Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiogenic Effects of Secreted Factors from Periodontal Ligament Stem Cells

Periodontal disease is a chronic inflammation of tooth-supporting tissues, and the destruction of these tissues results in tooth loss. Regeneration of periodontal tissues is the ultimate goal of periodontal treatment. We previously reported that transplantation of conditioned medium (CM) of periodontal ligament stem cells (PDLSCs) demonstrated the enhancement of periodontal tissue regeneration, compared to CM from fibroblasts (Fibroblast-CM). We hypothesized that the angiogenic effects of PDLSC-CM might participate in the enhanced wound healing of periodontal tissues. The aim of this study was to investigate the effect of PDLSC-CM on the functions of endothelial cells. PDLSCs were cultured from periodontal ligament tissues obtained from healthy volunteers. Human gingival epithelial cells, dermal fibroblasts, osteoblasts, and umbilical vein endothelial cells (HUVECs) were purchased from commercial sources. The functions of endothelial cells were examined using immunostaining of Ki67, observation of nuclear fragmentation and condensation (apoptosis), and network formation on Matrigel. Vascular endothelial cell growth factor (VEGF) level was measured using an ELISA kit. HUVECs demonstrated higher cell viability in PDLSC-CM when compared with those in Fibroblast-CM. HUVECs demonstrated a higher number of Ki67-positive cells and lower apoptosis cells in PDLSC-CM, compared to Fibroblast-CM. Additionally, HUVECs formed more capillary-like structures in PDLSC-CM than Fibroblast-CM. PDLSC-CM contained higher levels of angiogenic growth factor, VEGF, than Fibroblast-CM. Our results showed that PDLSC-CM increased cell viability, proliferation, and capillary formation of HUVECs compared to Fibroblast-CM, suggesting the angiogenic effects of PDLSC-CM, and the effect is a potential regenerative mechanism of periodontal tissues by PDLSC-CM.
Asymmetric organocatalytic vinylogous Michael addition triggered triple-cascade reactions of 2-hydroxycinnamaldehydes and vinylogous nucleophiles: construction of benzofused oxabicyclo[3.3.1]nonane scaffolds.

An organocatalytic vinylogous Michael addition triggered triple-cascade reaction has been developed. 2-Hydroxycinnamaldehydes worked under iminium activation with either acyclic or cyclic ketone-derived α,α-dicyanoalkenes, yielding the benzofused oxabicyclo[3.3. 1]nonanes bearing one quaternary stereocenter with excellent stereoselectivities.
Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.
Incidence and Factors Associated With Acne Among Transgender Patients Receiving Masculinizing Hormone Therapy.

Importance Acne is a common condition among transgender patients receiving masculinizing hormone therapy (MHT), but the incident risk and predictors of developing acne in this population have not yet been studied on a large scale. Objective To assess risk of acne among a large population of transgender patients receiving MHT and clinical risk factors for acne diagnosis. Design, Setting, and Participants A retrospective cohort study that included 988 patients who started MHT between January 1, 2014, and December 31, 2017, with at least 1 year of follow-up was performed. Data analysis was conducted from September 1 to 15, 2019. Data were obtained using electronic health records from a community health center serving the sexual and gender minority community. The population included every patient who began receiving MHT during the study period who was aged 18 years or older at the time of MHT initiation and whose assigned sex at birth was female. Main Outcomes and Measures The main outcome was acne defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes for acne. Overall prevalence and incidence proportions over 2 years after initiation of MHT were calculated. Baseline demographic and clinical characteristics were collected at the time of MHT initiation. A series of univariate analyses for all factors was calculated to test for an association with acne diagnosis, followed by multivariate analyses to test for independent predictors. Results For 988 patients (median age, 25.8 years; interquartile range, 20.8-28.2 years), there was an overall acne prevalence of 31.1% (n = 307). The 1-year post-MHT acne incidence proportion was 19.0% and the 2-year incidence proportion was 25.1%. A younger age at MHT initiation was associated with a higher likelihood of developing acne, with a median of 22.4 years (interquartile range, 19.7-25.6 years) among patients who developed acne vs 24.7 years (interquartile range, 21.3-29.4 years) among patients who did not (P = .002). Conclusions and Relevance Acne is a common condition among transgender patients on MHT, with a prevalence increasing from 6.3% to 31.1% following MHT initiation. Patients aged 18 to 21 years appear to be the most likely to develop acne after MHT initiation.
The efficacy of different seed priming agents for promoting sorghum germination under salt stress

