Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence That Curcumin Suppresses the Growth of Malignant Gliomas In Vitro and In Vivo Through Induction of Autophagy: Role of Akt and ERK Signaling Pathways

Autophagy is a response of cancer cells to various anticancer therapies. It is designated as programmed cell death type II and characterized by formation of autophagic vacuoles in the cytoplasm. The Akt/mammalian target of rapamycin (mTOR)/p70S6K and the extracellular signal–regulated kinases 1/2 (ERK1/2) pathways are two major pathways which regulate autophagy induced by nutrient starvation. These pathways are also frequently associated with oncogenesis in a variety of cancer cell types, including malignant gliomas. However, few studies have examined both of these signal pathways in the context of anticancer therapy–induced autophagy in cancer cells, and autophagy’s effect on cell death remains unclear. Here, we examined the anticancer efficacy and mechanisms of curcumin, a natural compound with low toxicity in normal cells, in U87-MG and U373-MG malignant glioma cells. Curcumin induced G 2 /M arrest and non-apoptotic autophagic cell death in both cell types. It inhibited the Akt/mTOR/p70S6K pathway and activated the ERK1/2 pathway, resulting in induction of autophagy. Interestingly, activation of the Akt pathway inhibited curcumin-induced autophagy and cytotoxicity, whereas inhibition of the ERK1/2 pathway inhibited curcumin-induced autophagy and induced apoptosis, thus resulting in enhanced cytotoxicity. These results imply that the effect of autophagy on cell death may be pathway specific. In the subcutaneous xenograft model of U87-MG cells, curcumin inhibited tumor growth significantly ( P < 0.05) and induced autophagy. These results suggest that curcumin has high anticancer efficacy in vitro and in vivo by inducing autophagy and warrant further investigation toward possible clinical application in patients with malignant glioma.
Initial findings: primary diabetes care responsibility among emerging adults with type 1 diabetes post high school and move out of parental home.

BACKGROUND Emerging adults with diabetes are assuming diabetes care responsibility, graduating from high school and leaving their parental homes. We examined: (1) how diabetes care responsibility changed in relation to time (high school to post high school) and living situation (living independently or not of parents) and (2) the association of diabetes self-efficacy, worry about hypoglycaemia, gender and glycaemic control with these changes in responsibility among emerging adults with type 1 diabetes. METHODS During the last 6 months in high school (T1), 113 participants completed diabetes care responsibility (total, daily and non-daily), diabetes self-efficacy and worry about hypoglycaemia scales. Participants again completed the responsibility scales post high school graduation (T2). We used a linear mixed-effects model with diabetes self-efficacy, worry about hypoglycaemia, time since graduation, living situation, gender and glycaemic control as independent variables; and diabetes care responsibility (total, daily and non-daily) as dependent variables. Moderation involving diabetes self-efficacy, worry about hypoglycaemia, gender and glycaemic control was also tested. FINDINGS Diabetes care responsibility increased over time for total (P < 0.001), daily (P= 0.002) and non-daily (P < 0.001), but the associations of self-efficacy and gender with diabetes care responsibility were moderated by living situation. Self-efficacy was negatively related to total (P= 0.006), daily (P= 0.010) and non-daily (P= 0.030) responsibility for those not living independently while positively related only to total responsibility (P= 0.028) for those living independently. Being female was positively related to total (P= 0.007) and non-daily (P= 0.001) responsibility for those living independently. CONCLUSION Diabetes care responsibility increased from high school to post high school among these emerging adults with diabetes. There is a complex relationship between self-efficacy, gender and responsibility related to living independently of parents for these youth.
Arachidonic Acid–Induced Dilation in Human Coronary Arterioles: Convergence of Signaling Mechanisms on Endothelial TRPV4‐Mediated Ca2+ Entry

