Wharton’s jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications

Accumulating evidence indicates that most primary Wharton’s jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., their ability to modulate their microenvironment by releasing bioactive molecules and factors collectively known as secretome. These bioactive molecules and factors can either be released directly into the surrounding microenvironment or can be embedded within the membrane-bound extracellular bioactive nano-sized (usually 30–150 nm) messenger particles or vesicles of endosomal origin with specific route of biogenesis, known as exosomes or carried by relatively larger particles (100 nm–1 μm) formed by outward blebbing of plasma membrane called microvesicles (MVs); exosomes and MVs are collectively known as extracellular vesicles (EVs). The bioactive molecules and factors found in secretome are of various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, and regulatory nucleic acid molecules. As expected, the secretome performs different biological functions, such as immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory and anti-fibrotic effects. This review highlights the current advances in research on the WJ-MSCs’ secretome and its prospective clinical applications

Neural Network-Based Water Quality Prediction

Water quality assessment is critical for environmental sustainability and public health. This research employs neural networks to predict water quality, utilizing a dataset of 21 diverse features, including metals, chemicals, and biological indicators. With 8000 samples, our neural network model, consisting of four layers, achieved an impressive 94.22% accuracy with an average error of 0.031. Feature importance analysis revealed arsenic, perchlorate, cadmium, and others as pivotal factors in water quality prediction. This study offers a valuable contribution to enhancing water quality monitoring and decision-making for stakeholders and policymakers

Gli2 and MEF2C activate each other's expression and function synergistically during cardiomyogenesis in vitro

The transcription factors Gli2 (glioma-associated factor 2), which is a transactivator of Sonic Hedgehog (Shh) signalling, and myocyte enhancer factor 2C (MEF2C) play important roles in the development of embryonic heart muscle and enhance cardiomyogenesis in stem cells. Although the physiological importance of Shh signalling and MEF2 factors in heart development is well known, the mechanistic understanding of their roles is unclear. Here, we demonstrate that Gli2 and MEF2C activated each other's expression while enhancing cardiomyogenesis in differentiating P19 EC cells. Furthermore, dominant-negative mutant proteins of either Gli2 or MEF2C repressed each other's expression, while impairing cardiomyogenesis in P19 EC cells. In addition, chromatin immunoprecipitation (ChIP) revealed association of Gli2 to the Mef2c gene, and of MEF2C to the Gli2 gene in differentiating P19 cells. Finally, co-immunoprecipitation studies showed that Gli2 and MEF2C proteins formed a complex, capable of synergizing on cardiomyogenesis-related promoters containing both Gli- and MEF2-binding elements. We propose a model whereby Gli2 and MEF2C bind each other's regulatory elements, activate each other's expression and form a protein complex that synergistically activates transcription, enhancing cardiac muscle development. This model links Shh signalling to MEF2C function during cardiomyogenesis and offers mechanistic insight into their in vivo functions

Gli2 and MEF2C activate each other's expression and function synergistically during cardiomyogenesis in vitro

The transcription factors Gli2 (glioma-associated factor 2), which is a transactivator of Sonic Hedgehog (Shh) signalling, and myocyte enhancer factor 2C (MEF2C) play important roles in the development of embryonic heart muscle and enhance cardiomyogenesis in stem cells. Although the physiological importance of Shh signalling and MEF2 factors in heart development is well known, the mechanistic understanding of their roles is unclear. Here, we demonstrate that Gli2 and MEF2C activated each other's expression while enhancing cardiomyogenesis in differentiating P19 EC cells. Furthermore, dominant-negative mutant proteins of either Gli2 or MEF2C repressed each other's expression, while impairing cardiomyogenesis in P19 EC cells. In addition, chromatin immunoprecipitation (ChIP) revealed association of Gli2 to the Mef2c gene, and of MEF2C to the Gli2 gene in differentiating P19 cells. Finally, co-immunoprecipitation studies showed that Gli2 and MEF2C proteins formed a complex, capable of synergizing on cardiomyogenesis-related promoters containing both Gli- and MEF2-binding elements. We propose a model whereby Gli2 and MEF2C bind each other's regulatory elements, activate each other's expression and form a protein complex that synergistically activates transcription, enhancing cardiac muscle development. This model links Shh signalling to MEF2C function during cardiomyogenesis and offers mechanistic insight into their in vivo functions

Histologic and histomorphometric evaluation of a new bioactive liquid bbl on implant surface: a preclinical study in foxhound dogs