Sorghum [Sorghum bicolor (L.) Moench] seed germination is sensitive to salinity, and seed priming is an effective method for alleviating the negative effects of salt stress on seed germination. However, few studies have compared the effects of different priming agents on sorghum germination under salt stress. In this study, we quantified the effects of priming with distilled water (HP), sodium chloride (NaCl), potassium chloride (KCl), calcium chloride (CaCl2), and polyethylene glycol (PEG) on sorghum seed germination under 150 mM NaCl stress. The germination potential, germination rate, germination index, vigor index, root length, shoot length, root fresh weight, shoot fresh weight, root dry weight, and shoot dry weight were significantly reduced by salt stress. Different priming treatments alleviated the germination inhibition caused by salt stress to varying degrees, and 50 mM CaCl2 was the most effective treatment. In addition, the mitigation effect of priming was stronger on root traits than on shoot traits. Mitigation efficacy was closely related to both the type of agent and the concentration of the solution. Principal component analysis showed that all concentrations of CaCl2 had higher scores and were clearly distinguished from other treatments based on their positive effects on all germination traits. The effects of the other agents varied with concentration. The priming treatments were divided into three categories based on their priming efficacy, and the 50, 100, and 150 mM CaCl2 treatments were placed in the first category. The 150 mM KCl, 10% PEG, HP, 150 mM NaCl, 30% PEG, and 50 mM KCl treatments were placed in the second category, and the 100 mM NaCl, 100 mM KCl, 20% PEG, and 50 mM NaCl treatments were least effective and were placed in the third category. Choosing appropriate priming agents and methods for future research and applications can ensure that crop seeds germinate healthily under saline conditions.
Healthy Diet Perceptions of Pregnant Women from Sub-Saharan Africa Residing in the U.S

ABSTRACT Several consumers lack a clear understanding of what makes a healthy diet. This uncertainty may be worsened by immigration due to socio-cultural differences. The purpose of this study was to explore Sub-Saharan African (SSA) pregnant women’s perceptions of a healthy diet and the sources of dietary information available to them in the context of immigration. We used narrative interviews and photo-food diaries, followed by photo-elucidated interviews to obtain data. Participants defined and illustrated a healthy diet as having four characteristics: (a) Familiar, (b) balanced, (c) made of fresh and organically grown ingredients, and (d) able to build the consumer’s body. Participants indicated that the overwhelming nature of dietary information made it difficult to navigate. Participants trusted dietary recommendations offered by family and peers the most, while those offered by health care providers were reported to be difficult to understand or incorporate due to not being culturally specific. This paper highlights the importance of considering consumers’ socio-cultural backgrounds and building partnerships between health care providers and the communities they serve to design culturally relevant dietary education.
Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells—A Strategy Used by Coxsackie B Virus to Evade the Host’s Innate Immune Response at the Primary Site of Infection?

Increasing evidence highlights the importance of the antiviral activities of the type III interferons (IFNλs; IL-28A, IL-28B, IL29, and IFNλ4) in the intestine. However, many viruses have developed strategies to counteract these defense mechanisms by preventing the production of IFNs. Here we use infection models, a clinical virus isolate, and several molecular biology techniques to demonstrate that both type I and III IFNs induce an antiviral state and attenuate Coxsackievirus group B (CVB) replication in human intestinal epithelial cells (IECs). While treatment of IECs with a viral mimic (poly (I:C)) induced a robust expression of both type I and III IFNs, no such up-regulation was observed after CVB infection. The blunted IFN response was paralleled by a reduction in the abundance of proteins involved in the induction of interferon gene transcription, including TIR-domain-containing adapter-inducing interferon-β (TRIF), mitochondrial antiviral-signaling protein (MAVS), and the global protein translation initiator eukaryotic translation initiation factor 4G (eIF4G). Taken together, this study highlights a potent anti-Coxsackieviral effect of both type I and III IFNs in cells located at the primary site of infection. Furthermore, we show for the first time that the production of type I and III IFNs in IECs is blocked by CVBs. These findings suggest that CVBs evade the host immune response in order to successfully infect the intestine.
The Search for an Interesting Partner to Combine with PD-L1 Blockade in Mesothelioma: Focus on TIM-3 and LAG-3

