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In recent years, the functionality of myoelectric prosthetic hands has improved as motors have become smaller and controls have become more advanced. Attempts have been made to reproduce the rotation and flexion of the wrist by adding degrees of freedom to the wrist joint. However, it is still difficult to fully reproduce the functionality of the wrist joint owing to the weight of the prosthesis and size limitations. In this study, we developed a new socket and prosthetic hand control system that does not interfere with the wrist joint motion. This allows individuals with hand defects who previously used prosthetic hands with fixed wrist joints to freely use their remaining wrist functionality. In the pick-and-place experiment, where blocks were moved from higher to lower locations, we confirmed that the proposed system resulted in a lower elbow position compared with the traditional prosthesis, and the number of blocks transported increased. This significantly reduced the compensatory motion of the elbow and improved the user's performance compared with the use of a conventional prosthetic hand. This study demonstrates the usefulness of a new myoelectric prosthetic hand that utilizes the residual functions of people with hand deficiencies, which have not been utilized in the past, and the direction of its development.
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Anime has become a global phenomenon due to its diverse cultural representations, relatable characters, and unique storytelling. However, there is limited research on the relationship between character personality and popularity. The aim of this study is to understand the relevance of the characters' personalities to the audience's evaluation of various characters. This study analyzed the correlation between the MBTI personality evaluations of characters in anime and their popularity, based on the data of the personality of each animation character reviewed by audiences. In this study, 885 characters from 200 anime aimed at a male audience were selected as a sample for research. The results showed that personality traits such as introversion, intuition, and thinking had an impact on the popularity of female characters but not male characters. The overall results were influenced by the larger sample size of female characters. By addressing this question, the study can contribute to the design of a character's personality and overall success in anime.
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Global methylation levels differ in in vitro- and in vivo-developed embryos. Follicular fluid (FF) contains extracellular vesicles (EVs) containing miRNAs that affect embryonic development. Here, we examined our hypothesis that components in FF affect global DNA methylation and embryonic development. Oocytes and FF were collected from bovine ovaries. Treatment of zygotes with a low concentration of FF induced global DNA demethylation, improved embryonic development, and reduced DNMT1/3A levels. We show that embryos take up EVs containing labeled miRNA secreted from granulosa cells and the treatment of zygotes with EVs derived from FF reduces global DNA methylation in embryos. Furthermore, the methylation levels of in vitro-developed blastocysts were higher than those of in their vivo counterparts. Based on small RNA-sequencing and in silico analysis, we predicted miR-29b, -199a-3p, and -148a to target DNMTs and to induce DNA demethylation, thereby improving embryonic development. Moreover, among FF from 30 cows, FF with a high content of these miRNAs demethylated more DNA in the embryos than FF with a lower miRNA content. Thus, miRNAs in FF play a role in early embryonic development.
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Desarrollo Embrionario , Vesículas Extracelulares , Líquido Folicular , MicroARNs , Animales , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Bovinos , Líquido Folicular/metabolismo , Vesículas Extracelulares/metabolismo , Desarrollo Embrionario/genética , Metilación de ADN , Desmetilación del ADN , Oocitos/metabolismo , Blastocisto/metabolismo , Embrión de Mamíferos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Cigoto/metabolismoRESUMEN
Improvement in vitro maturation culture conditions has been achieved by mimicking in vivo culture environments such as the follicular fluid. Acetic acid is an energy substrate that is abundantly present in the follicular fluid but has not been considered in vitro maturation. This study examined the effects of acetic acid on oocyte quality during nuclear maturation. Cumulus cells and oocyte complexes were collected from the porcine antral follicles of gilt ovaries and matured with 0, 0.1 or 1 mmol/L of acetic acid. After 44 h of in vitro maturation, the energy status, mitochondrial quality and function and embryonic developmental rate following parthenogenetic activation were determined. RNA-sequencing and protein expression analyses were conducted to predict the effects of acetic acid. Supplementation of the in vitro maturation medium with acetic acid (1 mmol/L) improved embryonic development. Oocytes matured with acetic acid had low adenosine triphosphate and lipid contents, mitochondrial membrane potential and reactive oxygen species levels. RNA-sequencing revealed differential expression of genes associated with the adenosine monophosphate-activated protein kinase signalling pathway. Immunostaining revealed that acetic acid increased the levels of phospho-adenosine monophosphate-activated protein kinase, phospho-acetyl-coenzyme A carboxylase, and sirtuin 1 and decreased those of fatty acid synthase and acetyl-coenzyme A synthetase 1. In summary, the use of acetic acid during oocyte maturation improved oocyte developmental ability and metabolism by altering mitochondrial activity and lipid metabolism.
