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Creatine kinases are essential for maintaining cellular energy balance by facilitating the reversible transfer of a phosphoryl group from ATP to creatine, however, their role in mitochondrial ATP production remains unknown. This study shows creatine kinases, including CKMT1A, CKMT1B, and CKB, are highly expressed in cells relying on the mitochondrial F1F0 ATP synthase for survival. Interestingly, silencing CKB, but not CKMT1A or CKMT1B, leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in these cells. Mechanistically, CKB promotes mitochondrial ATP but reduces glycolytic ATP production by suppressing mitochondrial calcium (mCa2+) levels, thereby preventing the activation of mitochondrial permeability transition pore (mPTP) and ensuring efficient mitochondrial ATP generation. Further, CKB achieves this regulation by suppressing mCa2+ levels through the inhibition of AKT activity. Notably, the CKB‐AKT signaling axis boosts mitochondrial ATP production in cancer cells growing in a mouse tumor model. Moreover, this study also uncovers a decline in CKB expression in peripheral blood mononuclear cells with aging, accompanied by an increase in AKT signaling in these cells. These findings thus shed light on a novel signaling pathway involving CKB that directly regulates mitochondrial ATP production, potentially playing a role in both pathological and physiological conditions. [ABSTRACT FROM AUTHOR]

Sleep apnea syndrome (SAS) exposes cells throughout the body to intermittent hypoxia (IH). Intermittent hypoxia is a risk factor not only for hypertension and insulin resistance but also for vascular dysfunction. We have reported correlations between IH, insulin resistance and hypertension. However, the details of why IH leads to vascular dysfunction remain unclear. In this study, we investigated inflammation‐related transcripts in vascular endothelial cells (human HUEhT‐1 and mouse UV2) exposed to IH by real‐time RT‐PCR and found that intercellular adhesion molecule‐1 (ICAM‐1) and endothelial cell‐specific molecule‐1 (ESM1) mRNAs were significantly increased. ELISA confirmed that, in the UV2 cell medium, ICAM‐1 and ESM1 were significantly increased by IH. However, the promoter activities of ICAM‐1 and ESM1 were not upregulated. On the other hand, IH treatment significantly decreased microRNA (miR)‐181a1 in IH‐treated cells. The introduction of miR‐181a1 mimic but not miR‐181a1 mimic NC abolished the IH‐induced upregulation of Ican‐1 and ESM1. These results indicated that ICAM‐1 and ESM1 were upregulated by IH via the IH‐induced downregulation of miR‐181a1 in vascular endothelial cells and suggested that SAS patients developed atherosclerosis via the IH‐induced upregulation of ICAM‐1 and ESM1. [ABSTRACT FROM AUTHOR]

Sonoporation refers to the formation of tiny transient pores in cell plasma membranes by using ultrasound to increase the permeability to bioactive materials. Recently, the Sonoporation technique has been widely researched in cell treatment applications, such as gene transfection. However, due to the random distribution of microbubbles, it is challenging to perform controllable and precise localized sonoporation of a target cell. In this work, a device based on the surface acoustic wave is developed to achieve a selective manipulation and cavitation of microbubbles. The device consists of a pair of microbubble positioning slant‐finger interdigital transducers (SFITs) for moving a selected microbubble in a two‐dimensional plane. Meanwhile, another narrow‐frequency‐band SFIT is integrated into the device for local cavitation control of the same microbubble. As a result, a microbubble can be transported orthogonal to and along the acoustic transmission path by continuously adjusting the input frequency and relative phase. Upon reaching the target cell, the selected microbubble can be cavitated without exciting other microbubbles, resulting in local sonoporation. The resolution of phase‐based positioning and frequency‐based transportation are 8.3 and 7.0 µm with 45° and 10 kHz settings, respectively. [ABSTRACT FROM AUTHOR]

