Miracle-dz/UniFAR-FTUs huggingface dataset:
Macrophages Are a Potent Source of Streptococcus-Induced IFN-β

Key Points Bone marrow GM-CSF culture gives rise to four distinct populations. GM-CSF MΦ can produce IFN-β. GBS-stimulated GM-CSF MΦ have the ability to adapt their phenotype to be more DC like. Visual Abstract IFN-β essentially modulates the host response against mucocutaneous colonizers and potential pathogens, such as group B Streptococcus (GBS). It has been reported that the dominant signaling cascade driving IFN-β in macrophages (MΦ) in streptococcal infection is the cGAS–STING pathway, whereas conventional dendritic cells (DC) exploit endosomal recognition by intracellular TLRs. In this study, we revisited this issue by precisely monitoring the phenotypic dynamics in mixed mouse MΦ/DC cultures with GM-CSF, which requires snapshot definition of cellular identities. We identified four mononuclear phagocyte populations, of which two were transcriptionally and morphologically distinct MΦ–DC-like subsets, and two were transitional types. Notably, GBS induced a TLR7-dependent IFN-β signal only in MΦ-like but not in DC-like cells. IFN-β induction did not require live bacteria (i.e., the formation of cytolytic toxins), which are essential for IFN-β induction via cGAS–STING. In contrast to IFN-β, GBS induced TNF-α independently of TLR7. Subsequent to the interaction with streptococci, MΦ changed their immunophenotype and gained some typical DC markers and DC-like morphology. In summary, we identify IFN-β formation as part of the antistreptococcal repertoire of GM-CSF differentiated MΦ in vitro and in vivo and delineate their plasticity.
Effect of Aromatherapy on Anxiety Level Among Preoperative patients

Abstract Background and Objective: Surgery can cause high levels of anxiety in patients. Preoperative anxiety can increase postoperative pain and need for postoperative analgesia, delay wound healing and increase stay in hospital. Nurses often look for ways to help control anxiety following surgery and disease. Aromatherapy is currently recognized as a comple- mentary therapy and tool holistic nursing care in many countries that may help patients and lower their anxiety. The aim of this study was evaluation the effect of inhalation aroma- therapy on level of anxiety in patient before abdominal and heart surgery. Subjects and Methods: This research is a randomized clinical trial on 72 preoperative patients who admitted to Golestan and Emam Khomeini hospitals in Ahvaz city in 2008. Patients divided in two groups; first group took inhalation aromatherapy with lavender oil and second group took water vapor as inhalation placebo. The level of anxiety evaluated by Spielberger’s State Anxiety questionnaire before and after intervention and vital sign docum- ented. The data were analyzed by t and chi square tests. Results: The results of study showed that mean of anxiety rate before intervention in inhalation aromatherapy group was 51.00±8.94 and after intervention decreased to 38.61±9.79, whiles this mean before placebo group was 50.67±9.69 and after, received to 49.53±9.37. Statical paires t-test reveals no significant difference between mean before intervention in two groups (P=0.88), but after intervention the result showed significant statistic difference between them (p=0.001). Conclusion: The findings imply that inhalation aromatherapy decreased anxiety in preope- rative patients and can use as a complementary therapy. Sci Med J 2010; 9(5):507-516
Expression of Developmentally Important Axon Guidance Cues in the Adult Optic Chiasm

