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Background: Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression.Methods: Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses.Results: We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02).Conclusion: Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for tumour progression, encoding at least 13 genes with a putative role in carcinoma development. Thus, we propose that this region of 8p comprises a metastatic susceptibility locus involved in tumour progression whose disruption increases metastatic potential. [ABSTRACT FROM AUTHOR]

Background: To explore the independent association between lumbar endplate damage and bone mineral density (BMD) in patients with degenerative disc disease (DDD)., Methods: This retrospective investigation was based out of a prospectively collected database from the Affiliated Kunshan Hospital of Jiangsu University. Data from 192 DDD patients, collected between December 2018 and January 2022, were chosen for the final analysis. The average total endplate score (TEPS) of lumbar(L) 1-L4 was assessed by magnetic resonance imaging (MRI), and represents the extent of endplate damage. Osteoporosis severity was assessed via the L1-L4 BMD evidenced by dual-energy x-ray absorptiometry (DXA). Other analyzed information included gender, age, body mass index (BMI), and osteophyte score (OSTS). Uni- and multivariate linear regression analyses were employed to evaluate the association between average TEPS and BMD of L1-L4. Moreover, the generalized additive model (GAM) was employed for non-linear association analysis., Results: Upon gender, age, BMI, and OSTS adjustments, a strong independent inverse relationship was observed between average TEPS and BMD (β, -0.021; 95% CI, -0.035 to -0.007, P-value = 0.00449). In addition, the gender stratification analysis revealed a linear relationship in males, and a non-linear relationship in females. Specifically, there was a significantly stronger negative relationship between average TEPS and BMD in females, when the average TEPS was < 3.75 (β, -0.063; 95% CI, -0.114 to -0.013; P-value = 0.0157). However, at an average TEPS > 3.75, the relationship did not reach significance (β, 0.007; 95% CI, -0.012 to 0.027; P-value = 0.4592)., Conclusions: This study demonstrated the independent negative association between average TEPS and BMD values of L1-L4. Upon gender stratification, a linear relationship was observed in males, and a non-linear association in females. The findings reveal that patients with osteoporosis or endplate damage require more detailed examinations and treatment regimen., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Schools play an organizational role in managing myopia-related behavioral habits among students. We evaluated the effects of school myopia management measures on myopia onset and progression in a school-based prospective 1-year observational study., Methods: In total, 8319 children from 26 elementary schools were included. Online questionnaire completed by a parent, in which school myopia management experience including outdoor activities in recess or physical education class, teachers' supervision, and teaching facilities. Variables were defined as implemented well or poorly, according to the Comprehensive Plan to Prevent Myopia among Children and Teenagers. Children underwent ophthalmic examinations, and the incidence and progression of myopia from 2019 to 2020 were estimated. Multilevel logistic regression models were constructed to analyze the association between school management measures and myopia development in 8,9 years and 10,11 years students., Results: From 2019 to 2020, the incidence of myopia among primary school students was 36.49%; the mean difference of spherical equivalent in myopic children was - 0.29 ± 1.22 diopters. The risk of incident myopia was reduced by 20% in 8,9 years participants with well-implemented class recess compared with those with poorly implemented class recess (adjusted odds ratio [aOR]: 0.80, p = 0.032). PE outdoor time was significantly associated with myopia incidence in 10,11 years students (aOR: 0.76, p = 0.043). Compared with poorly implemented reading and writing posture, desk and chair height, 10,11 participants with well-implemented desk and chair height were less likely to have rapid myopic progression (p = 0.029, p = 0.022)., Conclusion: In Shanghai, children's myopia is associated with better implementation of school myopia management measures. The present findings suggest that outdoor activities during class recess or PE class, providing suitable desks and chairs, and adequate instruction in reading and writing postures might protect against pathological eye growth. An age-specific myopia prevention and control programs in school is of primary importance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The timing of adiposity peak (AP) or adiposity rebound (AR) is a determinant of overweight or obesity in adolescence and adulthood. However, limited studies have reported the association in young school-age children. We aimed to evaluate this association and explore the role of health behaviours in it., Methods: Routinely collected, sequential, anthropometric data from the 1st to 80th months of age were used to estimate AP and AR timings in 2330 children born in Shanghai between 2010 and 2013. Multivariate regression analyses were applied to identify the associations between the AP or AR timings and the risk of developing overweight or obesity in first-grade school children. The roles of health behaviours, including dietary patterns, physical activity level, sleep and snacking habits, and screen time, were also evaluated., Results: Children with a late AP or an early AR were at higher risk of overweight but not obesity or central obesity in their first grade. A high physical activity level was associated with a lower risk of having overweight in children with a late AP, and limited screen time was associated with a decreased risk of having overweight or obesity in children with an early AR. The absence of a late-night snacking habit in children with a non-early AR indicated a decreased risk of having overweight. However, this association was not observed among children with an early AR., Conclusion: The timings of AP and AR are tied to overweight in middle childhood. Prevention strategies are suggested to move forward to control late AP and early AR., (© 2022. The Author(s).)

