Miracle-dz/UniFAR-FTUs huggingface dataset:
Secreted Factors from Stem Cells of Human Exfoliated Deciduous Teeth Directly Activate Endothelial Cells to Promote All Processes of Angiogenesis

Diabetes is a major risk factor for atherosclerosis and ischemic vascular diseases. Recently, regenerative medicine is expected to be a novel therapy for ischemic diseases. Our previous studies have reported that transplantation of stem cells promoted therapeutic angiogenesis for diabetic neuropathy and ischemic vascular disease in a paracrine manner, but the precise mechanism is unclear. Therefore, we examined whether secreted factors from stem cells had direct beneficial effects on endothelial cells to promote angiogenesis. The soluble factors were collected as conditioned medium (CM) 48 h after culturing stem cells from human exfoliated deciduous teeth (SHED) in serum-free DMEM. SHED-CM significantly increased cell viability of human umbilical vein endothelial cells (HUVECs) in MTT assays and accelerated HUVECs migration in wound healing and Boyden chamber assays. In a Matrigel plug assay of mice, the migrated number of primary endothelial cells was markedly increased in the plug containing SHED-CM or SHED suspension. SHED-CM induced complex tubular structures of HUVECs in a tube formation assay. Furthermore, SHED-CM significantly increased neovascularization from the primary rat aorta, indicating that SHED-CM stimulated primary endothelial cells to promote comprehensive angiogenesis processes. The angiogenic effects of SHED-CM were the same or greater than the effective concentration of VEGF. In conclusion, SHED-CM directly stimulates vascular endothelial cells to promote angiogenesis and is promising for future clinical application.
Quantitative Evaluation of Retinal Vessel Density in Central Serous Chorioretinopathy after Half-dose Photodynamic Therapy

ABSTRACT Purpose To determine vessel changes in retinochoroid with optical coherence tomographic angiography (OCT angiography) and spectral-domain OCT (SD-OCT) of patients with central serous chorioretinopathy (CSC) after half-dose photodynamic therapy (hd-PDT). Methods A prospective observational study of 62 eyes of 58 patients undergoing hd-PDT was followed for 3 months. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed at baseline; best-corrected visual acuity (BCVA), fundus photography, OCT angiography and SD-OCT were performed at baseline, 1-month, and 3-month follow-up visits. Results The mean vessel density of inner retina (VDIR) layer was 50.72 ± 3.17 at baseline, then decreased to 48.97 ± 4.34 at 1-month follow-up (p < .001), and partially recovered to 49.00 ± 4.28 at 3-month follow-up (p < .001); the mean area of foveal avascular zone (FAZ) was 0.303 ± 0.107 mm2 at baseline, and then increased to 0.339 ± 0.121 mm2 and 0.342 ± 0.125 mm2 at 1-month and 3-month follow-up after hd-PDT (p < .001, p < .001). The mean diameters of choroidal big vessels (DCV) were 309.66 ± 72.24 microns at baseline, then decreased to 300.13 ± 69.38 microns at 1-month and 293.39 ± 69.92 microns at 3-month after treatment (p < .001, p < .001). Conclusions Currently common applied hd-PDT for patients with CSC has significantly impact on both retinal and choroidal vessels. The retinal capillary flow decreased, therefore optimizing PDT parameters for treating CSC may still be necessary in the future.
Acid Treatment Enhances the Antioxidant Activity of Enzymatically Synthesized Phenolic Polymers

Phenolic polymers produced by enzymatic oxidation under biomimetic and eco-friendly reaction conditions are usually endowed with potent antioxidant properties. These properties, coupled with the higher biocompatibility, stability and processability compared to low-molecular weight phenolic compounds, open important perspectives for various applications. Herein, we report the marked boosting effect of acid treatment on the antioxidant properties of a series of polymers obtained by peroxidase-catalyzed oxidation of natural phenolic compounds. Both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays indicated a remarkable increase in the antioxidant properties for most phenolic polymers further to the acid treatment. In particular, up to a ca. 60% decrease in the EC50 value in the DPPH assay and a 5-fold increase in the Trolox equivalents were observed. Nitric oxide- and superoxide-scavenging assays also indicated highly specific boosting effects of the acid treatment. Spectroscopic evidence suggested, in most cases, that the occurrence of structural modifications induced by the acid treatment led to more extended π-electron-conjugated species endowed with more efficient electron transfer properties. These results open new perspectives toward the design of new bioinspired antioxidants for application in food, biomedicine and material sciences.
Liquid Biopsy Enables Quantification of the Abundance and Interindividual Variability of Hepatic Enzymes and Transporters

