Semaphorin 3C exacerbates liver fibrosis.

BACKGROUND AND AIMS: Chronic liver disease is a growing epidemic, leading to fibrosis and cirrhosis. TGF-ß is the pivotal profibrogenic cytokine that activates HSC, yet other molecules can modulate TGF-ß signaling during liver fibrosis. Expression of the axon guidance molecules semaphorins (SEMAs), which signal through plexins and neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis. This study aims at determining their function in the regulation of HSCs. APPROACH AND RESULTS: We analyzed publicly available patient databases and liver biopsies. We used transgenic mice, in which genes are deleted only in activated HSCs to perform ex vivo analysis and animal models. SEMA3C is the most enriched member of the semaphorin family in liver samples from patients with cirrhosis. Higher expression of SEMA3C in patients with NASH, alcoholic hepatitis, or HBV-induced hepatitis discriminates those with a more profibrotic transcriptomic profile. SEMA3C expression is also elevated in different mouse models of liver fibrosis and in isolated HSCs on activation. In keeping with this, deletion of SEMA3C in activated HSCs reduces myofibroblast marker expression. Conversely, SEMA3C overexpression exacerbates TGF-ß-mediated myofibroblast activation, as shown by increased SMAD2 phosphorylation and target gene expression. Among SEMA3C receptors, only NRP2 expression is maintained on activation of isolated HSCs. Interestingly, lack of NRP2 in those cells reduces myofibroblast marker expression. Finally, deletion of either SEMA3C or NRP2, specifically in activated HSCs, reduces liver fibrosis in mice. CONCLUSION: SEMA3C is a novel marker for activated HSCs that plays a fundamental role in the acquisition of the myofibroblastic phenotype and liver fibrosis.

Oxygen-Promoted on-Surface Synthesis of Polyboroxine Molecules.

We present a protocol for the on-surface synthesis of polyboroxine molecules derived from boroxine molecules precursors. This process is promoted by oxygen species present on the Au(111) surface: oxygen atoms facilitate the detachment of naphthalene units of trinaphthyl-boroxine molecules and bridge two unsaturated boroxine centers to form a boroxine-O-boroxine chemical motif. X-ray spectroscopic characterization shows that, as the synthesis process proceeds, it progressively tunes the electronic properties of the interface, thus providing a promising route to control the electron level alignment.

A Molecular Rheology Dynamics Study on 3D Printing of Liquid Crystal Elastomers.

This work presents a rheological study of a biocompatible and biodegradable liquid crystal elastomer (LCE) ink for three dimensional (3D) printing. These materials have shown that their structural variations have an effect on morphology, mechanical properties, alignment, and their impact on cell response. Within the last decade LCEs are extensively studied as potential printing materials for soft robotics applications, due to the actuation properties that are produced when liquid crystal (LC) moieties are induced through external stimuli. This report utilizes experiments and coarse-grained molecular dynamics to study the macroscopic rheology of LCEs in nonlinear shear flow. Results from the shear flow simulations are in line with the outcomes of these experimental investigations. This work believes the insights from these results can be used to design and print new material with desirable properties necessary for targeted applications.

The investigation of hippo signaling pathway in mouse uterus during peri-implantation period.

PURPOSE: Events in the uterus during the peri-implantation period include embryo development, acquisition of uterine receptivity, implantation and decidualization. Hippo signaling pathway regulates cell proliferation, apoptosis and differentiation. We aimed to determine localization and expressions of pYAP (Phospho Yes-associated protein), YAP (Yes-associated protein), TEAD1 (TEA domain family member 1) and CTGF (Connective tissue growth factor), members of the Hippo signaling pathway, in the mouse uterus during the peri-implantation period. METHODS: Pregnant mice were randomly separated into 5 groups: 1st, 4th, 5th, 6th, and 8th days of pregnancy groups. Non-pregnant female mice in estrous phase were included in the estrous group. Uteri and implantation sites were collected. Also, inter-implantation sites were collected from the 5th day of pregnancy group. pYAP, YAP, TEAD-1 and CTGF were detected by immunohistochemistry and Western blotting. RESULTS: We observed that the expressions of YAP, TEAD-1 and CTGF were increased in the luminal and glandular epithelium on the 1st and 4th days of pregnancy when epithelial proliferation occurred. pYAP expression was high, and YAP and CTGF expressions were low in the luminal epithelium of the implantation sites on the 5th day of pregnancy, when epithelial differentiation occurred. pYAP expression was low, YAP and CTGF expressions were high at implantation sites on the 6th and 8th days of pregnancy, where decidua was formed. CONCLUSION: Our findings suggest that the Hippo signaling pathway might be involved in implantation and decidualization. Our findings will guide further studies and may help to elucidate underlying causes of implantation failure and pregnancy loss.