Background Arachidonic acid (AA) and/or its enzymatic metabolites are important lipid mediators contributing to endothelium‐derived hyperpolarizing factor (EDHF)–mediated dilation in multiple vascular beds, including human coronary arterioles (HCAs). However, the mechanisms of action of these lipid mediators in endothelial cells (ECs) remain incompletely defined. In this study, we investigated the role of the transient receptor potential vanilloid 4 (TRPV4) channel in AA‐induced endothelial Ca2+ response and dilation of HCAs. Methods and Results AA induced concentration‐dependent dilation in isolated HCAs. The dilation was largely abolished by the TRPV4 antagonist RN‐1734 and by inhibition of endothelial Ca2+‐activated K+ channels. In native and TRPV4‐overexpressing human coronary artery ECs (HCAECs), AA increased intracellular Ca2+ concentration ([Ca2+]i), which was mediated by TRPV4‐dependent Ca2+ entry. The AA‐induced [Ca2+]i increase was inhibited by cytochrome P450 (CYP) inhibitors. Surprisingly, the CYP metabolites of AA, epoxyeicosatrienoic acids (EETs), were much less potent activators of TRPV4, and CYP inhibitors did not affect EET production in HCAECs. Apart from its effect on [Ca2+]i, AA induced endothelial hyperpolarization, and this effect was required for Ca2+ entry through TRPV4. AA‐induced and TRPV4‐mediated Ca2+ entry was also inhibited by the protein kinase A inhibitor PKI. TRPV4 exhibited a basal level of phosphorylation, which was inhibited by PKI. Patch‐clamp studies indicated that AA activated TRPV4 single‐channel currents in cell‐attached and inside‐out patches of HCAECs. Conclusions AA dilates HCAs through a novel mechanism involving endothelial TRPV4 channel‐dependent Ca2+ entry that requires endothelial hyperpolarization, PKA‐mediated basal phosphorylation of TRPV4, and direct activation of TRPV4 channels by AA.
Composite Medicago truncatula plants harbouring Agrobacterium rhizogenes-transformed roots reveal normal mycorrhization by Glomus intraradices

Composite plants consisting of a wild-type shoot and a transgenic root are frequently used for functional genomics in legume research. Although transformation of roots using Agrobacterium rhizogenes leads to morphologically normal roots, the question arises as to whether such roots interact with arbuscular mycorrhizal (AM) fungi in the same way as wild-type roots. To address this question, roots transformed with a vector containing the fluorescence marker DsRed were used to analyse AM in terms of mycorrhization rate, morphology of fungal and plant subcellular structures, as well as transcript and secondary metabolite accumulations. Mycorrhization rate, appearance, and developmental stages of arbuscules were identical in both types of roots. Using Mt16kOLI1Plus microarrays, transcript profiling of mycorrhizal roots showed that 222 and 73 genes exhibited at least a 2-fold induction and less than half of the expression, respectively, most of them described as AM regulated in the same direction in wild-type roots. To verify this, typical AM marker genes were analysed by quantitative reverse transcription-PCR and revealed equal transcript accumulation in transgenic and wild-type roots. Regarding secondary metabolites, several isoflavonoids and apocarotenoids, all known to accumulate in mycorrhizal wild-type roots, have been found to be up-regulated in mycorrhizal in comparison with non-mycorrhizal transgenic roots. This set of data revealed a substantial similarity in mycorrhization of transgenic and wild-type roots of Medicago truncatula, validating the use of composite plants for studying AM-related effects.
Like a `rolling stone': quantitative analysis of the body movement and skeletal dynamics of the sponge Tethya wilhelma

SUMMARY Although sponges (Porifera) are basal Metazoa without muscles and a central nervous system, they are able to locomote, which is generally correlated to drastic morphological changes. This behaviour has been known for more almost 150 years, but it is only partly understood. The sponge T. wilhelma displays extraordinary movement and rhythmic body contractions, and is thus a valuable model for the investigation of sponge movement. The aims of the present study were to track T. wilhelma quantitatively on natural and artificial substrates, to test for a peristaltic movement mechanism and to check for the influence of morphological changes. T. wilhelma displays a unique mode of locomotion among sponges, without reorganizing the whole sponge body. The overall morphology was stable, and skeletal rotation during movement was shown; this is the first time that such movement has been demonstrated in a sponge. The stability of the skeletal superstructure arrangement during movement suggests that only the cortical tissue is involved in movement, with only local tissue rearrangements. The movement track followed a straight direction for long periods, but directions could be altered instantly. It is most likely that environmental conditions play an important roll in induction of movement. In summary, T. wilhelma resembles the proverbial `rolling stone' that stays at a given location if the conditions are favourable and starts moving when conditions change for the worse.
The impact of degumming conditions on the properties of silk films for biomedical applications

The degumming process to remove sericin decreases silk fiber strength; however, the impact of degumming on the mechanical properties of regenerated silk biomaterials has not been established. This study investigated the effect of degumming temperature, time, alkaline component and alkaline concentration on the mechanical properties of silk fibroin films. Sericin removal was estimated using weight loss; 10 samples with 12.2–29.4% weight loss were then further characterized in terms of fiber mechanical properties, fiber surface morphology, molecular weight distribution and film tensile strength. A negative correlation was found between weight loss and fiber tensile strength. This loss of fiber strength under harsher degumming conditions had a direct impact on the tensile strength of regenerated films. Mild degumming conditions (weight loss of 12.2%) led to higher film strength (8.9 MPa), whereas aggressive degumming conditions (with 29.4% weight loss) resulted in significantly weaker films (4.3 MPa). The presence of some residual sericin, after mild degumming, is likely to affect the mechanical properties of the regenerated silk films. These results will assist in the development of materials with mechanical and biocompatibility properties tuned to specific biomedical applications.
Effects of amlodipine administration and withdrawal on rat pituitary gonadotropins.

