The Roles of H19 in Regulating Inflammation and Aging.

Accumulating evidence suggests that long non-coding RNA H19 correlates with several aging processes. However, the role of H19 in aging remains unclear. Many studies have elucidated a close connection between H19 and inflammatory genes. Chronic systemic inflammation is an established factor associated with various diseases during aging. Thus, H19 might participate in the development of age-related diseases by interplay with inflammation and therefore provide a protective function against age-related diseases. We investigated the inflammatory gene network of H19 to understand its regulatory mechanisms. H19 usually controls gene expression by acting as a microRNA sponge, or through mir-675, or by leading various protein complexes to genes at the chromosome level. The regulatory gene network has been intensively studied, whereas the biogenesis of H19 remains largely unknown. This literature review found that the epithelial-mesenchymal transition (EMT) and an imprinting gene network (IGN) might link H19 with inflammation. Evidence indicates that EMT and IGN are also tightly controlled by environmental stress. We propose that H19 is a stress-induced long non-coding RNA. Because environmental stress is a recognized age-related factor, inflammation and H19 might serve as a therapeutic axis to fight against age-related diseases

GPR120 is an important inflammatory regulator in the development of osteoarthritis.

BACKGROUND: The aim of this study was to investigate the regulatory role of G-protein coupled receptor 120 (GPR120) in the development and progression of osteoarthritis (OA). METHODS: GPR120 knockout (KO) and wild-type (WT) mice were used to create an animal model of OA by means of anterior cruciate ligament transection (ACLT) surgery. The severity of OA was staged and evaluated by histological examination, microcomputed tomography scan and enzyme-linked immunosorbent assay (ELISA). The anti-inflammatory effects of the GPR120 agonist docosahexaenoic acid (DHA) on human chondrocytes were further evaluated by specific inflammatory markers. In addition, the healing progression of a skin defect model was determined with histological assays. RESULTS: The GPR120-KO mice displayed an accelerated development of OA after ACLT. The secondary inflammation, cartilage degeneration, and subchondral bone aberrant changes were significantly elevated in the early phase of OA in KO mice relative to those in WT mice. In addition, we found that GPR120 levels were downregulated in OA patients compared with control subjects, whereas GPR120 activation with DHA exhibited anti-inflammatory effects in primary human chondrocytes in vitro. Moreover, results from the skin defect model showed that GPR120 agonism with DHA enhanced wound repair in mice, as shown by the downregulation of the number of CD68+ cells. CONCLUSIONS: Our study suggests that GPR120 is an important inflammatory mediator during the development of OA, and that it is a potential marker for the diagnosis of high-risk patients with OA

Return to work, work productivity loss and activity impairment in Chinese breast cancer survivors 12-month post-surgery: a longitudinal study

IntroductionExisting evidence of returning-to-work (RTW) after cancer comes predominately from Western settings, with none prospectively examined since the initial diagnostic phase. This study prospectively documents RTW-rate, time-to-RTW, work productivity loss, and activity impairment, within the first-year post-surgery among Chinese women with breast cancer (BCW) and identify potential causal co-variants.MethodsThis observational longitudinal study followed 371 Chinese BCW who were employed/self-employed at the time of diagnosis at 4-week post-surgery (baseline). RTW-status and time-to-RTW were assessed at baseline (T1), 4-month (T2), 6-month (T3), and 12-month (T4) post-baseline. WPAI work productivity loss and activity impairment were assessed at T4. Baseline covariates included demographics, medical-related factors, work satisfaction, perceived work demand, work condition, RTW self-efficacy, B-IPQ illness perception, COST financial well-being, EORTC QLQ-C30 and QLQ-BR23 physical and psychosocial functioning, and HADS psychological distress.ResultsA 68.2% RTW-rate (at 12-month post-surgery), prolonged delay in RTW (median = 183 days), and significant proportions of T4 work productivity loss (20%), and activity impairment (26%), were seen. BCW who were blue-collar workers with lower household income, poorer financial well-being, lower RTW self-efficacy, poorer job satisfaction, poorer illness perception, greater physical symptom distress, impaired physical functioning, and unfavorable work conditions were more likely to experience undesired work-related outcomes.DiscussionUsing a multifactorial approach, effective RTW interventions should focus on not only symptom management, but also to address psychosocial and work-environmental concerns. An organizational or policy level intervention involving a multidisciplinary team comprising nurses, psychologists, occupational health professionals, and relevant stakeholders in the workplace might be helpful in developing a tailored organizational policy promoting work-related outcomes in BCW

Modulation of microglia by Wolfberry on the survival of retinal ganglion cells in a rat ocular hypertension model

The active component of Wolfberry (Lycium barbarum), lycium barbarum polysaccharides (LBP), has been shown to be neuroprotective to retinal ganglion cells (RGCs) against ocular hypertension (OH). Aiming to study whether this neuroprotection is mediated via modulating immune cells in the retina, we used multiphoton confocal microscopy to investigate morphological changes of microglia in whole-mounted retinas. Retinas under OH displayed slightly activated microglia. One to 100 mg/kg LBP exerted the best neuroprotection and elicited moderately activated microglia in the inner retina with ramified appearance but thicker and focally enlarged processes. Intravitreous injection of lipopolysaccharide decreased the survival of RGCs at 4 weeks, and the activated microglia exhibited amoeboid appearance as fully activated phenotype. When activation of microglia was attenuated by intravitreous injection of macrophage/microglia inhibitory factor, protective effect of 10 mg/kg LBP was attenuated. The results implicated that neuroprotective effects of LBP were partly due to modulating the activation of microglia