Variability in individual capacity for hepatic elimination of therapeutic drugs is well recognized and is associated with variable expression and activity of liver enzymes and transporters. Although genotyping offers some degree of stratification, there is often large variability within the same genotype. Direct measurement of protein expression is impractical due to limited access to tissue biopsies. Hence, determination of variability in hepatic drug metabolism and disposition using liquid biopsy (blood samples) is an attractive proposition during drug development and in clinical practice. This study used a multi‐“omic” strategy to establish a liquid biopsy technology intended to assess hepatic capacity for metabolism and disposition in individual patients. Plasma exosomal analysis (n = 29) revealed expression of 533 pharmacologically relevant genes at the RNA level, with 147 genes showing evidence of expression at the protein level in matching liver tissue. Correction of exosomal RNA expression using a novel shedding factor improved correlation against liver protein expression for 97 liver‐enriched genes. Strong correlation was demonstrated for 12 key drug‐metabolizing enzymes and 4 drug transporters. The developed test allowed reliable patient stratification, and in silico trials demonstrated utility in adjusting drug dose to achieve similar drug exposure between patients with variable hepatic elimination. Accordingly, this approach can be applied in characterization of volunteers prior to enrollment in clinical trials and for patient stratification in clinical practice to achieve more precise individual dosing.
Mycorrhizal Fungi as Bioprotectors of Crops Against Verticillium Wilt—A Hypothetical Scenario Under Changing Environmental Conditions

The association that many crops can establish with the arbuscular mycorrhizal fungi (AMF) present in soils can enhance the resistance of the host plants against several pathogens, including Verticillium spp. The increased resistance of mycorrhizal plants is mainly due to the improved nutritional and water status of crops and to enhanced antioxidant metabolism and/or increased production of secondary metabolites in the plant tissues. However, the effectiveness of AMF in protecting their host plants against Verticillium spp. may vary depending on the environmental factors. Some environmental factors, such as the concentration of carbon dioxide in the atmosphere, the availability of soil water and the air and soil temperatures, are predicted to change drastically by the end of the century. The present paper discusses to what extent the climate change may influence the role of AMF in protecting crops against Verticillium-induced wilt, taking into account the current knowledge about the direct and indirect effects that the changing environment can exert on AMF communities in soils and on the symbiosis between crops and AMF, as well as on the development, incidence and impact of diseases caused by soil-borne pathogens.
Analysis of the phoretic relationships between mites of the genus Trichouropoda Berlese (Parasitiformes: Uropodina) and the longhorn beetle Plagionotus detritus (Linnaeus) (Coleoptera: Cerambycidae) based on multiannual observations in Białowieża Primeval Forest, Central Europe

ABSTRACT We studied the phoretic relationships between the mites of the genus Trichouropoda Berlese, 1916 (Uropodina) and the longhorn beetle Plagionotus detritus (Linnaeus, 1758) based on large samples of specimens (2050 beetles and 19,216 mites) collected in the Białowieża Primeval Forest in Central Europe. Phoresy was studied over the years 2014, 2015, and 2016, with the emphasis on multi-annual trends in host–phoront associations, seasonal changes in intensity of phoresy, proportion of carriers of mites in the beetle population, and preferences of phoretic deutonymphs for specific parts of the host’s body. The high repeatability in all the variables we studied indicates high stability of the phoretic relationships, probably resulting from the synchronization of life cycles of beetle dispersants and phoretic mites. The long-term coevolution of phoronts and carriers in a natural forest ecosystem, as well as the expected close association of mites with specific beetle-generated microhabitats in larval galleries, may be important factors affecting the strength of the phoretic relationship.
In Vitro Bioaccessibility of Extractable Compounds from Tannat Grape Skin Possessing Health Promoting Properties with Potential to Reduce the Risk of Diabetes

