. It can conclude that the ability of proliferation and invasion in T24 cells can be inhibited by RNAi-targeting MACC1. As a result, MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma.
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  • Article
    Karunarathne S, Kannangara YY, Ratwani CR, Sandaruwan C, Wijesinghe WPSL, Kamali AR, Abdelkader AM.
    Nanoscale. 2024 Apr 25;16(16):7937-7950.
    Li-air battery (LAB) technology is making continuous progress toward its theoretical capacity, which is comparable to gasoline. However, the sluggish reaction at the cathode is still a challenge. We propose a simple strategy to optimize the surface eg occupancy by adjusting the stoichiometric ratios of transition metal-based spinel structures through a controlled hydrothermal synthesis. Three distinct stoichiometries of Ni-Co oxides were used to demonstrate the direct correlation between stoichiometry and catalytic performance. The groundsel flower-like structure having a 1 : 1.4 Ni : Co atomic ratio with high surface area, high defect density, and an abundance of Ni3+ at the surface with semi-filled eg orbitals was found to benefit the structure promoting high catalytic activities in aqueous and aprotic media. The assembled LAB cells employing this cathode demonstrate an exceptional lifespan, operating for 3460 hours and completing 173 cycles while achieving the highest discharge capacity of 13 759 mA h g-1 and low charging overpotentials. The key to this prolonged performance lies in the full reversibility of the cell, attributed to its excellent OER performance. A well-surface adsorbed, amorphous LiO2/Li2O2 discharge product is found to possess high diffusivity and ease of decomposition, contributing significantly to the enhanced longevity of the cell.
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  • Article
    Han WGH, Swart A, Bonačić Marinović A, Eggink D, Reimerink J, Wijsman LA, van der Veer B, ... Show More van den Brink S, van den Brandt AM, van Tol S, Godeke GJ, Brouwer F, Hoogerwerf M, Dutch F. F. X.-COVID-19 Research Group, Reukers DFM, Rots N, Reusken C, Meijer A.
    Sci Rep. 2022 05 13;12(1):7937.
    This study investigated the dynamics of SARS-CoV-2 infection and diagnostics in 242 household members of different ages and with different symptom severity after SARS-CoV-2 exposure early in the pandemic (March-April 2020). Households with a SARS-CoV-2 confirmed positive case and at least one child in the Netherlands were followed for 6 weeks. Naso (NP)- and oropharyngeal (OP) swabs, oral fluid and feces specimens were analyzed for SARS-CoV-2 RNA and serum for SARS-CoV-2-specific antibodies. The dynamics of the presence of viral RNA and the serological response was modeled to determine the sampling time-frame and sample type with the highest sensitivity to confirm or reject a SARS-CoV-2 diagnosis. In children higher viral loads compared to adults were detected at symptom onset. Early in infection, higher viral loads were detected in NP and OP specimens, while RNA in especially feces were longer detectable. SARS-CoV-2-specific antibodies have 90% probability of detection from 7 days (total Ig) and 18 days (IgG) since symptom onset. For highest probability of detection in SARS-CoV-2 diagnostics early in infection, RT-PCR on NP and OP specimens are more sensitive than on oral fluid and feces. For SARS-CoV-2 diagnostics late after infection, RT-PCR on feces specimens and serology are more valuable.
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  • Article
    Li HB, Page AJ, Wang Y, Irle S, Morokuma K.
    Chem Commun (Camb). 2012 Aug 18;48(64):7937-9.
    Graphene nucleation on Ni(111) has been modeled using QM/MD simulations. We demonstrate that graphene precursor nucleation can occur underneath the catalyst surface. In addition, a Ni(111) step-edge is not a static structure, as is often assumed; it is instead highly malleable, being deformed and subsequently healed during graphene nucleation.
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  • Article
    Manfredi M, Sanchez Mello de Pinho P, Murrins Marques L, de Oliveira Ribeiro B, Boggio PS.
    Heliyon. 2021 Sep;7(9):e07937.
    To investigate the processing of environmental sounds, previous researchers have compared the semantic processing of words and sounds, yielding mixed results. This study aimed to specifically investigate the electrophysiological mechanism underlying the semantic processing of environmental sounds presented in a naturalistic visual scene. We recorded event-related brain potentials in a group of young adults over the presentation of everyday life actions that were either congruent or incongruent with environmental sounds. Our results showed that incongruent environmental sounds evoked both a P400 and an N400 effect, reflecting sensitivity to physical and semantic violations of environmental sounds' properties, respectively. In addition, our findings showed an enhanced late positivity in response to incongruous environmental sounds, probably reflecting additional reanalysis costs. In conclusion, these results indicate that the crossmodal processing of the environmental sounds might require the simultaneous involvement of different cognitive processes.
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  • Article
    Wakabayashi K, Isozaki T, Tsubokura Y, Fukuse S, Kasama T.
    Sci Rep. 2021 04 12;11(1):7937.
