Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteoprotective Effect of Radix Scutellariae in Female Hindlimb-Suspended Sprague-Dawley Rats and the Osteogenic Differentiation Effect of Its Major Constituent

A number of medicinal herbs have demonstrated therapeutic effects for the prevention and treatment of disuse-induced osteoporosis. As a common ingredient in proprietary traditional Chinese medicines, the anti-osteoporosis effects of Radix Scutellariae extract (RSE, 50 mg/kg/day) were evaluated in a hindlimb suspended rat model. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the micro-architecture observed by MicroCT assay with bone biomechanical properties evaluated by a three-point bending test. To elucidate potential mechanisms, the osteogenic differentiation effect of baicalin as the most abundant ingredient in RSE was investigated in rat bone marrow derived mesenchymal stem cells (rBMSC). After drug administration for 42 days, tibia-BMD was significantly increased to 0.176 ± 0.007 and 0.183 ± 0.011 g/cm2 and f-BMD was enhanced to 0.200 ± 0.017 and 0.207 ± 0.021 g/cm2 for RSE and ALE treatment, respectively, whereas tibia-BMD and femur-BMD of the HLS group were 0.157 ± 0.009 and 0.176 ± 0.008 g/cm2. Deterioration of bone trabecula microstructure was improved by RSE and ALE with increased morphological parameters such as bone volume fraction, trabecular thickness, and trabecular number, as well as connectivity density compared to the HLS group (p < 0.01). A three-point bending test suggested that bone mechanical strength was also enhanced by RSE and ALE treatments with increased maximum stress, young’s modulus, maximum load, and stiffness compared to those of the HLS group (p < 0.05). Besides, serum TRACP levels were significantly suppressed by RSE and ALE treatments. Furthermore, in vitro studies demonstrated that baicalin significantly increased ALP activities and the formation of mineralized nodules in rBMSC. Conclusively, supplementation of RSE could significantly prevent weightlessness induced osteoporosis, which might attribute to the osteogenic differentiation enhancement effect of baicalin.
Cardiovascular actions of ET-B activation in vivo and modulation by receptor antagonism.

The endothelin (ET)-B receptor subtype is expressed on vascular endothelial and smooth muscle cells and participates in vasodilatation and vasoconstriction. Controversy exists regarding the role of the ET-B receptor as a mediator of systemic, pulmonary, and renal vasoconstriction in states of marked ET-1 activation. Moreover, the potential activation of endogenous ET-1 with secondary stimulation of the ET-A receptor in response to sarafotoxin S6c (S6c) remains unclear. This study was designed to assess the cardiovascular actions of ET-B activation with S6c in the presence and absence of selective ET-A antagonism with FR-139317 and dual ET-A/ET-B antagonism with SB-209670 in the anesthetized dog. Compared with time control ( n = 5), S6c increased from baseline systemic vascular resistance (SVR) [28 ± 7 vs. 14 ± 3 resistance units (RU), P < 0.05] and pulmonary vascular resistance (PVR) (3.2 ± 0.7 vs. 0.9 ± 0.3 RU, P < 0.05) and decreased cardiac output (CO) (-1.7 ± 0.3 vs. -0.5 ± 0.1 l/min, P < 0.05), with no differences in renal vascular resistance in association with increases in plasma ET-1. S6c also decreased mixed venous oxygen saturation ([Formula: see text]) (56 ± 6 vs. 76 ± 5%, P < 0.05). Selective ET-A receptor antagonism did not affect the actions of S6c, with the exception that ET-A receptor antagonism blocked the increase in SVR to high-dose S6c. Dual ET-A/ET-B receptor antagonism attenuated the increase from baseline in SVR (7 ± 1 vs. 28 ± 7 RU, P < 0.05) and PVR (0.7 ± 0.2 vs. 3.2 ± 0.7 RU, P < 0.05) and decrease from baseline in CO (-0.9 ± 0.1 vs. -1.7 ± 0.3 l/min, P < 0.05) and[Formula: see text] (-7 ± 3 vs. -20 ± 3%, P < 0.05) observed with S6c alone. In summary, this study demonstrates an important role of ET-B receptor activation in vivo, which results in increases in plasma ET-1 and systemic and pulmonary vasoconstriction and reductions in CO and [Formula: see text]. This study also supports a modest role for the ET-A receptor in mediating the systemic vasoconstrictor response to high-dose S6c.
High expression of hnRNPA1 promotes cell invasion by inducing EMT in gastric cancer