Background: bioactive chemical surface modifications improve the wettability and osse-ointegration properties of titanium implants in both animals and humans. The objective of this animal study was to investigate and compare the bioreactivity characteristics of titanium implants (BLT) pre‐treated with a novel bone bioactive liquid (BBL) and the commercially available BLT‐SLA active. Methods: forty BLT‐SLA titanium implants were placed in in four foxhound dogs. Animals were divided into two groups (n = 20): test (BLT‐SLA pre‐treated with BBL) and control (BLT‐SLA active) implants. The implants were inserted in the post extraction sockets. After 8 and 12 weeks, the animals were sacrificed, and mandibles were extracted, containing the implants and the surrounding soft and hard tissues. Bone‐to‐implant contact (BIC), inter‐thread bone area percentage (ITBA), soft tissue, and crestal bone loss were evaluated by histology and histomorphometry. Results: all animals were healthy with no implant loss or inflammation symptoms. All implants were clinically and histologically osseo‐integrated. Relative to control groups, test implants demon-strated a significant 1.5‐ and 1.7‐fold increase in BIC and ITBA values, respectively, at both assessment intervals. Crestal bone loss was also significantly reduced in the test group, as compared with controls, at week 8 in both the buccal crests (0.47 ± 0.32 vs 0.98 ± 0.51 mm, p < 0.05) and lingual crests (0.39* ± 0.3 vs. 0.89 ± 0.41 mm, p < 0.05). At week 12, a pronounced crestal bone loss improvement was observed in the test group (buccal, 0.41 ± 0.29 mm and lingual, 0.54 ± 0.23 mm). Tissue thickness showed comparable values at both the buccal and lingual regions and was significantly improved in the studied groups (0.82–0.92 mm vs. 33–48 mm in the control group). Conclusions: Relative to the commercially available BLT‐SLA active implants, BLT‐SLA pre‐treated with BBL showed improved histological and histomorphometric characteristics indicating a reduced titanium surface roughness and improved wettability, promoting healing and soft and hard tissue regeneration at the implant site.This research was funded by: Biointelligent Technology Systems SL, Barcelona, Spain

Chemically defined conditions mediate an efficient induction of dental pulp pluripotent-like stem cells into hepatocyte-like cells

Liver diseases are major causes of morbidity and mortality. Dental pulp pluripotent-like stem cells (DPPSCs) are of a considerable promise in tissue engineering and regenerative medicine as a new source of tissue-specific cells; therefore, this study is aimed at demonstrating their ability to generate functional hepatocyte-like cells in vitro. Cells were differentiated on a collagen scaffold in serum-free media supplemented with growth factors and cytokines to recapitulate liver development. At day 5, the differentiated DPPSC cells expressed the endodermal markers FOXA1 and FOXA2. Then, the cells were derived into the hepatic lineage generating hepatocyte-like cells. In addition to the associated morphological changes, the cells expressed the hepatic genes HNF6 and AFP. The terminally differentiated hepatocyte-like cells expressed the liver functional proteins albumin and CYP3A4. In this study, we report an efficient serum-free protocol to differentiate DPPSCs into functional hepatocyte-like cells. Our approach promotes the use of DPPSCs as a new source of adult stem cells for prospective use in liver regenerative medicine.This study was funded by the Universitat Internacional de Catalunya (UIC), the Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya project number (SGR 1060 for MA), the Kuwait Foundation for the Advancement of Sciences (KFAS), and the Dasman Diabetes Institute under project number (RA-2013-009 for AAM). CGR, EMS, and RNT were funded by the predoctoral grant Junior Faculty award from the Obra Social, 'la Caixa' Foundation, and UIC

Differential effects of fish-oil and cocoa-butter based high-fat/high-sucrose diets on endocrine pancreas morphology and function in mice