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Ácido Acético , Técnicas de Maduración In Vitro de los Oocitos , Oocitos , Animales , Oocitos/efectos de los fármacos , Oocitos/fisiología , Porcinos , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Ácido Acético/farmacología , Femenino , Desarrollo Embrionario/efectos de los fármacosRESUMEN
Ethanol affects pre-conceptional oocyte quality in women. In this study, we examined the effect of low ethanol concentrations on mouse oocytes. Oocytes were collected from the ovaries of 9-10 week old mice and allowed to mature in vitro in the presence of low concentrations of ethanol (0.1% and 0.2% v/v) for 24 h. Treatment of oocytes with ethanol (0.2%) during maturation decreased the mitochondrial DNA content and membrane potential compared to that in untreated ones, whereas the ATP content did not differ between the groups. Both 0.1% and 0.2% ethanol reduced the lipid content in the oocytes. In addition, immunostaining revealed that oocytes cultured in maturation medium containing ethanol (0.2%) had reduced levels of global DNA methylation and DNMT3A compared with untreated oocytes, and decreased rate of blastocyst development with low mitochondrial protein levels (TOMM40) in embryo. RNA-sequencing of the ethanol-treated (0.2%) and untreated oocytes revealed that mitochondria were a major target of ethanol. In conclusion, treatment of oocytes with low concentration of ethanol reduces the developmental rate to the blastocyst stage, with a lower total cell number and global DNA methylation. In addition, ethanol affected mitochondrial function and mitochondria-related gene expression.
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Metilación de ADN , Etanol , Técnicas de Maduración In Vitro de los Oocitos , Mitocondrias , Oocitos , Animales , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Etanol/farmacología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Femenino , Metilación de ADN/efectos de los fármacos , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Desarrollo Embrionario/efectos de los fármacos , Medios de Cultivo/química , Blastocisto/efectos de los fármacos , Blastocisto/metabolismo , ADN Mitocondrial/metabolismo , Transcriptoma/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
Telomere length (TL) and mitochondrial DNA copy number (mt-cn) are associated with embryonic development. Here, we investigated the correlation between TL and mt-cn in bovine embryos to determine whether TL regulates mt-cn. TL and mt-cn were closely correlated in embryos derived from six bulls. Treatment of embryos with a telomerase inhibitor (TMPyP) and siTERT shortened the TL and reduced mt-cn in blastocysts. RNA-sequencing of blastocysts developed with TMPyP revealed differentially expressed genes associated with transforming growth factor-ß1 signaling and inflammation. In conclusion, TL regulates mt-cn in embryos.
