Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Immunomodulatory Drug Fingolimod (FTY720) on Chlamydia Dissemination and Pathogenesis

Fingolimod (FTY720), an FDA-approved immunomodulatory drug for treating multiple sclerosis, is an agonist of sphingosine-1-phosphate receptor (S1PR), which has been used as a research tool for inhibiting immune cell trafficking. FTY720 was recently reported to inhibit Chlamydia dissemination. Since genital Chlamydia spreading to the gastrointestinal tract correlated with its pathogenicity in the upper genital tract, we evaluated the effect of FTY720 on chlamydial pathogenicity in the current study. ABSTRACT Fingolimod (FTY720), an FDA-approved immunomodulatory drug for treating multiple sclerosis, is an agonist of sphingosine-1-phosphate receptor (S1PR), which has been used as a research tool for inhibiting immune cell trafficking. FTY720 was recently reported to inhibit Chlamydia dissemination. Since genital Chlamydia spreading to the gastrointestinal tract correlated with its pathogenicity in the upper genital tract, we evaluated the effect of FTY720 on chlamydial pathogenicity in the current study. Following an intravaginal inoculation, live chlamydial organisms were detected in mouse rectal swabs. FTY720 treatment significantly delayed live organism shedding in the rectal swabs. However, FTY720 failed to block chlamydial spreading to the gastrointestinal tract. The live chlamydial organisms recovered from rectal swabs reached similar levels between mice with or without FTY720 treatment by day 42 in C57BL/6J and day 28 in CBA/J mice, respectively. Thus, genital Chlamydia is able to launch a 2nd wave of spreading via an FTY720-resistant pathway after the 1st wave of spreading is inhibited by FTY720. As a result, all mice developed significant hydrosalpinx. The FTY720-resistant spreading led to stable colonization of chlamydial organisms in the colon. Consistently, FTY720 did not alter the colonization of intracolonically inoculated Chlamydia. Thus, we have demonstrated that, following a delay in chlamydial spreading caused by FTY720, genital Chlamydia is able to both spread to the gastrointestinal tract via an FTY720-resistant pathway and maintain its pathogenicity in the upper genital tract. Further characterization of the FTY720-resistant pathway(s) explored by Chlamydia for spreading to the gastrointestinal tract may promote our understanding of Chlamydia pathogenic mechanisms.
Safety considerations when using non-ergot dopamine agonists to treat Parkinson’s disease

ABSTRACT Introduction Nonergot dopamine agonists (NEDA) represent an excellent treatment option for Parkinson’s disease (PD) patients, in both early and advanced stages of the disease. The post-marketing phase of NEDA has highlighted, though, the occurrence of important long-term adverse events. Areas covered This review reports recent updates on NEDA adverse events, analyzing neurobiological bases and risk factors of these complications. A literature search has been performed using Medline and reviewing the bibliographies of selected articles. Expert opinion NEDA represents a very important option in the treatment of PD. Criticisms on their use can be overcome through a better knowledge of these molecules and of the risk factors for adverse events which allow specialists to prevent the occurrence of undesired complications and consent a tailor-based approach. Abbreviations: PD: Parkinson’s disease, DA: dopamine agonists, NEDA: non-ergot dopamine agonists, ICD: impulse control disorders, DAWS: dopamine agonist withdrawal syndrome, CYP: Cytochrome P, PK: pharmacokinetic, AUC: area under the curve, HRT: hormone replacement therapy, AV: atrioventricular, HF: heart failure, OH: orthostatic hypotension, RBD: REM behavior disorders, PDP: Parkinson’s disease psychosis, DRT: dopamine replacement therapy, DDS: dopamine dysregulation syndrome, MMSE: Mini-Mental state examination, EDS: excessive daytime somnolence.
Nonexercise Activity Thermogenesis-Induced Energy Shortage Improves Postprandial Lipemia and Fat Oxidation