IntroductionA high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or increase this adverse effect. Fish oil and cocoa butter are a significant part of our diets. Yet comparisons of these commonly used fat sources with high sucrose on pancreas morphology and function are not made. This study investigated the comparative effects of a fish oil-based high-fat/high-sucrose diet (Fish-HFDS) versus a cocoa butter-based high-fat/high-sucrose diet (Cocoa-HFDS) on endocrine pancreas morphology and function in mice.MethodsC57BL/6 male mice (n=12) were randomly assigned to dietary intervention either Fish-HFDS (n=6) or Cocoa-HFDS (n=6) for 22 weeks. Intraperitoneal glucose and insulin tolerance tests (IP-GTT and IP-ITT) were performed after 20-21 weeks of dietary intervention. Plasma concentrations of c-peptide, insulin, glucagon, GLP-1, and leptin were measured by Milliplex kit. Pancreatic tissues were collected for immunohistochemistry to measure islet number and composition. Tissues were multi-labelled with antibodies against insulin and glucagon, also including expression on Pdx1-positive cells.Results and discussionFish-HFDS-fed mice showed significantly reduced food intake and body weight gain compared to Cocoa-HFDS-fed mice. Fish-HFDS group had lower fasting blood glucose concentration and area under the curve (AUC) for both GTT and ITT. Plasma c-peptide, insulin, glucagon, and GLP-1 concentrations were increased in the Fish-HFDS group. Interestingly, mice fed the Fish-HFDS diet displayed higher plasma leptin concentration. Histochemical analysis revealed a significant increase in endocrine pancreas β-cells and islet numbers in mice fed Fish-HFDS compared to the Cocoa-HFDS group. Taken together, these findings suggest that in a high-fat/high-sucrose dietary setting, the source of the fat, especially fish oil, can ameliorate the effect of sucrose on glucose homeostasis and endocrine pancreas morphology and function

Caveolin-1 Variant Is Associated With the Metabolic Syndrome in Kuwaiti Children

Caveolin-1 (CAV1) variants have been suggested to be associated with obesity and related metabolic disorders, but information based on human studies is limited. In the present study, we aimed to investigate the potential association between the CAV1 rs1997623 C/A variant and metabolic syndrome (MetS) in Kuwaiti children. DNA from saliva samples collected from 1313 Kuwaiti children (mean age: 12 years) were genotyped using the TaqMan SNP genotyping assay. The classification of MetS was based on the presence/absence of four indicators; (1) central obesity, (2) elevated systolic or diastolic blood pressure, (3) low salivary high-density lipoprotein cholesterol (HDLC), and (4) high salivary glucose. In this study, children with MetS scored ≥3, children in the intermediate metabolic group scored 1 or 2 and children without MetS scored 0. About one-third of the children were obese. A total of 246 children (18.7%) were classified as having MetS; 834 children (63.5%) were in the intermediate metabolic group, and 233 children (17.7%) had no indication of MetS. Obesity was highly prevalent in the MetS group (91.9%) while 26.8% of children were obese in the intermediate metabolic group. None of the children were obese in the group without MetS. Analysis of the CAV1 rs1997623 variant revealed a significant association of the A-allele (p = 0.01, Odds Ratio (OR) = 1.66) and the heterozygous CA-genotype (p = 0.005, OR = 1.88) with MetS. Consistently, the A-allele (p = 0.002, OR = 1.71) and CA-genotype (p = 0.005, OR = 1.70) also showed significant association with the intermediate metabolic group. Furthermore, the A-allele (p = 0.01, OR = 1.33) and the CA-genotype (p = 0.008, OR = 1.55) were associated with low levels of saliva HDLC. Individuals who were heterozygous or homozygous for the variant (CA/AA) showed significantly lower levels of high HDLC compared to those harboring the CC-genotype (p = 0.023). Our study revealed a novel association of the CAV1 rs1997623 variant with the MetS and with low saliva HDLC levels in young Kuwaiti children and indicated the need for further in-depth studies to unravel the role of CAV1 gene in the genetic etiology of MetS

Psychological impact of COVID-19 on healthcare workers: cross-sectional analyses from 14 countries

Abstract Background Healthcare workers (HCWs) have been impacted psychologically due to their professional responsibilities over the prolonged era of the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to identify the predictors of psychological distress, fear, and coping during the COVID-19 pandemic among HCWs. Methods A cross-sectional online survey was conducted among self-identified HCWs across 14 countries (12 from Asia and two from Africa). The Kessler Psychological Distress Scale, the Fear of COVID-19 Scale, and the Brief Resilient Coping Scale were used to assess the psychological distress, fear, and coping of HCWs, respectively. Results A total of 2447 HCWs participated; 36% were doctors, and 42% were nurses, with a mean age of 36 (±12) years, and 70% were females. Moderate to very-high psychological distress was prevalent in 67% of the HCWs; the lowest rate was reported in the United Arab Emirates (1%) and the highest in Indonesia (16%). The prevalence of high levels of fear was 20%; the lowest rate was reported in Libya (9%) and the highest in Egypt (32%). The prevalence of medium-to-high resilient coping was 63%; the lowest rate was reported in Libya (28%) and the highest in Syria (76%). Conclusion COVID-19 has augmented the psychological distress among HCWs. Factors identified in this study should be considered in managing the wellbeing of HCWs, who had been serving as the frontline drivers in managing the crisis successfully across all participating countries. Furthermore, interventions to address their psychological distress should be considered