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Blastocisto , Variaciones en el Número de Copia de ADN , Animales , Bovinos , Blastocisto/metabolismo , Blastocisto/efectos de los fármacos , Telómero/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Masculino , Femenino , Homeostasis del Telómero/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/genética , Desarrollo Embrionario/efectos de los fármacos , Desarrollo Embrionario/genéticaRESUMEN
Ocular abnormal angiogenesis and edema are featured in several ocular diseases. S1P signaling via S1P1 likely is part of the negative feedback mechanism necessary to maintain vascular health. In this study, we conducted pharmacological experiments to determine whether ASP4058, a sphingosine 1-phosphate receptor 1/5 (S1P1/5) agonist, is useful in abnormal vascular pathology in the eye. First, human retinal microvascular endothelial cells (HRMECs) were examined using vascular endothelial growth factor (VEGF)-induced cell proliferation and hyperpermeability. ASP4058 showed high affinity and inhibited VEGF-induced proliferation and hyperpermeability of HRMECs. Furthermore, S1P1 expression and localization changes were examined in the murine laser-induced choroidal neovascularization (CNV) model, a mouse model of exudative age-related macular degeneration, and the efficacy of ASP4058 was verified. In the CNV model mice, S1P1 tended to decrease in expression immediately after laser irradiation and colocalized with endothelial cells and Müller glial cells. Oral administration of ASP4058 also suppressed vascular hyperpermeability and CNV, and the effect was comparable to that of the intravitreal administration of aflibercept, an anti-VEGF drug. Next, efficacy was also examined in a retinal vein occlusion (RVO) model in which retinal vascular permeability was increased. ASP4058 dose-dependently suppressed the intraretinal edema. In addition, it suppressed the expansion of the perfusion area observed in the RVO model. ASP4058 also suppressed the production of VEGF in the eye. Collectively, ASP4058 can be a potential therapeutic agent that normalizes abnormal vascular pathology, such as age-related macular degeneration and RVO, through its direct action on endothelial cells.
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Neovascularización Coroidal , Modelos Animales de Enfermedad , Animales , Humanos , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/patología , Ratones , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/agonistas , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos C57BL , Receptores de Lisoesfingolípidos/agonistas , Receptores de Lisoesfingolípidos/metabolismo , MasculinoRESUMEN
The homozygous Bronx waltzer (bv) mouse, which shows hearing impairment, also exhibits anxiety accompanied by a reduction in cortical parvalbumin (PV)-positive GABAergic interneurons. Recently, a mutation in splicing factor Ser/Arg repetitive matrix 4 (Srrm4) was found in bv mice. However, the cellular consequences of the Srrm4 mutation for anxiety remain unknown. Here, we tested our hypothesis that bv mutant primarily affects interneurons through a cell-intrinsic pathology that leads to a reduction of interneurons and consequently causes anxiety. We found that the anxiety becomes apparent at 6 weeks of age in bv/bv mice. However, in situ hybridization revealed that Srrm4 is not expressed in interneurons, but rather dominates in pyramidal neurons. In addition, the PV-positive GABAergic interneurons were not reduced in number in the bv/bv cortex when anxiety became evident. However, electrophysiological abnormality of GABAergic transmission from interneurons was concomitantly present. Pharmacological blockage of GABAA receptors revealed increased excitability in bv/bv mice, although no gross change occurred in the expression of an Srrm4-downstream gene, Kcc2, which regulates chloride flux upon GABAergic transmission. These findings suggest that the bv-associated Srrm4 mutation mainly involves post-synaptic GABAergic transmission in the central nervous system, which may be associated with the anxiety phenotype in bv/bv mice.
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Purpose: Oocyte and embryo quality differs significantly among individuals. Follicular fluid (FF) is a solo environment of oocyte maturation and may flux into the oviduct. Supplementation of in vitro maturation (IVM) and culture (IVC) medium with extracellular vesicles of FFs supports oocyte maturation and embryonic development. We addressed a hypothesis that miRNA profiles in FFs are crucial background of oocyte maturation and embryonic development. Methods: FFs were collected from the ovaries of individual cows, and the FFs were classified into Good or Poor FF based on the developmental rate to the blastocyst stage of enclosed oocytes. miRNAs associated with the Good FFs were explored using small RNA sequencing. In addition, FFs were classified using the concentration of Good-FF-associated miRNAs. These classified FFs or miRNA were added to the IVM or IVC mediums. Results: Supplementation of IVM and IVC medium with Good FF improved embryonic development. Good FFs contained miR-151-3p and miR-425-5p at a high concentration compared with those in Poor FFs. FFs selected by the concentration of miR-151-3p and miR-425-5p improved oocyte maturation and embryonic development. Supplementation of IVM or IVC medium with either miR-151-3p or miR-425-5p improved embryonic development to the blastocyst stage. Conclusion: miRNAs were associated with the Good FFs determined oocyte maturation and embryonic development.
