Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA) is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA-10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD). We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed

Altered neuronatin expression in the rat dorsal root ganglion after sciatic nerve transection

<p>Abstract</p> <p>Background</p> <p>Several molecular changes occur following axotomy, such as gene up-regulation and down-regulation. In our previous study using Affymetrix arrays, it was found that after the axotomy of sciatic nerve, there were many novel genes with significant expression changes. Among them, neuronatin (Nnat) was the one which expression was significantly up-regulated. Nnat was identified as a gene selectively expressed in neonatal brains and markedly reduced in adult brains. The present study investigated whether the expression of Nnat correlates with symptoms of neuropathic pain in adult rats with transected sciatic nerve.</p> <p>Methods</p> <p>Western blotting, immunohistochemistry, and the Randall and Selitto test were used to study the protein content, and subcellular localization of Nnat in correlation with pain-related animal behavior.</p> <p>Results</p> <p>It was found that after nerve injury, the expression of Nnat was increased in total protein extracts. Unmyelinated C-fiber and thinly myelinated A-δ fiber in adult dorsal root ganglions (DRGs) were the principal sub-population of primary afferent neurons with distributed Nnat. The increased expression of Nnat and its subcellular localization were related to mechanical hyperalgesia.</p> <p>Conclusions</p> <p>The results indicated that there was significant correlation between mechanical hyperalgesia in axotomy of sciatic nerve and the increased expression of Nnat in C-fiber and A-δ fiber of adult DRG neurons.</p

Observation of interlayer phonon modes in van der Waals heterostructures

We have investigated the vibrational properties of van der Waals heterostructures of monolayer transition metal dichalcogenides (TMDs), specifically MoS2/WSe2 and MoSe2/MoS2 heterobilayers as well as twisted MoS2 bilayers, by means of ultralow-frequency Raman spectroscopy. We discovered Raman features (at 30 ~ 40 cm-1) that arise from the layer-breathing mode (LBM) vibrations between the two incommensurate TMD monolayers in these structures. The LBM Raman intensity correlates strongly with the suppression of photoluminescence that arises from interlayer charge transfer. The LBM is generated only in bilayer areas with direct layer-layer contact and atomically clean interface. Its frequency also evolves systematically with the relative orientation between of the two layers. Our research demonstrates that LBM can serve as a sensitive probe to the interface environment and interlayer interactions in van der Waals materials

Sonoporation-mediated gene transfer into adult rat dorsal root ganglion cells

<p>Abstract</p> <p>Background</p> <p>Gene transfer into many cell types has been successfully used to develop alternative and adjunct approaches to conventional medical treatment. However, effective transfection of postmitotic neurons remains a challenge. The aim of this study was to develop a method for gene transfer into rat primary dorsal root ganglion neurons using sonoporation.</p> <p>Methods</p> <p>Dissociated cells from adult rat dorsal root ganglion (DRG) cells were sonicated for 1-8 s at 2.5-10 W to determine the optimal ultrasound duration and power for gene transfection and cell survival. Transfection efficiency was compared between sonoporation, liposome and lentiviral vector gene transfer techniques.</p> <p>Results</p> <p>The optimum ultrasound intensity was 5 W for 2 s and yielded an efficiency of gene transfection of 31% and a survival rate of 35%.</p> <p>Conclusions</p> <p>Sonoporation can be optimized to minimize cell death and yield a high percentage of transfected neurons and that this technique can be easily applied to primary cultures of rat dorsal root ganglion neurons.</p

Mortality associated with the use of non-vitamin K antagonist oral anticoagulants in cancer patients:Dabigatran versus rivaroxaban

Abstract Objective This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality

Association between maternal pre-delivery body mass index and offspring overweight/obesity at 1 and 2 years of age among residents of a suburb in Taiwan

Background Overweight and obesity among children can cause metabolic syndrome in adulthood and are a significant public health issue. Some studies suggest that maternal pre-pregnancy body mass index (BMI) and excessive gestational weight gain during pregnancy are associated with overweight and obesity in offspring. However, it is difficult to collect information on accurate pre-pregnancy BMI and pregnancy weight gain for women living in areas where medical resources are scarce. Maternal pre-delivery BMI might be predictive of the risk of overweight and obesity among offspring of pregnant mothers living in suburban areas. Methods We retrospectively collected data on term neonates with appropriate weights for their gestational age born between April 2013 and October 2015. We excluded neonates with major congenital anomalies or diseases and incomplete data. Mothers with systemic diseases or drug abuse were also excluded. Offspring body weights and heights at 1- and 2-years-old were recorded. Maternal pre-delivery BMI was divided into following groups: <25, 25–29.9, and ≧30 kg/m2. Results We included 261 mother-child pairs in this study. The BMIs of the offspring differed significantly among the three maternal pre-delivery BMI groups at the age of 2 years (15.18 ± 1.04, 15.83 ± 1.28, and 16.29 ± 1.61 kg/m2, p < 0.001, respectively). After adjusting for potential cofounders possibly affecting weight using multivariate linear regression, the children’s BMIs (adjusted 95% CI: 0.71 [0.31–1.11]; p = 0.001) and BMI percentiles (adjusted 95% CI 15.80 [7.32–24.28]; p < 0.001) at the age of 2 years were significantly higher in those born to mothers with pre-delivery BMIs of 25–29.9 kg/m2 compared to mothers with pre-delivery BMIs <25 kg/m2. Maternal pre-delivery BMI ≧30 kg/m2 was significantly associated with increased BMIs (adjusted 95% CI: 1.17 [0.72–1.63]; p < 0.001) and BMI percentiles (adjusted 95% CI: 23.48 [13.87–33.09]; p < 0.001) in their children. A maternal pre-delivery BMI of 27.16 kg/m2 was the optimal cut-off for predicting offspring overweight/obesity at the age of 2 years. Discussion Our results indicate that the maternal pre-delivery BMI was significantly associated with offspring BMI and weight gain at the age of 2 years. A maternal pre-delivery BMI of 27.16 kg/m2 might be a useful predictor for estimating the risk of overweight or obesity in offspring at the age of 2 years