Autoimmunity is reported involving in reproductive failures, and antinuclear antibody (ANA) positivity has been regarded as a typical feature of autoimmunity. Published studies on the association of ANA with reproductive failures including infertility are controversial. The aim of this meta‐analysis was to analyse whether the presence of ANA positivity increases the risk of infertility in women. We searched the PubMed and Embase databases for relevant literature without any restrictions prior to April 28, 2021. All analyses were performed using the RevMan 5.3 software. Twelve studies with 2734 participants, including 1482 patients with infertility, met the inclusion and exclusion criteria. The total positivity rate of ANA was 23.8% (353/1482) in all infertile patients and 8.5% (107/1252) in the control group. Infertile females had a significantly higher ANA positivity rate than the control group (odds ratio [OR] = 2.90, 95% confidence interval [CI]: 1.72–4.87, I2 = 65%, P <.0001). Several subgroup analyses were performed to reduce the heterogeneity. ANA positivity was associated with female infertility in studies either performed by indirect immunofluorescence (OR = 2.26, 95% CI:1.67–3.06, P <.00001) or by ELISA (OR = 10.76, 95% CI:1.82–63.64, P <.00001). ANA was significantly associated with increased risk of women infertility either after the definite exclusion of individuals with autoimmune diseases (AID) or without exclusion [(OR = 1.99, 95% CI:1.29–3.06, P =.002), (OR = 2.76, 95% CI:1.56–4.88, P =.0005), respectively]. This meta‐analysis provides a comprehensive overview of the prevalence of antinuclear antibodies (ANA) in infertile women and suggests that ANA positivity increases the risk of infertility. [ABSTRACT FROM AUTHOR]

Spin caloritronic devices, as multifunctional devices, combining spintronics, and caloritronics, are essential for the sustainable development of humans. Here, a novel spin caloritronic device is presented using a diarylethene molecule photoswitch sandwiched among two semi-infinite zigzag graphene nanoribbons containing asymmetrical edge hydrogenation electrodes. We demonstrate that the temperature gradient between the right and the left electrodes can generate spin-up (SU) and spin-down (SD) currents moving in opposite orientations. Moreover, the mentioned currents possess approximately the same magnitudes, indicating a nearly nondissipative spin Seebeck effect. We also find that these currents are significantly dissimilar for the two photochromic isomers at different temperature gradients, demonstrating the excellent system's switching nature. The obtained results reveal that the light can control the thermal spin transport properties. [ABSTRACT FROM AUTHOR]

Facile fabrication of rapid, firm, and reversible underwater adhesion used on different adherets is challenging but is of primary importance for many industrial and biomedical applications. Herein, tough, stretchy, moldable, and semitransparent gels are developed for self‐contained underwater adhesives. The selected structural components, well‐defined double‐network (DN) structures, and one‐pot synthesis realize synergistic adhesion and cohesion engineering, which deliver instant, solid, reversible, and long‐term adhesives with a high underwater adhesion strength of over 0.84 MPa. The underwater adhesion strength is among the best‐performing tape‐type underwater adhesives. In order to develop new energy‐related applications for underwater adhesion, the first example of combining underwater adhesion with solar power applications is demonstrated. Taking the benefits of the direct‐contact design at the air/water interface, the click‐gel‐mounted floating photovoltaic (FPV) system significantly increases the power conversion efficiency by 20% due to the enhanced active cooling effects, surpassing several conventional photovoltaic technologies on both land and water. The click‐gel also rapidly responds to several oscillatory motions on the FPV platform. This study shines a light on the facile fabrication of DN click‐gels for underwater adhesives and provides their future perspectives in energy‐wise, low‐maintenance, and stimuli‐responsive applications. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of anti‐nuclear antibodies (ANAs) on the outcome of in vitro fertilization‐embryo transplantation (IVF‐ET) and to study the effect of ANAs in follicular fluid (FF) on embryonic development. Methods: The expression of ANAs in FF of patients treated with IVF‐ET and healthy group. The patients were divided into ANAs‐positive group and ANA‐negative group. The age, duration of infertility, body mass index (BMI), basic follicle stimulating hormone (bFSH), anti‐Mullerian hormone (AMH), number of retrieved oocytes, portion of metaphase II oocytes (MII), number of embryos in the cleavage stage, bipronuclear (2PN), number of embryos, number of high‐quality embryos and the outcome of IVF‐ET were compared between the two groups. In vitro, HTR8/SVneo trophoblast cells were cultivated and divided into ANAs‐negative group (control group) and ANAs‐positive group (ANAs‐positive FF was added to cytotrophoblasts). The ANAs titer in the serum and FF of patients who treated with IVF‐ET was detected using ELSIA method. CCK‐8 assay and flow cytometry (at 24 h and at 48 h) were used to detect the cell proliferation and apoptosis frequency of the two groups, respectively. Results: Among those who underwent IVF‐ET treatment, the number of retrieved oocytes, the number of fertilization and the portion of MII oocytes in the FF‐positive group were significantly lower than those in the FF‐negative group. Furthermore, the implantation rate and the clinical pregnancy rate were decreased, and early miscarriage rate was increased in the FF‐positive patients than those in the FF‐negative patients. In vitro, the cytotrophoblasts proliferation activity in the ANAs group was significantly lower than that in the control group. Moreover, the cytotrophoblasts apoptosis rate in the ANAs group was significantly higher than that in the control group. Conclusions: Our data suggested that ANAs in FF might become an obstacle to embryonic development through promoting trophoblast apoptosis and inhibiting trophoblast proliferation. ANAs in FF might be an unfavorable factor for the outcome of those who undergo IVF‐ET treatment. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocytes (PHH) in fatty acid-enriched media. This study compared the lipidome of PHH cultured in fatty acid-enriched media to hepatocytes from patients with NASH and healthy controls. Hepatocytes from NASH patients displayed increased total cellular abundance of glycerolipids and phospholipids compared to healthy control hepatocytes. PHH cultured in fatty acidenriched media demonstrated increased glycerolipids. However, these culture conditions did not induce elevated phospholipid levels. Thus, culturing PHH in fatty acid-enriched media has limited capacity to emulate the environment of hepatocytes in NASH patients. [ABSTRACT FROM AUTHOR]

