Pineapple Leaf Phenols Attenuate DSS-Induced Colitis in Mice and Inhibit Inflammatory Damage by Targeting the NF-κB Pathway

Colitis is not fully curable, although currently, some treatment options are being adopted. In this study, we investigated the effects of pineapple leaf phenols (PLPs), natural phenol products from pineapple leaves, on DSS-induced colitis in mice. The results showed that PLPs dramatically decreased the inflammatory response by inhibiting NF-κB activation and the secretion of pro-inflammatory factors. Moreover, PLPs provided protection against DSS-induced acute colitis by maintaining epithelial integrity. Caffeic and P-coumaric acids had similar effects and could be the active components responsible for PLPs’ effect on colitis. These results indicate that the oral administration of PLPs might be considered as a therapeutic strategy in the treatment of patients with colitis. However, further research on clinical applications and the exact effect of PLPs on colitis is required.

Effect of Electrical Stimulation on Ocular Cells: A Means for Improving Ocular Tissue Engineering and Treatments of Eye Diseases

Tissue engineering is biomedical engineering that uses suitable biochemical and physicochemical factors to assemble functional constructs that restore or improve damaged tissues. Recently, cell therapies as a subset of tissue engineering have been very promising in the treatment of ocular diseases. One of the most important biophysical factors to make this happen is noninvasive electrical stimulation (ES) to target ocular cells that may preserve vision in multiple retinal and optic nerve diseases. The science of cellular and biophysical interactions is very exciting in regenerative medicine now. Although the exact effect of ES on cells is unknown, multiple mechanisms are considered to underlie the effects of ES, including increased production of neurotrophic agents, improved cell migration, and inhibition of proinflammatory cytokines and cellular apoptosis. In this review, we highlighted the effects of ES on ocular cells, especially on the corneal, retinal, and optic nerve cells. Initially, we summarized the current literature on the in vitro and in vivo effects of ES on ocular cells and then we provided the clinical studies describing the effect of ES on ocular complications. For each area, we used some of the most impactful articles to show the important concepts and results that advanced the state of these interactions. We conclude with reflections on emerging new areas and perspectives for future development in this field.

Knockdown of PPARδ Induces VEGFA-Mediated Angiogenesis via Interaction With ERO1A in Human Colorectal Cancer

Angiogenesis is an important mechanism underlying the development and metastasis of colorectal cancer (CRC) and has emerged as a therapeutic target for metastatic CRC (mCRC). Our recent studies found that Peroxisome proliferator-activated receptor β/δ/D (PPARδ) regulates vascular endothelial growth factor A(VEGFA) secretion and the sensitivity to bevacizumab in CRC. However, its exact effect and underlying mechanisms remain unidentified. In this study, we showed that PPARδ expression was inversely associated with the microvascular density in human CRC tissues. Knockdown of PPARδ enhanced VEGFA expression in HCT116 cells and HUVEC angiogenesis in vitro; these phenomena were replicated in the experimental in vivo studies. By tandem mass tag (TMT)-labeling proteomics and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) was screened and predicted as a target gene of PPARδ. This was verified by exploring the effect of coregulation of PPARδ and ERO1A on the VEGFA expression in HCT116 cells. The results revealed that PPARδ induced VEGFA by interacting with ERO1A. In conclusion, our results suggest that knockdown of PPARδ can promote CRC angiogenesis by upregulating VEGFA through ERO1A. This pathway may be a potential target for mCRC treatment.

3×Tg-AD Mice Overexpressing Phospholipid Transfer Protein Improves Cognition Through Decreasing Amyloid-β Production and Tau Hyperphosphorylation

Background: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer’s disease (AD); however, the exact effect and mechanism remain unknown. Objective: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. Methods: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. Results: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-β42 (Aβ 42) and Aβ 40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3β (GSK3β) inactivation via upregulating GSK3β (pSer9). Conclusion: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aβ production and tau phosphorylation, which is related to GSK3β inactivation.