Advanced gastric cancer (GC) has a poor prognosis and its treatment strategies are not very efficient. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has emerged as a plausible GC marker, however the role and molecular mechanism of hnRNPA1 in cell invasion and migration remains unknown. In the present study, the gene expression across normal and tumor tissue (GENT) database was used to evaluate the mRNA expression of hnRNPA1 in various types of cancer. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to detect the protein expression of hnRNPA1 in GC tissues and adjacent non-tumor tissues. The expression of multiple oncogenes was detected by western blot analysis and quantitative RT-PCR in hnRNPA1 overexpressing GC cells. Soft agar colony formation, EdU incorporation, wound healing and invasion assays were applied to verify the role of hnRNPA1 in anchorage-independent cell growth, migration and invasion in GC cells. Epithelial-to-mesenchymal transition (EMT) markers were detected by immunofluorescence, western blot analysis and IHC in vitro. A nude mice model of metastasis carcinoma was established to confirm the role of hnRNPA1 during EMT in vivo. Our results revealed that hnRNPA1 was significantly upregulated in GC tissue. HnRNPA1 overexpression significantly induced cell growth, migration and invasion ability in GC cells. In addition, hnRNPA1 promoted EMT of GC cells in vitro and in vivo. These findings indicated that hnRNPA1 is highly expressed in GC and promoted invasion by inducing EMT transition in GC cells. Thus, hnRNPA1 may be a potential therapeutic target for GC.
Calcium requirements: new estimations for men and women by cross-sectional statistical analyses of calcium balance data from metabolic studies.

BACKGROUND Low intakes of calcium are associated with an increased risk of both osteoporosis and cardiovascular disease. OBJECTIVE To provide new estimates of the average calcium requirement for men and women, we determined the dietary calcium intake required to maintain neutral calcium balance. DESIGN Calcium balance data [calcium intake -(fecal calcium + urinary calcium)] were collected from 155 subjects [women: n = 73; weight: 77.1 +/- 18.5 kg; age: 47.0 +/- 18.5 y (range: 20-75 y); men: n = 82; weight: 76.6 +/- 12.5 kg; age: 28.2 +/- 7.7 y (range: 19-64 y)] who participated in 19 feeding studies conducted in a metabolic unit. Balance data from the final 6-12 d of each dietary period (minimum length:18 d) of each study (1-9 observations per subject) were analyzed. Data were excluded if individual intakes of magnesium, copper, iron, phosphorus, or zinc fell below the estimated average requirements or exceeded the 99 th percentile of usual intakes from the 1994 Continuing Survey of Food Intakes by Individuals (for iron, above the upper limit). Daily intakes of calcium ranged between 415 and 1740 mg. The relation between intake and output was examined by fitting random coefficient models. Coefficients were included to test for sex and age differences. RESULTS The models predicted a neutral calcium balance [defined as calcium output (Y) equal to calcium intake (C)] at intakes of 741 mg/d [95% prediction interval (PI): 507, 1035; Y = 148.29 + 0.80C], 9.4 mg kg body wt(-1) d(-1) [95% PI: 6.4, 12.9; Y = 1.44 + 0.85C], or 0.28 mg kcal(-1) d(-1) [95% PI: 0.19, 0.38; Y = 0.051 + 0.816C]. Neither age nor sex affected the estimates when calcium intakes were expressed as mg/d or as mg kg body wt(-1) d(-1). CONCLUSION The findings suggest that the calcium requirement for men and women is lower than previously estimated.
Comparison of the effects of zinc delivered in a fortified food or a liquid supplement on the growth, morbidity, and plasma zinc concentrations of young Peruvian children.