Simple Summary Malignant pleural mesothelioma is an aggressive cancer most commonly associated with asbestos exposure. Its prognosis is very poor, and the current treatments have only a limited impact on survival. Therefore, there is an urgent need to develop new treatment strategies. We investigated combinations of different immune checkpoint blocking antibodies that have already shown promising results in several cancer types. We suggested that the effect of a combination treatment might even be better than one, single therapy. Based on our in vitro results about the secretion of several immune related molecules we selected promising treatments for further investigation in a mesothelioma mouse model. We found that monotherapy with an immune checkpoint blocking antibody against programmed death-1 (PD-1), and its combination with another blocking antibody against lymphocyte activation gene-3 (LAG-3), resulted in delayed tumor growth and survival benefit in our mice. Further research is warranted to optimize the treatment schedule of the combination therapy. Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer that is causally associated with previous asbestos exposure in most afflicted patients. The prognosis of patients remains dismal, with a median overall survival of only 9–12 months, due to the limited effectiveness of any conventional anti-cancer treatment. New therapeutic strategies are needed to complement the limited armamentarium against MPM. We decided to focus on the combination of different immune checkpoint (IC) blocking antibodies (Abs). Programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), T-cell immunoglobulin mucin-3 (TIM-3), and lymphocyte activation gene-3 (LAG-3) blocking Abs were tested as monotherapies, and as part of a combination strategy with a second IC inhibitor. We investigated their effect in vitro by examining the changes in the immune-related cytokine secretion profile of supernatant collected from treated allogeneic MPM-peripheral blood mononuclear cell (PBMC) co-cultures. Based on our in vitro results of cytokine secretion, and flow cytometry data that showed a significant upregulation of PD-L1 on PBMC after co-culture, we chose to further investigate the combinations of anti PD-L1 + anti TIM-3 versus anti PD-L1 + anti LAG-3 therapies in vivo in the AB1-HA BALB/cJ mesothelioma mouse model. PD-L1 monotherapy, as well as its combination with LAG-3 blockade, resulted in in-vivo delayed tumor growth and significant survival benefit.
Reticuloendothelial activation correlates with disease severity and predicts mortality in severe alcoholic hepatitis

Background Overactivation of reticuloendothelial cells lining liver sinusoids – Kupffer cells (macrophages) and sinusoidal endothelial cells – may narrow the sinusoidal lumen, impair perfusion in liver microcirculation and contribute to disease severity in alcoholic hepatitis. Aim The aim of the article was to assess reticuloendothelial activation in patients with severe alcoholic hepatitis (SAH). Methods In SAH patients, we prospectively studied baseline reticuloendothelial activation markers [serum ferritin, sCD163 and plasma von Willebrand factor (VWF) antigen] and Macrophage Activation Syndrome (MAS) criteria, correlated them with disease severity scores [model for end-stage liver disease (MELD) and Sequential Organ Failure Assessment (SOFA) scores] and analyzed their ability to predict survival over a 90-day follow-up period. Results A total of 50 SAH patients [45 (37–49) years, median (interquartile range), 49 males, discriminant function, 76.2 (54.5–106.6); MELD score, 30 (26.2–36)] were studied. 41 SAH patients (82%) had ferritin >500 ng/mL, and all (100%) had markedly raised sCD163 and VWF levels. The median sCD163 level was 10-fold higher than healthy controls and the median VWF level was 5-fold above the upper limit of normal. In total, 37 SAH patients (74%) met MAS criteria. Reticuloendothelial activation markers correlated with MELD and SOFA scores (P < 0.05). VWF was an independent marker to predict mortality in SAH [adjusted hazard ratio, 1.002 (1.000–1.004)]. Conclusions The reticuloendothelial system was markedly activated and correlated with disease severity scores in SAH patients.VWF predicted short-term mortality independent of MELD and sCD163. Further larger multicentric studies are needed to validate these findings.
The effectiveness of acupoint herbal patching for functional constipation

Abstract Background: Functional constipation is a common functional problem of the digestive system that has a negative impact on physical, mental health of patients and quality of life. At present, acupoint herbal patching as an adjuvant therapy is currently undergoing clinical trials in different medical centers. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of acupoint herbal patching on functional constipation. There is also a lack of systematic evaluation and analysis of acupoints and herbs. Methods: We will search the following 8 databases from their inception to November 15, 2020, without language restrictions: the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database and the China National Knowledge Infrastructure. The primary outcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5. 3 software. Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the GRADE approach to assess the overall quality of evidence supporting the primary outcomes. We will also use Spass software (Version19.0) for complex network analysis to explore the potential core prescription of acupoint herbal patching for functional constipation. Results: This study will analyze the clinical effective rate, functional outcomes, quality of life, improvement of clinical symptoms of functional constipation, and effective prescriptions of acupoint herbal patching for patients with functional constipation. Conclusion: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint herbal patching for patients with functional constipation. PROSPERO registration number: PROSPERO CRD 42020193489.
Mediterranean Diet and Healthy Eating in Subjects with Prediabetes from the Mollerussa Prospective Observational Cohort Study

We aimed to assess differences in dietary patterns (i.e., Mediterranean diet and healthy eating indexes) between participants with prediabetes and those with normal glucose tolerance. Secondarily, we analyzed factors related to prediabetes and dietary patterns. This was a cross-sectional study design. From a sample of 594 participants recruited in the Mollerussa study cohort, a total of 535 participants (216 with prediabetes and 319 with normal glucose tolerance) were included. The alternate Mediterranean Diet score (aMED) and the alternate Healthy Eating Index (aHEI) were calculated. Bivariable and multivariable analyses were performed. There was no difference in the mean aMED and aHEI scores between groups (3.2 (1.8) in the normoglycemic group and 3.4 (1.8) in the prediabetes group, p = 0.164 for the aMED and 38.6 (7.3) in the normoglycemic group and 38.7 (6.7) in the prediabetes group, p = 0.877 for the aHEI, respectively). Nevertheless, women had a higher mean of aMED and aHEI scores in the prediabetes group (3.7 (1.9), p = 0.001 and 40.5 (6.9), p < 0.001, respectively); moreover, they had a higher mean of aHEI in the group with normoglycemia (39.8 (6.6); p = 0.001). No differences were observed in daily food intake between both study groups; consistent with this finding, we did not find major differences in nutrient intake between groups. In the multivariable analyses, the aMED and aHEI were not associated with prediabetes (odds ratio (OR): 1.19, 95% confidence interval (CI): 0.75–1.87; p = 0.460 and OR: 1.32, 95% CI: 0.83–2.10; p = 0.246, respectively); however, age (OR: 1.04, 95% CI: 1.02–1.05; p < 0.001), dyslipidemia (OR: 2.02, 95% CI: 1.27–3.22; p = 0.003) and body mass index (BMI) (OR: 1.09, 95% CI: 1.05–1.14; p < 0.001) were positively associated with prediabetes. Physical activity was associated with a lower frequency of prediabetes (OR: 0.48, 95% CI: 0.31–0.72; p = 0.001). In conclusion, subjects with prediabetes did not show a different dietary pattern compared with a normal glucose tolerance group. However, further research is needed on this issue.
Unravelling Heterogeneity of Amplified Human Amniotic Fluid Stem Cells Sub-Populations