The Effect of Preoperative Fear of Pain on Postoperative Pain Levels and the Amount of Analgesic Consumption.

BACKGROUND: Preoperative fear of pain can increase the surgical stress response along with anxiety, increasing postoperative pain and the amount of analgesia consumption. AIMS: To determine the effect of preoperative fear of pain on postoperative pain level and analgesic consumption. DESIGN: A descriptive, cross-sectional design was used. METHODS: A total of 532 patients who were scheduled for a variety of surgical procedures in a tertiary hospital were included in the study. Data were collected using Patient Identification Information Form and Fear of Pain Questionnaire-III. RESULTS: 86.1% of the patients thought that they would experience postoperative pain, and 70% of the patients reported moderate-to-severe postoperative pain. The examination of the postoperative first 24-hour pain levels indicated that there was a significant positive correlation between patients' pain levels within 0-2 hours and their mean scores on the fear of severe and minor pain sub-dimensions and the total scale and between pain experienced within 3-8 hours and their scores on the fear of severe pain sub-dimension (p <.05). Also, a significant positive correlation was found between patients' mean scores on the total fear of pain scale and the amount of nonopioid (diclofenac sodium) consumption (p <0.05). CONCLUSIONS: The fear of pain increased patients' postoperative pain levels, and thus the amount of analgesic consumption. Therefore, patients' fear of pain should be determined in the preoperative period, and pain management practices should be initiated in this period. As a matter of fact, effective pain management will positively affect patient outcomes by reducing the amount of analgesic consumption.

Application of diffuse optical back reflection spectroscopy for determining articular cartilage thickness in a clinical setting.

PURPOSE: Develop a spectroscopic method to assess cartilage thickness during the arthroscopic examination. METHODS: Currently, arthroscopy assesses cartilage damage visually; outcomes are based on the surgeon's subjective experience. Light reflection spectroscopy is a promising method for measuring cartilage thickness based on the absorption of light by the subchondral bone. In the presented study, in vivo diffuse optical back reflection spectroscopic measurements were acquired by gently placing an optical fibre probe on different locations of the articular cartilage of 50 patients during complete knee replacement surgery. The optical fibre probe consists of two optical fibers with a diameter of 1 mm to deliver the light and detect back-reflected light from the cartilage. Centre to centre distance between the source and the detector fibers was 2.4 mm. Actual thicknesses of the articular cartilage samples were measured under microscopy using histopathological staining. RESULTS: Using half of the samples in the patient data, a linear regression model was formed to estimate cartilage thicknesses from the spectroscopic measurements. The regression model was then used to predict the cartilage thickness in the second half of the data. The cartilage thickness was predicted with a mean error of 8.7% if the actual thickness was less than 2.5 mm (R2 = 0.97). CONCLUSION: The outer diameter of the optical fibre probe was 3 mm, which can fit into the arthroscopy channel and can be used to measure the cartilage thickness in real-time during the arthroscopic examination of the articular cartilage.

Effect of Surface Pt Doping on the Reactivity of Au(111) Surfaces towards Methanol Dehydrogenation: A First-Principles Density Functional Theory Investigation.

The surprisingly high catalytic activity of gold has been known to the heterogeneous catalysis community since the mid-1980s. Significant efforts have been directed towards improving the reactivity of these surfaces towards important industrial reactions. One such strategy is the introduction of small amounts of other metals to create Au-based surface alloys. In this work, we investigated the synergistic effect of the Pt doping of a Au(111) surface on decreasing the activation barrier of the methanol dehydrogenation elementary step within first-principles density functional theory. To this end, we constructed several models of Pt-doped Au(111) surfaces, including a full Pt overlayer and monolayer. The effect of Pt surface doping was then investigated via the computation of the adsorption energies of the various chemical species involved in the catalytic step and the estimation of the activation barriers of methanol dehydrogenation. Both the electronic and strain effects induced by Pt surface doping substantially lowered the activation energy barrier of this important elementary reaction step. Moreover, in the presence of preadsorbed atomic oxygen, Pt surface doping could be used to reduce the activation energy for methanol dehydrogenation to as low as 0.1 eV.