(1) Background: This study investigated the effect of nonexercise activity thermogenesis on postprandial triglyceride (TG) concentrations; (2) Methods: Ten healthy males completed a sedentary trial (ST) and a physical activity trial (PA) in a random order separated by at least 7 days. After each intervention on day 1, the participants consumed a high-fat test meal on the next day. The blood samples and gas sample were observed in the fasted state and for 4 h after consuming the oral fat tolerance test; (3) Results: The postprandial TG concentrations of total (AUC) (p = 0.008) and incremental area under the curve (IAUC) (p = 0.023) in the plasma of participants in the PA trial were significantly lower than those in the plasma of participants in the ST trial. The postprandial fat oxidation rate AUC of the PA trial was significantly higher than that of the ST trial (p = 0.009); (4) Conclusions: The results of this study indicated that nonexercise energy expenditure decrease the postprandial TG concentration and increase the fat oxidation the next day.
Comparison of acetylsalicylic acid and clopidogrel non-responsiveness assessed by light transmittance aggregometry and PFA-100® in patients undergoing neuroendovascular procedures

Abstract Objectives Dual platelet inhibition is commonly used for prevention of cardiovascular events in patients undergoing neuroendovascular procedures. Non-responsiveness to platelet inhibitors may be associated with adverse outcomes. The aim of this study was to evaluate the reliability of the platelet function analyzer PFA-100® in comparison to light transmittance aggregometry (LTA) for monitoring clopidogrel and acetylsalicylic acid (ASA) non-responsiveness in a cohort of patients treated for intracranial aneurysm or cranial artery stenosis. Methods Non-responsiveness to clopidogrel and ASA was assessed by LTA using adenosine diphosphate (ADP) and arachidonic acid and by PFA-100® with the ADP/prostaglandin E1 (PGE1) and collagen/epinephrine cartridges, respectively. Results A total of 203 patients (145 females; median age, 57 years) were analyzed. Agreement between the two tests was poor for clopidogrel non-responsiveness (ƙ=0.19) and not better than chance for ASA non-responsiveness (ƙ=0.01). Clopidogrel non-responsiveness by LTA and PFA-100® was associated with higher von Willebrand factor antigen and activity levels. ADP-induced platelet disaggregation was lower in patients with clopidogrel non-responsiveness as assessed by PFA-100®. Clopidogrel non-responsiveness by LTA was associated with a higher prevalence of diabetes and a higher body mass index (BMI). Adverse outcomes (death, thromboembolism, or in-stent thrombosis) occurred in 13% (n=26) of all patients independently of ASA and clopidogrel non-responsiveness as assessed by both devices. Conclusions Our results show that LTA and PFA-100® are not interchangeable in the assessment of ASA and clopidogrel non-responsiveness in patients undergoing neuroendovascular interventions.
Virgin Olive Oil Extracts Reduce Oxidative Stress and Modulate Cholesterol Metabolism: Comparison between Oils Obtained with Traditional and Innovative Processes

This study was aimed at demonstrating the substantial equivalence of two extra virgin olive oil samples extracted from the same batch of Coratina olives with (OMU) or without (OMN) using ultrasound technology, by performing chemical, biochemical, and cellular investigations. The volatile organic compounds compositions and phenolic profiles were very similar, showing that, while increasing the extraction yields, the innovative process does not change these features. The antioxidant and hypocholesterolemic activities of the extra virgin olive oil (EVOO) phenol extracts were also preserved, since OMU and OMN had equivalent abilities to scavenge the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals in vitro and to protect HepG2 cells from oxidative stress induced by H2O2, reducing intracellular reactive oxygen species (ROS) and lipid peroxidation levels. In addition, by inhibiting 3-hydroxy-3-methylglutarylcoenzyme a reductase, both samples modulated the low-density lipoprotein receptor (LDLR) pathway leading to increased LDLR protein levels and activity.
Physiological and biochemical analyses of resistance of different rape varieties to Sclerotinia sclerotiorum

