Miracle-dz/UniFAR-FTUs huggingface dataset:
microRNA-203 suppresses invasion of gastric cancer cells by targeting ERK1/2/Slug/ E-cadherin signaling.

BACKGROUND AND AIMS Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumors, including gastric cancer (GC). Expression of microRNA-203 (miR-203) has been reported to decrease in GC. In addition, overexpression of miR-203 inhibits grow of GC cells in vitro and in vivo. However, whether miR-203 affects cell migration and invasion of GC remains unclear. This study aimed to reveal the role of miR-203 on migration and invasion of GC, and its potential mechanisms. METHODS Synthetic pre-miR-203 (miR-203), anti-miR-203 and scrambled negative control RNAs was transfected into the gastric cancer SGC7901 cells to generate miR-203 or anti-miR-203-transfected stable clones. The roles of miR-203 on cell invasion and motility were then analyzed by Transwell migration assay and Wound healing assay in vitro. Using siRNA to targeting ERK1/2, Slug, and E-cadherin or Slug cDNA transfection (to increase Slug expression) to examine the miR-203 signaling pathway. We also examined the efficacies of miR-203 or anti-miR-203 on peritoneal metastasis of SGC7901 cells in the nude mouse model. RESULTS Overexpression of miR-203 inhibits SGC7901 cell invasion and motility, followed by decreased phospho-ERK1/2 (pERK1/2) and Slug expression, as well as increased E-cadherin expression. Re-expression of Slug in miR-203/SGC7901cells decreased E-cadherin expression and restored the invasive phenotypes. Targeting E-cadherin in miR-203/SGC7901cells also restored the invasive phenotypes. Inhibition of miR-203 promotes SGC7901 cell invasion and motility, followed by increased phospho-ERK1/2 (pERK1/2) and Slug expression, as well as decreased E-cadherin expression. Targeting ERK1/2 or Slug in anti-miR-203/SGC7901cells increased E-cadherin expression and reversed the invasive phenotypes. In addition, targeting ERK1/2 decreased Slug and increased the E-cadherin expression. Significantly, we found that miR-203 could exert marked inhibition of the peritoneal metastasis of SGC7901 in nude mice in vivo. Targeting miR-203 could exert marked promotion of the peritoneal metastasis of SGC7901 in nude mice in vivo. CONCLUSIONS miR-203/ERK1/2/Slug/E-cadherin signaling pathway plays an essential role on SGC7901 cell invasion and motility. miR-203 can be novel modalities to prevent peritoneal metastasis of invasive cancers such as gastric cancer.
Role of uterine forces in intrauterine device embedment, perforation, and expulsion

Background The purpose of this study was to examine factors that could help reduce primary perforation during insertion of a framed intrauterine device (IUD) and to determine factors that contribute in generating enough uterine muscle force to cause embedment and secondary perforation of an IUD. The objective was also to evaluate the main underlying mechanism of IUD expulsion. Methods We compared known IUD insertion forces for “framed” devices with known perforation forces in vitro (hysterectomy specimens) and known IUD removal forces and calculated a range of possible intrauterine forces using pressure and surface area. These were compared with known perforation forces. Results IUD insertion forces range from 1.5 N to 6.5 N. Removal forces range from 1 N to 5.8 N and fracture forces from 8.7 N to 30 N depending upon device. Measured perforation forces are from 20 N to 54 N, and calculations show the uterus is capable of generating up to 50 N of myometrial force depending on internal pressure and surface area. Conclusion Primary perforation with conventional framed IUDs may occur if the insertion pressure exceeds the perforation resistance of the uterine fundus. This is more likely to occur if the front end of the inserter/IUD is narrow, the passage through the cervix is difficult, and the procedure is complex. IUD embedment and secondary perforation and IUD expulsion may be due to imbalance between the size of the IUD and that of the uterine cavity, causing production of asymmetrical uterine forces. The uterine muscle seems capable of generating enough force to cause an IUD to perforate the myometrium provided it is applied asymmetrically. A physical theory for IUD expulsion and secondary IUD perforation is given.
Environmental Exposures and Invasive Meningococcal Disease: An Evaluation of Effects on Varying Time Scales