QPCR Screening of Pediatric Saliva Samples to Evaluate Effects of Dental Sealants on Cariogenic Bacteria Streptococcus Mutans and Scardovia Wiggsiae

Dental caries is an alarmingly prevalent multifactorial disease worldwide but is most common as a chronic disease among children and adolescents. Within the oral cavity there are hundreds bacterial species, including specific cariogenic pathogens such as Streptococcus mutans and Scardoviawiggsiae. Although dental caries are highly prevalent, it may also be preventable using methods such as dental sealants or fluoride treatment, which have proven to be highly effective in reducing caries risk – although there is limited evidence on the exact effect of these treatments on S. wiggsiaeinparticular. Due to the lack of conclusive evidence, this study is aimed to evaluate the microbial burden of S. mutans and S. wiggsiae among pediatric saliva samples to analyze the effects dental sealants have on these oral microbiota. Saliva samples derived from pediatric patients pre- and post-sealant were obtained from an existing repository. DNA was extracted and screened using qPCR and primers specific for the cariogenic organisms, S. mutans (SM) and S. wiggsiae (SW). These data demonstrated an overall reduction in SW among Post-sealant samples (11.14 U/uL) compared with Pre-sealant samples (11.68 U/uL), as well as a reduction in the overall number of samples harboring S. wiggsiae (n=8). The Pre-sealant average amount of SM (14.54 U/uL) was slightly increased among the Post-sealant samples (15.67 U/uL) with half of the samples analyzed (n=13) exhibiting slight increases in SM levels, and nearly one-third (n=8) exhibiting slight decreases in SM levels. The data from this study may suggest that dental sealants have an impact on certain cariogenic pathogens in the oral microbiota. Whether or not the impact is positive or not in light of the increase in S. mutans remains an observation that should be further analyzed. More research is required to address the limitations found in this study in order to localize the exact effect on the teeth with dental sealants.

How Surface Tension Matters in Polymer-Free Graphene Transfer

Objectives The main goal of this work is to achieve a direct transfer of graphene and examine the exact effect of surface tension (ST) on graphene during this type of transfer. Methods To reach this target, we designed a specific transfer container with two-sided ports to facilitate replacing liquids underneath graphene and monitor the effect of ST. We prepared liquids with various STs by mixing pure DI-water with different ratios of isopropanol (IPA). Results Our results indicate that high ST does not break the graphene structure if graphene has good quality. Besides, a surface tension gap (STG) can be applied to graphene at a specific level without damaging the graphene monolayer. Comparing those results to the defective graphene features after applying high ST and varied STGs confirms that standing high ST and STG can be considered a key feature of good quality graphene. Conclusion Thus, good quality graphene can be transferred at high ST (ST of water: 72 dyne/cm) with no sign of structural damage. In addition, this type of graphene can stand STG ≤ 40 dyne/cm. This new understanding of the ST effect on graphene could simplify the current direct transfer techniques and widen the graphene applications by expanding the choices of the target substrates and transfer liquids.

Nowhere to Go: Parents' Descriptions of Children's Physical Activity During a Global Pandemic

Background: Schools and outdoor public spaces play a substantial role in children's physical activity. Yet, the COVID-19 shelter-in-place mandates bound many children to their available home spaces for learning, movement, and development. The exact effect this mandate had on children's physical activity may vary among families.Objective: To understand, from the perspective of parents, how the COVID-19 shelter-in-place mandates affected children's physical activity, while also considering families' socioeconomic status.Design: Open-ended survey.Setting: Online.Method: Data were collected from 321 parents living in the United States of America. Parents answered an open-ended prompt to describe their children's physical activity during COVID-19 shelter-in-place mandates. Following data collection, inductive and deductive content analysis examined patterns in the data.Results: Analyses indicated that shelter-in-place mandates restricted children's opportunities for physical activity. However, if families had access to outdoor spaces or equipment, they could encourage and support more physical activity opportunities than those without. Families in the lower-income bracket had less access to outdoor space and subsequently those children had fewer opportunities to be physically active. Parents supported their children's physical activity through their involvement and encouragement.Conclusion: These findings underscore the importance of access to outdoor spaces and equipment for increasing children's physical activity. Findings can be used by educators and policymakers to equitably support families of lower socioeconomic status who reported less access to outdoor spaces.