Comparing the predictive values of procalcitonin/albumin ratio and other inflammatory markers in determining COVID-19 severity.

Objective: To examine the relationship between COVID-19 severity and procalcitonin/albumin ratio (PAR) and compare the PAR with oft-reported inflammatory markers, including procalcitonin, white blood cell (WBC), neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP). Methods: In this retrospective research study conducted at Sanliurfa Training and Research Hospital during May to September 2020; total, 577 adult subjects diagnosed with COVID-19 were included and categorized into two groups based on place of hospitalization: the intensive care unit (ICU) group (n=151) and the general ward (GW) group (n=426). Laboratory test results and demographic characteristics of the subjects were recorded. Results: PAR, NLR, CRP, WBC, neutrophil and procalcitonin values were markedly higher in the ICU group than in the GW group. On the contrary, lymphocyte count and albumin level were markedly lower. PAR showed positive correlations with WBC, NLR, and CRP. Multivariate analysis showed that advanced age, presence of hypertension, elevated PAR, WBC, NLR, urea and lactate dehydrogenase levels were independent risk factors associated with the need for intensive care in COVID-19 subjects. Among them, the PAR showed the highest odds ratio (5.564) for ICU admission. Additionally, the area under the ROC curve of the PAR (0.888) was markedly greater than that of WBC (0.777), NLR (0.822), CRP (0.842) and procalcitonin (0.870). Conclusions: This study revealed that PAR was superior to procalcitonin, WBC, NLR and CRP in determining COVID-19 severity. PAR was an important predictor of ICU requirement in COVID-19 cases.

The IKK-related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists.

The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogene-induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through site-specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGF-receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i.e., TLR3; TLR4), revealing a stimulus-selective role for TBK1 in mTORC1 regulation. By studying cultured macrophages and those isolated from genome edited mTOR S2159A knock-in mice, we show that mTOR S2159 phosphorylation promotes mTORC1 signaling, IRF3 nuclear translocation, and IFN-ß production. These data demonstrate a direct mechanistic link between TBK1 and mTORC1 function as well as physiologic significance of the TBK1-mTORC1 axis in control of innate immune function. These data unveil TBK1 as a direct mTORC1 activator and suggest unanticipated roles for mTORC1 downstream of TBK1 in control of innate immunity, tumorigenesis, and disorders linked to chronic inflammation.

TSC22D4 promotes TGFß1-induced activation of hepatic stellate cells.

Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and liver fibrosis emerge as progressive liver diseases that accompany metabolic syndrome usually characterized by obesity, insulin resistance and type 2 diabetes. Currently no FDA approved treatments exist for the treatment of NASH and liver fibrosis, which requires a better knowledge of the underlying molecular mechanisms. TSC22D4 belongs to the TSC-22 protein family, the members of which are regulated by inflammatory and stress signals. Interestingly, patients with type 2 diabetes, with NAFLD as well as with NASH all have elevated levels of hepatic TSC22D4 expression. Previous studies with targeted deletion of TSC22D4 specifically in hepatocytes showed that TSC22D4 not only acts as a critical controller of diabetic hyperglycemia, but also contributes to NAFLD/NASH progression. To gain better insight into the development of progressive liver diseases, here we studied the function of TSC22D4 in hepatic stellate cells (HSCs), which play a key role in the pathogenesis of liver fibrosis. Our results indicated that TSC22D4 contributes to TGFß1-mediated activation of HSCs and promotes their proliferation and migration. RNA-Sequencing analysis revealed that TSC22D4 initiates transcriptional events associated with HSC activation. Overall, our findings establish TSC22D4 as a key hub in the development of liver fibrosis, acting across different cellular compartments. Combinatorial TSC22D4 targeting in both hepatocytes and HSC may thus show superior efficacy against progressive liver disease.

Altered expression of Notch signaling, Tlr receptors, and surfactant protein expression after prostaglandin inhibition may be associated with the delayed labor in LPS-induced mice.