Invasive meningococcal disease (IMD) is an important cause of meningitis and bacteremia worldwide. Seasonal variation in IMD incidence has long been recognized, but mechanisms responsible for this phenomenon remain poorly understood. The authors sought to evaluate the effect of environmental factors on IMD risk in Philadelphia, Pennsylvania, a major urban center. Associations between monthly weather patterns and IMD incidence were evaluated using multivariable Poisson regression models controlling for seasonal oscillation. Short-term weather effects were identified using a case-crossover approach. Both study designs control for seasonal factors that might otherwise confound the relation between environment and IMD. Incidence displayed significant wintertime seasonality (for oscillation, P < 0.001), and Poisson regression identified elevated monthly risk with increasing relative humidity (per 1% increase, incidence rate ratio = 1.04, 95% confidence interval: 1.004, 1.08). Case-crossover methods identified an inverse relation between ultraviolet B radiation index 1–4 days prior to onset and disease risk (odds ratio = 0.54, 95% confidence interval: 0.34, 0.85). Extended periods of high humidity and acute changes in ambient ultraviolet B radiation predict IMD occurrence in Philadelphia. The latter effect may be due to decreased pathogen survival or virulence and may explain the wintertime seasonality of IMD in temperate regions of North America.
Local Anesthetics Induce Human Renal Cell Apoptosis

Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Local anesthetics induce apoptosis in neuronal and lymphocytic cell lines. We examined the effects of chronic (48 h) local anesthetic treatment (lidocaine, bupivacaine and tetracaine) on human proximal tubular (HK-2) cells. Apoptosis induction was assessed by detecting poly(ADP)-ribose polymerase fragmentation, caspase activation, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, DNA laddering and by cellular morphology. Cell death was quantified by measuring neutral red dye uptake and lactate dehydrogenase released into the cell culture medium. All 3 local anesthetics caused concentration-dependent cell death, induced HK-2 cell apoptosis and potentiated TNF-α induced apoptosis. Local anesthetics induced HK-2 cell apoptosis by activation of caspases 3, 6, 7, 8 and 9. ZVAD-fmk, a pan-caspase inhibitor, blocked the local anesthetic induced HK-2 cell apoptosis. Local anesthetics also inhibited the activities of anti-apoptotic kinases protein kinase B (Akt) and extracellular signal regulated mitrogen-activated protein kinase. Local anesthetic’s pro-apoptotic effects are independent of sodium channel inhibition as tetrodotoxin, a selective voltage-gated sodium channel blocker, failed to mimic local anesthetic-mediated induction or potentiation of HK-2 cell apoptosis. We conclude that local anesthetics induce human renal cell apoptotic signaling by caspase activation and via inhibition of pro-survival signaling pathways.
Perennial Allergen-Specific Immunoglobulin E Levels Among Inner-City Elderly Asthmatics

Background. The role of allergen sensitization has been well established among children and young adults with asthma. Some studies have suggested that allergens play a less important role among older patients with asthma. However, whether older asthmatics have a lower prevalence of allergen sensitization than younger adults remains controversial. The aim of this study was to access the prevalence of sensitization to indoor allergens in older compared to younger inner-city adults with persistent asthma. Methods. The authors used data collected as part of a cohort study of inner-city adults with persistent asthma. Sensitization to indoor allergens (specifically Dermatophagoides pteronyssinus, D. farinae, cat, mouse, Aspergillus fumigates, Alternaria, German and American cockroaches) was evaluated by specific immunoglobulin E (IgE) antibodies measured from peripheral blood. Univariate and multiple regression analyses were used to compare ratios of sensitization according to age (≤35, 36–59, ≥60 years of age). Results. Of the 245 patients in the study, 19% were over the age of 60 years. Overall 73%, 61%, and 41% of patients ≤35, 36–59, and ≥60 years old, respectively were sensitized to at least one indoor allergen (p = .01). Multivariate analysis showed that patients ≥60 years of age were significantly less likely to be sensitized (odds ratio 0.32, 95% confidence interval 0.11 to 0.89) compared to younger adults after controlling for potential confounders. Conclusions. Allergen sensitization is less common in older patients with persistent asthma. However, sensitization to any indoor allergen is relatively frequent in the elderly. Physicians should consider routinely accessing exposure and sensitization to these allergens as part of the evaluation of older inner-city patients with persistent asthma.
A mouse model for Glut1 haploinsufficiency