Purpose Regeneration of optic nerve axons after injury can be facilitated by several approaches, but misguidance at the optic chiasm is often observed. We characterized guidance cues in the embryonic visual system and adult optic chiasm before and after optic nerve crush (ONC) injury to better understand barriers to optic nerve regeneration in adults. Methods Radial glial (RC2/BLBP/Slit1), developmental (Pax2) and extracellular markers (CSPG: H2B/CS-56) were assessed in C57BL/6J mice by immunohistochemistry. RC2, BLBP, Slit1, and CSPG are known inhibitory guidance cues while Pax2 is a permissive guidance cue. Results At embryonic day 15.5 (E.15.5), RC2 and BLBP were identified superior to, and extending through, the optic chiasm. The optic chiasm was BLBP−ve in adult uninjured mice but BLBP+ve in adult mice 10 days after ONC injury. The reverse was true for RC2. Both BLBP and RC2 were absent in adult mice 6 weeks post-ONC. Slit1 was present in the optic chiasm midline and optic tracts in embryonic samples but was absent in uninjured adult tissue. Slit1 was observed superior to and at the midline of the optic chiasm 10 days post-ONC but absent 6 weeks after injury. Pax2 was expressed at the junction between the optic nerve and optic chiasm in embryonic brain tissue. In embryonic sections, CS-56 was observed at the junction between the optic chiasm and optic tract, and immediately superior to the optic chiasm. Both 2H6 and CS-56 staining was absent in uninjured and ONC-injured adult brains. Conclusion Differences in guidance cue expression during development, in adulthood and after injury may contribute to misguidance of regenerating RGC axons in the adult optic chiasm.
Extended 5-Year Follow-up Results of a Phase Ib Study (BRIM7) of Vemurafenib and Cobimetinib in BRAF-Mutant Melanoma

Purpose: To report the 5-year overall survival (OS) landmark and the long-term safety profile of vemurafenib plus cobimetinib (BRAF plus MEK inhibition, respectively) in the BRIM7 study. Patients and Methods: This phase Ib, dose-finding, and expansion study evaluated combination treatment with vemurafenib and cobimetinib in two cohorts of patients with advanced BRAFV600-mutated melanoma: patients who were BRAF inhibitor (BRAFi)-naïve (n = 63) or patients who had progressed on prior treatment with BRAFi monotherapy [vemurafenib monotherapy–progressive disease (PD); n = 66]. Patients in the dose-escalation phase received vemurafenib at 720 or 960 mg twice daily in combination with cobimetinib at 60, 80, or 100 mg/d for 14 days on/14 days off, 21 days on/7 days off, or continuously. Two regimens were selected for expansion: vemurafenib (720 and 960 mg twice daily) and cobimetinib (60 mg/d 21/7). Results: Median OS was 31.8 months [95% confidence interval (CI), 24.5–not estimable] in the BRAFi-naïve cohort. The landmark OS rate plateaued at 39.2% at years 4 and 5 of follow-up. In the vemurafenib monotherapy–PD cohort, the median OS was 8.5 months (95% CI, 6.7–11.1), and the landmark OS rate plateaued at 14.0% from 3 years of follow-up. No increase was observed in the frequency and severity of adverse events with long-term follow-up. No new toxicities were detected, and there was no increase in the frequency of symptomatic MEK inhibitor class-effect adverse events. Conclusions: A subset of patients with advanced BRAFV600-mutated melanoma treated with a combination regimen of vemurafenib and cobimetinib achieve favorable long-term outcomes.
Iris biopsy to investigate feline iris hyperpigmentation.

OBJECTIVE To evaluate the benefit of iris biopsy in cats with iris hyperpigmentation to differentiate melanosis from early feline diffuse iris melanoma (FDIM). METHODS The medical records of cats with unilateral iris hyperpigmentation that had undergone iris biopsy between February 2013 and September 2016 at Willows Veterinary Centre & Referral Service were reviewed. RESULTS Seven cats with unilateral iris hyperpigmentation were included in this retrospective study. The biopsy procedure was performed under general anesthesia (n = 7) with neuromuscular blockade (n = 6) following pre-operative topical miotic therapy (n = 5). One to six biopsy samples per eye were harvested from areas of hyperpigmentation. The samples were partial thickness (n = 4 eyes) and full thickness (n = 3 eyes). Complications were minor: mild intra-operative hemorrhage (n = 4), fibrin clot (n = 2), corneal ulcer (n = 1), post-operative ocular hypertension (n = 1), dyscoria (n = 1), and pseudopolycoria (n = 2). The first biopsy was diagnostic in six cats; a repeat biopsy was necessary in one cat. Histopathology was consistent with melanosis in five cats and with early FDIM in two cats. Screening for signs of metastatic disease (thoracic computed tomography and abdominal ultrasonography) was negative in the two cats with a preliminary diagnosis of early FDIM. Subsequent enucleation and histopathology confirmed the initial diagnosis in both cases. CONCLUSIONS Iris biopsy in cats with iris hyperpigmentation can be beneficial to differentiate melanosis from early FDIM and thereby help to justify the decision for early enucleation.
New gadget in the membrane trafficking toolbox: A novel inhibitor of SNARE priming

