Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of cytochrome P450 enzyme activity and expression by nitric oxide in the context of inflammatory disease

Abstract Many hepatic cytochrome P450 enzymes and their associated drug metabolizing activities are down-regulated in disease states, and much of this has been associated with inflammatory cytokines and their signaling pathways. One such pathway is the induction of inducible nitric oxide synthase (NOS2) and generation of nitric oxide (NO) in many tissues and cells including the liver and hepatocytes. Experiments in the 1990s demonstrated that NO could bind to and inhibit P450 enzymes, and suggested that inhibition of NOS could attenuate, and NO generation could mimic, the down-regulation by inflammatory stimuli of not only P450 catalytic activities but also of mRNA expression and protein levels of certain P450 enzymes. This review will summarize and examine the evidence that NO functionally inhibits and down-regulates P450 enzymes in vivo and in vitro, with a particular focus on the mechanisms by which these effects are achieved.
Gut Microbiota and Intestinal Trans-Epithelial Permeability

Constant remodeling of tight junctions to regulate trans-epithelial permeability is essential in maintaining intestinal barrier functions and thus preventing diffusion of small molecules and bacteria to host systemic circulation. Gut microbiota dysbiosis and dysfunctional gut barrier have been correlated to a large number of diseases such as obesity, type 2 diabetes and inflammatory bowel disease. This led to the hypothesis that gut bacteria-epithelial cell interactions are key regulators of epithelial permeability through the modulation of tight junctions. Nevertheless, the molecular basis of host-pathogen interactions remains unclear mostly due to the inability of most in vitro models to recreate the differentiated tissue structure and components observed in the normal intestinal epithelium. Recent advances have led to the development of a novel cellular model derived from intestinal epithelial stem cells, the so-called organoids, encompassing all epithelial cell types and reproducing physiological properties of the intestinal tissue. We summarize herein knowledge on molecular aspects of intestinal barrier functions and the involvement of gut bacteria-epithelial cell interactions. This review also focuses on epithelial organoids as a promising model for epithelial barrier functions to study molecular aspects of gut microbiota-host interaction.
Effect of Stereolithography 3D Printing on the Properties of PEGDMA Hydrogels

Stereolithography (SLA)-based 3D printing has proven to have several advantages over traditional fabrication techniques as it allows for the control of hydrogel synthesis at a very high resolution, making possible the creation of tissue-engineered devices with microarchitecture similar to the tissues they are replacing. Much of the previous work in hydrogels for tissue engineering applications have utilised the ultraviolet (UV) chamber bulk photopolymerisation method for preparing test specimens. Therefore, it is essential to directly compare SLA 3D printing to this more traditional approach to elucidate the differences in hydrogels prepared by each fabrication method. Polyethyleneglycol dimethacrylate (PEGDMA) is an ideally suited material for a comparative study of the impact that SLA fabrication has on performance, as the properties of traditional UV chamber-cured hydrogels have been extensively characterised. The present study was conducted to compare the material properties of PEGDMA hydrogels prepared using UV chamber photopolymerisation and SLA 3D printing. From the subsequent testing, SLA-fabricated hydrogels were shown to maintain similar thermal and chemical performance to UV chamber-cured hydrogels but had a higher compressive strength and tensile stiffness, as well as increased hydrophilicity. These differences are attributed to the increased exposure to UV light SLA samples received compared to traditionally UV chamber-cured samples.
Trends of the Dengue Serotype-4 Circulation with Epidemiological, Phylogenetic, and Entomological Insights in Lao PDR between 2015 and 2019

Dengue outbreaks have regularly been recorded in Lao People’s Democratic Republic (PDR) since the first detection of the disease in 1979. In 2012, an integrated arbovirus surveillance network was set up in Lao PDR and an entomological surveillance has been implemented since 2016 in Vientiane Capital. Here, we report a study combining epidemiological, phylogenetic, and entomological analyzes during the largest DENV-4 epidemic ever recorded in Lao PDR (2015–2019). Strikingly, from 2015 to 2019, we reported the DENV-4 emergence and spread at the country level after two large epidemics predominated by DENV-3 and DENV-1, respectively, in 2012–2013 and 2015. Our data revealed a significant difference in the median age of the patient infected by DENV-4 compared to the other serotypes. Phylogenetic analysis demonstrated the circulation of DENV-4 Genotype I at the country level since at least 2013. The entomological surveillance showed a predominance of Aedes aegypti compared to Aedes albopictus and high abundance of these vectors in dry and rainy seasons between 2016 and 2019, in Vientiane Capital. Overall, these results emphasized the importance of an integrated approach to evaluate factors, which could impact the circulation and the epidemiological profile of dengue viruses, especially in endemic countries like Lao PDR.
Sexually dimorphic effects of forkhead box a2 (FOXA2) and uterine glands on decidualization and fetoplacental development