PURPOSE: This study aims to investigate whether indomethacin (IND) delays preterm birth by regulating the Notch pathway, Tlr receptors, and Sp-A in the placenta in lipopolysaccharide (LPS)-induced preterm labor (PTL) model. METHODS: CD-1 mice were distributed to the pregnant control (PC), Sham, PBS, IND (2 mg/kg; i.p.), LPS (25 µg/100 µl; intrauterine), and LPS + IND groups. The injections were performed on day 14.5 of pregnancy. Placentae were collected on day 15.5 of pregnancy, and immunohistochemical analyzes were performed. Differences in staining intensities between the Cox-1, Notch-1 (N1), Dll-1, Jagged-2 (Jag-2), Tlr-2, and Tlr-4 proteins were compared. RESULTS: Preterm labor rates were 100% and 66% (preterm delivery delayed 5 h) in the LPS and LPS + IND groups, respectively. In LPS-treated mice, a general morphological deterioration was observed in the placenta. Total placental mid-sagittal measurement was significantly reduced in the LPS-treated group, while it was similar to the PC group in the LPS + IND group. Cox-1 expression in the LZ increased, and Sp-A expression decreased after LPS injection, and IND administration diminished this increase. N1 expression increased in the labyrinth zone (LZ) and the junctional zone (JZ). Dll-1 and Jag-2 expression increased in the JZ after LPS injection (p < 0.0001). IND administration diminished Tlr-2 expression in the LZ and Tlr-4 expression in the JZ after LPS injection. CONCLUSION: In conclusion, PG (prostaglandin) inhibition may alter Notch signaling, Tlr, and Sp-A protein expression and may be associated with delayed labor in LPS-induced mice.

The effectiveness of scaling and root planing with combined application of air polishing and Nd:YAG laser in periodontal pockets of stage III grade C periodontitis patients: a single-blinded randomized clinical trial.

OBJECTIVES: Evaluating the efficiency of combined air polishing and Nd:YAG laser application in addition to scaling and root planning (SRP) in treatment of periodontal pockets of stage III grade C periodontitis patients was the aim of this clinical trial. MATERIALS AND METHODS: Twenty-four systemically healthy, stage III grade C periodontitis patients were recruited for this clinical trial. In this split-mouth study, the quadrants were randomly allocated to either SRP with combined air polishing (erythritol/chlorhexidine powder) and Nd:YAG laser (2 W, 200 mJ/pulse, 10 Hz) therapy (test group) or SRP alone (control group). A masked examiner recorded clinical parameters such as plaque index (PI), gingival index (GI), bleeding on probing (%) (BOP %), probing depth (PD), and clinical attachment level (CAL) on periodontal charts at baseline, 1 month and 3 months after treatment. RESULTS: The clinical parameters had significantly reduced 1 and 3 months after treatment compared to baseline for both study groups (p < 0.05). Considering PI, GI, and BOP (%) parameters, there were no significant differences between the study groups at any time points (p > 0.05). While PD and CAL reductions were similar in study groups for moderately deep pockets (5 to 6 mm) (p > 0.05), PD and CAL reductions were significantly greater in test group compared to control group for deep pockets (PD ≥ 7 mm) (p < 0.05). CONCLUSIONS: The present clinical trial demonstrated that SRP with combined application of air polishing and Nd:YAG laser may be advantageous in sites where mechanical debridement alone cannot access, such as deep pockets in the short term. Long-term, well-designed future studies including clinical, biochemical, and microbiological analyses are needed to determine the effectiveness of this procedure. CLINICAL RELEVANCE: SRP with combined application of air polishing and Nd:YAG laser provided more reductions in probing depth and clinical attachment level parameters in deep pockets compared to SRP alone.

Evaluation of Fear of Pain Among Surgical Patients in the Preoperative Period.