NSF (N-ethylmaleimide sensitive factor) and its yeast counterpart Sec18 are highly conserved homohexameric proteins that play vital roles in eukaryotic membrane trafficking. Sec18 functions by disrupting SNARE complexes formed in cis, on the same membrane. However, the molecular mechanisms of this process are poorly understood, in large part due to the lack of selective, reversible inhibitors. A new study by Sparks et al. now reports a small molecule that appears to selectively inhibit Sec18 action in an in vitro assay. Their finding now paves the way to elucidate further details of Sec18-mediated SNARE priming.
The Role of Nanovaccine in Cross-Presentation of Antigen-Presenting Cells for the Activation of CD8+ T Cell Responses

Explosive growth in nanotechnology has merged with vaccine development in the battle against diseases caused by bacterial or viral infections and malignant tumors. Due to physicochemical characteristics including size, viscosity, density and electrostatic properties, nanomaterials have been applied to various vaccination strategies. Nanovaccines, as they are called, have been the subject of many studies, including review papers from a material science point of view, although a mode of action based on a biological and immunological understanding has yet to emerge. In this review, we discuss nanovaccines in terms of CD8+ T cell responses, which are essential for antiviral and anticancer therapies. We focus mainly on the role and mechanism, with particular attention to the functional aspects, of nanovaccines in inducing cross-presentation, an unconventional type of antigen-presentation that activates CD8+ T cells upon administration of exogenous antigens, in dendritic cells followed by activation of antigen-specific CD8+ T cell responses. Two major intracellular mechanisms that nanovaccines harness for cross-presentation are described; one is endosomal swelling and rupture, and the other is membrane fusion. Both processes eventually allow exogenous vaccine antigens to be exported from phagosomes to the cytosol followed by loading on major histocompatibility complex class I, triggering clonal expansion of CD8+ T cells. Advancement of nanotechnology with an enhanced understanding of how nanovaccines work will contribute to the design of more effective and safer nanovaccines.
Role of Citrate in Pathophysiology and Medical Management of Bone Diseases

Citrate is an intermediate in the “Tricarboxylic Acid Cycle” and is used by all aerobic organisms to produce usable chemical energy. It is a derivative of citric acid, a weak organic acid which can be introduced with diet since it naturally exists in a variety of fruits and vegetables, and can be consumed as a dietary supplement. The close association between this compound and bone was pointed out for the first time by Dickens in 1941, who showed that approximately 90% of the citrate bulk of the human body resides in mineralised tissues. Since then, the number of published articles has increased exponentially, and considerable progress in understanding how citrate is involved in bone metabolism has been made. This review summarises current knowledge regarding the role of citrate in the pathophysiology and medical management of bone disorders.
Meta-iAVP: A Sequence-Based Meta-Predictor for Improving the Prediction of Antiviral Peptides Using Effective Feature Representation

In spite of the large-scale production and widespread distribution of vaccines and antiviral drugs, viruses remain a prominent human disease. Recently, the discovery of antiviral peptides (AVPs) has become an influential antiviral agent due to their extraordinary advantages. With the avalanche of newly-found peptide sequences in the post-genomic era, there is a great demand to develop a sequence-based predictor for timely identifying AVPs as this information is very useful for both basic research and drug development. In this study, we propose a novel sequence-based meta-predictor with an effective feature representation, called Meta-iAVP, for the accurate prediction of AVPs from given peptide sequences. Herein, the effective feature representation was extracted from a set of prediction scores derived from various machine learning algorithms and types of features. To the best of our knowledge, the model proposed herein represents the first meta-based approach for the prediction of AVPs. An overall accuracy and Matthews correlation coefficient of 95.20% and 0.90, respectively, was achieved from the independent test set on an objective benchmark dataset. Comparative analysis suggested that Meta-iAVP was superior to that of existing methods and therefore represents a useful tool for AVP prediction. Finally, in an effort to facilitate high-throughput prediction of AVPs, the model was deployed as the Meta-iAVP web server and is made freely available online at http://codes.bio/meta-iavp/ where users can submit query peptide sequences for determining the likelihood of whether or not these peptides are AVPs.
Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen- dependent hyperprolactinemia