Significance Uterine glands play a critical role in embryo implantation and pregnancy establishment. Using mouse genetic models, we found that FOXA2-regulated genes in the uterine glands influence development of the decidua, as well as the placenta and fetus in a sex-dependent manner. These findings support the idea that uterine gland dysfunction affects placental and fetal growth with sexually dimorphic impacts on offspring adult health and disease. Glands of the uterus are essential for pregnancy establishment. Forkhead box A2 (FOXA2) is expressed specifically in the glands of the uterus and a critical regulator of glandular epithelium (GE) differentiation, development, and function. Mice with a conditional deletion of FOXA2 in the adult uterus, created using the lactotransferrin iCre (Ltf-iCre) model, have a morphologically normal uterus with glands, but lack FOXA2-dependent GE-expressed genes, such as leukemia inhibitory factor (LIF). Adult FOXA2 conditional knockout (cKO; LtfiCre/+Foxa2f/f) mice are infertile due to defective embryo implantation arising from a lack of LIF, a critical implantation factor of uterine gland origin. However, intraperitoneal injections of LIF can initiate embryo implantation in the uterus of adult FOXA2 cKO mice with pregnancies maintained to term. Here, we tested the hypothesis that FOXA2-regulated genes in the uterine glands impact development of the decidua, placenta, and fetus. On gestational day 8.5, the antimesometrial and mesometrial decidua transcriptome was noticeably altered in LIF-replaced FOXA2 cKO mice. Viable fetuses were reduced in FOXA2 cKO mice on gestational days 12.5 and 17.5. Sex-dependent differences in fetal weight, placenta histoarchitecture, and the placenta and metrial gland transcriptome were observed between control and FOXA2 cKO mice. The transcriptome of the placenta with a female fetus was considerably more altered than the placenta with a male fetus in FOXA2 cKO dams. These studies reveal previously unrecognized sexually dimorphic effects of FOXA2 and uterine glands on fetoplacental development with potential impacts on offspring health into adulthood.
Dichotic listening while walking: A dual-task paradigm examining gait asymmetries in healthy older and younger adults

ABSTRACT Dual-task studies have employed various cognitive tasks to evaluate the relationship between gait and cognition. Most of these tests are not specific to a single cognitive ability or sensory modality and have limited ecological validity. In this study, we employed a dual-task paradigm using Dichotic Listening (DL) as concomitant cognitive task to walking. We argue that DL is a robust task to unravel the gait-cognition link in different healthy populations of different age groups. Thirty-six healthy older adults (Mean = 67.11) and forty younger adults (Mean = 22.75) participated in the study. DL consists of three conditions where spontaneous attention and attention directed to right or left-ear are tested while walking. We calculated dual-task costs (DTCs) and percent of baseline values for three spatio-temporal gait parameters as compared to single-walking during three DL conditions. Results showed that both groups had larger DTCs on gait during volitional control of attention, i.e., directing attention to one specific ear. Group differences were present across all DL conditions where older adults reported consistently less correct stimuli than younger participants. Similar findings were observed in the neuropsychological battery where older participants showed restricted abilities for executive functioning and processing speed. However, the main finding of this investigation was that younger adults exhibited unique adjustments in step length variability as shown by changes in DTCs and percent of baseline values. Particularly, an asymmetric effect was observed on the young group when attending right-ear stimuli. We interpreted this gait asymmetry as a compensatory outcome in the younger participants due to their optimal perceptual and motor abilities, which allow them to cope suitably with the dual-task situation. Many studies suggest that gait asymmetries are indicators of pathology, the present data demonstrate that gait asymmetries arise under specific constraints in healthy people as an adaptation to task requirements.
A Systematic Review of the Efficacy and Safety of Microneedling in the Treatment of Melasma.

