Physicochemical Properties and Biological Activities of Quinoa Polysaccharides.

Quinoa, known as the "golden grain" for its high nutritional value, has polysaccharides as one of its sources of important nutrients. However, the biological functions of quinoa polysaccharides remain understudied. In this study, two crude polysaccharide extracts of quinoa (Q-40 and Q-60) were obtained through sequential precipitation with 40% and 60% ethanol, with purities of 58.29% (HPLC) and 62.15% (HPLC) and a protein content of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47,484 to 626,488 Da, while Q-60 showed a range of 10,025 to 47,990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA (MD Anderson Cancer Center) cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in the application of quinoa in the food and functional food industries.

Identification of prognostic signatures in remnant gastric cancer through an interpretable risk model based on machine learning: a multicenter cohort study.

OBJECTIVE: The purpose of this study was to develop an individual survival prediction model based on multiple machine learning (ML) algorithms to predict survival probability for remnant gastric cancer (RGC). METHODS: Clinicopathologic data of 286 patients with RGC undergoing operation (radical resection and palliative resection) from a multi-institution database were enrolled and analyzed retrospectively. These individuals were split into training (80%) and test cohort (20%) by using random allocation. Nine commonly used ML methods were employed to construct survival prediction models. Algorithm performance was estimated by analyzing accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), confusion matrices, five-fold cross-validation, decision curve analysis (DCA), and calibration curve. The best model was selected through appropriate verification and validation and was suitably explained by the SHapley Additive exPlanations (SHAP) approach. RESULTS: Compared with the traditional methods, the RGC survival prediction models employing ML exhibited good performance. Except for the decision tree model, all other models performed well, with a mean ROC AUC above 0.7. The DCA findings suggest that the developed models have the potential to enhance clinical decision-making processes, thereby improving patient outcomes. The calibration curve reveals that all models except the decision tree model displayed commendable predictive performance. Through CatBoost-based modeling and SHAP analysis, the five-year survival probability is significantly influenced by several factors: the lymph node ratio (LNR), T stage, tumor size, resection margins, perineural invasion, and distant metastasis. CONCLUSIONS: This study established predictive models for survival probability at five years in RGC patients based on ML algorithms which showed high accuracy and applicative value.

The efficacy and safety of hydrotherapy in patients with knee osteoarthritis: a meta-analysis of randomized controlled trials.

BACKGROUND: Currently, there is poor evidence of the effect of hydrotherapy on patients with knee osteoarthritis (OA). The authors performed a meta-analysis from randomized controlled trials to determine the efficacy and safety of a hydrotherapy program on measures of pain and knee function in individuals living with knee OA. METHODS: A literature review included PubMed, EMBASE, Cochrane Library, Science Citation Index, ScienceDirect, and Ovid. Studies evaluating the efficacy of hydrotherapy for knee OA up to August 2023 were included. The research was reported based on the preferred reporting items for systematic reviews and meta-analysis guidelines to ensure the reliability and verity of results. Statistical analysis was performed using Stata/SE version 15.0. RESULTS: A total of six randomized controlled trials were included for data extraction and meta-analysis. The present study revealed that there were significant differences between the two groups regarding the pain intensity at 1 week (WMD=-0.429; 95% CI: -0.679 to -0.179; P =0.001), 4 week (WMD=-0.308; 95% CI: -0.587 to -0.030; P =0.030) and 8 week (WMD=-0.724; 95% CI: -1.099 to -0.348, P <0.001). Furthermore, hydrotherapy was associated with improved outcome of the Western Ontario and McMaster Universities Arthritis index at 1 week (WMD=-3.314; 95% CI: -6.484 to -0.145, P =0.040), 4 week (WMD= -3.630; 95% CI: -6.893 to -0.366, P =0.029) and 8 week (WMD=-3.775; 95% CI: -7.315 to -0.235; P =0.037). No serious adverse events were observed in all patients who received hydrotherapy. CONCLUSION: Hydrotherapy is efficacious and safe for reducing pain and improving functional status in individuals with knee OA, without increasing the risk of adverse effects.

A reduction of Syndecan-4 in macrophages promotes atherosclerosis by aggravating the proinflammatory capacity of macrophages.

BACKGROUND: Cardiovascular diseases (CVDs) are a significant cause of mortality worldwide and are characterized by severe atherosclerosis (AS) in patients. However, the molecular mechanism of AS formation remains elusive. In the present study, we investigated the role of syndecan-4 (SDC4), a member of the syndecan family, in atherogenesis. METHODS AND RESULTS: The expression of SDC4 decreased in mouse severe AS models. Moreover, knockout of SDC4 accelerated high-cholesterol diets (HCD)-induced AS in ApoE-/- mice. Mechanistically, the decrease of SDC4 increased macrophage proinflammatory capacity may be through the PKCα-ABCA1/ABCG1 signaling pathway. CONCLUSION: These findings provide evidence that SDC4 reduction links macrophages and inflammation to AS and that SDC4 in macrophages provides a therapeutic target for preventing AS formation.