Background: Identifying practical and distinguished indicators and influencing factors of male aging may be useful in predicting subsequent aging trends, designing personalized prevention, and improving lifestyle and health., Methods: A cross-sectional, population-based study was performed in Jiashan County, China in 2016. A total of 690 local male residents, aged 40 to 80 years, were eligible for recruitment. Demographic and lifestyle information was collected through structured interviews. A self-designed head scale, the Medical Outcomes Study 36-item Short Form (SF-36), International Index of Erectile Function (IIEF5), Aging Males' Symptoms (AMS), and International Prostate Symptom Score (IPSS) were used. Analysis of variance, local polynomial regression smoothing curves, multiple linear regression, and partial correlation analyses were performed., Results: All the scales deteriorated with increasing age (P < 0.01), especially from the age of 60. The most significant changes between adjacent age groups were found in IIEF5 scores (16.7, 43.5 and 39.4%). Income, nutrition, personality and neighborhood relationship had an effect on SF-36 and AMS after adjusting for age (P < 0.01). Furthermore, neighborhood relationship modified the age effect on the head scale score and IIEF5 (P = 0.03); nutrition modified the relationship between age and SF-36 (P < 0.01)., Conclusions: Recession of reproductive health may be a distinct predictor of male aging. The associations of social inequalities or personality and health offer potential interventions for men's health in aging. Self-reported scales may limit the precision and more physical fitness tests could be combined for a more precise assessment., (© 2021. The Author(s).)

Background: Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model., Methods: Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention., Results: Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction., Conclusion: Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

Background: Implantation failure is not only a major cause of early pregnancy loss, but it is also an obstacle to assisted reproductive technologies. The identification of potential circulating biomarkers for recurrent miscarriage (RM) and/or recurrent implantation failure would contribute to the development of novel diagnosis and prediction techniques., Methods: MiR (miR-23a-3p, 27a-3p, 29a-3p, 100-5p, 127-3p and 486-5p) expression in the villi, decidual tissues and peripheral blood plasma and serum were validated by qPCR, and the localization of miRs in the villi and decidual tissues of RM and normal pregnancy (NP) women were detected by in situ hybridization. The invasiveness of HTR8/SVneo cells was determined using a Transwell assay. The predictive values of miRs for RM and the outcome of IVF-ET were respectively calculated by the receiver operating characteristic analysis., Results: The signals of six miRs were observed in the villi and decidual tissues of RM and NP women. The villus miR-27a-3p, miR-29a-3p and miR-100-5p were significantly up-regulated, whereas miR-127-3p and miR-486-5p appeared to be down-regulated in RM women compared to NP women. The invasiveness of HTR8/SVneo cells transfected with miR-23a-3p mimics was evidently weakened, whereas that of cells transfected with miR-127-3p mimics was obviously enhanced. The peripheral blood plasma levels of miR-27a-3p, miR-29a-3p, miR-100-5p and miR-127-3p were significantly increased, whereas that of miR-486-5p was remarkably decreased in RM compared to NP women. By contrast, serum miR-23a-3p and miR-127-3p were significantly decreased, whereas that of miR-486-5p was remarkably increased. The combination of six plasma miRs levels discriminated RM with a sensitivity of 100% and a specificity of 83.3%, whereas that of six serum miRs levels showed a sensitivity of 78.3% and a specificity of 93.1%. In the IVF-ET cohort, the significantly decreased peripheral blood plasma levels of miR-23a-3p, miR-27a-3p, miR-100-5p and miR-127-3p, and the serum levels of miR-100-5p and miR-486-5p, in addition to the significantly increased serum level of miR-27a-3p, were found to be associated with the failure of ET. Moreover, the combination of plasma miR-23a-3p, miR-27a-3p, miR-29a-3p, miR-100-5p, miR-127-3p and miR-486-5p levels discriminated the outcome of IVF-ET with a sensitivity of 68.1% and a specificity of 54.1%, whereas the combination of plasma miR-127-3p and miR-486-5p levels showed a sensitivity of 50.0% and a specificity of 75.3%., Conclusions: Circulating miR-23a-3p, miR-27a-3p, miR-29a-3p, miR-100-5p, miR-127-3p and miR-486-5 might be involved in RM pathogenesis and present potential diagnostic biomarkers for RM. Meanwhile, these miRs, in particular miR-127-3p and miR-486-5p, provide promising prediction indexes for the outcomes of IVF-ET.