The use of optical coherence tomography (OCT) technology in anterior segment diseases allows for precise assessment of the changes following anterior segment surgery. Advances in microscope-integrated OCT systems have allowed the utilization of intraoperative OCT (iOCT) in anterior segment surgeries, i.e., cornea, cataract, and refractive surgery. iOCT has enabled real-time precise visualization of anterior segment tissues as well as interactions between surgical instruments and ocular tissue; thus, the device can facilitate surgical procedures and provide valuable information for decision-making during anterior segment surgeries. In this review, the authors will introduce studies regarding the development of iOCT technology and its application in various anterior segment surgeries. Multiple studies have shown the efficacy of the iOCT for intraoperative assistance and guidance, suggesting the potential of the device for optimizing the surgical outcomes after cornea, cataract, and refractive surgery. [ABSTRACT FROM AUTHOR]

An optical resolution of 3‐chloromandelic acid (3‐ClMA) using threo‐(1S,2S)‐2‐amino‐l‐p‐nitrophenyl‐1,3‐propanediol ([S,S]‐SA) as a resolving agent was presented. The effects of the type of solvents, the amount of solvent, molar ratio of the resolving agent to racemate and filtration temperature on resolution were investigated. Under the optimal resolution conditions, the content of less soluble salt reached 98%, and the resolution efficiency was as high as 94%. The weak intermolecular interactions (such as hydrogen bond, halogen bond, CH/π and van der Waals interactions) and molecular packing mode in crystal structure of the less soluble salt (R)‐3‐ClMA(S,S)‐SA were investigated. A wall‐like 2‐D hydrogen‐bonding network and hydrophobic structure between hydrogen‐bonding walls were revealed. (S,S)‐SA was also used to resolve 2‐ClMA and 4‐ClMA respectively and the corresponding less soluble salts (R)‐2‐ClMA·(R,R)‐SA and (R)‐4‐ClMA·(R,R)‐SA were obtained using threo‐(1R,2R)‐2‐amino‐l‐p‐nitrophenyl‐1,3‐propanediol ((R,R)‐SA) as a resolving agent. In addition, two other resolving agents, (R)‐ɑ‐phenethylamine ((R)‐PEA) and (R)‐N‐benzyl phenethylamine ((R)‐BPA) reported in the literature for the resolution of 3‐ClMA were examined along with the newly proposed resolving agent, (S,S)‐SA. The crystal structures of the resulting less soluble salts (R)‐3‐ClMA·(S,S)‐SA, (R)‐3‐ClMA·(R)‐PEA and (R)‐3‐ClMA·(R)‐BPA were compared and examined. [ABSTRACT FROM AUTHOR]