PURPOSE: To evaluate the fear of surgery-related pain of patients in the preoperative period. DESIGN: A descriptive, cross-sectional study. METHODS: A total of 419 patients who were scheduled for a variety of surgical procedures in a tertiary hospital were included. Data were collected using a Patient Identification Information Form and fear of pain was evaluated using the Fear of Pain Questionnaire-III. FINDINGS: 50.8% of the patients were males with a mean age of 49.2 ± 17.3 years. A total of 88.8% patients had a fear of pain after surgery, and 89.3% of them had a moderate to severe fear of pain. 84.5% of female patients, 82.5% of literate patients, and 86.1% of patients who had previously experienced severe pain had a fear of pain of moderate to severe intensity (P < .05). The mean Fear of Pain Questionnaire-III score was 75.1 ± 20.2, and the most commonly identified fears were severe pain (30.64 ± 9.5), and medical pain (24.17 ± 7.7). Patients who had a higher score of fear of severe pain and medical pain were those who had experienced severe pain previously and those who believed that they would experience postoperative pain (P < .05). CONCLUSIONS: Almost all patients included in this study had a fear of moderate to severe postoperative pain while in the preoperative period. Nurses should question pain history with each patient, obtain a detailed pain history, and identify the degree of fear of pain in the preoperative period. Fear of pain should be reduced using necessary interventions and pain control should be maintained. Reduced fear of pain in the preoperative period may decrease postoperative pain and yield favorable patient outcomes.

Evaluation of angiogenic apelin/apelin receptor axis in normal prostate, high grade prostatic intraepithelial neoplasia and prostatic adenocarcinoma.

INTRODUCTION AND OBJECTIVES: Prostate cancer is one of the most commonly diagnosed cancers in American men. Apelin is an endogenous peptide identified as the ligand of the G protein-associated apelin receptor. Apelin and apelin receptor have many tissues distribution and they participate in pathological processes, such as cancer. Apelin stimulates cancer angiogenesis. However, there are insufficient data in the literature regarding the role of apelin/apelin receptor in normal tissue, highgrade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma tissues. Therefore, this study aimed to investigate the apelin and apelin receptor expression levels in tissues of normal prostate tissue, high-grade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. MATERIALS AND METHODS: In this study, 38 samples of patients undergoing radical prostatectomy were used. Among 38 samples; 20 patients were with prostatic adenocarcinoma, 18 patients were with high-grade prostatic intraepithelial neoplasia and adjacent normal prostatic tissue areas. The immunolocalisation of apelin and apelin receptor in these tissues were determined immunohistochemically. RESULTS: Apelin and apelin receptor expressions were higher in prostatic adenocarcinoma than normal prostate tissue and high-grade prostatic intraepithelial neoplasia. Apelin receptor expression was also increased in high-grade prostatic intraepithelial neoplasia compared to normal tissue. CONCLUSION: Apelin and apelin receptor are increase in the process of prostate carcinogenesis. This increase may adversely affect the clinical course of prostate cancer patients by stimulating angiogenesis, which is important for invasion and metastasis in prostate cancer.

Antiandrogen abiraterone and docetaxel treatments affect Notch1, Jagged1 and Hes1 expressions in metastatic prostate cancer cells.

BACKGROUND: Prostate cancer is the most common cancer in men. A Notch signaling pathway is an important pathway in cell proliferation, differentiation, and fate. However, currently, the effects of abiraterone based-anti-androgene therapy and docetaxel, the most commonly used standard chemotherapy in prostate cancer treatment, on Notch signaling pathway are unknown. This study aimed to investigate the effects of abiraterone acetate and docetaxel on the expression of Notch1, Jagged1 and Hes1 in prostate cancer cell lines. METHODS: In vitro effects of abiraterone acetate and docetaxel were examined on Notch1, Jagged1, and Hes1 expression in LNCaP and PC3 PCa cell lines by immunofluorescence, Western blot, and qRT-PCR. MTT proliferation assay was used to evaluate cell proliferation and survival. RESULTS: We found that in the treatment of PC3 cells with abiraterone acetate, docetaxel, and their combination, only mRNA expressions of Notch1, Jagged1 and Hes1 were affected compared to control, but these expression differences were not observed in protein expression. In LNCaP cells, abiraterone acetate and the combination groups reduced Notch1 protein expression. All treatment groups did not alter Jagged1 expression compared to control, but significantly increased the Hes1 gene and protein expression. CONCLUSION: Our findings suggest that abiraterone and docetaxel treatments affects the expression of Notch signal pathway proteins. But these drugs especially cause significant upregulation in Hes1 expression in PCa cells. Therefore, co-application of Notch signaling inhibitors together with docetaxel and abiraterone chemotherapy, it was thought that decreased Hes1 expression could be stopped the deterioration of the prognosis of the patient.