Background: Semen cryopreservation has been widely applied in assisted reproductive technologies and sperm bank, but it causes considerable impairments on sperm quality. It is necessary to find an evaluation indicator for determining the sperm-freezing tolerance., Methods: The glycocalyx of good freezability ejaculates was compared with poor freezability ejaculates by lectin microarray. The significant different lectins were validated by flow cytometry (FACS). To analyze the relationship between the potential biomarker and the tolerance of sperm to cryopreservation, 60 samples with different recovery rates were collected and detected the lectin-binding intensity by FACS. The receiver operating characteristic (ROC) curve was analyzed to test the capability of the lectin as a potential biomarker for detecting the sperm freezablility., Results: ABA and DSL were found to develop significant differences between them. Further validation showed that ABA was significantly negative correlated with the sperm recovery rates ( r  = - 0.618, P  < 0.000) and could be a potential biomarker for predicting sperm freezability (AUC = 0.733 ± 0.067, 95% CI 0.601 - 0.865, P  < 0.01)., Conclusion: ABA could be a potential biomarker for predicting sperm freezability. It will help to reduce sperm-freezing recovery tests and improve the efficiency of cryopreservation in human sperm bank.

Background: Activated hepatic stellate cells are the main source of excessive collagen deposition in liver fibrosis. Here we report the inhibitory effects of the combinational treatment of two natural products, astragalus polysaccharide (APS) and β-elemene (ELE) on the activation of human liver hepatic stellate cell line LX-2 cells., Methods: Cultured LX-2 cells were treated with different concentrations of APS or ELE for 24 or 48 hours. Cell viability/apoptosis was measured by MTT assay and Annexin V/PI staining , activation related genes including α-SMA and CD44 expressions were measured by real-time PCR and western blot respectively., Results: The majority of LX-2 cells showed morphological change in the presence of APS or ELE for 24 hours. Treatment with APS + ELE for 24 or 48 hours significantly inhabited the cell proliferation compared with APS or ELE treatment alone on LX-2 cells. APS + ELE may block the up-regulation of α-SMA and CD44 both in mRNA and protein levels through TGF-β pathway in LX-2 cells., Conclusion: APS or ELE treatment alone on LX-2 cells could inhibit cell proliferation and induce apoptosis. The combinational treatment using APS + ELE significantly increased the killing efficiency on LX-2 cells. α-SMA and CD44 expressions was inhibited upon APS + ELE treatment through TGF-β pathway in LX-2 cells. The results indicated a novel treatment using natural products for liver diseases with anti-fibrotic effect.

It is well known that cell surface glycans or glycocalyx play important roles in sperm motility, maturation and fertilization. A comprehensive profile of the sperm surface glycans will greatly facilitate both basic research (sperm glycobiology) and clinical studies, such as diagnostics of infertility. As a group of natural glycan binders, lectin is an ideal tool for cell surface glycan profiling. However, because of the lack of effective technology, only a few lectins have been tested for lectin-sperm binding profiles. To address this challenge, we have developed a procedure for high-throughput probing of mammalian sperm with 91 lectins on lectin microarrays. Normal sperm from human, boar, bull, goat and rabbit were collected and analyzed on the lectin microarrays. Positive bindings of a set of ~50 lectins were observed for all the sperm of 5 species, which indicated a wide range of glycans are on the surface of mammalian sperm. Species specific lectin bindings were also observed. Clustering analysis revealed that the distances of the five species according to the lectin binding profiles are consistent with that of the genome sequence based phylogenetic tree except for rabbit. The procedure that we established in this study could be generally applicable for sperm from other species or defect sperm from the same species. We believe the lectin binding profiles of the mammalian sperm that we established in this study are valuable for both basic research and clinical studies.