Diabetes pathogenesis encompasses oxidative stress, inflammation, insulin malfunctioning and partial or total insulin secretion impairment, which leads to a constant hyperglycemia. Polyphenols are known to possess bioactive properties, being Tannat grape skin a natural and sustainable source of these compounds. The present study aimed to find out the bioaccessibility of health-promoting molecules composing a multifunctional extract from Tannat grape skin obtained under hydro-alcoholic-acid conditions. The identification of phenolic compounds in the samples was performed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Subsequently, the samples were in vitro digested mimicking the human oral gastrointestinal conditions and the bioactivity of the digest (antioxidant, anti-inflammatory and modulation of glucose metabolism) was assessed. Effect on glucose metabolism was estimated by measuring carbohydrases activity and the functionality of glucose transporters of small intestine cells in presence and absence of the digested extract. Flavonoids, phenolic acids and phenolic alcohols were the major phenol compounds detected in the extract. The bioaccessible compounds protected the intestinal cells and macrophages against the induced formation of reactive oxygen species (ROS) and nitric oxide (NO). In addition, glucose transporters were inhibited by the digested extract. In conclusion, the bioaccessible compounds of the extract, including phenols, modulated key biochemical events involved in the pathogenesis of diabetes such as oxidative stress, inflammation and glucose absorption. The extract was effective under prevention with co-administration conditions supporting its potential for either reducing the risk or treating this disease.
Failing to forget? Evidence for both impaired and preserved working memory control in older adults

ABSTRACT Voluntary forgetting is accomplished via top-down control over memory contents. Age-related declines in cognitive control may compromise voluntary forgetting. Using a working-memory variant of a directed forgetting task, we examined age differences in forgetting efficacy by analyzing direct measures of memory accuracy and two indirect measures of retention: proactive interference and semantic distortions. The directed forgetting effect in long-term memory was virtually absent in older adults. Further, compared to young adults, older adults recognized fewer to-be-remembered and more to-be-forgotten items in working memory. However, indirect measures of forgetting efficacy suggest some spared ability to control working memory contents in older adults: Both young and older adult participants exhibited reduced proactive interference for to-be-forgotten words (Experiment 1) and reduced semantic errors to to-be-forgotten list associates (Experiment 2) in working memory. Indirect memory measures of forgetting efficacy can provide a fuller understanding of spared and impaired control processes in older adults.
Antibacterial activity of a DNA topoisomerase I inhibitor versus fluoroquinolones in Streptococcus pneumoniae

The DNA topoisomerase complement of Streptococcus pneumoniae is constituted by two type II enzymes (topoisomerase IV and gyrase), and a single type I enzyme (topoisomerase I). These enzymes maintain the DNA topology, which is essential for replication and transcription. While fluoroquinolones target the type II enzymes, seconeolitsine, a new antimicrobial agent, targets topoisomerase I. We compared for the first time the in vitro effect of inhibition of topoisomerase I by seconeolitsine and of the type II topoisomerases by the fluoroquinolones levofloxacin and moxifloxacin. We used three isogenic non-encapsulated strains and five non-vaccine serotypes isolates belonging to two circulating pneumococcal clones, ST638 (2 strains) and ST1569V (3 strains). Each group contained strains with diverse susceptibility to fluoroquinolones. Minimal inhibitory concentrations, killing curves and postantibiotic effects were determined. Seconeolitsine demonstrated the fastest and highest bactericidal activity against planktonic bacteria and biofilms. When fluoroquinolone-susceptible planktonic bacteria were considered, seconeolitsine induced postantibiotic effects (1.00−1.87 h) similar than levofloxacin (1.00−2.22 h), but longer than moxifloxacin (0.39−1.71 h). The same effect was observed in sessile bacteria forming biofilms. Seconeolitsine induced postantibiotic effects (0.84−2.31 h) that were similar to those of levofloxacin (0.99−3.32 h) but longer than those of moxifloxacin (0.89−1.91 h). The greatest effect was observed in the viability and adherence of bacteria in the postantibiotic phase. Seconeolitsine greatly reduced the thickness of the biofilms formed in comparison with fluoroquinolones: 2.91 ± 0.43 μm (seconeolitsine), 7.18 ± 0.58 μm (levofloxacin), 17.08 ± 1.02 μm (moxifloxacin). When fluoroquinolone-resistant bacteria were considered, postantibiotic effects induced by levofloxacin and moxifloxacin, but not by seconeolitsine, were shorter, decreasing up to 5-fold (levofloxacin) or 2-fold (moxifloxacin) in planktonic cells, and up to 1.7 (levofloxacin) or 1.4-fold (moxifloxacin) during biofilm formation. Therefore, topoisomerase I inhibitors could be an alternative for the treatment of pneumococcal diseases, including those caused by fluoroquinolone-resistant isolates.
Incidence of and risk factors for post-parathyroidectomy hungry bone syndrome in patients with secondary hyperparathyroidism

Abstract Background Hungry bone syndrome (HBS) following parathyroidectomy is associated with severe hypocalcemia and increased morbidity. This study aims to determine the incidence and risk factors of post-parathyroidectomy HBS in dialysis patients with secondary hyperparathyroidism (SHPT). Methods A retrospective cohort study was conducted, and medical records of patients with SHPT requiring parathyroidectomy between January 2014 and January 2020 were reviewed. HBS was defined as the requirement of intravenous calcium administration due to hypocalcemia-related symptoms and/or reductions in serum calcium concentration (<8.4 mg/dL) within 72 h after parathyroidectomy. Results A total of 130 dialysis patients were enrolled. The majority of patients (85.4%) received hemodialysis and the remaining patients (14.6%) received peritoneal dialysis. Ectopic parathyroid glands were identified in 6.6% of patients by preoperative parathyroid scintigraphy. Diffuse parathyroid hyperplasia was the most common histopathological characteristic of SHPT (90.8%). HBS occurred in 82.3% of patients following parathyroidectomy. Preoperative serum intact parathyroid hormone (iPTH) concentration was significantly correlated with serum calcium (r = −0.48, p < 0.01) and alkaline phosphatase (ALP) concentration (r = 0.71, p < 0.01). Patients with HBS had significantly longer hospital stays than patients without (8 versus 3 days, p < 0.01). Based on multiple logistic regression analysis, young age (≤45 years), high preoperative serum ALP (>420 IU/L) and iPTH (>1,000 pg/mL), and absence of preoperative hypercalcemia (>10.2 mg/dL) were significantly associated with HBS. Conclusions Post-parathyroidectomy HBS is common in dialysis patients with SHPT. Young age, high preoperative serum ALP and iPTH, and low preoperative serum calcium concentrations were important risk factors for HBS.
COVID-19 gender susceptibility and outcomes: A systematic review

Background Epidemiological differences between men and women have been reported with regards to sepsis, influenza and severe coronavirus infections including SARS-CoV and MERS-CoV. Aim To systematically review the literature relating to men versus women on SARS-CoV-2 in order to seek differences in disease characteristics (e.g. infectivity, severity) and outcomes (e.g. mortality). Methods We searched 3 electronic databases up or observational studies reporting differences between men and women in the SARS-CoV-2 disease characteristics stated. We identified and included 47 studies, reporting data for 21,454 patients mainly from China. Results The unadjusted mortality rates of men were higher than those of women, with a mortality OR 0.51 [0.42, 0.61] (p<0.001) for women. The proportion of men presenting with severe disease and admitted to the intensive care unit (ICU) was also higher than that of women (OR 0.75 [0.60–0.93] p<0.001 and OR 0.45 [0.40–0.52] p<0.001 respectively). Adjusted analyses could not be conducted due to lack of data. Conclusion COVID-19 may be associated with worse outcomes in males than in females. However, until more detailed data are provided in further studies enabling adjusted analysis, this remains an unproven assumption.
Towards Rational Design of Biosynthesis Pathways