BACKGROUND Melasma is an acquired disorder of hyperpigmentation that is often recalcitrant to current therapies. Microneedling is used to treat scars, striae, and rhytides and has a relatively low risk of post-treatment dyspigmentation. Several studies have examined its use in melasma. OBJECTIVE To review the published evidence on the efficacy and safety of microneedling in the treatment of melasma. METHODS A systematic review was performed. A meta-analysis could not be performed because of methodological differences across studies and data heterogeneity. RESULTS Eight studies were included for analysis. Most studies assessed the utility of microneedling in combination with other topical therapies and detected some success. However, microneedling-mediated transdermal delivery of medications is not superior to microinjections of medications. There is less evidence supporting the use of microneedling as monotherapy. Microneedling, when used with a 1064-nm Q-switched Nd:YAG laser, may provide additional benefit, although with a risk of post-treatment dyspigmentation. CONCLUSION Based on low-quality evidence, microneedling may play a role in the treatment of melasma, with the mechanism of action likely being the facilitation of delivery of topical therapies to the epidermis and dermis, and one ancillary benefit of this approach being the very low risk of postinflammatory hyperpigmentation.
Long sleep duration and risk of increased arterial stiffness in a Chinese population

Abstract To examine the relationship between self-reported sleep duration and arterial stiffness in a large Chinese population from Kailuan. From July 2010 to December 2015, a total of 17,018 participants aged 18 to 98 years were enrolled after excluding those with a history of cerebrovascular events and coronary artery disease. Participants were divided into 5 categories according to self-reported night sleep duration: ≤5.0, 6.0, 7 (ref), 8, and ≥9.0 hours. A brachial-ankle pulse wave velocity ≥1400 cm/s was considered to represent arterial stiffness. Multivariate logistic regression models were used to calculate the odds ratio (OR) and confidence interval (CI) for arterial stiffness according to the sleep duration. Using 7 hours of sleep as the reference group, the multivariable adjusted ORs (95% CI) for arterial stiffness were 1.00 (0.87–1.16), 1.00 (0.90–1.11), 1.0 (ref), 1.03 (0.93–1.14), and 1.48 (1.05–2.08) from the lowest to highest category of sleep duration, respectively. Secondary analysis showed no evidence of interactions between sleep duration and age/sex on the risk of arterial stiffness (P-interaction = .390/.198). A long night sleep duration was associated with increased arterial stiffness.
Evaluation Des Attaques De Termites (Isoptera Brulle, 1832) Sur Quatre Essences Forestieres D’importance Economique Au Togo (Afrique De L’ouest)

Termites are one of the most abundant invertebrates in tropical ecosystems, where they play a major ecological role in litter decomposition. Despite their important role, termites can cause considerable damage to wood structures in most tropical countries. The aims of this study was to evaluate termite attack in four economically important species in Togo including Antiaris africana Engl (Moraceae), Pterocarpus erinaceus Poir (Fabaceae), Triplochiton scleroxylon Schum (Malvaceae) (all local species) and teak or Tectona grandis Linne (Lamiaceae). For the latter species, termites were infested on 83.49% of 630 feet examined. However, the rate and type attacks differ from one plantation to another. On the studied forest species, termites were collected on about 97% of Triplochiton scleroxylon feet. For this species, at least 31% of examined feet have had their wood attacked. For the other two species, Pterocarpus erinaceus and Antiaris africana respectively about 80% and 67% of examined feet were attacked by termites. Amitermes evuncifer, Ancistrotermes guineensis and Microtermes lepidus were species of termite often harvested from trees examined. However the last two species namely A. guineensis and M. lepidus are encountered on the bark of trees inside veneers unlike A. evuncifer harvested in the heart of the wood. Therefore, the latter species deserves special attention as likely to cause serious damage not only to these species but also other species not taken into account in this study. It is therefore necessary to consider adequate control methods against these species.
Sex-Dependent Wheel Running Effects on High Fat Diet Preference, Metabolic Outcomes, and Performance on the Barnes Maze in Rats