Glut-1 deficiency syndrome (Glut-1 DS, OMIM #606777) is characterized by infantile seizures, developmental delay, acquired microcephaly and hypoglycorrhachia. It is caused by haploinsufficiency of the blood–brain barrier hexose carrier. Heterozygous mutations or hemizygosity of the GLUT-1 gene cause Glut-1 DS. We generated a heterozygous haploinsufficient mouse model by targeted disruption of the promoter and exon 1 regions of the mouse GLUT-1 gene. GLUT-1 mice have epileptiform discharges on electroencephalography (EEG), impaired motor activity, incoordination, hypoglycorrhachia, microencephaly, decreased brain glucose uptake as measured by positron emission tomography (PET) scan and decreased brain Glut-1 expression by western blot (66%). The GLUT-1 murine phenotype mimics the classical human presentation of Glut-1 DS. This GLUT-1 mouse model creates an opportunity to investigate Glut-1 function, to examine the pathophysiology of Glut-1 DS in vivo and to evaluate new treatment strategies.
Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.

BACKGROUND Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. METHODS The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. RESULTS A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. CONCLUSION Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals.
Strength improvements through occlusal splints? The effects of different lower jaw positions on maximal isometric force production and performance in different jumping types

Objective The influence of the jaw position on postural control, body posture, walking and running pattern has been reported in the literature. All these movements have in common that a relatively small, but well controlled muscle activation is required. The induced effects on motor output through changed jaw positions have been small. Therefore, it has been questioned if it could still be observed in maximal muscle activation. Method Twenty-three healthy, mid age recreational runners (mean age = 34.0 ± 10.3 years) participated in this study. Three different jump tests (squat jump, counter movement jump, and drop jumps from four different heights) and three maximal strength tests (trunk flexion and extension, leg press of the right and left leg) were conducted. Four different dental occlusion conditions and an additional familiarization condition were tested. Subjects performed the tests on different days for which the four occlusion conditions were randomly changed. Results No familiarization effect was found. Occlusion conditions with a relaxation position and with a myocentric condylar position showed significantly higher values for several tests compared to the neutral condition and the maximal occlusion position. Significance was found in the squat jump, countermovement jump, the drop jump from 32cm and 40cm, trunk extension, leg press force and rate of force development. The effect due to the splint conditions is an improvement between 3% and 12% (min and max). No influence of the jaw position on symmetry or balance between extension and flexion muscle was found. Conclusion An influence of occlusion splints on rate of force development (RFD) and maximal strength tests could be confirmed. A small, but consistent increase in the performance parameters could be measured. The influence of the occlusion condition is most likely small compared to other influences as for example training status, age, gender and circadian rhythm.
Cross-Domain Collaborative Filtering with Review Text

Most existing cross-domain recommendation algorithms focus on modeling ratings, while ignoring review texts. The review text, however, contains rich information, which can be utilized to alleviate data sparsity limitations, and interpret transfer patterns. In this paper, we investigate how to utilize the review text to improve cross-domain collaborative filtering models. The challenge lies in the existence of non-linear properties in some transfer patterns. Given this, we extend previous transfer learning models in collaborative filtering, from linear mapping functions to non-linear ones, and propose a cross-domain recommendation framework with the review text incorporated. Experimental verifications have demonstrated, for new users with sparse feedback, utilizing the review text obtains 10% improvement in the AUC metric, and the nonlinear method outperforms the linear ones by 4%.
Effect of Metarhizium anisopliae on the fertility and fecundity of two species of fruit flies and horizontal transmission of mycotic infection