Thrombocytes circulate in the blood of nonmammalian vertebrates and are involved in hemostasis; however, many detailed characteristics of thrombocytes remain unclear. Recently, we established an amphibian thrombocyte cell line. Here, we report the finding that thrombocytes produce integrin alpha IIb (CD41)‐positive extracellular vesicles (EVs), which include microRNAs (miRs). Flow cytometric analysis showed the expression of CD41+ and phosphatidylserine on the surface of EVs. Nanotracking analysis showed that these CD41+ EVs were approximately 100 nm in diameter. As CD41+ EVs were also observed from African clawed frogs, the production of CD41+ EVs might be common to amphibians. Microarray analysis showed that the CD41+ EVs contain many kinds of miRs. These CD41+ EVs were phagocytosed by endothelial cells and macrophages. qPCR analysis showed that many angiogenesis‐related genes were up‐regulated in CD41+ EV‐treated endothelial cells. Over‐expression of some miRs in the CD41+ EVs increased the proliferation of endothelial cells. These results indicated that thrombocytes produced CD41+ EVs, including miRs, that were received by endothelial cells to induce the expression of angiogenesis‐related genes. These results indicated that the CD41+ EVs produced from thrombocytes act as signaling molecules to repair damaged blood vessels. [ABSTRACT FROM AUTHOR]

Wearable and implantable electroceuticals (WIEs) for therapeutic electrostimulation (ES) have become indispensable medical devices in modern healthcare. In addition to functionality, device miniaturization, conformability, biocompatibility, and/or biodegradability are the main engineering targets for the development and clinical translation of WIEs. Recent innovations are mainly focused on wearable/implantable power sources, advanced conformable electrodes, and efficient ES on targeted organs and tissues. Herein, nanogenerators as a hotspot wearable/implantable energy‐harvesting technique suitable for powering WIEs are reviewed. Then, electrodes for comfortable attachment and efficient delivery of electrical signals to targeted tissue/organ are introduced and compared. A few promising application directions of ES are discussed, including heart stimulation, nerve modulation, skin regeneration, muscle activation, and assistance to other therapeutic modalities. [ABSTRACT FROM AUTHOR]

Purpose. To present applications of anterior segment optical coherent tomography (AS OCT) for anomalies of the eye in a Polish paediatric cohort. Materials and Methods. Seventy-four eyes of infants and older children were examined. The majority of them underwent general anaesthesia to allow OCT to be performed in the operating room, but a few were examined in a routine way. We focused on corneal, anterior chamber, iris, and lens disorders. Measurements included corneal morphology, anatomy of the anterior chamber, and general involvement of surrounding tissues in pathologic lesions. Results. We divided the paediatric patients into several groups by considering the type of disease and involvement of particular tissues. The groups were selected based on OCT usefulness in describing their ocular disorders. Conclusion. The collected anterior segment disorders showed huge usefulness for paediatric diagnosis and treatment planning. [ABSTRACT FROM AUTHOR]

Anticentromere antibodies (ACA) were associated with lower oocyte maturation rates and cleavage rates, while the mechanism was not clear. Aims of this study were to examine whether active immunization with centromere protein C could elicit the CENP-C autoantibody in mice and the impacts of the CENP-C autoantibody on oocyte meiosis. Mice were divided into two groups, one was the experimental group immunized with human centromere protein C and Freund's adjuvant (CFA), and the other was the control group injected with CFA only. Serum and oocytes of BALB/c mice immunized with human centromere protein C (CENP-C) in complete Freund's adjuvant (CFA) or injected with only CFA were studied for the development of the CENP-C antibody. Rates of germinal vesicle breakdown (GVBD), first polar body (Pb1) extrusion, abnormal spindle morphology, and chromosome misalignment were compared between the experimental group and the control group. The CENP-C antibody was only observed in serum and oocytes of mice immunized with the centromere protein C antigen. The first polar body (Pb1) extrusion rate was lower in the experimental group (P < 0.01). A higher percentage of spindle defects and chromosome congression failure were also detected in the experimental group (spindle defects: 64.67 ± 1.16% vs. 9.27 ± 2.28% control; chromosome misalignment: 50.80 ± 2.40% vs. 8.30 ± 1.16% control; P < 0.01 for both). Oocyte meiosis was severely impaired by the CENP-C antibody, which may be the main mechanism of adverse reproductive outcomes for ACA-positive women who have no clinical symptoms of any autoimmune diseases. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to investigate immune-related signatures and immune infiltration in melanoma. The transcriptome profiling and clinical data of melanoma were downloaded from The Cancer Genome Atlas database, and their matched normal samples were obtained from the Genotype-Tissue Expression database. After merging the genome expression data using Perl, the limma package was used for data normalization. We screened the differentially expressed genes (DEGs) and obtained immune signatures associated with melanoma by an immune-related signature list from the InnateDB database. Univariate Cox regression analysis was used to identify potential prognostic immune genes, and LASSO analysis was used to identify the hub genes. Next, based on the results of multivariate Cox regression analysis, we constructed a risk model for melanoma. We investigated the correlation between risk score and clinical characteristics and overall survival (OS) of patients. Based on the TIMER database, the association between selected immune signatures and immune cell distribution was evaluated. Next, the Wilcoxon rank-sum test was performed using CIBERSORT, which confirmed the differential distribution of immune-infiltrating cells between different risk groups. We obtained a list of 91 differentially expressed immune-related signatures. Functional enrichment analysis indicated that these immune-related DEGs participated in several areas of immune-related crosstalk, including cytokine-cytokine receptor interactions, JAK–STAT signaling pathway, chemokine signaling pathway, and Th17 cell differentiation pathway. A risk model was established based on multivariate Cox analysis results, and Kaplan-Meier analysis was performed. The Kruskal-Wallis test suggested that a high risk score indicated a poorer OS and correlated with higher American Joint Committee on Cancer-TNM (AJCC-TNM) stages and advanced pathological stages (P < 0.01). Furthermore, the association between hub immune signatures and immune cell distribution was evaluated in specific tumor samples. The Wilcoxon rank-sum test was used to estimate immune infiltration density in the two groups, and results showed that the high-risk group exhibited a lower infiltration density, and the dominant immune cells included M0 macrophages (P = 0.023) and activated mast cells (P = 0.005). [ABSTRACT FROM AUTHOR]

