Miracle-dz/UniFAR-FTUs huggingface dataset:
New Opportunities to Mitigate the Burden of Disease Caused by Traffic Related Air Pollution: Antioxidant-Rich Diets and Supplements

Air pollution is associated with premature mortality and a wide spectrum of diseases. Traffic-related air pollution (TRAP) is one of the most concerning sources of air pollution for human exposure and health. Until TRAP levels can be significantly reduced on a global scale, there is a need for effective shorter-term strategies to prevent the adverse health effects of TRAP. A growing number of studies suggest that increasing antioxidant intake, through diet or supplementation, may reduce this burden of disease. In this paper, we conducted a non-systematic literature review to assess the available evidence on antioxidant-rich diets and antioxidant supplements as a strategy to mitigate adverse health effects of TRAP in human subjects. We identified 11 studies that fit our inclusion criteria; 3 of which investigated antioxidant-rich diets and 8 of which investigated antioxidant supplements. Overall, we found consistent evidence that dietary intake of antioxidants from adherence to the Mediterranean diet and increased fruit and vegetable consumption is effective in mitigating adverse health effects associated with TRAP. In contrast, antioxidant supplements, including fish oil, olive oil, and vitamin C and E supplements, presented conflicting evidence. Further research is needed to determine why antioxidant supplementation has limited efficacy and whether this relates to effective dose, supplement formulation, timing of administration, or population being studied. There is also a need to better ascertain if susceptible populations, such as children, the elderly, asthmatics and occupational workers consistently exposed to TRAP, should be recommended to increase their antioxidant intake to reduce their burden of disease. Policymakers should consider increasing populations’ antioxidant intake, through antioxidant-rich diets, as a relatively cheap and easy preventive measure to lower the burden of disease associated with TRAP.
Comparative Evaluation of the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes and Platelet-Rich Plasma: An In Vitro Analysis

Blood-derived factor preparations are being clinically employed as tools for promoting tissue repair and regeneration. Here we set out to characterize the in vitro angiogenic potential of two types of frequently used autologous blood-derived secretomes: platelet-rich plasma (PRP) and hypoxia preconditioned plasma (HPP)/serum (HPS). The concentration of key pro-angiogenic (VEGF) and anti-angiogenic (TSP-1, PF-4) protein factors in these secretomes was analyzed via ELISA, while their ability to induce microvessel formation and sprouting was examined in endothelial cell and aortic ring cultures, respectively. We found higher concentrations of VEGF in PRP and HPP/HPS compared to normal plasma and serum. This correlated with improved induction of microvessel formation by PRP and HPP/HPS. HPP had a significantly lower TSP-1 and PF-4 concentration than PRP and HPS. PRP and HPP/HPS appeared to induce similar levels of microvessel sprouting; however, the length of these sprouts was greater in HPP/HPS than in PRP cultures. A bell-shaped angiogenic response profile was observed with increasing HPP/HPS dilutions, with peak values significantly exceeding the PRP response. Our findings demonstrate that optimization of peripheral blood cell-derived angiogenic factor signalling through hypoxic preconditioning offers an improved alternative to simple platelet concentration and release of growth factors pre-stored in platelets.
Cannabinoid Signaling Recruits Astrocytes to Modulate Presynaptic Function in the Suprachiasmatic Nucleus

Visual Abstract Circadian rhythms are 24-h cycles in physiology regulated by the suprachiasmatic nucleus (SCN) in the brain, where daily cues act on SCN neurons to alter clock timing. Cannabinoid signaling modulates SCN neuronal activity, although the mechanism remains unclear. We propose that neuronal activity generates endocannabinoid release, activating astrocyte Ca2+ signaling, which releases adenosine and activates adenosine-1 receptors (A1Rs) on the presynaptic axon terminals, decreasing GABA release. We demonstrated, in mice, that activation of cannabinoid-1 receptors (CB1R) with the agonist WIN 55,212-2 (WIN) reduced the miniature GABA receptor-mediated postsynaptic current (mGPSC) frequency by a mechanism that requires astrocytes and A1R. WIN activated an intracellular Ca2+ signaling pathway in astrocytes. Activating this intracellular Ca2+ pathway with designer receptors exclusively activated by designer drugs (DREADDs) also decreased the mGPSC frequency and required A1R activation. The frequency of spontaneous Ca2+ events, including those induced by depolarization of a postsynaptic SCN neuron, was reduced by blocking CB1R activation with AM251, demonstrating neuronal endocannabinoid signaling modulates astrocytic Ca2+ signaling in the SCN. Finally, daytime application of WIN or adenosine phase advanced the molecular circadian clock, indicating that this cannabinoid signaling pathway is vital for the timing of circadian rhythms.
MicroRNA-17-92 Regulates Beta-Cell Restoration After Streptozotocin Treatment

Objective: To clarify the role and mechanism of miR-17-92 cluster in islet beta-cell repair after streptozotocin intervention. Methods: Genetically engineered mice (miR-17-92βKO) and control RIP-Cre mice were intraperitoneally injected with multiple low dose streptozotocin. Body weight, random blood glucose (RBG), fasting blood glucose, and intraperitoneal glucose tolerance test (IPGTT) were monitored regularly. Mice were sacrificed for histological analysis 8 weeks later. Morphological changes of pancreas islets, quantity, quality, apoptosis, and proliferation of beta-cells were measured. Islets from four groups were isolated. MiRNA and mRNA were extracted and quantified. Results: MiR-17-92βKO mice showed dramatically elevated fasting blood glucose and impaired glucose tolerance after streptozotocin treatment in contrast to control mice, the reason of which is reduced beta-cell number and total mass resulting from reduced proliferation, enhanced apoptosis of beta-cells. Genes related to cell proliferation and insulin transcription repression were significantly elevated in miR-17-92βKO mice treated with streptozotocin. Furthermore, genes involved in DNA biosynthesis and damage repair were dramatically increased in miR-17-92βKO mice with streptozotocin treatment. Conclusion: Collectively, our results demonstrate that homozygous deletion of miR-17-92 cluster in mouse pancreatic beta-cells promotes the development of experimental diabetes, indicating that miR-17-92 cluster may be positively related to beta-cells restoration and adaptation after streptozotocin-induced damage.
Assessment of the protective and therapeutic effect of melatonin against thioacetamide‐induced acute liver damage

Acute or chronic damage to the liver may occur through alcohol, drugs, viruses, genetic disorders, and toxicity. In this study, we planned to investigate the protective and therapeutic effects of melatonin (Mel) by causing damage to the liver with thioacetamide (TAA). Thirty‐five rats were used. Group I: control group (seven pieces), group II: Mel group (seven pieces) the single dose on the first day of the experiment was 10 mg/kg, group III: TAA (seven pieces) 300 mg/kg with 24‐hour intervals, two doses, group IV: Mel + TAA group (seven pieces) 10 mg/kg single dose Mel was applied 24 hours before TAA application, group V: TAA + Mel group (seven pieces) single dose (24th hour) of 10 mg/kg Mel was administered after TAA (300 mg/kg) two doses. The liver histology was evaluated. Apoptosis, autophagy, and necrosis markers in tissue were determined by immunohistochemistry. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in blood serum samples and transforming growth factor‐β (TGF‐β) and tumor necrosis factor‐α (TNF‐α) levels were determined in liver tissue. TAA affected histologically the classical lobule structure both in cell cords and sinusoids. Caspase‐3, RIP3, and LC3 levels were increased in group III compared with the control group. TAA did not cause a statistically significant change in TNF‐α level but decreased the TGF‐β level significantly. AST and ALT levels were statistically significant in group II and V compared with group I, the ALP level was significant in group IV compared with group II. The results of this study showed that TAA caused significant damage to tissues and increased cell death, Mel was found to have more therapeutic than the protective effect on tissues.
Transcriptome Modifications in the Porcine Intramuscular Adipocytes during Differentiation and Exogenous Stimulation with TNF-α and Serotonin

Adipocytes are dynamic cells that have critical functions to maintain body energy homeostasis. Adipocyte physiology is affected by the adipogenic differentiation, cell program, as well as by the exogenous stimulation of biochemical factors, such as serotonin and TNF-α. In this work, we investigated the global transcriptome modifications when porcine intramuscular preadipocyte (PIP) was differentiated into porcine mature adipocyte (pMA). Moreover, we studied transcriptome changes in pMA after stimulation with serotonin or TNF-α by using a microarray approach. Transcriptome analysis revealed that the expression of 270, 261, and 249 genes were modified after differentiation, or after serotonin and TNF-α stimulation, respectively. Expression changes in APP, HNF4A, ESR1, EGR1, SRC, HNF1A, FN1, ALB, STAT3, CBL, CEBPB, AR, FOS, CFTR, PAN2, PTPN6, VDR, PPARG, STAT5A and NCOA3 genes which are enriched in the ‘PPAR signaling’ and ‘insulin resistance’ pathways were found in adipocytes during the differentiation process. Dose-dependent serotonin stimulation resulted in a decreased fat accumulation in pMAs. Serotonin-induced differentially expressed genes in pMAs were found to be involved in the significant enrichment of ′GPCR ligand-binding′, ‘cell chemotaxis’, ‘blood coagulation and complement’, ‘metabolism of lipid and lipoproteins’, ‘regulation of lipid metabolism by PPARA’, and ‘lipid digestion, mobilization and transport’ pathways. TNF-α stimulation also resulted in transcriptome modifications linked with proinflammatory responses in the pMA of intramuscular origin. Our results provide a landscape of transcriptome modifications and their linked-biological pathways in response to adipogenesis, and exogenous stimulation of serotonin- and TNF-α to the pMA of intramuscular origin.
Epidemiology of knee osteoarthritis in general practice: a registry-based study

Objectives The present study investigated (1) trends in the prevalence and incidence of knee osteoarthritis over a 20-year period (1996–2015); (2) trends in multimorbidity and (3) trends in drug prescriptions. Design Registry-based study. Setting Primary healthcare, Flanders, Belgium. Participants Data were collected from Intego, a general practice-based morbidity registration network. In the study period between 1996 and 2015, data from 440 140 unique patients were available. Outcome measures Trends in prevalence and incidence rate of knee osteoarthritis were computed using joinpoint regression analysis. The mean disease count was calculated to assess trends in multimorbidity. In addition, the number of drug prescriptions was identified by the Anatomical Therapeutic Chemical Classification code and trends were equally recorded with joinpoint regression. Results The total age-standardised prevalence of knee osteoarthritis increased from 2.0% in 1996 to 3.6% in 2015. An upward trend was observed with an average annual percentage change (AAPC) of 2.5 (95% CI 2.2 to 2.9). In 2015, the prevalence rates in the 10 year age groups from the 45–54 years age group onwards were 3.1%, 5.6%, 9.0% and 13.9%, to reach 15.0% in people aged 85 years and older. The incidence remained stable with 3.75‰ in 2015 (AAPC=−0.5, 95% CI −1.4 to 0.5). The mean disease count significantly increased from 1.63 to 2.34 (p<0.001) for incident cases with knee osteoarthritis. Finally, we observed a significantly positive trend in the overall prescription of acetaminophen (AAPC=6.7, 95% CI 5.6 to 7.7), weak opioids (AAPC=4.0, 95% CI 0.9 to 7.3) and glucosamine (AAPC=8.6, 95% CI 2.4 to 15.1). Oral non-steroidal anti-inflammatory drugs were most prescribed, with a prevalence rate of 29.8% in 2015, but remained stable during the study period (AAPC=0.0, 95% CI −1.1 to 1.1). Conclusions Increased prevalence, multimorbidity, and number of drug prescriptions confirm an increased burden of knee osteoarthritis. In future, these trends can be used to prioritise initiatives for improvement in care.
Family members' experiences with adult participation in weight management programs: Triadic perspectives from patients, partners and children

Spouses are known to influence the outcomes of an individual's attempt at weight loss, but little is known about the broader influence of, and on, the family. The objectives were to explore: (a) the effects of an adult weight management program on the family and (b) family factors that help or hinder patient weight loss.
The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation

The genetic codes inscribed during two key developmental processes, namely gametogenesis and embryogenesis, are believed to determine subsequent development and survival of adult life. Once the embryo is formed, its further development mainly depends on its intrinsic characteristics, maternal environment (the endometrial receptivity), and the embryo–maternal interactions established during each phase of development. These developmental processes are under strict genetic regulation that could be manifested temporally and spatially depending on the physiological and developmental status of the cell. MicroRNAs (miRNAs), one of the small non-coding classes of RNAs, approximately 19–22 nucleotides in length, are one of the candidates for post-transcriptional developmental regulators. These tiny non-coding RNAs are expressed in ovarian tissue, granulosa cells, testis, oocytes, follicular fluid, and embryos and are implicated in diverse biological processes such as cell-to-cell communication. Moreover, accumulated evidences have also highlighted that miRNAs can be released into the extracellular environment through different mechanisms facilitating intercellular communication. Therefore, understanding miRNAs mediated regulatory mechanisms during gametogenesis and embryogenesis provides further insights about the molecular mechanisms underlying oocyte/sperm formation, early embryo development, and implantation. Thus, this review highlights the role of miRNAs in mammalian gametogenesis and embryogenesis and summarizes recent findings about miRNA-mediated post-transcriptional regulatory mechanisms occurring during early mammalian development.
Roles of CD38 in the Immune Response to Infection

CD38 is a multifunctional protein widely expressed in cells from the immune system and as a soluble form in biological fluids. CD38 expression is up-regulated by an array of inflammatory mediators, and it is frequently used as a cell activation marker. Studies in animal models indicate that CD38 functional expression confers protection against infection by several bacterial and parasitic pathogens. In addition, infectious complications are associated with anti-CD38 immunotherapy. Although CD38 displays receptor and enzymatic activities that contribute to the establishment of an effective immune response, recent work raises the possibility that CD38 might also enhance the immunosuppressive potential of regulatory leukocytes. This review integrates the current knowledge on the diversity of functions mediated by CD38 in the host defense to infection.
Stress, Burnout, and Associated Risk Factors in Medical Students

Objectives To determine the prevalence of and the risk factors associated with burnout and stress for medical students in Saudi Arabia. Methods A cross-sectional, survey-based study was distributed between January and February 2018 among all 500 medical students from the first to fifth years in a medical college; 356 of the students responded (71.2% response rate). Burnout was measured using the Maslach Burnout Inventory-Student Survey (MBI-SS) while the stress level was measured using the 12-item General Health Questionnaire (GHQ-12). Socio-demographics, professional characteristics, and participation in extracurricular activities were also included as possible predictors of burnout and stress. Results The study revealed that the stress level was (51.7%, n= 184) and the rate of high burnout was (38.2%, n= 136), expressing high exhaustion (77.8%, n=277), high cynicism (65.7%, n=234), and low academic efficiency (45.5%, n=162). Half of the students (50%, n=178) participated in extracurricular activities and were involved in one or more activities such as organizing activities and medical volunteering (n = 52, 14.6%), research (n = 59, 16.6%), and physical exercise (n = 71, 10.4%). There was a statistically significant positive correlation between overall burnout and a lower grade point average (GPA) (OR = 0.581, p 0.004, 95% CI = 0.400 to 0.843). A statistically significant positive correlation was found between stress and students with a lower GPA (OR = 0.737, P = 0.0.23, 95% CI = 0.566 to 0.959); stress was also higher in students who were not involved in any extracurricular activities (OR 1.893, P = 0.004, 95% CI = 1.22 to 2.918). Conclusion Our study shows high burnout rates among medical students. Low GPA students in this study showed a higher overall burnout. Stress was high in our study participants and was higher in students with a low GPA and in students who were not involved in any extracurricular activities.
Inner Workings: A massive star dies without a bang, revealing the sensitive nature of supernovae