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Modelling Embryonic Haematopoiesis Using In Vitro State-of-art Gastruloid Culture

Haematopoietic stem cell progenitor cells (HSPCs) have substantial research and therapeutic value, but the in vitro production of HSPCs from pluripotent stem cells remains elusive. A novel 3D culture method, known as a gastruloid, can mimic gastrulation in embryogenesis, which is crucial to the emergence of HSPC precursors, highlighting the potential to develop this protocol as an in vitro platform for haematopoietic research. This project aims to adapt the previously published gastruloid culture protocol and develop it into a haemogenic gastruloid protocol to produce HSPCs from mouse ES cells and model haematopoiesis which occurs at the aorta-gonad-mesonephros (AGM) region of the mouse embryo. In this project, the gastruloid culture protocol is modified to maintain a gastruloid (gastrulation organoid) for up to 216 hr by introducing a 2iLIF pretreatment and a panel of cytokines throughout the culture. Under the new culture conditions, gastruloids can generate haemogenic endothelium and pro- and pre-HSCs in sequential order, as detected by a combination of markers in flow cytometry assays (Flk-1, c-Kit, CD41 and CD45). Concomitant use of cytokines VEGF and FGF2 can facilitate the emergence of cells with the property of haemogenic endothelial cells, pro-HSCs and type 1 pre-HSCs from 96 to 144 hr. Applying Shh, Flt-3l, TPO, and SCF accordingly can promote the formation CD45+ cells, which is indicative of the formation of type 2 pre-HSCs at 192 and 216 hr. The emergence of these haematopoietic makers suggests stepwise haematopoiesis is recapitulated in the haemogenic gastruloid. The AGM-like haematopoietic clusters are observed at 192 and 216 hr under confocal imaging, further suggesting that definitive haematopoiesis likely occurs in the gastruloid under the optimised protocol. The CFC assay shows that gastruloid cells have the potential to form multipotential myeloid and lymphoid haematopoietic progenitors. The CD45+ cells from the 216 hr gastruloids can occasionally be enriched in OP9 co-culture, and they can also sometimes form committed B-cell linage progenitors with OP9 cells. The chick embryo chorioallantoic membrane (CAM) assay and mouse transplantation experiments imply that the haemogenic gastruloid cells may possess engraftment capability. Single cell SMART sequencing data confirms that gastruloids have haematopoietic gene expression profiles similar to the AGM region of the mouse embryo and captures successive progenitors with erythroid, myeloid-lymphoid and HSC-like signatures. Finally, this haemogenic gastruloid protocol has been applied to other mouse ES cell lines to generate gastruloids, and they can also recapitulate stepwise haematopoiesis. This study has successfully developed a haemogenic gastruloid protocol with a cocktail of haematopoietic cytokines. This haemogenic gastruloid is able to form AGM-like haematopoietic clusters and recapitulate stepwise definitive haematopoiesis to produce haematopoietic progenitors. In the future, this protocol could be developed to validate and reduce the use of animals in scientific research. The results from this study could also be useful preliminary data for developing a human haemogenic gastruloid protocol. Finally, this protocol could be applied as a drug screening or disease modelling tool, such as an infant leukaemia disease model

Current concepts on tenogenic differentiation and clinical applications

Tendon is a tissue that transmits force from muscle to bone. Chronic or acute tendon injuries are very common, and are always accompanied by pain and a limited range of motion in patients. In clinical settings, management of tendon injuries still remains a big challenge. Cell therapies, such as the application of stem cells for tenogenic differentiation, were suggested to be an ideal strategy for clinical translation. However, there is still a lack of specific methods for tenogenic differentiation due to the limited understanding of tendon biology currently. This review focuses on the summary of current published strategies for tenogenic differentiation, such as the application of growth factors, mechanical stimulation, biomaterials, coculture, or induced pluripotent stem cells. Current clinical applications of stem cells for treatment of tendon injuries and their limitations have also been discussed in this review

GPR120 is an important inflammatory regulator in the development of osteoarthritis.

BACKGROUND: The aim of this study was to investigate the regulatory role of G-protein coupled receptor 120 (GPR120) in the development and progression of osteoarthritis (OA). METHODS: GPR120 knockout (KO) and wild-type (WT) mice were used to create an animal model of OA by means of anterior cruciate ligament transection (ACLT) surgery. The severity of OA was staged and evaluated by histological examination, microcomputed tomography scan and enzyme-linked immunosorbent assay (ELISA). The anti-inflammatory effects of the GPR120 agonist docosahexaenoic acid (DHA) on human chondrocytes were further evaluated by specific inflammatory markers. In addition, the healing progression of a skin defect model was determined with histological assays. RESULTS: The GPR120-KO mice displayed an accelerated development of OA after ACLT. The secondary inflammation, cartilage degeneration, and subchondral bone aberrant changes were significantly elevated in the early phase of OA in KO mice relative to those in WT mice. In addition, we found that GPR120 levels were downregulated in OA patients compared with control subjects, whereas GPR120 activation with DHA exhibited anti-inflammatory effects in primary human chondrocytes in vitro. Moreover, results from the skin defect model showed that GPR120 agonism with DHA enhanced wound repair in mice, as shown by the downregulation of the number of CD68+ cells. CONCLUSIONS: Our study suggests that GPR120 is an important inflammatory mediator during the development of OA, and that it is a potential marker for the diagnosis of high-risk patients with OA