The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradioltreated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 µg rat -1 week -1 ) for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat -1 day -1 ) was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 µg estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 µg estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05). Therefore, the increase in serum prolactin levels observed in rats treated with 50 µg estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a “functional” estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 µg estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats.
MicroRNA-29a Mitigates Subacromial Bursa Fibrosis in Rotator Cuff Lesion with Shoulder Stiffness

Rotator cuff lesion with shoulder stiffness is a major cause of shoulder pain and motionlessness. Subacromial bursa fibrosis is a prominent pathological feature of the shoulder disorder. MicroRNA-29a (miR-29a) regulates fibrosis in various tissues; however, the miR-29a action to subacromial bursa fibrosis remains elusive. Here, we reveal that subacromial synovium in patients with rotator cuff tear with shoulder stiffness showed severe fibrosis, hypertrophy, and hyperangiogenesis histopathology along with significant increases in fibrotic matrices collagen (COL) 1A1, 3A1, and 4A1 and inflammatory cytokines, whereas miR-29a expression was downregulated. Supraspinatus and infraspinatus tenotomy-injured shoulders in transgenic mice overexpressing miR-29a showed mild swelling, vascularization, fibrosis, and regular gait profiles as compared to severe rotator cuff damage in wild-type mice. Treatment with miR-29a precursor compromised COL3A1 production and hypervascularization in injured shoulders. In vitro, gain of miR-29a function attenuated COL3A1 expression through binding to the 3’-untranslated region (3′-UTR) of COL3A1 in inflamed tenocytes, whereas silencing miR-29a increased the matrix expression. Taken together, miR-29a loss is correlated with subacromial bursa inflammation and fibrosis in rotator cuff tear with shoulder stiffness. miR-29a repressed subacromial bursa fibrosis through directly targeting COL3A1 mRNA, improving rotator cuff integrity and shoulder function. Collective analysis offers a new insight into the molecular mechanism underlying rotator cuff tear with shoulder stiffness. This study also highlights the remedial potential of miR-29a precursor for alleviating the shoulder disorder.
Altilix® Supplement Containing Chlorogenic Acid and Luteolin Improved Hepatic and Cardiometabolic Parameters in Subjects with Metabolic Syndrome: A 6 Month Randomized, Double-Blind, Placebo-Controlled Study

The objective was to evaluate the effects of 6 months of supplementation with Altilix®, containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix® (26 men and 24 women, mean age 63 ± 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 ± 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endothelial function were assessed by doppler ultrasound and by flow-mediated dilation of the brachial artery, respectively. The presence and degree of non-alcoholic fatty liver disease (NAFLD) was assessed by the fatty liver index (FLI), and subjects were divided into three subgroups: (1) without NAFLD; (2) with borderline NAFLD; and (3) with NAFLD. After 6 months of Altilix® supplementation, we found a significant improvement vs. placebo in most of the evaluated parameters, including body weight (-2.40% (95% CI -3.79, -1.01); p < 0.001), waist circumference (-2.76% (95% CI -4.55, -0.96); p = 0.003), HbA1c (-0.95% (95% CI -1.22, -0.67); p < 0.001), plasma lipids, FLI (-21.83% (95% CI -27.39, -16.27); p < 0.001), hepatic transaminases, flow-mediated dilation (10.56% (95% CI 5.00, 16.12); p < 0.001), and carotid intima-media thickness (-39.48% (95% CI -47.98, -30.97); p < 0.001). Further, the improvement in cardiometabolic variables was independent of the degree of hepatic steatosis. Altilix® supplementation improved hepatic and cardio-metabolic parameters in MetS subjects. Altilix® supplementation was a beneficial approach in the management of hepatic and cardiometabolic alterations in MetS subjects.
IN-VITRO RESISTANCE PATTERN OF ESCHERICHIA COLI ISOLATED FROM PATIENTS WITH URINARY TRACT INFECTION IN TEHRAN