Increased Malat1 Expression Predicts Poor Prognosis in Primary Gastrointestinal Diffuse Large B-cell Lymphoma

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been involved in the pathogenesis and progression of several cancers. However, the exact effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in PGI-DLBCL patients. Quantitative real-time Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably up-regulated in PGI-DLBCL tissues as compared to that of paired adjacent non-tumor tissues (P<0.001), and the area under the ROC curve (AUC) was 0.838. MALAT1 expression was further increased in the non-germinal center B-cell-like (non-GCB) group, advanced stage (stages IIE-IV) group and International Prognostic Index (IPI) score (3-5) group (P=0.01, P<0.001and P<0.001, respectively). Furthermore, Kaplan-Meier analysis showed that elevated MALAT1 expression was correlated with inferior Overall survival (OS) and progression free survival (PFS) in PGI-DLBCL patients (P<0.001and P<0.001, respectively), and multivariate analysis suggested that up-regulation of MALAT1 and high IPI score (3-5) were two unfavorable prognostic factors of PGI-DLBCL. In conclusion, our results demonstrates that MALAT1 might serve as a novel prognostic biomarker and an ideal therapeutic target for PGI-DLBCL patients in the future.

Chronic overload of concentration-dependent iron exerts different effects on ovarian function in C57BL/6J mice†

Overloaded iron can deposit in the reproductive system and impair ovarian function. But few studies have identified the exact effect of overloaded iron on the endocrine function and fertility capacity in female mice. Here, we established iron-overloaded mouse models by intraperitoneal injection of iron dextran to adult female C57BL/6J mice at 0.1 g/kg (LF group), 0.5 g/kg (MF group), and 1.0 g/kg (HF group) concentrations once a week for eight consecutive weeks. We found that overloaded iron resulted in smaller ovaries, as well as accumulated oxidative damages. The endocrine function and follicle development were also impeded in the MF and HF groups. The 10-month breeding trial indicated that (1) Low concentration of iron (0.1 g/kg) wasn’t detrimental to the ovary; (2) Middle concentration of iron (0.5 g/kg) impeded the childbearing process, though it could be recovered following the iron excretion; and (3) High concentration of iron (1.0 g/kg) damaged the fertility, even gave rise to sterility. Yet for those fertile mice, litter number and litter size were smaller and the ovarian reserve of their offspring was impaired. Transcriptome profiling results indicated that overloaded iron could compromise ovarian function by disrupting ovarian steroidogenesis, interfering with ovarian microenvironment, and inhibiting Wnt signaling. Taken together, we have demonstrated the effect that chronic concentration-dependent iron overload exerted on mouse ovarian function, which may act as a preliminary basis for further mechanism and intervention investigations.

The path to minimizing instability in developmental dysplasia of the hip: is Capsulorrhaphy a necessity or a futile habit?

Background To evaluate and quantify the intraoperative effect of capsulorrhaphy on the deep seating of femoral head within the acetabulum as measured by medial joint space, a surrogate measure of acetabular-head contact. Methods In order to determine the exact effect of capsulorrhaphy, we prospectively scrutinized a consecutive sample of 18 patients with unilateral dysplastic hips aging > 18 months and followed them for a period of at least 12 months. The procedure of open reduction is described in detail. Two pediatric orthopedists carried out the operations from August 2014 to January 2019 at a tertiary pediatric hospital. Intraoperatively, AP radiographs of the pelvis were obtained before and after capsulorrhaphy. The distance between the inferomedial edge of the proximal femoral metaphysis and the lateral edge of the obturator foramen was recorded. To determine if there were differences in medial joint space due to capsulorrhaphy, a generalized linear model was run on the study sample. All patients were followed for at least 12 months to determine the rate of re-dislocation. Results Mean age (±standard deviation) of the participants was 37.5 (±24.7) months. All cases underwent Salter osteotomy, 5 cases needed femoral shortening (27.8%) and none needed derotational osteotomy. Capsulorrhaphy lead to a statistically significant decrease in the mean medial joint space from 1.59 cm before (95% CI: 1.12–2.05) to 0.76 cm after (95% CI: 0.50–1.02) the capsulorrhaphy (P < 0.001). When we took the effect of age into account the corresponding figures were 1.47 (95% CI: 1.22–1.75) and 0.67 (95% CI: 0.39–0.94), respectively (P < 0.001). After follow up periods of 1 to 5.5 years, none of the patients experienced instability or re-dislocation. Conclusions Capsulorrhaphy, independently, of age was associated with a 1-cm decrease in the mean medial hip joint space and a more deeply seated femoral head. Furthermore, this study presents a successful experience with capsulorrhaphy to prevent hip instability.