Potential Osteoporosis Recovery by Deep Sea Water through Bone Regeneration in SAMP8 Mice

The aim of this study is to examine the therapeutic potential of deep sea water (DSW) on osteoporosis. Previously, we have established the ovariectomized senescence-accelerated mice (OVX-SAMP8) and demonstrated strong recovery of osteoporosis by stem cell and platelet-rich plasma (PRP). Deep sea water at hardness (HD) 1000 showed significant increase in proliferation of osteoblastic cell (MC3T3) by MTT assay. For in vivo animal study, bone mineral density (BMD) was strongly enhanced followed by the significantly increased trabecular numbers through micro-CT examination after a 4-month deep sea water treatment, and biochemistry analysis showed that serum alkaline phosphatase (ALP) activity was decreased. For stage-specific osteogenesis, bone marrow-derived stromal cells (BMSCs) were harvested and examined. Deep sea water-treated BMSCs showed stronger osteogenic differentiation such as BMP2, RUNX2, OPN, and OCN, and enhanced colony forming abilities, compared to the control group. Interestingly, most untreated OVX-SAMP8 mice died around 10 months; however, approximately 57% of DSW-treated groups lived up to 16.6 months, a life expectancy similar to the previously reported life expectancy for SAMR1 24 months. The results demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy as a complementary and alternative medicine (CAM)

Observation of Interlayer Phonon Modes in van der Waals Heterostructures

We have investigated the vibrational properties of van der Waals heterostructures of monolayer transition metal dichalcogenides (TMDs), specifically MoS2/WSe2 and MoSe2/MoS2 heterobilayers and twisted MoS2 bilayers, by means of ultralow-frequency Raman spectroscopy. We discovered Raman features (at 30–40 cm−1) that arise from the layer-breathing mode (LBM) vibration between the two incommensurate TMD monolayers in these structures. The LBM Raman intensity correlates strongly with the suppression of photoluminescence that arises from interlayer charge transfer. The LBM is generated only in bilayer areas with direct layer-layer contact and an atomically clean interface. Its frequency also evolves systematically with the relative orientation between the two layers. Our research demonstrates that the LBM can serve as a sensitive probe to the interface environment and interlayer interactions in van der Waals materials

The Adhesion G Protein-Coupled Receptor GPR97/ADGRG3 Is Expressed in Human Granulocytes and Triggers Antimicrobial Effector Functions

The adhesion family of G protein-coupled receptors (aGPCRs) comprises 33 members in human, several of which are distinctly expressed and functionally involved in polymorphonuclear cells (PMNs). As former work indicated the possible presence of the aGPCR GPR97 in granulocytes, we studied its cellular distribution, molecular structure, signal transduction, and biological function in PMNs. RNA sequencing and mass-spectrometry revealed abundant RNA and protein expression of ADGRG3/GPR97 in granulocyte precursors and terminally differentiated neutrophilic, eosinophilic, and basophilic granulocytes. Using a newly generated GPR97-specific monoclonal antibody, we confirmed that endogenous GPR97 is a proteolytically processed, dichotomous, N-glycosylated receptor. GPR97 was detected in tissue-infiltrating PMNs and upregulated during systemic inflammation. Antibody ligation of GPR97 increased neutrophil reactive oxygen species production and proteolytic enzyme activity, which is accompanied by an increase in mitogen-activated protein kinases and IκBα phosphorylation. In-depth analysis of the GPR97 signaling cascade revealed a possible switch from basal Gαs/cAMP-mediated signal transduction to a Gαi-induced reduction in cAMP levels upon mutation-induced activation of the receptor, in combination with an increase in downstream effectors of Gβγ, such as SRE and NF-κB. Finally, ligation of GPR97 increased the bacteria uptake and killing activity of neutrophils. We conclude that the specific presence of GPR97 regulates antimicrobial activity in human granulocytes

Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery

Introduction Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome. Methods A multicenter prospective observational study based on the NSARF ( National Taiwan University Surgical ICU Associated Renal Failure) Study Group database. 98 patients (41 female, mean age 66.4 +/- 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006. Results The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality. Conclusions The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification