Miracle-dz/UniFAR-FTUs huggingface dataset:
TL1A inhibits atherosclerosis in apoE-deficient mice by regulating the phenotype of vascular smooth muscle cells

TNF ligand-related molecule 1A (TL1A) is a vascular endothelial growth inhibitor to reduce neovascularization. Lack of apoE a expression results in hypercholesterolemia and atherosclerosis. In this study, we determined the precise effects of TL1A on the development of atherosclerosis and the underlying mechanisms in apoE-deficient mice. After 12 weeks of pro-atherogenic high-fat diet feeding and TL1A treatment, mouse aorta, serum, and liver samples were collected and used to assess atherosclerotic lesions, fatty liver, and expression of related molecules. We found that TL1A treatment significantly reduced lesions and enhanced plaque stability. Mechanistically, TL1A inhibited formation of foam cells derived from vascular smooth muscle cells (VSMCs) but not macrophages by activating expression of ABC transporter A1 (ABCA1), ABCG1, and cholesterol efflux in a liver X receptor–dependent manner. TL1A reduced the transformation of VSMCs from contractile phenotype into synthetic phenotypes by activating expression of contractile marker α smooth muscle actin and inhibiting expression of synthetic marker osteopontin, or osteoblast-like phenotype by reducing calcification. In addition, TL1A ameliorated high-fat diet–induced lipid metabolic disorders in the liver. Taken together, our work shows that TL1A can inhibit the development of atherosclerosis by regulating VSMC/foam cell formation and switch of VSMC phenotypes and suggests further investigation of its potential for atherosclerosis treatment.
Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion

Cdc48/p97 is a ring-shaped, ATP-driven hexameric motor, essential for cellular viability. It specifically unfolds and extracts ubiquitylated proteins from membranes or protein complexes, mostly targeting them for proteolytic degradation by the proteasome. Cdc48/p97 is involved in a multitude of cellular processes, reaching from cell cycle regulation to signal transduction, also participating in growth or death decisions. The role of Cdc48/p97 in endoplasmic reticulum-associated degradation (ERAD), where it extracts proteins targeted for degradation from the ER membrane, has been extensively described. Here, we present the roles of Cdc48/p97 in mitochondrial regulation. We discuss mitochondrial quality control surveillance by Cdc48/p97 in mitochondrial-associated degradation (MAD), highlighting the potential pathologic significance thereof. Furthermore, we present the current knowledge of how Cdc48/p97 regulates mitofusin activity in outer membrane fusion and how this may impact on neurodegeneration.
Psychosocial Aspects of Female Breast Cancer in the Middle East and North Africa

Breast cancer, the most common cancer among women in the Middle East and North Africa (MENA) region, is associated with social and psychological implications deriving from women’s socio-cultural contexts. Examining 74 articles published between 2007 and 2019, this literature/narrative review explores the psychosocial aspects of female breast cancer in the MENA region. It highlights socio-cultural barriers to seeking help and socio-political factors influencing women’s experience with the disease. In 17 of 22 Arab countries, common findings emerge which derive from shared cultural values. Findings indicate that women lack knowledge of breast cancer screening (BCS) and breast cancer self-examination (BSE) benefits/techniques due to a lack of physicians’ recommendations, fear, embarrassment, cultural beliefs, and a lack of formal and informal support systems. Women in rural areas or with low socioeconomic status further lack access to health services. Women with breast cancer, report low self-esteem due to gender dynamics and a tendency towards fatalism. Collaboration between mass media, health and education systems, and leading social-religious figures plays a major role in overcoming psychological and cultural barriers, including beliefs surrounding pain, fear, embarrassment, and modesty, particularly for women of lower socioeconomic status and women living in crises and conflict zones.
Light-regulated allosteric switch enables temporal and subcellular control of enzyme activity

Engineered allosteric regulation of protein activity provides significant advantages for the development of robust and broadly applicable tools. However, the application of allosteric switches in optogenetics has been scarce and suffers from critical limitations. Here, we report an optogenetic approach that utilizes an engineered Light-Regulated (LightR) allosteric switch module to achieve tight spatiotemporal control of enzymatic activity. Using the tyrosine kinase Src as a model, we demonstrate efficient regulation of the kinase and identify temporally distinct signaling responses ranging from seconds to minutes. LightR-Src off-kinetics can be tuned by modulating the LightR photoconversion cycle. A fast cycling variant enables the stimulation of transient pulses and local regulation of activity in a selected region of a cell. The design of the LightR module ensures broad applicability of the tool, as we demonstrate by achieving light-mediated regulation of Abl and bRaf kinases as well as Cre recombinase.
Targeted muscle reinnervation at the time of amputation in the management of complex regional pain syndrome of the lower extremity