Abstract In Mauritius, the peach fruit fly, Bactrocera zonata Saunders (Diptera: Tephritidae), and the melon fly, Bactrocera cucurbitae (Coquillett), are the major pest of fruits and vegetables, respectively. Fruit growers make use of broad-spectrum insecticides to protect their crops from fruit fly attack. This method of fruit fly control is hazardous to the environment and is a threat to beneficial insects. The entomopathogenic fungus, Metarhizium anisopliae (Metchnikoff) Sorokin (Hypocreales: Clavicipitaceae), which was isolated from the soils of Mauritius, was used to investigate whether fungus-treated adult fruit flies could transfer conidia to non-treated flies during mating, and whether fungal infection could have an effect on mating behavior, fecundity, and fertility of the two female fruit fly species. When treated male flies were maintained together with non-treated female flies, they were able to transmit infection to untreated females, resulting in high mortalities. Similarly, fungus-infected female flies mixed with untreated males also transmitted infections to males, also resulting in high mortalities. Infection by M. anisopliae also resulted in the reduction of the number of eggs produced by females of B. cucurbitae. The results suggest that M. anisopliae may have potential for use in integrated control programs of B. zonata and B. cucurbitae using the sterile insect technique in Mauritius.
Investigations of Cosmic-Ray-Produced Nuclides in Iron Meteorites: 5. More Data on the Nuclides of Potassium and Noble Gases, on Exposure Ages and Meteoroid Sizes

Abstract The concentrations of the cosmic-ray-produced He-, Ne-, and Ar-nuclides in samples of 31 iron meteorites have been determined by mass spectrometry. Thereby, the number of samples analyzed in this laboratory has grown to 83. A critical examination of all these results was performed. The data of at least 52 samples prove to be useful to describe the "normal" abundance patterns of cosmogenic noble gases in iron meteorites; the description is accomplished by a new system of equations that correlate some properly selected abundance ratios with one another. The correlations serve as an instrument to recognize and diagnose certain abundance anomalies (3He-or 38Ar-deficiencies) which occur in about 25% of all samples analyzed. They allow to select those data which may unhesitatingly be applied in calculations concerning the irradiation histories of the respective meteorites. Another matter of concern for establishing these histories are the cosmic-ray-exposure ages. Mass spectrometric abundance analyses on meteoritic potassium have provided new data on the 41K/40K exposure ages of about 10 iron meteorites as well as on meteoroid sizes and sample depths. For two meteorites of the chemical group IIIAB, Joe Wright Mountains and Picacho, the age values obtained are 685 and 635 Ma, respectively. The results confirm our previous conclusion that the IIIAB-irons resided originally within a more or less contiguous partial volume (metallic core? ) of their parent body and were ejected in consequence of a single impact event that happened about 670 Ma ago. Another motive for the present investigation was to measure the exposure ages for meteorites of the chemical groups IIICD and HIE. However, the new information obtained on their age distributions is still inadequate to answer some old questions concerning a possible relationship to the event that produced the IIIAB-meteoroids 670 Ma ago.
Liposomes as Triggerable Carrier for Intracellular Drug Delivery