Background: There are limited data available regarding the use of diastolic deceleration time (DDT) of three major arteries measured by transthoracic echocardiography (TTE) for assessing coronary microvascular damage after acute myocardial infarction (AMI). Therefore, we aimed to compare the DDT of three major arteries using TTE with the transmural extent of infarction (TEI) and infarct size, which were classified using contrast‐enhanced magnetic resonance imaging (CE‐MRI), in patients with AMI. Methods: The DDT of the culprit coronary artery was measured in 74 patients using TTE and CE‐MRI 1 week after the onset of AMI. The TEI was graded based on the transmural extent of the hyper‐enhanced tissue (grades 1–4). Results: The assessable rate for the DDT was 95%; individual rates were 100% for the left anterior descending coronary artery, 90% for the left circumflex artery, and 93% for the right coronary artery. The DDT decreased gradually as the TEI grade progressed (P =.021). Infarct size was significantly correlated with the DDT (r = −0.51, P <.0001). Univariate analysis revealed that the left ventricular (LV) end‐systolic volume, LV ejection fraction, and DDT were significantly associated with TEI grade 4. After adjustment via multiple logistic regression analysis, the DDT was independently remained. With a cutoff value of 950ms, as determined by the ROC curve, DDT could detect TEI grade 4 with 81.1% sensitivity and 80.1% specificity. Conclusion: The DDT of three major coronary arteries measured by TTE 1 week after the onset of AMI can assess the extent of myocardial damage, which is determined by CE‐MRI. [ABSTRACT FROM AUTHOR]

Problem: The mechanism(s) by which antinuclear antibodies (ANA) induce implantation failure are not clear, and little information regarding the function of autoantibodies in reproductive tissues is available. Methods of Study: A total of 380 patients who underwent in vitro fertilization and embryo transfer (IVF‐ET) were divided into control, serum positive, and follicular fluid (FF) positive groups based on the results of indirect immunofluorescence assay for ANA in the serum and FF. Immunofluorescence assay was performed to evaluate the existence of ANA in granular cells and endometrial tissues. Presence in FF of soluble apoptotic markers, including Bcl‐2, Caspase‐3, cleaved PARP, Cytochrome C, GAPDH, and p53, was assessed using magnetic bead based assays. Results: The patients in the FF positive group had the lowest numbers of retrieved oocytes, fertilizations, and high‐quality embryos. The fertilization rate, and the proportion of two pronuclear (2PN) embryos in patients in the FF positive group were significantly lower than those in the other two groups. The FF positive group also had the lowest clinical pregnancy rate, and the highest early miscarriage rate. Granulosa cells and endometrial tissues in patients in the FF positive group were ANA positive. High levels of BCL‐2, Caspase‐3, Cytochrome C, GAPDH, and p53 were found in the FF of patients in the FF positive group. Conclusions: Antinuclear antibodies in FF and endometrial tissues may cause imbalanced apoptosis, resulting in poor IVF‐ET treatment outcomes. Local autoimmunity and cell apoptosis in reproductive tissues could be considered new therapeutic targets for improving IVF‐ET treatment efficacy. [ABSTRACT FROM AUTHOR]