Excessive and prolonged intake of highly palatable, high fat (HF) foods contributes to the pathogenesis of obesity, metabolic syndrome, and cognitive impairment. Exercise can restore energy homeostasis and suppress HF diet preference in rats. However, it is unclear if exercise confers similar protection against the detrimental outcomes associated with a chronic HF diet preference and feeding in both sexes. We used our wheel running (WR) and two-diet choice (chow vs. HF) paradigm to investigate the efficacy of exercise in reversing HF diet-associated metabolic and cognitive dysregulation in rats, hypothesizing that beneficial effects of exercise would be more pronounced in males. All WR rats showed HF diet avoidance upon running initiation, and males, but not females, had a prolonged reduction in HF diet preference. Moreover, exercise only improved glucose tolerance and insulin profile in males. Compared to sedentary controls, all WR rats improved learning to escape on the Barnes maze. Only WR females increased errors made during subsequent reversal learning trials, indicating a sex-dependent effect of exercise on behavioral flexibility. Taken together, our results suggest that exercise is more effective at attenuating HF-associated metabolic deficits in males, and highlights the importance of developing sex-specific treatment interventions for obesity and cognitive dysfunction.
Association of intrinsic sphincter deficiency with urine flow acceleration measurement

Intrinsic sphincter deficiency (ISD) is associated with an inability to maintain mucosal coaptation either at rest or in the presence of stress resulting from damage to muscles or nerves that maintain tonus. The purpose of our trial was to determine the role of urodynamic measurements of flow such as maximum flow rate, flow time, and acceleration speed of flow to assess the urethral resistance on prediction of stress incontinence and ISD.
iDPPIV-SCM: A sequence-based predictor for identifying and analyzing dipeptidyl peptidase IV (DPP-IV) inhibitory peptides using a scoring card method.

The inhibition of dipeptidyl peptidase IV (DPP-IV, E.C.3.4.14.5) is well recognized as a new avenue for the treatment of Type 2 diabetes (T2D). Until now, peptide-like DDP-IV inhibitors have been shown to normalize the blood glucose concentration in T2D subjects. To the best of our knowledge, there is yet no computational model for predicting and analyzing DPP-IV inhibitory peptides using sequence information. In this study, we present for the first time a simple and easily interpretable sequence-based predictor using the scoring card method (SCM) for modeling the bioactivity of DPP-IV inhibitory peptides (iDPPIV-SCM). Particularly, the iDPPIV-SCM was developed by employing the SCM method together with the propensity scores of amino acids. Rigorous independent test results demonstrated that the proposed iDPPIV-SCM was found to be superior to those of well-known machine learning (ML) classifiers (e.g. k-nearest neighbor, logistic regression and decision tree) with demonstrated improvements of 2-11%, 4-22% and 7-10% for accuracy, MCC and AUC, respectively, while also achieving comparable results to that of support vector machine. Furthermore, the analysis of estimated propensity scores of amino acids as derived from the iDPPIV-SCM was performed so as to provide a more in-depth understanding on the molecular basis for enhancing the DPP-IV inhibitory potency. Taken together, these results revealed that iDPPIV-SCM was superior to those of other well-known ML classifiers owing to its simplicity, interpretability and validity. For the convenience of biologists, the predictive model is deployed as a publicly accessible web server at http://camt.pythonanywhere. com/iDPPIV-SCM. It is anticipated that iDPPIV-SCM can serve as an important tool for the rapid screening of promising DPP-IV inhibitory peptides prior to their synthesis.
Differential expression and inhibitory effects of aquaporins on the development of adenomyosis

Aquaporin 2 (AQP2), AQP5 and AQP8 participate in adenomyosis (AM). Ηowever, the roles of these three molecules in AM have not been fully elucidated. In the present study, Institute of Cancer Research female mice were used to establish a model of AM. Subsequently, the endometrial tissues of the mice were observed by hematoxylin-eosin staining, and AM severity, uterus diameter, uterus index, ovary index and numbers of nodules on the uterine surface were evaluated and counted. In addition, eutopic and ectopic endometrial stromal cells (ESCs) were isolated from eutopic and ectopic endometrial samples derived from patients with AM and were then identified by immunofluorescence. The viability, and migratory and invasive ability of ESCs transfected with small interfering RNA targeting AQP5 (siAQP5) were determined by Cell Counting Κit-8, scratch wound-healing and Transwell assays, respectively. Reverse transcription-quantitative polymerase chain reaction was performed to determine the mRNA expression levels of AQP5, epithelial-mesenchymal transition (EMT)-related genes (E-and N-cadherin), matrix metalloproteinase (MMP)-2 and −9. Protein expression levels of AQP2, AQP5, AQP8, E-, N-cadherin, MMP-2 and −9 were detected by western blotting. AM severity and uterus index were higher, and there were a greater number of nodules on the uterine surface in the AM group compared with the sham group. AQP2, AQP5 and AQP8 proteins were highly expressed in eutopic and ectopic endometrium of the AM group, and AQP5 was more highly expressed than AQP2 or AQP8. In addition, the data showed that Vimentin was positively expressed in ESCs, and that siAQP5 suppressed the mRNA expression levels of AQP5, cell viability, migration, invasion, EMT and MMP-2 and −9 expression in ESCs. In conclusion, AQP2, AQP5 and AQP8 were highly expressed in eutopic and ectopic endometrium. Notably, AQP5 silencing may suppress AM by inhibiting viability, migration, invasion, EMT, and MMP-2 and −9 expression in ESCs.
Molecular Profile of Barrett’s Esophagus and Gastroesophageal Reflux Disease in the Development of Translational Physiological and Pharmacological Studies