The investigation of the role of sirtuin-1 on embryo implantation in oxidative stress-induced mice.

PURPOSE: Implantation is essential for a successful pregnancy. Despite the increasing number of studies, implantation is still an unknown process. This study aimed to determine whether sirtuin-1 has a role in embryo implantation in oxidative stress-induced mice. METHODS: Pregnant mice were separated into 5 groups: control, vehicle, paraquat, SRT1720, and SRT1720+Paraquat. Paraquat is a herbicide and is used to induce oxidative stress. SRT1720 is a specific sirtuin-1 activator. Implantation and inter-implantation sites were removed in the morning of the 5th day of pregnancy after Chicago blue injection was performed. Sirtuin-1 and Forkhead box O1 (FoxO1) were detected by immunohistochemistry and Western blot while acetylated lysine was evaluated by Western blot analysis. Reactive oxygen and nitrogen species (ROS/RNS) and superoxide dismutase (SOD) activity were determined by fluorometric and spectrometric methods, respectively. RESULTS: Although there was no embryo implantation in paraquat-treated mice, 5 out of 9 SRT1720+Paraquat-treated mice had implantation sites which were significantly higher compared to the paraquat-treated group. Sirtuin-1 and FoxO1 expressions were increased at implantation sites of SRT1720-treated mice. ROS/RNS levels were decreased, while deacetylated FoxO1 levels and SOD activity were increased in SRT1720-treated mice. CONCLUSION: Our findings suggest that sirtuin-1 may play a role in embryo implantation against oxidative stress through FoxO1-SOD signaling.

The effects of iloprost and beta3 receptor agonist on TRPA1 and TRPC1 immunreactivity in an experimental lower extremty ischemia-reperfusion injury model.

BACKGROUND: In this study, we aimed to investigate the effects of antioxidant iloprost (ILO) and ß3 adrenergic receptor agonist (BRL) on transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential canonical 1 (TRPC1) ion channels on an experimental ischemia and reperfusion injury model in 30 male Wistar albino rats aged 8-10 weeks. METHODS: Wistar Albino rats aged were divided into 5 equal groups. Group I Sham operation, Group II IR (ischemiareperfusion) procedure, Group III IR + intravenous ILO administration, Group IV IR + intraperitoneal BRL administration, and Group V IR + intravenous ILO + intraperitoneal BRL administration group. Two ng/kg/min ILO intravenous infusion was applied to the ILO group. A single dose of 5 mcg/kg BRL intraperitoneal was applied to BRL group. TOS (total oxidant status), TRPA1, and TRPC1 levels were measured with ELISA (enzyme linked immunosorbent assay) in serum, immunohistochemical staining in musculus quadriceps femoris tissue. RESULTS: Compared with the sham group, the IR group had a statistically significant increase in serum levels of TOS (p = 0.004), TRPA1 (p = 0.002), and TRPC1 (p = 0.008) along with TRPA1- and TRPC1-immunoreactivity (p = 0.005, each) in the tissue. When compared with the IR group in terms of serum levels of TRPA1 and tissue TRPA1-immunoreactivity, although there was no statistically significant difference in the IR+Ilo (p = 0.257 and p = 0.429, respectively), IR+Brl (p = 0.024 and p = 0.177, respectively), and IR+Ilo+Brl (p = 0.024 and p = 0.329, respectively) groups, serum levels of TOS and TRPC1 along with tissue TRPC1-immunoreactivity were statistically significantly reduced in the IR+Ilo (p = 0.002, p = 0.008, and p = 0.004, respectively), IR+Brl (p = 0.004, p = 0.008, and p = 0.004, respectively), and IR+Ilo+Brl groups (p = 0.002, p = 0.008, and p = 0.004, respectively). DISCUSSION: In IR group serum TOS, TRPA1 and TRPC1 levels ,and tissue TRPA1 and TRPC1 immunoreactivity were statistically significant increase when compared to the sham group. In IR+ILO, IR+BRL and IR+ILO+BRL groups serum TRPA1 and tissue TRPA1 immunoreactivity did not change when compared to IR group. Serum TOS and TRPC1 levels, tissue TRPC1 immunoreactivty were statistically significant decreased when compared to IR group. More detailed and expanded population studies are needed to discuss our results.