A Novel miR-98 Negatively Regulates the Resistance of Endometrial Cancer Cells to Paclitaxel by Suppressing ABCC10/MRP-7.

Endometrial cancer (EC) is one of the most frequent gynecological tumors, and chemoresistance is a major obstacle to improving the prognosis of EC patients. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have recently emerged as crucial chemoresistance regulators that alter the levels of downstream target genes. Multidrug Resistance Protein 7 (MRP-7/ABCC10) is an ATP-binding cassette transporter that causes the resistance to anti-cancer drugs. The purpose of this research is to determine whether MRP-7 has a role in mediating the sensitivity of EC cells to paclitaxel and whether the expression of MRP-7 is regulated by miR-98 and lncRNA NEAT1. We reported that the levels of MRP-7 were significantly increased in EC tissues and associated with an unfavorable prognosis. Downregulation of MRP-7 in EC cells sensitized these cells to paclitaxel and reduced cell invasion. PLAUR serves as a downstream molecule of MRP-7 and facilitates paclitaxel resistance and EC cell invasiveness. Moreover, miR-98 serves as a tumor suppressor to inhibit MRP-7 expression, leading to the repression of paclitaxel resistance. Furthermore, a novel lncRNA, NEAT1, was identified as a suppressor of miR-98, and NEAT1 could upregulate MRP-7 levels by reducing the expression of miR-98. Taken together, these findings demonstrate that upregulation of MRP-7 and NEAT1, and downregulation of miR-98 have important roles in conferring paclitaxel resistance to EC cells. The modulation of these molecules may help overcome the chemoresistance against paclitaxel in EC cells.

Evaluation of Dry Eye after Implantable Collamer Lens Surgery.

OBJECTIVES: To evaluate dry eye (DE) and associated meibomian gland dysfunction parameters after Implantable Collamer Lens (ICL) surgery. METHODS: This is a prospective observational case series. Patients who underwent ICL implantation without previous ocular diseases or ophthalmic treatments were enrolled. Their Ocular Surface Disease Index (OSDI), noninvasive breakup time (NIBUT), meibography, slit-lamp examination of the lid margin, corneal fluorescein staining (CFS), and Schirmer test I were examined preoperatively and at 1 and 3 months postoperatively. RESULTS: A total of 117 eyes of 60 patients were enrolled, and 107 eyes completed 3-month follow-up period. OSDI, lid marginal abnormality, and meibomian gland (MG) secretion, and meibum quality score were significantly higher at 1 month postoperatively and recovered partially at 3 months after surgeries, while NIBUT was significantly decreased all the time. Patients with previous DE symptoms (OSDI score ≥12) showed not only lower Schirmer and TBUT values but also higher CFS, lid margin score, MG loss, MG secretion, and meibum quality scores compared with those in the control group after operations. Low Schirmer, NIBUT values, and high meibum quality score were determined as risk factors for DE symptoms after ICL surgery. CONCLUSIONS: ICL implantation has a bad influence on the ocular surface and MG functions. The influence may be more obvious in patients with existing DE.

Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Plumbagin induces RPE cell cycle arrest and apoptosis via p38 MARK and PI3K/AKT/mTOR signaling pathways in PVR.

BACKGROUND: This study aimed to explore the effects of plumbagin (PLB) on ARPE-19 cells and underlying mechanism. METHODS: Cultured ARPE-19 cells were treated with various concentrations (0, 5, 15, and 25 µM) of PLB for 24 h or with 15 µM PLB for 12, 24 and 48 h. Then cell viability was evaluated by MTT assay and DAPI staining, while apoptosis and cell cycle progression of ARPE cells were assessed by flow cytometric analysis. Furthermore, the level of main regulatory proteins was examinated by Western boltting and the expression of relative mRNA was tested by Real-Time PCR. RESULTS: PLB exhibited potent inducing effects on cell cycle arrest at G2/M phase and apoptosis of ARPE cells via the modulation of Bcl-2 family regulators in a concentration- and time-dependent manner. PLB induced inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways contributing to the anti-proliferative activities in ARPE cells. CONCLUSIONS: This is the first report to show that PLB could inhibit the proliferation of RPE cells through down-regulation of modulatory signaling pathways. The results open new avenues for the use of PLB in prevention and treatment of proliferative vitreoretinopathy.