In order to explore the resistance mechanism of different rapeseed varieties to Sclerotinia sclerotiorum,we chose two resistant varieties(Zhongyou 821,Deyou 5) and two susceptible varieties(Wanyou 14,Zayou 1) as experimental materials for analyzing the content changes of malondialdehyde(MDA),proline(Pro),soluble sugar and soluble protein(SP) after inoculation with different virulence of S.sclerotiorum isolates NG4,WW2 and oxalic acid treatment.The results showed that the content of MDA in the resistant and susceptible materials had no significant difference.After infection,all increased and MDA in susceptible varieties grew more significantly than that of resistant varieties.Contents of Pro in the resistant varieties were higher than that in the susceptible varieties when non-vaccinated.After inoculation,all increased and resistant varieties grew more significantly than that of susceptible varieties.The content of soluble sugar was first increased and then decreased,and susceptible varieties grew more significantly than that of resistant varieties.The content of SP in resistant varieties reached a minimum value 24 hours after inoculation,reached the maximum 48 hours after inoculation,and then decreased but was still higher than that in the control.The content of SP in susceptible varieties reached a maximum value 24 hours after inoculation,and then decreased.
The sexual dimorphism of Shastasaurus tangae(Reptilia:Ichthyosauria) from the Triassic Guanling Biota,China

Marine reptiles,especially large-sized long-snout ichthyosaurs,are highly controversial in taxonomy in Guanling Biota(early Carnian,Guizhou,SW China). A large number of largesized long-snout ichthyosaur skeletons have been excavated from Guanling and adjacent areas since 2000.Totally 14 specimens were used for taxonomical research and morphological description in previous works,which were originally named as different genera and species(Yin et al.,2000:Gmr 009,Gmr 015; Li and You,2002:IVPP V 11865,V 11869; Chen and Cheng,2003:TR 00001,SPCV 30014; Maisch et al.,2006:GNP dq-46,D-41,dq-22; Pan et al.,2006:GMPKU P1062; Chen et al.,2007:SPCV 10305,10306; Shang and Li,2009:IVPP V 11853; Shang et al.,2012:IGGCAS 2005F001). Based on the similarity of cranial morphology,Shang et al.(2012) referred all of these specimens to one species Shastasaurus tangae.
Classical and Non-Classical Progesterone Signaling in Breast Cancers

Much emphasis is placed on estrogen (E2) and estrogen receptor (ER) signaling as most research is focused on understanding E2 and ER’s ability to enhance proliferative signals in breast cancers. Progesterone (P4) is important for normal mammary gland development, function and menstrual control. However, P4 and its receptors (PRs) in breast cancer etiology continue to be understudied and its role in breast cancer remains controversial. The Women’s Health Initiative (WHI) clinical trial clearly demonstrated the importance of progestogens in breast cancer development. P4 has historically been associated with classical-signaling through nuclear receptors, however non-classical P4 signaling via membrane receptors has been described. Progestogens have the ability to bind to nuclear and membrane receptors and studies have demonstrated that both can promote breast cancer cell proliferation and breast tumor growth. In this review, we attempt to understand the classical and non-classical signaling role of P4 in breast cancers because both nuclear and membrane receptors could become viable therapeutic options for breast cancer patients.
Supergene evolution via stepwise duplications and neofunctionalization of a floral-organ identity gene

Significance Heterostyly is an adaptation to promote outbreeding in plants. In heterostylous primroses, plants form flowers either with long styles and low anthers or with short styles and high anthers. This difference is due to a chromosomal segment containing five predicted genes, yet their roles and the evolution of this segment remain unclear. Here we identify the gene responsible for raising the anthers in short-styled flowers. This gene arose by duplication from a classical floral-organ identity gene and gained a novel function. Surprisingly, the responsible chromosomal segment appears to have evolved by stepwise gene duplications rather than duplication of an entire chromosomal block. These findings thus provide detailed insight into the evolution of complex polymorphisms involving different individual traits. Heterostyly represents a fascinating adaptation to promote outbreeding in plants that evolved multiple times independently. While l-morph individuals form flowers with long styles, short anthers, and small pollen grains, S-morph individuals have flowers with short styles, long anthers, and large pollen grains. The difference between the morphs is controlled by an S-locus “supergene” consisting of several distinct genes that determine different traits of the syndrome and are held together, because recombination between them is suppressed. In Primula, the S locus is a roughly 300-kb hemizygous region containing five predicted genes. However, with one exception, their roles remain unclear, as does the evolutionary buildup of the S locus. Here we demonstrate that the MADS-box GLOBOSA2 (GLO2) gene at the S locus determines anther position. In Primula forbesii S-morph plants, GLO2 promotes growth by cell expansion in the fused tube of petals and stamen filaments beneath the anther insertion point; by contrast, neither pollen size nor male incompatibility is affected by GLO2 activity. The paralogue GLO1, from which GLO2 arose by duplication, has maintained the ancestral B-class function in specifying petal and stamen identity, indicating that GLO2 underwent neofunctionalization, likely at the level of the encoded protein. Genetic mapping and phylogenetic analysis indicate that the duplications giving rise to the style-length-determining gene CYP734A50 and to GLO2 occurred sequentially, with the CYP734A50 duplication likely the first. Together these results provide the most detailed insight into the assembly of a plant supergene yet and have important implications for the evolution of heterostyly.
Diallel analysis in sunflower