BACKGROUND Zinc supplementation decreases morbidity from infections and increases growth of stunted children, but there is little information on functional responses to zinc delivered in fortified foods. OBJECTIVE The aim was to examine the effects of zinc fortification on the growth, morbidity from infections, and plasma zinc concentrations of young children. DESIGN We compared the physical growth, morbidity, and micronutrient status of 6-8-mo-old Peruvian children with initial length-for-age z score (LAZ) < -0.50 who were randomly assigned to receive one of the following treatments daily for 6 mo: 1) 30 g dry weight of an iron-fortified cereal porridge and a separate dose of an aqueous multivitamin (MV) supplement between meals (control group), 2) the same porridge and MV with 3 mg Zn added to the supplement dose (ZnSuppl group), or 3) the porridge with added zinc (150 mg/kg dry weight) and MV without zinc (ZnFort group). RESULTS The children consumed a mean of 22-26 g dry porridge/d and 96% of the possible MV doses. After adjustment for small baseline differences in socioeconomic status and morbidity, no significant differences in weight or length increments were observed between the groups, even among the subset with an initial LAZ < -1.5, and no significant differences in the rates of common illnesses were observed. Mean plasma zinc concentrations decreased in the control group (-3.9 microg/dL), increased in the ZnSuppl group (4.3 microg/dL), and did not change significantly in the ZnFort group (-1.5 microg/dL; P < 0.001 for group-wise comparison). CONCLUSIONS Provision of additional zinc, either in an aqueous supplement or a fortified porridge, did not significantly affect the children's physical growth or morbidity from infections, possibly because they were not sufficiently growth-restricted or zinc-deficient initially or because the level of zinc intake or absorption was inadequate. Additional studies of the functional effect of zinc-fortified foods are needed in populations that are known to respond to zinc supplements.
Plasma arginine concentrations are reduced in cancer patients: evidence for arginine deficiency?

BACKGROUND The disturbances leading to cancer cachexia remain to be unraveled. Preliminary evidence suggests that arginine availability in cancer is reduced. However, no valid data are available on plasma arginine concentrations in cancer patients. OBJECTIVE We aimed to determine whether there is evidence for disturbed arginine metabolism in cancer. DESIGN We measured plasma arginine concentrations postabsorptively in patients with various types of tumors, hypothesizing that arginine concentrations would be lower than those in age- and sex-matched control subjects. Patients with localized tumors with a range of metabolic implications were studied: breast cancer (no weight loss), colonic cancer (sometimes weight loss), and pancreatic cancer (usually weight loss). Plasma amino acid concentrations were measured by HPLC. RESULTS Plasma arginine concentrations were lower in patients with cancer (breast cancer: 80 +/- 3 compared with 103 +/- 9 micromol/L; colonic cancer: 80 +/- 3 compared with 96 +/- 7 micromol/L; pancreatic cancer: 76 +/- 5 compared with 99 +/- 7 micromol/L; P < 0.05 versus respective age- and sex-matched control subjects), irrespective of tumor type, weight loss, tumor stage, or body mass index (correlations with P > 0.05). CONCLUSIONS Malignant tumors associated with various degrees of metabolic derangements are all associated with decreased plasma arginine concentrations, even without weight loss. This suggests that decreased arginine availability is a specific feature of the presence of cancer. These disturbances in arginine metabolism could contribute to the cascade of metabolic events leading to cancer cachexia.
Response of whole-body protein and urea turnover to exercise differs between patients with chronic obstructive pulmonary disease with and without emphysema.

BACKGROUND Exercise is known to improve physical capacity and muscle mass in patients with chronic obstructive pulmonary disease (COPD). However, recent evidence suggests that exercise may also negatively influence metabolism in COPD. OBJECTIVE The objective was to investigate whether exercise influences whole-body protein metabolism differently in COPD patients and control subjects and to elucidate the effect of the specific underlying lung disease. DESIGN Whole-body protein synthesis and breakdown and urea synthesis were measured by using stable-isotope methods in 14 male patients with severe COPD (forced expiratory volume in 1 s: 37 +/- 12% of predicted) and in 8 male control subjects during and after 20 min of exercise. Subjects were normal weight [body mass index (in kg/m2) of COPD patients and control subjects: 25.8 +/- 3.9 and 25.7 +/- 4.4, respectively]. The COPD group was selected to include patients with (Emph+, n = 7) and without (Emph-, n = 7) emphysema. Absolute workload was 35 +/- 5 W, corresponding to 17 +/- 2%, 33 +/- 9%, and 52 +/- 14% of the maximal obtained workload in the control, Emph-, and Emph+ groups. RESULTS Exercise induced a 9% increase in protein synthesis and breakdown in the Emph- and control groups, which normalized postexercise. In the Emph+ group, protein turnover did not change significantly during exercise but decreased postexercise (+/- 10%). Exercise did not change net protein breakdown (protein breakdown - synthesis) or urea synthesis, except in the Emph+ group, which showed a 14% reduction in urea synthesis postexercise (P < 0.05). CONCLUSION Low-intensity exercise suppresses whole-body protein and urea turnover in COPD patients with emphysema and needs to be considered when maximal anabolism is targeted through a combination of exercise and nutrition.
Tumor suppressor BLU promotes TRAIL-induced apoptosis by downregulating NF-κB signaling in nasopharyngeal carcinoma