Human amniotic fluid stem cells (hAFSCs) are broadly multipotent immature progenitor cells with high self-renewal and no tumorigenic properties. These cells, even amplified, present very variable morphology, density, intracellular composition and stemness potential, and this heterogeneity can hinder their characterization and potential use in regenerative medicine. Celector® (Stem Sel ltd.) is a new technology that exploits the Non-Equilibrium Earth Gravity Assisted Field Flow Fractionation principles to characterize and label-free sort stem cells based on their solely physical characteristics without any manipulation. Viable cells are collected and used for further studies or direct applications. In order to understand the intrapopulation heterogeneity, various fractions of hAFSCs were isolated using the Celector® profile and live imaging feature. The gene expression profile of each fraction was analysed using whole-transcriptome sequencing (RNAseq). Gene Set Enrichment Analysis identified significant differential expression in pathways related to Stemness, DNA repair, E2F targets, G2M checkpoint, hypoxia, EM transition, mTORC1 signalling, Unfold Protein Response and p53 signalling. These differences were validated by RT-PCR, immunofluorescence and differentiation assays. Interestingly, the different fractions showed distinct and unique stemness properties. These results suggest the existence of deep intra-population differences that can influence the stemness profile of hAFSCs. This study represents a proof-of-concept of the importance of selecting certain cellular fractions with the highest potential to use in regenerative medicine.
Chemopreventive Effect of 5-Flurouracil Polymeric Hybrid PLGA-Lecithin Nanoparticles against Colon Dysplasia Model in Mice and Impact on p53 Apoptosis

The use of 5-fluorouracil (5FU) is associated with multifaceted challenges and poor pharmacokinetics. Poly(lactic-co-glycolic acid)-lipid hybrid nanoparticles (PLNs)-based therapy has received attention as efficient carriers for a diversity of drugs. This study evaluated the in vivo chemotherapeutic and anti-proliferative efficacy of 5FU-loaded PLNs against 1,2-dimethylhydrazine (Di-MH) prompted colon dysplasia in mice compared to free 5FU. 5FU PLNs were prepared. Male Swiss albino mice were distributed to six experimental groups. Group 1: Saline group. All the other groups were injected weekly with Di-MH [20 mg/kg, s.c. ]. Group 2: Di-MH induced colon dysplasia control group. Groups 3 and 4: Di-MH + free 5FU treated group [2.5 and 5 mg/kg]. Groups 5 and 6: Di-MH + 5FU-PLNs treated group [2.5 and 5 mg/kg]. Free 5FU and 5FU-PLNs doses were administered orally, twice weekly. Treatment with 5FU-PLNs induced a higher cytoprotective effect compared to free 5FU as indicated by lower mucosal histopathologic score and reduction in number of Ki-67 immunpositive proliferating nuclei. Additionally, there was significant upregulation of p53 and caspase 3 genes in colon specimens. Our results support the validity of utilizing the PLNs technique to improve the chemopreventive action of 5FU in treating colon cancer.
Prenatal and Postpartum Maternal Iodide Intake from Diet and Supplements, Urinary Iodine and Thyroid Hormone Concentrations in a Region of the United Kingdom with Mild-to-Moderate Iodine Deficiency

Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Iodine requirements increase in pregnancy, but many women in regions without salt iodization have insufficient intakes. We explored associations between iodide intake and urinary iodine concentration (UIC), urinary iodine/creatinine ratio (I/Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. A total of 246 pregnant women aged 18–40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter at around 12, 26 and 36 weeks’ gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24 h recalls. During pregnancy, median (IQR) dietary iodide intake was 101 µg/day (54, 142), with 42% from dairy and 9% from white fish. Including supplements, intake was 143 µg/day (94, 196), with 49% < UK reference nutrient intake (140 µg/day). Women with Pakistani heritage had 129 µg/day (87, 190) median total intake. Total intake during pregnancy was associated with 4% (95% CI: 1%, 7%) higher UIC, 5% (3%, 7%) higher I/Cr, 4% (2%, 6%) lower thyroglobulin and 21% (9%, 32%) lower odds of palpable goiter per 50 µg/day. This cohort consumed less iodide in pregnancy than UK and World Health Organization dietary recommendations. UIC, I/Cr and thyroglobulin were associated with intake. Higher intake was associated with fewer goiters. Because dairy was the dominant source of iodide, women following plant-based or low-dairy diets may be at particular risk of iodine insufficiency.