Towards Rational Design of Biosynthesis Pathways Meshari Saud Alazmi Recent advances in genome editing and metabolic engineering enabled a precise construction of de novo biosynthesis pathways for high-value natural products. One important design decision to make for the engineering of heterologous biosynthesis systems is concerned with which foreign metabolic genes to introduce into a given host organism. Although this decision must be made based on multifaceted factors, a major one is the suitability of pathways for the endogenous metabolism of a host organism, in part because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. To address this point, we developed an open-access web server called MRE (metabolic route explorer) that systematically searches for promising heterologous pathways by considering competing endogenous reactions in a given host organism. MRE utilizes reaction Gibbs free energy information. However, 25% of the reactions do not have accurate estimations or cannot be estimated. To address this issue, we developed a method called FC (fingerprint contribution) to provide a more accurate and complete estimation of the reaction free energy. To rationally design a productive heterologous biosynthesis system, it is essential to consider the suitability of foreign reactions for the specific endogenous metabolic infrastructure of a host. For a given pair of starting and desired compounds in a given chassis organism, MRE ranks biosynthesis routes from the perspective of the integration of new reactions into the endogenous metabolic system. For each promising heterologous biosynthesis pathway, MRE suggests actual enzymes for foreign metabolic reactions and generates information on competing endogenous reactions for the consumption of metabolites. The URL of MRE is http://www.cbrc. kaust.edu.sa/mre/. 5 Accurate and wide-ranging prediction of thermodynamic parameters for biochemical reactions can facilitate deeper insights into the workings and the design of metabolic systems. Here, we introduce a machine learning method, referred to as fingerprint contribution (FC), with chemical fingerprint-based features for the prediction of the Gibbs free energy of biochemical reactions. From a large pool of 2D fingerprint-based features, this method systematically selects a small number of relevant ones and uses them to construct a regularized linear model. FC is freely available for download at http://sfb.kaust.edu.sa/Pages/Software.aspx.
Healthy Pain-Free Individuals with a History of Distal Radius Fracture Demonstrate an Expanded Distribution of Experimental Referred Pain Toward the Wrist.

OBJECTIVE Nociception caused by injuries may sensitize central mechanisms causing expanded pain areas. After recovery, the status of such pain distribution and sensitivity mechanisms is unknown. The present study investigated whether individuals who have fully recovered from a distal radius fracture demonstrate increased pain sensitivity and expanded distribution of pressure-induced pain. DESIGN Cross-sectional single-blinded study. SETTING Clinical setting. SUBJECTS Twenty-three pain-free individuals with a history of painful distal radius fracture and 22 nonfractured, age/gender-matched controls participated in two experimental sessions (day 0, day 1) 24 hours apart. METHODS Pressure pain thresholds (PPTs) were recorded bilaterally at the extensor carpi radialis longus (ECRL), infraspinatus, and gastrocnemius muscles. Spatial distribution of pain was assessed following 60-second painful pressure stimulation at the ECRL (bilateral) and the infraspinatus muscles on the fractured or dominant side. Participants drew pain areas on a body map. After day 0 assessments, prolonged pain was induced by eccentric exercise of wrist extensors on the fractured/dominant side. RESULTS Compared with controls, pressure-induced ECRL pain in the fracture group referred more frequently toward the distal forearm (P < 0.005) on day 0. Both groups showed larger pain areas on day 1 compared with day 0 (P < 0.005), although the fracture group showed a larger relative change between days (P < 0.005). The fracture group showed larger pain areas on the fracture side compared with the contralateral side on both days (P < 0.005). CONCLUSIONS Prolonged pain and recovered prior painful injuries like fractures may sensitize pain mechanisms manifested as expanded pain distribution. Pressure-induced referred pain can be a simple pain biomarker for clinical use.