A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate mouse model is one of the most important steps in the design of NASH studies. In addition to the histopathological and metabolic findings of NASH, a sufficient mouse model should guarantee a robust clinical status and good animal welfare. Three different NASH diets, a high-fat diet (HFD60), a western diet (WD), and a cafeteria diet (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline and before scheduled sacrifice, and liver inflammation was analyzed via fluorescence-associated cell sorting and histopathological examination. Clinical health conditions were scored weekly to assess the impact on animal welfare. The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare. Furthermore, the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3+ NK1.1+ cells. The WD represents a model of advanced-stage NASH, and the HFD60 is a strong model of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. However, the CAFD should not be considered a NASH model. [ABSTRACT FROM AUTHOR]

Hit, Lead & Candidate Discovery Antiangiogenesis therapy is a promising way for treatment of solid cancers, and many angiogenesis inhibitors that target vascular endothelial growth factor (VEGF) or its receptors have been developed. We explored novel antiangiogenic compounds other than anti‐VEGF drugs by screening our synthetic compound library and found that 6‐thiophen‐3‐yl‐2‐methoxy‐1,4‐naphthoquinone (6‐TMNQ) had potential as a novel angiogenesis inhibitor. This paper describes the effects of 6‐TMNQ on angiogenesis and tumor growth in vitro and in vivo. 6‐TMNQ inhibited serum‐, VEGF‐, and basic fibroblast growth factor (bFGF)‐stimulated proliferation of endothelial cells in a concentration‐dependent manner, but had no effect on the proliferation of fibroblasts. VEGF‐induced activation of VEGF receptor‐2 in endothelial cells was not affected by the compound. 6‐TMNQ markedly abrogated both migration and tube formation of endothelial cells. Orally administered 6‐TMNQ inhibited angiogenesis in response to VEGF or bFGF in mice in a dose‐dependent manner. Furthermore, when tumor‐bearing mice were treated with 6‐TMNQ, increase in tumor size was significantly prevented due to inhibition of angiogenesis in the tumor tissues. These results demonstrate that 6‐TMNQ is an orally available compound that selectively inhibits endothelial cell proliferation and migration, and abrogates angiogenesis, resulting in the prevention of tumor growth. The mechanism of 6‐TMNQ action is different from that of conventional anti‐VEGF drugs. [ABSTRACT FROM AUTHOR]

Aims: In vitro study showed that benidipine is exclusively metabolized by cytochrome P450 (CYP) 3A. This study evaluated the effect of rifampin on the enantioselective disposition and anti‐hypertensive effect of benidipine. Methods: Benidipine (8 mg) was administered to healthy subjects with or without repeated rifampin dosing, in a crossover design. Plasma concentrations of (S)‐(S)‐(+)‐α and (R)‐(R)‐(−)‐α isomers of benidipine and blood pressure were measured for up to 24 h after dosing. In addition, CYP3A metabolic capacity was evaluated in each subject using oral clearance of midazolam. Results: The exposure of (S)‐(S)‐(+)‐α‐benidipine was greater than that of (R)‐(R)‐(−)‐α‐benidipine by approximately three‐fold following single dose of benidipine. Repeated doses of rifampin significantly decreased the exposure of both isomers. Geometric mean ratios (GMRs) (95% CI) of Cmax and AUC∞ for (S)‐(S)‐(+)‐α‐benidipine were 0.14 (0.10–0.18) and 0.12 (0.08–0.18), respectively. GMRs (95% CI) of Cmax and AUC∞ for (R)‐(R)‐(−)‐α‐benidipine were 0.10 (0.06–0.17) and 0.10 (0.06–0.17), respectively. Oral clearances of both isomers were increased equally by approximately 10‐fold. There were no significant differences in cardiovascular effect following benidipine administration between control and rifampin treatment. CYP3A activity using midazolam did not appear to correlate with oral clearance of benidipine. Conclusions: After single administration of racemic benidipine, enantioselective disposition of (S)‐(S)‐(+)‐α‐ and (R)‐(R)‐(−)‐α‐benidipine was observed. Treatments with rifampin significantly decreased the exposure of both isomers but appeared to marginally affect its blood pressure‐lowering effect in healthy subjects. Impact of coadministration of rifampin on the treatment effects of benidipine should be assessed in hypertensive patients. [ABSTRACT FROM AUTHOR]