    Eotaxin-1 (CCL11) induces the migration of different leukocyte types by interacting with CCR3. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are pathogenic effectors and a major CCR3-expressing cell. The aim of this study was to investigate the expression and function of CCL11 in RA FLS. The expression of CCL11 and CCR3 was evaluated by ELISA, immunofluorescence and quantitative PCR analysis. The CCL11 levels in serum and synovial fluids (SFs) from RA patients were significantly higher than those in serum from healthy controls and SFs from osteoarthritis patients. CCL11 and CCR3 were expressed in the RA synovial tissue lining layers. The secretion of CCL11 in RA FLS-conditioned medium and the mRNA expression of CCL11 and CCR3 were induced by TNF-α. Furthermore, CCL11 induced the mRNA expression of CCL11 and CCR3. Application of a CCR3 antagonist reduced TNF-α-induced CCL11 secretion from RA FLS. CCL11 induced the migration of RA FLS and monocytes. RA FLS migration was decreased by treatment with CCL11 siRNA. The migration of monocytes to medium conditioned with CCL11 siRNA-transfected and TNF-α-stimulated RA FLS was reduced. These data indicate that the self-amplification of CCL11 via CCR3 may play an important role in cell migration in RA.
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  • Article
    Sedlak D.
    Environ Sci Technol. 2016 08 02;50(15):7937-8.
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  • Article
    Özçubukçu S, Mandal K, Wegner S, Jensen MP, He C.
    Inorg Chem. 2011 Sep 05;50(17):7937-9.
    The separation of lanthanides from minor actinides such as americium and curium is an important step during the recycling process in the treatment of nuclear waste. However, the similar chemistry and ionic size of lanthanide and actinide ions make the separation challenging. Here, we report that a peptide-based reagent can selectively bind trivalent actinides over trivalent lanthanides by means of introducing soft-donor atoms into a peptide known as a lanthanide-binding tag (LBT). Fluorescence spectroscopy has been used to measure the dissociation constant of each metal/peptide complex. A 10-fold selectivity was obtained for Am(3+) over the similarly sized lanthanide cation, Nd(3+), when the asparagine on the fifth position of a LBT was mutated to a cysteine and further functionalized by a pyridine moiety.
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  • Article
    Favero S, Li A, Wang M, Uddin F, Kuzuoglu B, Georgeson A, Stephens IEL, Titirici MM.
    ACS Catal. 2024 May 17;14(10):7937-7948.
    Anion exchange membrane fuel cells (AEMFCs) can produce clean electricity without the need for platinum-group metals at the cathode. To improve their durability and performance, most research investigations so far have focused on optimizing the catalyst and anion exchange membrane, while few studies have been dedicated to the effect of the ionomer. Herein, we address this gap by developing a poly(ionic liquid)-based ionomer and studying its effect on oxygen transport and oxygen reduction kinetics, in comparison to the commercial proton exchange and anion exchange ionomers Nafion and Fumion. Our study shows that the choice of ionomer has a dramatic effect on the morphology of the catalyst layer, in particular on iron aggregation. We also observed that the quality of the catalyst layer and the degree of iron aggregation can be correlated to the rheological properties of the catalyst ink. Moreover, this work highlights the impact of the ionomer on the resistance to oxygen transport and reports improved oxygen diffusion compared to Nafion, for poly(ionic liquid)s with fluorinated anions. Finally, the performance of the catalyst-ionomer layer for oxygen reduction was tested with a rotating disc electrode (RDE) and a gas diffusion electrode (GDE). We observed dramatic differences between the two configurations, which we attribute to the different morphologies of the catalyst layer. In summary, our study highlights the dramatic and overlooked effect of the ionomer and the limitations of the RDE in predicting fuel cell performance.
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  • Article
    Yang B, Xie C, Lv Y, Wang Y.
    J Inflamm Res. 2024;17:7929-7937.
    Objective: To unravel the effects of different laparoscopic inguinal hernia repairs (IHRs) on inflammatory factors, oxidative stress, and postoperative recovery of inguinal hernia (IH) patients.
    Methods: A total of 88 patients for laparoscopic treatment of IH were studied in a retrospective cohort, and were randomized into the transabdominal preperitoneal (TAPP) repair group (n = 44) and the total extraperitoneal (TEP) repair group (n = 44) according to the method of treatment. Patients in the TAPP group underwent laparoscopic TAPP IHR, while patients in the TEP group underwent laparoscopic TEP IHR. Visual analogue scores (VAS) were measured at 1, 3, and 7 d after repair. Gastrin (GAS), motilin (MTL), matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assessed by enzyme-linked immunosorbent assay. Superoxide dismutase (SOD) was tested by spectrophotometry and malondialdehyde (MDA) and β-endorphin (β-EP) were examined by radioimmunoprecipitation. Total antioxidant capacity (T-AOC) was evaluated by chemical colorimetry, quality of life was evaluated by SF-36, and fibrinogen (FIB), C-reactive protein (CRP), antitrypsin (al-AT), and interleukin-6 (IL-6) levels were determined by immunoturbidimetry. Complications and postoperative recurrence were recorded.