A putative tumor suppressor BLU mapped on the chromosomal 3p21 region, is frequently lost in human tumors including nasopharyngeal carcinoma (NPC). To explore the underlying mechanism of tumor suppression by BLU, its potential to promote apoptosis induced by TRAIL, an effector molecule elaborated by natural killer-T (NKT) cells was investigated. BLU was re-expressed in NPC-derived HNE1 cells by recombinant adenoviral infection and the cells were challenged with recombinant TRAIL. The growth inhibition of BLU was assayed and apoptosis was examined by flow cytometry-based tetramethylrhodamine ethyl ester (TMRE) and annexin V staining, cleavage of pro-caspase-8 and poly ADP ribose polymerase (PARP). The modulation of NF-κB pathway by BLU was evaluated by the reporter activity and estimation of the level of the molecules involved such as IKKalpha, p65 NF-κB, as well as NF-κB induced anti-apoptotic factors cFLIPL and cIAP2. The expression of BLU exerted in vitro and in vivo growth inhibitory effect and promoted TRAIL-induced apoptosis. This phenomenon was validated by FACS-based assays of mitochondrial membrane potential (BLU vs. Vector 87.8% ± 7.7% and 72.1%±6.7% at 6h exposure to TRAIL) and phosphatidylserine turnover (BLU vs. vector: 28.7%±2.9% and 22.6%±2.5%), as well as, enhanced caspapse-8 cleavage. Similar with the findings that BLU promotes chemotherapeutic agent-induced apoptosis, it also augmented death receptor-induced pathway through NF-κB pathway inhibition. In conclusion, BLU suppressed tumor formation by strengthening the antitumor immunity.
Phosphatidylinositol 5-phosphate 4-kinase regulates early endosomal dynamics during clathrin-mediated endocytosis

ABSTRACT Endocytic turnover is essential for the regulation of the protein composition and function of the plasma membrane, and thus affects the plasma membrane levels of many receptors. In Drosophila melanogaster photoreceptors, photon absorption by the G-protein-coupled receptor (GPCR) rhodopsin 1 (Rh1; also known as NinaE) triggers its endocytosis through clathrin-mediated endocytosis (CME). We find that CME of Rh1 is regulated by phosphatidylinositol 5 phosphate 4-kinase (PIP4K). Flies lacking PIP4K show mislocalization of Rh1 on expanded endomembranes within the cell body. This mislocalization of Rh1 was dependent on the formation of an expanded Rab5-positive compartment. The Rh1-trafficking defect in PIP4K-depleted cells could be suppressed by downregulating Rab5 function or by selectively reconstituting PIP4K in the PI3P-enriched early endosomal compartment of photoreceptors. We also found that loss of PIP4K was associated with increased CME and an enlarged Rab5-positive compartment in cultured Drosophila cells. Collectively, our findings define PIP4K as a novel regulator of early endosomal homeostasis during CME. Highlighted Article: Phosphatidylinositol 5-phosphate 4-kinase regulates early endosomal dynamics and trafficking of plasma membrane receptors through clathrin-mediated endocytosis in Drosophila cells.
Selection on Expected Maximum Haploid Breeding Values Can Increase Genetic Gain in Recurrent Genomic Selection