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In this study, we examined the effects of paternal aging on the mitochondrial DNA copy number (mt-cn), telomere length (TL), and gene expression in mouse embryos. The effects of vitrification on the mt-cn and TL of the embryos derived from young and aged male parents (YF and AF, respectively) were examined. C57BL/6N male mice were used for embryo production at 13-23 and 50-55 weeks of age. Two-cell stage embryos were collected from the oviducts of superovulated female mice (8-15 weeks old) and cultured for 24 h until the 8-cell stage, followed by embryo vitrification. Fresh and vitrified-warmed embryos were incubated for 2 days until the blastocyst stage, and mt-cn and TL were investigated. The cell-free mitochondrial DNA copy number (cf-mt-cn) in the spent culture medium (SCM) of the embryos was then investigated. RNA sequencing of blastocysts revealed that metabolic pathways, including oxidative phosphorylation and mTOR pathways, were enriched in differentially expressed genes. The mt-cn and TL of AF-derived blastocysts were lower and shorter, respectively, than those of YF-derived blastocysts. Paternal aging did not affect the blastocyst rate after vitrification. Vitrification of the 8-cell stage embryos did not affect the mt-cn of the blastocysts. However, it increased the cf-mt-cn (cell-free mt-cn) in the SCM of both YF- and AF-derived embryos. Vitrification did not affect the TL of either YF- or AF-derived embryos. Thus, paternal aging affected the mt-cn and TL of the embryos, but vitrification did not affect these parameters in either age groups.
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Criopreservación , Vitrificación , Masculino , Femenino , Animales , Ratones , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Variaciones en el Número de Copia de ADN , Ratones Endogámicos C57BL , Blastocisto/metabolismo , TelómeroRESUMEN
Strobilurins A and X, isolated from Mucidula venosolamellata culture extracts, demonstrated potent inhibition of human melanoma G-361 cell proliferation. Strobilurin X exhibited milder inhibitory effects on human fibroblast cells (NB1RGB) compared to strobilurin A. Additional strobilurin-related compounds were isolated from the other mushroom species. Oudemansins A and B displayed weaker activities on G-361 cells than strobilurins A and B, respectively, emphasizing the importance of a conjugated double-bond structure. Among isolated compounds, strobilurin G showed the lowest IC50 value for G-361 cells. Additional strobilurins bearing various substituents on the benzene ring were synthesized. Synthetic intermediates lacking the methyl ß-methoxyacrylate group and a strobilurin analogue bearing modified ß-methoxyacrylate moiety showed almost no inhibitory activity against G-361 cells. The introduction of long or bulky substituents at the 4' position of the benzene ring of strobilurins enhanced the activity and selectivity, suggesting differential recognition of the benzene ring by G-361 and NB1RGB cells.
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Agaricales , Fungicidas Industriales , Melanoma , Humanos , Estrobilurinas/química , Benceno , Proliferación Celular , Fungicidas Industriales/química , Fungicidas Industriales/farmacologíaRESUMEN
Using anticancer drugs as examples, we examined the possibility of reusing residual drugs. The use of residual drugs is not widespread owing to concerns regarding bacterial contamination. We combined anticancer drugs and bacteria to investigate their effects on bacterial growth. The anticancer drugs carboplatin, paclitaxel, etoposide, irinotecan, methotrexate, and 5-fluorouracil (5-FU) were mixed with Staphylococcus aureus, Enterococcus faecalis, Serratia marcescens, and Escherichia coli. After a certain period, the bacteria were counted. Irinotecan showed no antibacterial activity, whereas 5-FU exhibited high antibacterial activity against the tested bacteria. The 5-FU also showed a minimum inhibitory concentration value in the range of 8-80 µg/mL, depending on the bacterial species. 5-FU dose-dependently inhibited S. aureus growth at more than 0.8 µg/mL. Because protein synthesis systems are reportedly antibiotic targets, we used a cell-free protein synthesis system to confirm the mechanism of the antibacterial activity of the anticancer agent. 5-FU and methotrexate had direct inhibitory effects on protein synthesis. It has been suggested that even if residual drugs are contaminated with bacteria, there will be no microbial growth, or the microbes will be killed by the drug. With careful monitoring, 5-FU can potentially be used for antimicrobial purposes.