OBJECTIVE The study was aimed to observe the effect of amlodipine on rat pituitary gonadotropins after amlodipine administration and withdrawal. METHODS It was an experimental study done at Army Medical College, National University of Sciences and Technology, Islamabad, Pakistan from 2009-2010. Sixty adult male rats were divided into groups A and B. Each group was further subdivided into two subgroups of 15 rats each; A1 (control), A2 (control recovery), B1 (amlodipine-treated) and B2 (amlodipine recovery). Amlodipine, 0.04 mg/kg body weight daily for fifty days was given by means of gavage to groups B1 and B2. Groups A1 and A2 were given vehicle (0.5 ml distilled water). After 50 days, rats in groups A1 and B1 were sacrificed and their serum LH and FSH levels were measured by Enzyme Immunoassay method. Vehicle and amlodipine were withdrawn in groups A2 and B2, respectively, and the rats were left for recovery to take place for another fifty days. The above procedure was adopted for the measurement of LH and FSH levels in the recovered rats. RESULTS Amlodipine administration for 50 days resulted in a significant rise in serum LH (p < 0.01) whereas serum FSH remained unchanged (p ≥ 0.05). Serum LH in amlodipine-treated rats returned to normal after amlodipine withdrawal (p ≥ 0.05). CONCLUSION Amlodipine causes a reversible increase in serum LH but it has no effect on serum FSH (Fig. 2, Ref. 17).
St. John's wort and S-adenosyl methionine as "natural" alternatives to conventional antidepressants in the era of the suicidality boxed warning: what is the evidence for clinically relevant benefit?

INTRODUCTION A boxed-warning in antidepressant labeling now informs prescribers of the potential for treatment-emergent suicidality to occur. Consequently, alternative "natural" antidepressant therapies widely viewed to be devoid of this risk, such as St. John's wort (SJW) and s-adenosyl methionine (SAM-e), may experience a resurgence in popularity and expansion of use beyond mild forms of depressive illness. The purpose of this article is to critically assess whether the clinical evidence supports the use of SJW and SAM-e as alternatives to conventional antidepressants in the treatment of major depressive disorder (MDD). In addition, this article evaluates whether the behavioral adverse event profiles of SJW and SAM-e suggest an increased risk for suicidality, like their conventional counterparts. METHODS A comprehensive literature review was performed (Jan 1975-July 2010) to identify all English language reports of placebo-controlled studies of SJW and SAM-e conducted for psychiatric indications. MDD studies were categorized as "positive" or "negative" based on statistical superiority to placebo on prospectively-defined, primary, clinician-rated efficacy parameters (e.g., change in Hamilton Depression scores [HAM-D] or Montgomery-Asberg Depression Rating Scale [MADRS] total). Treatment effect size (Cohen's d) was also calculated in each case to assess the clinical relevance of the findings. Behavioral-related adverse events were summarized by treatment. RESULTS Ten of 14 (71%) SJW studies in mild-to-moderate MDD were positive. The mean and median effect sizes for HAM-D change in those studies were 0.64 and 0.48, respectively, indicative of a moderately-large treatment effect. In the few studies that included patients with severe symptoms, however, or which evaluated long-term maintenance of effect, SJW did not differentiate from placebo. The majority of SAM-e studies in MDD were also positive (8/14, 57%); however, most were methodologically flawed to some extent. Based on the magnitude of the treatment-effect size in a number of positive studies, SJW appears to be useful for the short-term treatment of mild-to-moderate depressive illness in adults. Existing data do not support the use of SJW in more severely depressed individuals. The SAM-e clinical data also are strongly suggestive of antidepressant efficacy; however, until more rigorously generated data become available it is not possible to reach a more definitive conclusion. There are no long-term treatment data that convincingly demonstrate long-term maintenance of effect for either product. The reviewed studies did not reveal evidence of treatment-emergent suicidality, suggesting that this risk for either product is low. However, the studies examined were not prospectively designed to detect such events and therefore were likely unable to reliably assess this risk.
Peripheral and spinal TRPA1 channels contribute to formalin-induced long-lasting mechanical hypersensitivity