Complex regional pain syndrome (CRPS) is a chronic, posttraumatic condition defined by severe pain and sensorimotor dysfunction. In cases of severe CRPS, patients request amputation, which may cause phantom limb pain (PLP) and residual limb pain (RLP). Targeted muscle reinnervation (TMR) reduces the risk of PLP and RLP. This report describes the use of TMR at the time of amputation in a series of patients with CRPS.
Recent Development to Explore the Use of Biodegradable Periodic Mesoporous Organosilica (BPMO) Nanomaterials for Cancer Therapy

Porous nanomaterials can be used to load various anti-cancer drugs efficiently and deliver them to a particular location in the body with minimal toxicity. Biodegradable periodic mesoporous organosilica nanoparticles (BPMOs) have recently emerged as promising candidates for disease targeting and drug delivery. They have a large functional surface and well-defined pores with a biodegradable organic group framework. Multiple biodegradation methods have been explored, such as the use of redox, pH, enzymatic activity, and light. Various drug delivery systems using BPMO have been developed. This review describes recent advances in the biomedical application of BPMOs.
Isolation and Characterization of Facultative-Anaerobic Antimonate-Reducing Bacteria

Microbial antimonate (Sb(V)) reduction is a promising approach to remove Sb(V) from wastewater. However, current knowledge regarding microbial Sb(V) reduction is limited to strictly anaerobic conditions. This study was the first to isolate three facultative-anaerobic Sb(V)-reducing bacterial strains from the sludge collected from a wastewater treatment facility in an antimony products plant. Two of the isolated strains, designated Dechloromonas sp. AR-2 and Propionivibrio sp. AR-3, were characterized based on their Sb(V)-reducing abilities. When cultivated under anaerobic conditions with Sb(V) and acetate as the electron acceptor and donor, respectively, both strains could efficiently reduce 5.0 mM Sb(V), removing most of it from the water phase within 7 d. Along with Sb(V) reduction by the strains, white precipitates, which were likely amorphous Sb(OH)3 solids, were formed with a minor generation of soluble antimonite. Additionally, respiratory Sb(V) reduction by both strains occurred not only under anaerobic but also microaerobic conditions. It was suggested that Sb(V) reduction and the growth abilities of the strains under microaerobic conditions presented a substantial advantage of the use of strains AR-2 and AR-3 for practical applications to Sb(V)-containing wastewater treatment.
Indication of clear aligners in the early treatment of anterior crossbite: a case series

ABSTRACT Introduction: Anterior crossbite (AC) is defined as a reverse sagittal relationship between maxillary and mandibular incisors. According to an evidence-based orthodontic triage, the treatment need of AC is indicated if any occlusal interference is forcing the mandible towards a Class III growth pattern. Removable and fixed appliances have been suggested to correct AC. Objective: The present report aims at presenting the benefits of an alternative therapy for the early treatment of anterior crossbite using clear aligners. Methods: Two cases of anterior crossbite corrected using clear aligners in 8-years-old children are presented. Results: In both cases, AC was successfully corrected within 5 months. At the end of the treatment, overjet and overbite were corrected. No major discomfort or speech impairment was noticed by the parents. Conclusions: Due to the perceived shortcomings of alternative approaches, the use of clear aligners for correcting AC in mixed dentition should be considered as a comfortable and well tolerated appliance for young patients.
The Macrophages-Microbiota Interplay in Colorectal Cancer (CRC)-Related Inflammation: Prognostic and Therapeutic Significance