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Antineoplásicos , Staphylococcus aureus , Metotrexato/farmacología , Irinotecán/farmacología , Antibacterianos/farmacología , Bacterias , Antineoplásicos/farmacología , Fluorouracilo/farmacología , Escherichia coli , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVES: This scoping review aims to map the literature on goal-setting tools in adult rehabilitation, exploring their characteristics, target users and supporting evidence to inform practice and future research in this area. METHODS: We completed a comprehensive search of four databases to identify relevant articles on tools for goal setting in rehabilitation. We followed Arkey and O'Malley's scoping review process to guide article selection, data extraction and data analysis. RESULTS: We identified a total of 165 studies that reported on 55 different goal-setting tools, including tools for goal selection and goal documentation (n = 31), goal setting and intervention planning (n = 15), and for measuring the quality of the goal-setting process (n = 9). Over half of the tools were primarily designed for use in rehabilitation of physical disabilities (n = 32). Some tools fell under multiple sub-categories based on their characteristics as follows: 22 framework tools, 12 interview tools, 9 outcome measurement tools for goal achievement, 6 outcome measurement tools for goal quality and 25 documentation tools. The majority of goal-setting instruments targeted goals at the level of activity and participation (n = 51) and aimed to facilitate a client-centred or shared decision-making approach to rehabilitation planning (n = 46). CONCLUSIONS: This study provides a comprehensive overview of existing goal-setting tools, highlighting their characteristics, target users and identified needs. These findings can enhance practitioners' awareness of the range of goal-setting tools available and can enable more effective utilization of these tools in clinical practice. Further research should investigate how clinicians can combine multiple tools to deliver goal setting.
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Personas con Discapacidad , Objetivos , Adulto , Humanos , Motivación , Personas con Discapacidad/rehabilitaciónRESUMEN
FCCP (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone) is known to inhibit oxidative phosphorylation as a protonophore, dissipating the proton gradient across the inner mitochondrial membrane. To understand the toxicity of FCCP, 3-day, 2- and 4-week repeated oral dose studies were performed in male rats. In the 3-day and 2-week repeated dose toxicity studies, observations included salivation, increased body temperature, and dead and moribund animals. Increased liver weight was observed in conjunction with hydropic degeneration and centrilobular necrosis of hepatocytes. In addition, pathological changes were observed in the pancreas, testis, epididymal duct, stomach and parotid gland. Electron microscopic examination revealed mitochondrial pleomorphism in the hepatocytes. Swelling of mitochondria was observed in the alpha cells and beta cells of the pancreas. Dilatation of rough endoplasmic reticulum, Golgi bodies and loss of secretory granules were also noted in the beta cells of the pancreas. FCCP was also compared with three other mUncouplers (DNP, OPC-163493 and tolcapone) with regard to in vitro mitochondrial uncoupling (mUncoupling) activities. FCCP produced the peak ΔOCR (oxygen consumption rate) at the lowest concentration (0.4 µM), followed by OPC-163493, tolcapone, and DNP, based on peak values in ascending order of concentration (2.5, 10, and 50 µM, respectively). Considering the relationship between the mUncoupling activity and toxicity profile of the four mUncouplers, there is no parallel relationship between the in vitro mUncoupling activity and the degree of in vivo toxicity. These findings may contribute to the efficient development of new mitochondrial uncoupler candidates. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00189-x.
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Bedside dialysis monitoring equipment for hemodialysis are located in the bioburden section upstream of the endotoxin-retentive filter for dialysis fluid sterilization. We observed 26 equipment at our institution for bacterial contamination at least once every 4 weeks for 5 years with another ultrafiltration membrane upstream to prevent bacterial contamination. Bacterial contamination levels were highest and most diverse at the time of the first flush. During subsequent initial cleanng, the contamination level decreased, and bacterial species converged almost exclusively to one genus, namely Methylobacterium spp. During clinical use, the equipment were cleaned and disinfected daily after dialysis, and daily operations and maintenance were performed using aseptic techniques. Although the frequency of bacterial detection decreased annually, the same bacterial genotypes observed at the first flush were isolated even after long time periods and were thought to persist in the equipment possibly by forming biofilm. Pseudomonas aeruginosa was newly detected after the replacement of parts during breakdown maintenance, indicating the need to sterilize replacement parts. Thus, the bioburden should be assessed regularly as part of the management of in-house-produced dialysis fluid.