Background Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed by a subset of nociceptive neurons that acts as a multimodal receptor. Its activity contributes to modulate nociceptive transmission in acute inflammatory pain. However, the role of this channel in chronic pain has been less studied. The purpose of this study was to investigate the local peripheral and spinal participation of TRPA1 channels in formalin-induced long-lasting hypersensitivity. Materials and methods Formalin (1%)-induced chronic hypersensitivity was determined by the application of von Frey filaments to ipsilateral and contralateral paws and through pharmacological testing using a selective TRPA1 blocker (A-967079). TRPA1 expression in the dorsal root ganglion (DRG) and spinal cord was analyzed by Western blotting. Results Formalin (1%) injection produced acute flinching behavior (1 h) as well as secondary allodynia and hyperalgesia (12 days). Local peripheral pretreatment (10 min before) or posttreatment (6 days later) with A-967079 (1–100 µM) partially prevented and reversed, respectively, in a dose-dependent manner, long-lasting secondary mechanical allodynia and hyperalgesia evoked by 1% formalin. Likewise, intrathecal pretreatment or posttreatment with A-967079 partially prevented and reversed, respectively, formalin-induced long-lasting hypersensitivity. A-967079 (100 µM) completely abolished the pro-nociceptive effect of formalin (adjusted to pH 7.4). Finally, formalin injection increased TRPA1 protein expression in the DRG and spinal cord. Conclusion Results indicate that TRPA1 expressed in the DRG and spinal cord plays a relevant role in formalin-induced long-lasting secondary nociceptive hypersensitivity.
Subgroups of chronic fatigue syndrome based on psychiatric disorder onset and current psychiatric status

Few studies have examined the effects of psy-chiatric disorders occurring over a long dura-tion among patients with chronic fatigue syn-drome (CFS). The role of premorbid and current psychiatric disorders in impairment was ex-plored with a sample of 113 participants with CFS. Subgroups were created based on past and current psychiatric status including those whose psychiatric history was premorbid and current, postmorbid and current, past but not current, and those with no lifetime diagnosis. Results from a one-way MANOVA revealed that patients with a premorbid and current psychiat-ric disorder reported significantly higher pain severity, more somatic symptoms, poorer sleep quality, and poorer quality of life than those with no psychiatric history. Levels of fatigue and physical functioning among patients with CFS were unrelated to the four subgroups in this study. Although those with a premorbid and current psychiatric disorder were differentiated from those with no psychiatric history on some markers of impairment, the sample as a whole had severe fatigue-related impairment, which is the cardinal symptom of CFS. Implications for research are discussed.
Verification of Data Races in Concurrent Interrupt Handlers

Data races are common in interrupt-driven programs and have already led to well-known real-world problems. Unfortunately, existing dynamic tools for reporting data races in interrupt-driven programs are not only unsound, but they also fail to verify the existence of data races in such programs. This paper presents an efficient and scalable on-the-fly technique that precisely detects, without false positives, apparent data races in interrupt-driven programs. The technique combines a tailored lightweight labeling scheme to maintain logical concurrency between the main program and every instance of its interrupt handlers with a precise detection protocol that analyzes conflicting shared memory accesses by storing at most two accesses for each shared variable. We implemented a prototype of this technique, called iRace, on top of the Avrora simulation framework. An empirical evaluation of iRace revealed the presence of data races in some existing TinyOS components and applications with a worst-case slowdown of only about 6 times on average and an increased average memory consumption of only about 20% in comparison with the original program execution. The evaluation also proved that the labeling scheme alone generates an average runtime overhead of only about 0.4x while consuming only about 12% more memory than the original program execution.
Recurrence of choledocholithiasis following endoscopic bile duct clearance: Long term results and factors associated with recurrent bile duct stones

AIM To evaluate the rate of recurrence of symptomatic choledocholithiasis and identify factors associated with the recurrence of bile duct stones in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) for bile duct stone disease. METHODS All patients who underwent ERCP and EST for bile duct stone disease and had their bile duct cleared from 1/1/2005 until 31/12/2008 was enrolled. All symptomatic recurrences during the study period (until 31/12/2015) were recorded. Clinical and laboratory data potentially associated with common bile duct (CBD) stone recurrence were retrospectively retrieved from patients’ files. RESULTS A total of 495 patients were included. Sixty seven (67) out of 495 patients (13.5%) presented with recurrent symptomatic choledocholithiasis after 35.28 ± 16.9 mo while twenty two (22) of these patients (32.8%) experienced a second recurrence after 35.19 ± 23.2 mo. Factors associated with recurrence were size (diameter) of the largest CBD stone found at first presentation (10.2 ± 6.9 mm vs 7.2 ± 4.1 mm, P = 0.024), diameter of the CBD at the first examination (15.5 ± 6.3 mm vs 12.0 ± 4.6 mm, P = 0.005), use of mechanical lithotripsy (ML) (P = 0.04) and presence of difficult lithiasis (P = 0.04). Periampullary diverticula showed a trend towards significance (P = 0.066). On the contrary, number of stones, angulation of the CBD, number of ERCP sessions required to clear the CBD at first presentation, more than one ERCP session needed to clear the bile duct initially and a gallbladder in situ did not influence recurrence. CONCLUSION Bile duct stone recurrence is a possible late complication following endoscopic stone extraction and CBD clearance. It appears to be associated with anatomical parameters (CBD diameter) and stone characteristics (stone size, use of ML, difficult lithiasis) at first presentation.