Tumor-associated macrophages (TAMs) are the main population of myeloid cells infiltrating solid tumors and the pivotal orchestrators of cancer-promoting inflammation. However, due to their exceptional plasticity, macrophages can be also key effector cells and powerful activators of adaptive anti-tumor immunity. This functional heterogeneity is emerging in human tumors, colorectal cancer (CRC) in particular, where the dynamic co-existence of different macrophage subtypes influences tumor development, outcome, and response to therapies. Intestinal macrophages are in close interaction with enteric microbiota, which contributes to carcinogenesis and affects treatment outcomes. This interplay may be particularly relevant in CRC, one of the most prevalent and lethal cancer types in the world. Therefore, both macrophages and intestinal microbiota are considered promising prognostic indicators and valuable targets for new therapeutic approaches. Here, we discuss the current understanding of the molecular circuits underlying the interplay between macrophages and microbiota in CRC development, progression, and response to both conventional therapies and immunotherapies.
Preliminary study of Yinhuapinggan granule against H1N1 influenza virus infection in mice through inhibition of apoptosis

Abstract Context Yinhuapinggan granule (YHPG) is frequently used for treating fever, cough, and viral pneumonia in traditional Chinese medicine. Objective This study investigated the antiviral effects of YHPG in H1N1 influenza virus (IFV)-infected mice and its possible mechanism. Materials and methods ICR mice were intranasally infected with 10 LD50 viral dose of IFV and then oral administration of YHPG (6, 12, and 18 g/kg) or oseltamivir (positive control) once a day for 2 or 4 consecutive days, six mice in each group. The lung, spleen and thymus indexes of IFV-infected mice, the expression of viral loads and pathological changes in lung tissues were performed to evaluate the antiviral effects of YHPG. Real-time PCR, immunohistochemistry and western blot assays were used to determine the expression of Bax, Bcl-2 and caspase-3. Results LD50 in mice was 10−3.5/0.02 mL. YHPG (6, 12, and 18 g/kg) dose-dependently decreased the lung index and viral load; the inhibition ratio of lung index was 5.31, 18.22, and 34.06%, respectively. Further detection revealed that YHPG (12 and 18 g/kg) significantly attenuated lung pathological changes, and increased the spleen and thymus indexes. Moreover, YHPG significantly down-regulated the mRNA and protein expression of Bax and caspase-3 in lung tissues of mice infected with IFV, and up-regulated the expression of Bcl-2. Conclusions YHPG has significant antiviral effects in IFV-infected mice, partially by inhibiting influenza virus replication and regulating the occurrence of apoptosis induced by influenza virus infection, suggesting that YHPG may be a promising antiviral agent with potential clinical application prospects.
Distinct peripheral blood monocyte and neutrophil transcriptional programs following intracerebral hemorrhage and different etiologies of ischemic stroke

Understanding cell-specific transcriptome responses following intracerebral hemorrhage (ICH) and ischemic stroke (IS) will improve knowledge of the immune response to brain injury. Transcriptomic profiles of 141 samples from 48 subjects with ICH, different IS etiologies, and vascular risk factor controls were characterized using RNA-seq in isolated neutrophils, monocytes and whole blood. In both IS and ICH, monocyte genes were down-regulated, whereas neutrophil gene expression changes were generally up-regulated. The monocyte down-regulated response to ICH included innate, adaptive immune, dendritic, NK cell and atherosclerosis signaling. Neutrophil responses to ICH included tRNA charging, mitochondrial dysfunction, and ER stress pathways. Common monocyte and neutrophil responses to ICH included interferon signaling, neuroinflammation, death receptor signaling, and NFAT pathways. Suppressed monocyte responses to IS included interferon and dendritic cell maturation signaling, phagosome formation, and IL-15 signaling. Activated neutrophil responses to IS included oxidative phosphorylation, mTOR, BMP, growth factor signaling, and calpain proteases-mediated blood–brain barrier (BBB) dysfunction. Common monocyte and neutrophil responses to IS included JAK1, JAK3, STAT3, and thrombopoietin signaling. Cell-type and cause-specific approaches will assist the search for future IS and ICH biomarkers and treatments.
PNEUMATIZATION OF THE SKULL IN THE PARULIDAE

Abstract Pneumatization of the skull roof and cerebellum region of the occipital bone was studied in 193 skulls of 18 genera and 56 species in the family Parulidae (wood warblers). The grundtypus type of pneumatization, which closes the windows anteriorly in immatures of migratory species, was present in fall migration and was completed on the wintering grounds during December and January. The only genera to show what I call the geospizid type of skull pneumatization were Basileuterus and Phaeothlypis, supporting their treatment as congeners. The geospizid type of skull pneumatization is typical of all species in the Galapagos Finches (Geospizidae). In this type the skull roof closes posteriorly in the parietal bone; large members of the family exhibited midline pneumatization, and smaller members the peripheral type. Genera Setophaga, Myioborus, and Basileuterus retained cerebellar windows for an extended period after skull roof pneumatization had been completed. Basileuterus is set apart from other parulids by four trenchant characters and is considered primitive.
Reference values of fat mass index and fat-free mass index in healthy Spanish adolescents.