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Bacterias , Diálisis Renal , Bacterias/genética , Soluciones para Diálisis , Ultrafiltración , EndotoxinasRESUMEN
PURPOSE: The purpose of this study is to develop a virtual CBCT simulator with a head and neck (HN) human phantom library and to demonstrate the feasibility of elemental material decomposition (EMD) for quantitative CBCT imaging using this virtual simulator. METHODS: The library of 36 HN human phantoms were developed by extending the ICRP 110 adult phantoms based on human age, height, and weight statistics. To create the CBCT database for the library, a virtual CBCT simulator that simulated the direct and scattered X-ray on a flat panel detector using ray-tracing and deep-learning (DL) models was used. Gaussian distributed noise was also included on the flat panel detector, which was evaluated using a real CBCT system. The usefulness of the virtual CBCT system was demonstrated through the application of the developed DL-based EMD model for case involving virtual phantom and real patient. RESULTS: The virtual simulator could generate various virtual CBCT images based on the human phantom library, and the prediction of the EMD could be successfully performed by preparing the CBCT database from the proposed virtual system, even for a real patient. The CBCT image degradation owing to the scattered X-ray and the statistical noise affected the prediction accuracy, although these effects were minimal. Furthermore, the elemental distribution using the real CBCT image was also predictable. CONCLUSIONS: This study demonstrated the potential of using computer vision for medical data preparation and analysis, which could have important implications for improving patient outcomes, especially in adaptive radiation therapy.
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Tomografía Computarizada de Haz Cónico , Cabeza , Adulto , Humanos , Fantasmas de Imagen , Bases de Datos Factuales , CuelloRESUMEN
The present study investigated the effects of low ethanol exposure on bovine oocytes. Cumulus-oocyte complexes (COCs) were aspirated for the antral follicles of slaughterhouse-derived ovaries. These COCs were incubated in maturation medium containing 0, 0.1, and 0.2% ethanol for 21 h and subjected to fertilization and in vitro development, and then the rates of nuclear maturation, mitochondrial DNA copy number (Mt-cn) and protein (TOMM40), ATP content and lipid content in oocyte, fertilization, and blastulation were examined. Furthermore, COCs were incubated with 0 or 0.1% ethanol and then mitochondrial membrane potential (MMP) and the glucose consumption of COCs was determined. In addition, gene expression in oocytes was examined by RNA sequencing. Ethanol (0.1 and 0.2%) increased Mt-cn and Mt-protein levels whereas 0.2% ethanol increased the blastulation rate and ATP content in oocytes and decreased lipid content in oocytes. Ethanol (0.1%) increased MMP in oocytes and decreased glucose consumption of COCs. Eight stage embryos derived from 0.1% ethanol treated oocytes had higher levels of trimethyl-H3K9 compared with that of nontreated counterpart. RNA sequencing revealed that differentially expressed genes were associated with glycolysis/gluconeogenesis, carbon metabolism, sphingolipid metabolism, amino acid metabolism, and fatty acid degradation pathways. In conclusion, even 0.1% concentrations of ethanol during in vitro maturation considerably affects oocyte metabolism and histone configuration of embryos.