Administration of drugs is often associated with basic problems such as toxicity, instability and improper biodistribution. Encapsulation of the drug in a suitable carrier such as liposomes is one of the well recognized methods that protects the drug from the body milieu to improve stability, safety and targeting efficiency of the drug towards the target site. However, while encapsulation provides a favorable biodistribution, low toxicity and improved stability of drugs, delivery carriers should be capable of releasing encapsulated material at the appropriate site to exert their activity. Effective intracellular drug delivery is desired for many therapeutic agents those having specific molecular targets in the cytoplasm, nucleus, or other subcellular compartments of a cell such as mitochondria. Several nanocarriers that are designed to release drugs at desired sites have been developed so far. Among these, exhaustive research has established liposomes as an effective triggerable drug carrier. This mini review covers various aspects of triggering modalities examined to date such as temperature, pH, enzymes and light using liposomes.
Cholesterol regulates ABCD 2 expression : implications for the therapy of X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder with impaired very longchain fatty acid (VLCFA) metabolism. The disease-associated ABCD1 (ALD) gene encodes a peroxisomal membrane protein, which belongs to the superfamily of ATP-binding cassette transporters. Several treatment regimes have been tried without satisfactory clinical benefit. Recently, the cholesterol-lowering drug lovastatin was reported to normalize VLCFA levels in two out of three clinical studies. This investigation aimed to disclose the molecular mechanism of successful reduction of VLCFA accumulation in order to fill in the gap in the understanding how dietary cholesterol lowering affects the levels of VLCFA in patients with XALD and to allow more efficacious treatment. Overexpression of ABCD2 (ALDR), the closest relative of ABCD1, restores VLCFA accumulation in cultured ABCD1-deficient cells. Here we show by real-time PCR that the ABCD2 gene is induced in cultured human fibroblasts and monocytes upon sterol depletion via a mechanism requiring the activation of sterol regulatory element-binding proteins (SREBPs), a family of transcription factors that control the metabolism of cholesterol and fatty acids. This is unexpected and the first report that extends the mechanism of transcriptional regulation by SREBPs to a peroxisomal protein, thus providing a closer link between peroxisomes, cholesterol and fatty acid biosynthesis. Using reporter gene studies, site-directed mutagenesis and gel shift assays, we identified a functional sterol regulatory element in the proximal promoter region of ABCD2. Finally, we demonstrated that ABCD2 induction by sterol depletion significantly reduced the accumulation of VLCFA in X-ALD fibroblasts. Thus, lowering cholesterol leads to SREBP maturation, increased ABCD2 expression and reduced VLCFA accumulation.
The monoamine stabilizer (−)‐OSU6162 prevents the alcohol deprivation effect and improves motor impulsive behavior in rats

Alcohol craving, in combination with impaired impulse control, often leads to relapse. The dopamine system mediates the rewarding properties of alcohol but is also involved in regulating impulsive behavior. The monoamine stabilizer (−)‐OSU6162 (OSU6162) has the ability to stabilize dopamine activity depending on the prevailing dopaminergic tone and may therefore normalize the dopaminergic transmission regulating both alcohol use disorder and impulsivity. We have recently showed that OSU6162 attenuates voluntary alcohol consumption, operant alcohol self‐administration, alcohol withdrawal symptoms and cue‐induced reinstatement of alcohol seeking in rats. Here, we evaluated OSU6162's effects on motor impulsivity in Wistar rats that had voluntarily consumed alcohol or water for 10 weeks. The five‐choice serial reaction time task was used to measure motor impulsivity, and a prolonged waiting period (changed from 5 to 7 seconds) was applied to induce premature responses. OSU6162‐testing was conducted twice a week (Tuesdays and Fridays), every other week with regular baseline training sessions in between. We also tested OSU6162's effects on the alcohol deprivation effect in long‐term alcohol drinking Wistar rats. The results showed that OSU6162 (30 mg/kg) pre‐treatment significantly improved motor impulsivity in the five‐choice serial reaction time task in both alcohol and alcohol‐naïve rats. Moreover, OSU6162 (30 mg/kg) pre‐treatment prevented the alcohol deprivation effect, i.e. relapse‐like drinking behavior after a forced period of abstinence in long‐term drinking rats. In conclusion, our results provide further support for OSU6162 as a novel treatment for alcohol use disorder. The results further indicate that improvement of motor impulse control might be one mechanism behind OSU6162's ability to attenuate alcohol‐mediated behaviors.