INTRODUCTION body mass index (BMI) does not allow to discriminate the composition of the different body compartments. The aim of this study was to develop reference values for the fat mass index (FMI) and fat-free mass index (FFMI) in healthy adolescents using anthropometric techniques in order to provide reference standards for daily clinical practice. METHODS a cross-sectional study in 1,040 healthy Caucasian adolescents (470 boys and 570 girls) aged 10.1 to 14.9 years. Weight, height, and skinfold thickness were recorded, and BMI, percentage of total body fat, FMI and FFMI, and FMI and FFMI percentiles were calculated. RESULTS FFMI and FMI percentiles for healthy adolescents (both sexes) categorized by age are displayed. In boys a significant increase in FFMI is observed, and both the percentage of total body fat and FMI significantly decreased. In contrast, in girls the percentage of body fat mass, FMI, and FFMI significantly increased. Except at 10 years of age, FMI was higher (p < 0.05) in girls at all ages. FFMI was higher (p < 0.05) in boys at all ages. CONCLUSIONS reference values of FMI and FFMI would be a very useful instrument in clinical practice for the diagnosis and, especially, the analysis of body composition changes during the treatment of childhood obesity.
Identification of Glycochenodeoxycholate 3‐O‐Glucuronide and Glycodeoxycholate 3‐O‐Glucuronide as Highly Sensitive and Specific OATP1B1 Biomarkers

The aim of this study was to investigate the sensitivity and specificity of endogenous glycochenodeoxycholate and glycodeoxycholate 3‐O‐glucuronides (GCDCA‐3G and GDCA‐3G) as substrates for organic anion transporting polypeptide 1B1 (OATP1B1) in humans. We measured fasting levels of plasma GCDCA‐3G and GDCA‐3G using liquid chromatography‐tandem mass spectrometry in 356 healthy volunteers. The mean plasma levels of both compounds were ~ 50% lower in women than in men (P = 2.25 × 10−18 and P = 4.73 × 10−9). In a microarray‐based genome‐wide association study, the SLCO1B1 rs4149056 (c.521T>C, p.Val174Ala) variation showed the strongest association with the plasma GCDCA‐3G (P = 3.09 × 10−30) and GDCA‐3G (P = 1.60 × 10−17) concentrations. The mean plasma concentration of GCDCA‐3G was 9.2‐fold (P = 8.77 × 10−31) and that of GDCA‐3G was 6.4‐fold (P = 2.45x10−13) higher in individuals with the SLCO1B1 c.521C/C genotype than in those with the c.521T/T genotype. No other variants showed independent genome‐wide significant associations with GCDCA‐3G or GDCA‐3G. GCDCA‐3G was highly efficacious in detecting the SLCO1B1 c.521C/C genotype with an area under the receiver operating characteristic curve of 0.996 (P < 0.0001). The sensitivity (98–99%) and specificity (100%) peaked at a cutoff value of 180 ng/mL for men and 90 ng/mL for women. In a haplotype‐based analysis, SLCO1B1*5 and *15 were associated with reduced, and SLCO1B1*1B, *14, and *35 with increased OATP1B1 function. In vitro, both GCDCA‐3G and GDCA‐3G showed at least 6 times higher uptake by OATP1B1 than OATP1B3 or OATP2B1. These data indicate that the hepatic uptake of GCDCA‐3G and GDCA‐3G is predominantly mediated by OATP1B1. GCDCA‐3G, in particular, is a highly sensitive and specific OATP1B1 biomarker in humans.
Structure of services and material health resources associated with the School Health Program.