3D Porous Liquid Crystal Elastomer Foams Supporting Long-term Neuronal Cultures.

3D liquid crystal elastomer (3D-LCE) foams are used to support long-term neuronal cultures for over 60 days. Sequential imaging shows that cell density remains relatively constant throughout the culture period while the number of cells per observational area increases. In a subset of samples, retinoic acid is used to stimulate extensive neuritic outgrowth and maturation of proliferated neurons within the LCEs, inducing a threefold increase in length with cells displaying morphologies indicative of mature neurons. Designed LCEs' micro-channels have a similar diameter to endogenous parenchymal arterioles, ensuring that neurons throughout the construct have constant access to growth media during extended experiments. Here it is shown that 3D-LCEs provide a unique environment and simple method to longitudinally study spatial neuronal function, not possible in conventional culture environments, with simplistic integration into existing methodological pipelines.

The effect of apelin-13 on gastric ischemia/reperfusion injury: the roles of sensory nerves and vagus nerve.

Apelin is a peptide that plays a role in physiological processes such as angiogenesis, apoptosis, and proliferation. The aim of this study was to investigate the role of capsaicin-sensitive afferent neurons and vagus in the effect of apelin against ischemia/reperfusion (I/R) injury. The experimental groups were (1) control, (2) I/R, (3) apelin + I/R, (4) vagotomy + I/R, (5) vagotomy + apelin + I/R, (6) capsaicin + I/R, (7) capsaicin + apelin + I/R, (8) lorglumide + I/R, and (9) lorglumide + apelin + I/R. To test the potential gastroprotective effect of apelin-13, apelin-13 (2 mg/kg i.v.) was administered just before both ischemia and reperfusion. A vagotomy was performed 1 week before I/R in the vagotomized groups; capsaicin (125 mg/kg s.c.) was administrated 2 weeks before I/R in the capsaicin-treated groups and lorglumide (5 mg/kg i.p.) was administered 30 min before I/R in the lorglumide-treated groups. After I/R, a variety parameters in gastric tissue were analyzed. cfos expression was determined in brainstem samples. In the I/R group, the lesion index, myeloperoxidase activity, lipid peroxidation, nitric oxide, and tumor necrosis factor-α increased, and mucosal blood flow, prostaglandin-E2, and calcitonin gene related peptide decreased. Apelin prevented the damaging effects of I/R and increased cfos expression in brainstem areas. Vagotomy, capsaicin, and lorglumide largely eliminated the gastroprotective effects of apelin-13. This study showed that sensory nerves and the vagus play regulatory roles in apelin-induced gastroprotection. Cholecystokinin may play a role in the effect of apelin through sensory neurons.

The effect of GnRH antagonist cetrorelix on Wnt signaling members in pubertal and adult mouse ovaries.

Wide application of gonadotropin-releasing hormone (GnRH) agonists and antagonists for clinical purposes determines their effects on ovarian signaling pathways. Our study aimed to determine the localization, expression levels of Wnt signaling members in the pubertal and adult mouse ovary and the impact of GnRH antagonist cetrorelix on these signaling members. 0.5 mg/kg of cetrorelix was injected to 3-and 6-week-old mice for 2 weeks. At the end of injection, ovaries from 5 (5Ce)- to 8-week (8Ce)-old mice were embedded in paraffin for immunohistochemistry and homogenized for western blot to compare with control (5C-8C) and sham groups (5S-8S). WNT2 and WNT4 showed higher expression in thecal and stromal cells in adult mouse ovaries and only WNT4 expression was affected by cetrorelix. FZD1 was localized mainly in oocytes of pubertal ovaries and granulosa cells and oocytes of adult ovaries. FZD1 was reduced by cetrorelix in pubertal ovaries. FZD4 was abundantly localized in thecal and stromal cells of all groups and protein level was not affected by cetrorelix. LRP-6 was expressed mainly in oocytes and stromal cells of pubertal, oocytes of adult ovaries and its expression was reduced by cetrorelix in adult ovaries. CTNNB1 intensity in granulosa cells was the lowest in pubertal and the highest in adult ovaries and its expression was decreased by cetrorelix in adult ovaries. Cetrorelix affected the expression of specific members of the Wnt signaling depending on the developmental stage of mice, pointing out its possible interaction with gonadotropins during pubertal and adult stages.