Genomic selection (GS) offers the possibility to estimate the effects of genome-wide molecular markers, which can be used to calculate genomic estimated breeding values (GEBVs) for individuals without phenotypes. GEBVs can serve as a selection criterion in recurrent GS, maximizing single-cycle but not necessarily long-term genetic gain. As simple genome-wide sums, GEBVs do not take into account other genomic information, such as the map positions of loci and linkage phases of alleles. Therefore, we herein propose a novel selection criterion called expected maximum haploid breeding value (EMBV). EMBV predicts the expected performance of the best among a limited number of gametes that a candidate contributes to the next generation, if selected. We used simulations to examine the performance of EMBV in comparison with GEBV as well as the recently proposed criterion optimal haploid value (OHV) and weighted GS. We considered different population sizes, numbers of selected candidates, chromosome numbers and levels of dominant gene action. Criterion EMBV outperformed GEBV after about 5 selection cycles, achieved higher long-term genetic gain and maintained higher diversity in the population. The other selection criteria showed the potential to surpass both GEBV and EMBV in advanced cycles of the breeding program, but yielded substantially lower genetic gain in early to intermediate cycles, which makes them unattractive for practical breeding. Moreover, they were largely inferior in scenarios with dominant gene action. Overall, EMBV shows high potential to be a promising alternative selection criterion to GEBV for recurrent genomic selection.
Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial.

BACKGROUND Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure (CHF). In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines. OBJECTIVE We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF. DESIGN One hundred twenty-three patients randomly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo. Biochemical variables were assessed at baseline and after 9 mo. The survival rate was calculated for a follow-up period of 15 mo. RESULTS Ninety-three patients completed the study. Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D (P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis factor alpha (P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+) group but increased only by 3.6 ng/mL in the D(-) group. Compared with baseline, parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+) group after 9 mo. The proinflammatory cytokine tumor necrosis factor alpha increased in the D(-) group but remained constant in the D(+) group. The survival rate did not differ significantly between the study groups during the follow-up period. CONCLUSIONS Vitamin D(3) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease. Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF.
Mechanical Properties and Damage Evolution of Siliceous Concrete Subjected to Elevated Temperatures

Siliceous concrete (SC) is applied in European Pressurized Water Reactor that is a key component of the third generation nuclear power plant. This paper investigates the mechanical properties and damage evolution of SC (with and without polypropylene fibers) exposed to high temperatures. The mass loss, compressive strength, splitting tensile strength and spalling sensitivity of SC before and after being heated to 200, 400, 600, 800, and 1000 °C are investigated. The ultrasonic testing technique was used to assess the thermal damage, by evaluating the variations of the ultrasonic wave velocity (UWV) for different temperature levels. According to the available literature, a new relationship between damage and UWV was proposed to establish a damage evolution model of SC. The results indicated that: (a) specimens without polypropylene (PP) fibers suffered severe spalling in the range 380-400°C and 470-510°C, while no spalling took place in the specimens with PP fibers in the whole range 25-1000°C; (b) the damage evolution with and without polypropylene fibers was similar, and could adequately be described by means of a Weibull distribution model.
Knowledge, attitudes, and practices of health-care workers regarding hand hygiene guidelines in Al-Qassim, Saudi Arabia: A multicenter study

Introduction: Hand hygiene is one of the most important ways to reduce the prevalence of nosocomial infections, morbidity, mortality, and health-care costs among hospitalized patients worldwide. Objectives: We addressed this study to assess knowledge, attitudes, and practices regarding hand hygiene guidelines among health-care workers. Methods: A multicenter cross-sectional study conducted from October to December 2015 including three hospitals in Al-Qassim, Saudi Arabia. A total of 354 participants completed a self-administered survey on knowledge, attitudes, and practices of hand hygiene. Analysis of variance was used to compare knowledge level across age, gender, profession, and hospitals. All analyses were performed with SPSS, version 21. Results: Overall, the average knowledge score was 63%. There were significant differences in knowledge level across groups. Health-care workers over the age of 30 had higher scores than those younger than 30. Health-care workers at the tertiary hospital had higher scores than those at the secondary hospitals. Nearly, all reported positive attitudes toward hand hygiene as well as adhering to the guidelines regularly. Further, they reported that soap and water were the most common agents for cleaning hands. Conclusion: The study findings indicate that there are gaps in the knowledge, which could be addressed with brief and more frequent training sessions, particularly in the secondary hospitals. However, the hand hygiene guidelines are well-known by the staff and well promoted in the hospitals reflected by the positive attitudes. Further improvements in adherence to the hand hygiene guidelines will continue to decrease the likelihood of nosocomial infections.