We aimed to nominate the sample of active bacteria resistance in Urinary Tract in Tehran as capital of Iran to find the best treatment for empirical therapy of Escherichia coli (E.coli) associated UTI for the first time in Tehran. In a descriptive cross sectional study, we studied 372 patients; 64 males and 308 females who were diagnosed with UTI. We collected all of the urine samples of patients with UTI in period of a year. First, all of the samples were collected using mid-stream clean catch method. Then, urine culture was done with 0.2 ml of urine samples in sterile containers using Eosin-methylene Blue (EMB) and blood agar special culture media (Merck, Germany). Samples were cultured in 20 minutes and plates were placed in incubator for 24hours at 37°C. All of the samples with colony count higher than 10 5 were considered positive, then genus level (families, orders, etc.) were determined using standard methods. After culture, we transmitted antibiogram disks. After 24 hours we measured the growth inhibition zone of disk. Statistical analysis was performed using SPSS software package for windows version 15. P value less than 0.05 was statistically considered significant in all steps. We studied 372 patients; 64 males (17.2%) and 308 females (82.8%) who were diagnosed with UTI. Mean age was 44.5 years of old (1-87 y/o). In view of incidence of dysuria, frequency, urgency, hematuria, pain in flanks and pain in hypogastria. There was not a significant statistical difference in both sexes. In pregnant cases the highest susceptibility is against ciprofloxacin and the highest resistance is against Cotrimaxazole. Ciprofloxacin is first choice of antimicrobial treatment for out-patients and Cotrimaxazole and Cefexime is not supposed to be first choice of treatment.
SON protects nascent transcripts from unproductive degradation by counteracting DIP1

Gene expression involves the transcription and splicing of nascent transcripts through the removal of introns. In Drosophila, a double-stranded RNA binding protein Disco-interacting protein 1 (DIP1) targets INE-1 stable intronic sequence RNAs (sisRNAs) for degradation after splicing. How nascent transcripts that also contain INE-1 sequences escape degradation remains unknown. Here we observe that these nascent transcripts can also be bound by DIP1 but the Drosophila homolog of SON (Dsn) protects them from unproductive degradation in ovaries. Dsn localizes to the satellite body where active decay of INE-1 sisRNAs by DIP1 occurs. Dsn is a repressor of DIP1 posttranslational modifications (primarily sumoylation) that are assumed to be required for efficient DIP1 activity. Moreover, the pre-mRNA destabilization caused by Dsn depletion is rescued in DIP1 or Sumo heterozygous mutants, suggesting that Dsn is a negative regulator of DIP1. Our results reveal that under normal circumstances nascent transcripts are susceptible to DIP1-mediated degradation, however intronic sequences are protected by Dsn until intron excision has taken place.
Comparative analysis of epigenetic inhibitors reveals different degrees of interference with transcriptional gene silencing and induction of DNA damage.

Repetitive DNA sequences and some genes are epigenetically repressed by transcriptional gene silencing (TGS). When genetic mutants are not available or problematic to use, TGS can be suppressed by chemical inhibitors. However, informed use of epigenetic inhibitors is partially hampered by the absence of their systematic comparison. In addition, there is emerging evidence that epigenetic inhibitors cause genome instability, but the nature of this damage and its repair remain unclear. To bridge these gaps, we compared effects of 5-azacytidine (AC), 2´-deoxy-5-azacytidine (DAC), zebularine and 3-deazaneplanocin A (DZNep) on TGS and DNA damage repair. The most effective TGS inhibitor was DAC, followed by DZNep, zebularine, and AC. We confirmed that all inhibitors induce DNA damage and suggest that this damage is repaired by multiple pathways with a critical role of homologous recombination and of the SMC5/6 complex. A strong positive link between the degree of cytidine analog-induced DNA demethylation and the amount of DNA damage suggests that DNA damage is an integral part of cytidine analog-induced DNA demethylation. This helps understanding function of DNA methylation in plants and opens the possibilities towards the use of epigenetic inhibitors in biotechnology.