Barrett’s esophagus (BE) is a premalignant condition caused by gastroesophageal reflux disease (GERD), where physiological squamous epithelium is replaced by columnar epithelium. Several in vivo and in vitro BE models were developed with questionable translational relevance when implemented separately. Therefore, we aimed to screen Gene Expression Omnibus 2R (GEO2R) databases to establish whether clinical BE molecular profile was comparable with animal and optimized human esophageal squamous cell lines-based in vitro models. The GEO2R tool and selected databases were used to establish human BE molecular profile. BE-specific mRNAs in human esophageal cell lines (Het-1A and EPC2) were determined after one, three and/or six-day treatment with acidified medium (pH 5.0) and/or 50 and 100 µM bile mixture (BM). Wistar rats underwent microsurgical procedures to generate esophagogastroduodenal anastomosis (EGDA) leading to BE. BE-specific genes (keratin (KRT)1, KRT4, KRT5, KRT6A, KRT13, KRT14, KRT15, KRT16, KRT23, KRT24, KRT7, KRT8, KRT18, KRT20, trefoil factor (TFF)1, TFF2, TFF3, villin (VIL)1, mucin (MUC)2, MUC3A/B, MUC5B, MUC6 and MUC13) mRNA expression was assessed by real-time PCR. Pro/anti-inflammatory factors (interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, tumor necrosis factor α, interferon γ, granulocyte-macrophage colony-stimulating factor) serum concentration was assessed by a Luminex assay. Expression profile in vivo reflected about 45% of clinical BE with accompanied inflammatory response. Six-day treatment with 100 µM BM (pH 5.0) altered gene expression in vitro reflecting in 73% human BE profile and making this the most reliable in vitro tool taking into account two tested cell lines. Our optimized and established combined in vitro and in vivo BE models can improve further physiological and pharmacological studies testing pathomechanisms and novel therapeutic targets of this disorder.
β-Cell function or insulin resistance was associated with the risk of type 2 diabetes among women with or without obesity and a history of gestational diabetes

Introduction To evaluate the single association of postpartum β-cell dysfunction and insulin resistance (IR), as well as different combinations of postpartum β-cell dysfunction, IR, obesity, and a history of gestational diabetes mellitus (GDM) with postpartum type 2 diabetes risk. Research design and methods The study included 1263 women with prior GDM and 705 women without GDM. Homeostatic model assessment was used to estimate homeostatic model assessment of β-cell secretory function (HOMA-%β) and homeostatic model assessment of insulin resistance (HOMA-IR). Results Multivariable-adjusted ORs of diabetes across quartiles of HOMA-%β and HOMA-IR were 1.00, 1.46, 2.15, and 6.25 (ptrend <0.001), and 1.00, 2.11, 5.59, and 9.36 (ptrend <0.001), respectively. Women with IR only had the same diabetes risk as women with β-cell dysfunction only. Obesity, together with IR or β-cell dysfunction, had a stronger effect on diabetes risk. This stronger effect was also found for a history of GDM with IR or β-cell dysfunction. Women with three risk factors, including obesity, a history of GDM and β-cell dysfunction/IR, showed the highest ORs of diabetes. Conclusions β-cell dysfunction or IR was significantly associated with postpartum diabetes. IR and β-cell dysfunction, together with obesity and a history of GDM, had the highest ORs of postpartum diabetes risk.