Five genotypes of sunflower namely 852 B, 336 B, TNHSF 239, TNAUSUF 207 and CO 4 were crossed in diallel fashion excluding reciprocals. The F1s and parents were evaluated for days to 50% flowering, plant height, head diameter and seed yield plant. Both additive and nonadditive gene action were important and preponderance of non-additive gene action was observed for all characters. The parents TNHSF 239 and CO 4 showed superior per se performance for all characters except days to 50 per cent flowering. The parent TNAUSUF 207 showed desirable gca for all characters and TNHSF 239 and CO 4 for all characters except plant height. Superior Per se performance and heterosis were recorded for TNHSF 239 x CO 4 and TNAUSUF 207 x CO 4. These hybrids could be considered desirable for commercial evaluation. Both the parents of the selected hybrids namely TNHSF 239 x TNAUSUF 207 and TNAUSUF 207 x CO 4 were good combiner for all characters and the combining ability of hybrids were also desirable for all characters. Selection should be postponed to later generation in these crosses due to the presence of additive type of epistasis. Hence these hybrids could be recommended for pedigree programme to evolve superior inbreds/variety.
Pharmacodynamic Evaluation of MRX-8, a Novel Polymyxin, in the Neutropenic Mouse Thigh and Lung Infection Models against Gram-Negative Pathogens

MRX-8 is a novel polymyxin analogue in development for the treatment of infections caused by Gram-negative pathogens, including those resistant to other antibiotic classes. In the present study, we examined the pharmacodynamic activity of MRX-8 against a variety of common Gram-negative pathogens in the neutropenic mouse thigh and lung models. Additionally, we examined polymyxin B (PMB) as a comparator. Plasma pharmacokinetics of MRX-8 and PMB were linear over a broad dosing range of 0.156 to 10 mg/kg of body weight and had similar AUC0–∞ (area under the drug concentration-time curve from 0 h to infinity) exposures of MRX-8, 0. ABSTRACT MRX-8 is a novel polymyxin analogue in development for the treatment of infections caused by Gram-negative pathogens, including those resistant to other antibiotic classes. In the present study, we examined the pharmacodynamic activity of MRX-8 against a variety of common Gram-negative pathogens in the neutropenic mouse thigh and lung models. Additionally, we examined polymyxin B (PMB) as a comparator. Plasma pharmacokinetics of MRX-8 and PMB were linear over a broad dosing range of 0.156 to 10 mg/kg of body weight and had similar AUC0–∞ (area under the drug concentration-time curve from 0 h to infinity) exposures of MRX-8, 0.22 to 12.64 mg · h/liter, and PMB, 0.12 to 13.22 mg · h/liter. Dose fractionation was performed for MRX-8 using a single Escherichia coli isolate, and the results demonstrated that both Cmax (maximum concentration of drug in serum)/MIC and AUC/MIC ratios were strongly associated with efficacy. In the thigh model, dose-ranging studies included strains of E. coli (n = 3), Pseudomonas aeruginosa (n = 2), Klebsiella pneumoniae (n = 3), and Acinetobacter baumannii (n = 1). Both MRX-8 and PMB exhibited increased effects with increasing doses. MRX-8 and PMB free AUC/MIC exposures for net stasis were similar for E. coli and K. pneumoniae at 20 to 30. Notably, for P. aeruginosa and A. baumannii, the free AUC/MIC ratio for stasis was numerically much smaller for MRX-8 at 6 to 8 than for PMB at 16 to 37. In the lung model, MRX-8 was also more effective than PMB when dosed to achieve similar free-drug AUC exposures over the study period. MRX-8 is a promising novel polymyxin analogue with in vivo activity against many different clinically relevant species in both the mouse thigh and lung models.
SARS-CoV-2 infection: diagnostic testing results occasionally require special attention