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ADN Mitocondrial , Oocitos , Bovinos , Animales , Femenino , Desarrollo Embrionario , Etanol/farmacología , Glucosa/farmacología , Lípidos , Adenosina Trifosfato , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Células del CúmuloRESUMEN
BACKGROUND AND OBJECTIVE: Therapeutic drug monitoring (TDM) is an effective tool for the management of patients who are administered linezolid. The use of saliva for TDM has potential advantages over the use of plasma; however, only a few reports have compared drug concentrations in the saliva and plasma. Moreover, there are no reports on the salivary concentration of tedizolid, an oxazolidinone antibiotic similar to linezolid. In the present study, the concentrations of tedizolid and linezolid in rat submandibular saliva were compared with those measured in the plasma. METHODS: Tedizolid (10 mg/kg, n = 6) and linezolid (12 mg/kg, n = 5) were administered via the rat tail vein. Submandibular saliva and plasma samples were collected for up to 8 h after the initiation of drug administration, and assayed for the concentrations of tedizolid and linezolid. RESULTS: A strong correlation was found between the saliva and plasma concentrations of tedizolid (r = 0.964, p < 0.001) and linezolid (r = 0.936, p < 0.001). The value of tedizolid maximum concentration of drug (Cmax) was 0.99 ± 0.08 µg/mL in the saliva and 14.46 ± 1.71 µg/mL in the plasma. Meanwhile, the Cmax of linezolid was 8.01 ± 1.42 µg/mL in the saliva and 13.00 ± 1.90 µg/mL in the plasma. According to these results, the saliva/plasma concentration ratios of tedizolid and linezolid in rats were 0.0513 ± 0.0080 and 0.6341 ± 0.0339, respectively. CONCLUSIONS: Considering the correlation between saliva and plasma concentrations of tedizolid and linezolid, as well as the characteristics of saliva, the results of this study suggest that saliva is a useful matrix for TDM.
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Oxazolidinonas , Ratas , Animales , Linezolid , Antibacterianos/uso terapéutico , TetrazolesRESUMEN
The elevation of intracellular very long-chain fatty acids (VLCFAs) augments pro-inflammatory activity of macrophages. VLCFAs are considered to function as regulators in macrophage inflammatory responses; however, the precise mechanism of regulating the production of VLCFAs is unclear. In this study, we focused on elongation of the verylongchain fatty acid protein (ELOVL) family, rate-determining enzymes for VLCFA synthesis, in macrophages. ELOVL7 mRNA was upregulated in human monocytic THP-1 cell-derived M1-like macrophages. Metascape analysis using the RNA-seq data set showed the involvement of NF-κB and STAT1 in transcriptional regulation of ELOVL7 highly correlated genes. Gene ontology (GO) enrichment analysis suggested that ELOVL7 highly correlated genes were closely associated with multiple pro-inflammatory responses, including response to virus and positive regulation of NF-κB signaling. Consistent with RNA-seq analysis, the NF-κB inhibitor BAY11-7082, but not the STAT1 inhibitor fludarabine, canceled ELOVL7 upregulation in M1-like macrophages. ELOVL7 knockdown decreased interleukin (IL)-6 and IL-12/IL-23 p40 production. Moreover, RNA-seq analysis of plasmacytoid dendritic cells (pDCs) revealed that ELOVL7 was upregulated in pDCs treated with TLR7 and TLR9 agonists. In conclusion, we propose that ELOVL7 is a novel pro-inflammatory gene that is upregulated by inflammatory stimuli, and regulates M1-like macrophage and pDC functions.
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Although the scope of pharmacists' work has expanded in Japan, people's perception of this is unclear. To contribute to medical care together with non- and health care professionals, clarifying the perceptions of these groups is important to best utilize pharmacist professionals. We conducted a cross-sectional questionnaire survey among non-health care professionals (n = 487) and nurses (n = 151), medical doctors (n = 133), and pharmacists (n = 204) regarding the work of pharmacists. The questionnaire comprised 56 items in four categories associated with the roles of pharmacists. For each questionnaire item, we performed logistic regression analysis to compare pharmacists' opinions with those of other professionals and non-health care professionals. Opinions were similar between pharmacists and nurses or medical doctors regarding "collecting patient information" and "providing drug information to patients." However, there were differences in perceptions regarding "medical collaboration" (nurses; 8/23 items, physicians; 11/23 items) and "community medicine" (nurses; 9/15 items, physicians; 11/15 items), and pharmacists themselves perceived greater roles related to health care collaboration and community health care. Perceptions of non-health care professionals were poorer than those of pharmacists in all categories (47/56 items). These results suggest that pharmacists must actively communicate to help others understand their specialty and build trusting relationships to improve patient care.