Over the past several decades, nanotechnology has contributed to the progress of biomedicine, biomarker discovery, and the development of highly sensitive electroanalytical / electrochemical biosensors for in vitro and in vivo monitoring, and quantification of oxidative and nitrosative stress markers like reactive oxygen species (ROS) and reactive nitrogen species (RNS). A major source of ROS and RNS is oxidative stress in cells, which can cause many human diseases, including cancer. Therefore, the detection of local concentrations of ROS (e. g. superoxide anion radical; O2•−) and RNS (e. g. nitric oxide radical; NO• and its metabolites) released from biological systems is increasingly important and needs a sophisticated detection strategy to monitor ROS and RNS in vitro and in vivo. In this review, we discuss the nanomaterials-based ROS and RNS biosensors utilizing electrochemical techniques with emphasis on their biomedical applications. [ABSTRACT FROM AUTHOR]

Problem A threefold higher prevalence of antinuclear antibodies (ANA) has been reported in patients with recurrent pregnancy loss (RPL). Nevertheless, the role of ANA in reproductive failure is still unclear. The aim of this study was to investigate the role of ANA during early pregnancy in vivo. Method of study We used pregnant mice treated with immunoglobulin G (IgG) obtained from normal healthy subjects (NHS); ANA+ sera of patients with RPL; and ANA+ sera from women with uncomplicated pregnancies (HW). Placental immunohistochemical/immunofluorescence staining was performed to detect complement and immune complex deposition. ELISA was performed to evaluate complement levels. Results ANA+ IgG from RPL women significantly increased embryo resorption rate, reduced C3, and increased C3a serum levels compared to NHS IgG or ANA+-HW IgG. Increased C3 deposition and increased immune complex staining in placental tissues from mice treated with ANA+-RPL IgG fraction compared to NHS- and ANA+-HW-IgG-treated mice were found. Conclusion ANA+ IgG injection in mice is able to induce fetal resorption and complement activation. The presence on placental tissues of immune complexes and complement fragments suggests the complement activation as a possible mechanism of placental damage. [ABSTRACT FROM AUTHOR]

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Targeting and stabilizing distinct kinase conformations is an instrumental strategy for dissecting conformation-dependent signaling of protein kinases. Herein the structure-based design, synthesis, and evaluation of pleckstrin homology (PH) domain-dependent covalent-allosteric inhibitors (CAIs) of the kinase Akt is reported. These inhibitors bind covalently to a distinct cysteine of the kinase and thereby stabilize the inactive kinase conformation. These modulators exhibit high potency and selectivity, and represent an innovative approach for chemical biology and medicinal chemistry research. [ABSTRACT FROM AUTHOR]

Problem: Several recent studies have investigated the relationship between antinuclear antibodies (ANAs) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. This meta-analysis evaluated the effect of ANA on clinical outcome for patients undergoing IVF/ICSI treatment., Method of Study: A systemic survey of the literature was performed using PubMed, EMBASE and the Cochrane Library databases, through January 2019. Evaluated outcomes included clinical pregnancy rate (CPR), miscarriage rate (MR) and implantation rate (IR). Relative risk ratio (RR) and 95% confidence intervals (95% CI) were used for dichotomous data. Meta-analyses were performed with Review Manager 5.3 software., Results: Eleven eligible studies were found. For IVF/ICSI cycles, compared with an ANA(-) group, infertile patients with ANA(+) had significantly reduced incidence of CPR (RR 0.66, 95% CI 0.56-0.79; I 2  = 60%) and IR (RR 0.61, 95% CI 0.49-0.76; I 2  = 75%), and had a higher MR (RR 1.81, 95% CI 1.40-2.36; I 2  = 48%)., Conclusion: This study suggested that ANA might cause poor pregnancy outcomes for infertile women undergoing IVF/ICSI treatment., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The article presents a case study of a 68-year-old Japanese man who was referred for evaluation of painful nodules on extremities. He was diagnosed with chronic myelogenous leukaemia (CML) and treated initially with dasatinib, but was replaced with nilotinib due to aggravating pleural effusion. His past medical history include atrial fibrillation and diabetes mellitus.