    Results: VAS scores in the TEP group were lower than those in the TAPP group. Operative time, hospital stay, time for postoperative activity out of bed, and time taken to exhaust were shorter in the TEP group than in the TAPP group. Intraoperative blood loss was less in the TEP group than in the TAPP group. GAS, MTL, SOD, and T-AOC were higher, and MDA, β-EP, CRP, FIB, alAT, IL-6, MMP-2, MMP-9, and TIMP-1 were lower in the TEP group than the TAPP group. Quality of life was improved in the TEP group compared with the TAPP group. There was no significant difference in the rate of postoperative complications and recurrence rates between both groups of patients.
    Conclusion: For IHs, laparoscopic TEP repair can effectively relieve pain, reduce inflammatory factors and oxidative stress indices, and facilitate postoperative recovery.
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  • Article
    Fernandes F, Stringhetta-Garcia CT, Peres-Ueno MJ, Fernandes F, Nicola AC, Castoldi RC, Ozaki G, Louzada MJQ, Chaves-Neto AH, Ervolino E, Dornelles RCM.
    Sci Rep. 2020 05 13;10(1):7937.
    The objective of this study is to identify whether oxytocin (OT) contributes to the reduction of osteopenia in the femoral neck of rats in periestropause. Animals in irregular estrous cycles received two NaCl injections (0.15 mol/L) or OT (134 μg/kg) over a 12-h interval, and after thirty-five days without treatments, the biological sample collection was performed. The oxytocin group (Ot) demonstrated the highest enzymatic activity of alkaline phosphatase (p = 0.0138), lowest enzymatic activity of tartrate-resistant acid phosphatase (p = 0.0045), higher percentage of compact bone (p = 0.0359), cortical expression of runt-related transcription factor 2 (p = 0.0101), osterix (p = 0.0101), bone morphogenetic protein-2/4 (p = 0.0101) and periostin (p = 0.0455). Furthermore, the mineral-to-matrix ratio (ν1PO4/Proline) was higher and type-B carbonate substitution (CO3/ν1PO4) was lower (p = 0.0008 and 0.0303) in Ot group. The Ot showed higher areal bone mineral density (p = 0.0050), cortical bone area (p = 0.0416), polar moment of inertia, maximum, minimum (p = 0.0480, 0.0480, 0.0035), bone volume fraction (p = 0.0166), connectivity density (p < 0.0001), maximal load (p = 0.0003) and bone stiffness (p = 0.0145). In Ot percentage of cortical pores (p = 0.0102) and trabecular number (p = 0.0088) was lower. The results evidence action of OT in the reduction of osteopenia, suggesting that it is a promising anabolic strategy for the prevention of primary osteoporosis during the periestropause period.
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  • Article
    Rasul A, Imran Khan M, Ur Rehman M, Abbas G, Aslam N, Ahmad S, Abbas K, Akhtar Shah P, Iqbal M, Ahmed Al Subari AM, Shaheer T, Shah S.
    Int J Nanomedicine. 2020;15:7937-7949.
    BACKGROUND: Cyclosporine A (CsA) is an exceptional immunosuppressant used for the treatment of immune disorders. Niosomal vesicles are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. The objective of the study was to formulate combined nonionic surfactant based vesicles and to evaluate their in vitro characterization, release studies and in vivo studies.
    MATERIALS AND METHODS: Five niosomal formulations (F7 to F11) were prepared using the thin film hydration method. The molar ratio of cholesterol and non-ionic surfactant taken was 1:1. In formulation F10, the combination of surfactants Span 20 and Brij 35 was used. The niosomes were characterized by zeta sizer and SEM for particle size analysis, in vitro drug release and stability studies. The pharmacokinetic studies were conducted on healthy albino rabbits.
    RESULTS: The size of niosome was found in the range of 427.1 nm to 972.3 nm. SEM image of optimized formulations F10 exhibit the spherical nature of niosomal vesicles. DSC thermograms of niosomal formulations exhibited a broadened endothermic peak. The stability study exhibited that all formulations are stable and negligible change of vesicle size and entrapment was observed with time. The percentage drug release was significantly higher as compared to CsA plain dispersion for all niosomal formulations at pH 1.2 and 7.4. The release kinetic behavior showed that all preparations were best described by zero order and can release active ingredient in a sustained manner. The pharmacokinetic data showed the test formulation (F10) possessed greater bioavailability as compared to the reference formulation (CsA aqueous dispersion).
    CONCLUSION: The formulation F10 demonstrated a comparatively more delayed rate of release with enhanced dissolution as compared to a single surfactant scheme. The F10 formulation can be a remarkable nanotechnology for prolonged delivery of CsA orally with improved dissolution profile and bioavailability.
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