ABSTRACT The case refers to a 51-year-old symptomatic man with a new SARS-CoV-2 RNA positive nasopharyngeal swab after two negative ones and the lack of significant development of antibody response measured by different diagnostic serological test. Our case underlines that a discrepancy between clinical course of SARS-CoV-2 infection and results from diagnostic tests may exist. This concept is rapidly emerging and supports the need for a deep knowledge of available and “in development” tests for a correct interpretation of their findings.
Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs

Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.
Usefulness of pointwise encoding time reduction with radial acquisition sequence in subtraction-based magnetic resonance angiography for follow-up of the Neuroform Atlas stent-assisted coil embolization for cerebral aneurysms

Background Although time-of-flight magnetic resonance angiography (TOF-MRA) is widely used, it has limited usefulness for follow-up after stent-assisted coil embolization. Contrast-enhanced MRA (CE-MRA) and ultrashort echo time MRA have been suggested as alternative methods for visualization after this procedure. Purpose To compare efficacy and usefulness of pointwise encoding time reduction with radial acquisition (PETRA) sequence in subtraction-based MRA (qMRA), TOF-MRA, and CE-MRA during the follow-up after Neuroform Atlas stent-assisted coil embolization for intracranial aneurysms. Material and Methods This retrospective study included 23 patients with 24 aneurysms who underwent Neuroform Atlas stent-assisted coil embolization for intracranial aneurysms. All patients were evaluated with PETRA qMRA, TOF-MRA, and CE-MRA at the same follow-up session. The flow within stents, occlusion status, and presence of pseudo-stenosis were evaluated; inter-observer and intermodality agreements for the three methods were also graded. Results The mean score for flow visualization within the stents was significantly higher for PETRA qMRA and CE-MRA than for TOF-MRA (although no significant difference was found between PETRA qMRA and CE-MRA). Good inter-observer agreement was observed for each modality. PETRA qMRA and CE-MRA were more consistent with digital subtraction angiography (DSA) than TOF-MRA for aneurysm occlusion status. The intermodality agreement was better between PETRA qMRA and DSA, and between CE-MRA and DSA, than between DSA and TOF-MRA. Pseudo-stenosis was most frequently observed in TOF-MRA, followed by CE-MRA and PETRA qMRA. Conclusion PETRA qMRA is useful for evaluating the parent artery patency and occlusion status of aneurysms after Neuroform Atlas stent-assisted coil embolization.
Gain of LINC00624 Enhances Liver Cancer Progression by Disrupting the Histone Deacetylase 6/Tripartite Motif Containing 28/Zinc Finger Protein 354C Corepressor Complex

Long noncoding RNAs (lncRNAs) are involved in almost every stage of tumor initiation and progression. Here, we have identified an antisense lncRNA, LINC00624, that arises from the antisense strand of chromo‐domain‐helicase‐DNA‐binding protein 1‐like (CHD1L), located on chr1q21.1, with significant copy number gain and transcriptional activation of CHD1L and B‐cell CLL/lymphoma 9 protein (BCL9), in hepatocellular carcinoma (HCC).
Sensory recovery after infraorbital nerve avulsion injury

The infraorbital nerve is a branch of the trigeminal nerve. Injury to the infraorbital nerve can be caused by trauma, including various facial fractures. Due to this nerve injury, patients complain of numbness and pain in the entire cheek, the ala of nose, and upper lip. In general, spontaneous sensory recovery is expected after decompressive surgery. If nerve transection is confirmed, however, neurorrhaphy is typically performed. Here, we present a case in which microsurgery was not performed in a patient with Sunderland grade V avulsion injury of the infraorbital nerve due to a facial bone fracture. Gradual nerve function recovery was confirmed to be possible with conservative treatment and rehabilitation alone. These findings suggest that the nerve function recovery can be expected with conservative treatment, even for severe nerve injury for which microsurgery cannot be considered.