OBJECTIVES to describe the structure used in the School Health Program and analyze the association between its material resources and the actions carried out. METHODS cross-sectional, quantitative, analytical, and normative study. A normative instrument of the program was applied to collect data from May to July 2017 with 105 Family Health Strategy professionals. Data were organized and analyzed using descriptive and inferential statistics on IBM SPSS Statistics 22.0 software. RESULTS financial resources were made available with low periodicity; the most used human resources were dentists; the most frequent infrastructure resource was the school; the most frequently used materials were those related to administrative support (legal-size paper and pen) and clinical resources (fluoride, toothbrush, and toothpaste). An association was identified between resources and anthropometric assessment activities and vaccination status. CONCLUSIONS the program structure showed reduced financial resources and priority participation of human resources from the health sector, and the actions were carried out by using the school infrastructure and administrative and clinical materials.
Response of Blood Biomarkers to Sprint Interval Swimming.

PURPOSE To evaluate and compare the effects of 2 sprint interval training (SIT) sets of different distances on biochemical markers indicative of metabolism, stress, and antioxidant capacity in competitive swimmers and, to investigate the potential influence of gender on these markers. METHODS Twenty-four adolescent, well-trained swimmers (12 men and 12 women) participated in the study. In a random and counterbalanced order, the swimmers completed 2 SIT sets (8 × 50 m and 8 × 25 m) in freestyle with maximal intensity on different days. Work-to-rest ratio was 1:1 in both sets. Blood samples were drawn preexercise, immediately postexercise, and 1 hour postexercise to evaluate the effects of the SIT sets on a number of biochemical parameters. RESULTS Swimming speed was higher at 8 × 25 m. The 2 SIT sets induced significant increases in lactate, glucose, insulin, glucagon, cortisol, and uric acid (P ≤ .001). No differences in these parameters were found between sets, except for irisin (higher in 8 × 50 m; P = .02). Male swimmers were faster and had higher lactate and uric acid concentrations, as well as lower reduced glutathione concentration, than female swimmers (P < .01). CONCLUSIONS The 2 swimming SIT sets induced increases in most of the biochemical markers studied. The 2-fold difference between sets in distance did not differentiate the effects of sprint interval exercise on most biochemical parameters. Thus, low-volume SIT sets seem to be effective stimuli for competitive swimmers.
Diagnosis of Sacroiliac Joint Pain: Predictive Value of Three Diagnostic Clinical Tests

To date, there have been no acceptable and accurate diagnostic criteria or standards of care for the management of sacroiliac joint (SIJ) pain. Several studies have yielded different contributions of clinical presentation, history, and physical examination in the diagnosis of SIJ pain. Our goal in this study was to assess the sensitivity and specificity of the diagnostic clinical tests and their predictive value in accurately diagnosing SIJ pain.
Human papillomavirus prevalence, genomic diversity and related risk factors in HIV-positive women from a countryside city in the state of Rio de Janeiro

ABSTRACT Human papillomavirus (HPV) can cause genital warts and HPV-related cancer.People living with human immunodeficiency virus (HIV)are more symptomatic for HPV infections.Campos dos Goytacazes,a municipality of Rio de Janeiro,introduced the quadrivalent HPV vaccine (4vHPV)for HIV-positive women four years before initiation of a public vaccination program.This study analyzed the prevalence of HPV infection in HIV-positive women and the variables associated with infectionTwo groups were evaluated:group 1,with Pap smear and HPV-negative polymerase chain reaction (PCR);group 2, individuals with at least one positive result for HPV in PCR or pap smear.PCR was performed in endocervical samples using generic primers, and the LCD-Array Kit was used for genotyping.Univariate and multivariate analyzes were performed.Results in 109 women (Group 1 n = 70; group 2 n = 39)showed an overall HPV prevalence of 36%. Results also showed that 88% (n = 23) and 96% (n = 25)of typed viruses (total of typed viruses n = 26)were included in 4vHPV and 9vHPV (nonavalent HPV),respectively.In univariate analysis,age less than 45 years, a high number of sexual partners,and HIV-viral load were risk factors for infection.However, a CD4 indicator was associated with protection.Although HIV infection is generally related to multiple and rare types of HPV,this study showed that a vast majority of the HPV types found are included in 4vHPV.Considering that age less than 45 years is a risk factor, the use of 4vHPV in Brazil should be extended in the public vaccination program to HIV seropositive women up to age 45 years