In 2008, a huge red star in another galaxy reached the end of its life. A star as heavy as this one, born with 25 times the mass of the Sun, was supposed to go out in a fiery flash of light known as a supernova, millions or billions of times brighter than our Sun. But this one refused to play the role of drama queen. Instead, it brightened just a little, then vanished, possibly leaving behind a black hole. The spiral galaxy NGC 6946 spawned the first, and so far the only, failed supernova ever seen: a red supergiant star that vanished from the heavens without exploding. Image credit: Science Source/Robert Gendler. No one had ever seen one of these huge red stars wink out of existence with so little fuss before. It was a sign that the lives and deaths of these stars are more complex than our simplest theories had claimed. “As amazing and important and fun and exciting as this is, it’s not a surprise,” says Stan Woosley at the University of California, Santa Cruz. In fact, the discovery may help explain why the massive stars in computer models often fail to blow up. Conventional theory says that nearly all stars born more than eight times as massive as the Sun explode as supernovae. When young, a massive star is bright and blue. Nuclear reactions in its core generate an immense amount of energy. This keeps the star hot so that gas pressure pushes outward and partially counteracts the inward pull of the star’s gravity; so does the pressure of the many photons streaming out of the star’s core. As long as it generates energy, the star can hold itself up. In the end, though, gravity always wins. Later in life, as a massive star begins …
miR-27b expression in diagnosis and evaluation prognosis of prostate cancer.

OBJECTIVE The aim of study was to investigate the expression of microRNA-27b in different prostate tissues and its anti-tumor effects in prostate cancer. METHODS Measuring the expression of microRNA-27b, evaluating the PI3K protein expression in 28 benign prostatic hyperplasia and 63 prostate cancer tissues, analyzing the correlation between miRNA-27b and PI3K, and miRNA-27b's correlation with Gleason Grading and clinical stages were analyzed. We divided the prostate cancer patients into two groups: low group and high group, comparing the overall survival and progression free survival. In the cell experiment, the PC3 was divided into three groups: NC group, BL group and miRNA group. The cells of difference groups were measuring the cell proliferation, apoptosis and cycle and evaluating PI3K, AKT and P21 protein expressions of difference groups. RESULTS The microRNA-27b expression of prostate cancer significantly increased Compared with benign prostatic hyperplasia (P<0.05). The PI3K protein expression of prostate cancer tissues were significantly enhanced compared with benign prostatic hyperplasia. The PI3K protein expression was positive correlation with miRNA-27b in cancer tissues. Furthermore, the microRNA-27b expression was significantly correlated with the Gleason Grading and clinical stages in prostate cancer (P<0.05, respectively). The patients with higher miR-27b expression level had both poorer overall survival and progression free survival. In cell experiment, the cell proliferation of miRNA group was significantly lower than NC group (P<0.05); the cell apoptosis and G1 phase of miRNA group were significantly difference compared with NC group (P<0.05, respectively); Compared with NC group, PI3K, AKT and P21 protein expressions were significantly down-regulation in miRNA group (P<0.05, respectively). CONCLUSIONS miR-27b was up-regulated in prostate cancer tissue compared with benign prostatic hyperplasia tissues, and its expression level was correlated with a variety of important clinical pathological parameters. In the treatment of prostate cancer, miR-27b inhibition had effects to suppress prostate cancer proliferation by regulation PI3K/AKT/P21 signaling pathway. Moreover; miR-27b may serve as a promising biomarker for predicting the prognosis of prostate cancer.
Effects of Lactobacillus plantarum Q180 on Postprandial Lipid Levels and Intestinal Environment: A Double-Blind, Randomized, Placebo-Controlled, Parallel Trial

Probiotics can improve the intestinal environment by enhancing beneficial bacteria to potentially regulate lipid levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the effect of Lactobacillus plantarum Q180 (LPQ180) on postprandial lipid metabolism and the intestinal microbiome environment from a clinical perspective. A double-blind, randomized, placebo-controlled study was conducted including 70 participants of both sexes, 20 years of age and older, with healthy blood triacylglyceride (TG) levels below 200 mg/dL. Treatment with LPQ180 for 12 weeks significantly decreased LDL-cholesterol (p = 0.042) and apolipoprotein (Apo)B-100 (p = 0.003) levels, and decreased postprandial maximum concentrations (Cmax) and areas under the curve (AUC) of TG, chylomicron TG, ApoB-48, and ApoB-100. LPQ180 treatment significantly decreased total indole and phenol levels (p = 0.019). In addition, there was a negative correlation between baseline microbiota abundance and lipid marker change, which was negatively correlated with metabolites. This study suggests that LPQ180 might be developed as a functional ingredient to help maintain healthy postprandial lipid levels through modulating gut environment.