Inhibitory Effects of Plumbagin on Retinal Pigment Epithelial Cell Epithelial-Mesenchymal Transition In Vitro and In Vivo.

BACKGROUND This study aimed to explore the effects of plumbagin (PLB) on epithelial-to-mesenchymal transition in retinal pigment epithelial (RPE) cells and in proliferative vitreoretinopathy (PVR) rabbit models. MATERIAL AND METHODS Rabbit RPE cells were exposed to various concentrations (0, 5, 15, and 25 µM) of PLB. Motility, migration, and invasion of PLB-treated cells were determined in vitro using Transwell chamber assays and scratch wound assays. The contractile ability was evaluated by cell contraction assay. Expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT) markers were assessed by western blotting. Furthermore, PLB was injected in rabbit eyes along with RPE cells after gas compression of the vitreous. The presence of PVR was determined by indirect ophthalmoscopy on days 1, 7, 14, and 21 after injection. Also, optical coherence tomography (OCT), ultrasound images, electroretinograms (ERG), and histopathology were used to assess efficacy and toxicity. RESULTS PLB significantly inhibited the migration and invasion of RPE cells. The agent also markedly reduced cell contractive ability. Furthermore, PLB treatment resulted in the decreased expression of MMP-1, MMP2, α-SMA, and the protection of ZO-1. In addition, the PLB-treated eyes showed lower PVR grades than the untreated eyes in rabbit models. PLB exhibited a wide safety margin, indicating no evidence of causing retinal toxicity. CONCLUSIONS PLB effectively inhibited the EMT of rabbit RPE cells in vitro and in the experimental PVR models. The results open new avenues for the use of PLB in prevention and treatment of PVR.

Excimer Laser Versus Phakic Intraocular Lenses for Myopia and Astigmatism: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs) which compared excimer laser refractive surgery and phakic intraocular lenses (PIOLs) for the treatment of myopia and astigmatism. METHODS: An electronic literature search was performed using the PubMed, EBSCO, CNKI, and Cochrane Library database to identify prospective RCTs which compared excimer laser refractive surgery and PIOL with a follow-up time of at least 12 months. Efficacy, accuracy, safety outcomes, and complications were analyzed by standardized mean difference, risk ratio, and the pooled estimates according to a fixed effect model or random effect model. RESULTS: This review included 5 RCTs with a sum of 405 eyes. The range of myopia was 6.0 to 20.0 D with up to 4.0 D of astigmatism. The PIOL group was more likely to achieve a spherical equivalence within±1.0 D of target refraction at 12 months postoperatively (P=0.009), and was less likely to lose one or more lines of best spectacle corrected visual acuity than the LASER group (P=0.002). On the whole, there is no significant difference in efficacy and complications between the two kinds of surgeries. CONCLUSIONS: This meta-analysis indicated that PIOLs were safer and more accurate within 12 months of follow-up compared with excimer laser surgical for refractive errors.

Crocetin inhibits the proliferation, migration and TGF-ß2-induced epithelial-mesenchymal transition of retinal pigment epithelial cells.

Retinal pigment epithelial (RPE) cells, the major cell type in the fibrotic membrane of proliferative vitreoretinopathy, display enhanced proliferative and migratory capacities and epithelial-mesenchymal transition (EMT). In this study, we investigated the potential impact of crocetin on the proliferation, migration and EMT of cultured ARPE-19 cells. The cells were treated with crocetin alone or in combination with transforming growth factor-ß2 (TGF-ß2). Cell proliferation was examined using the CCK-8 assay. Cell cycle distribution was analyzed by flow cytometry after propidium iodide staining. The expression levels of proliferating cell nuclear antigen (PCNA), p21 and p53 were examined by Western blot analysis. Cell migration was assessed by in vitro scratch and Transwell assays. Real-time PCR, Western blotting and immunofluorescence were used to assess EMT features. Treatment of ARPE-19 cells with crocetin (50-200µM) significantly inhibited their proliferation and migration in a concentration- and time-dependent manner. Crocetin induced G1 arrest, reduced PCNA protein expression and increased the p21 and p53 accumulation in ARPE-19 cells. Crocetin inhibited TGF-ß2-induced EMT in ARPE-19 cells by maintaining the expression of E-cadherin and ZO-1 and by reducing the expression of vimentin and α-SMA through the suppression of phosphorylation of p38. These results indicate that crocetin is an effective inhibitor of the proliferation, migration and TGF-ß2-mediated EMT of ARPE-19 cells.

Analysis of gene expression and functional characterization of XPR1: a pathogenic gene for primary familial brain calcification.

Primary familial brain calcification (PFBC) is a neuropsychiatric disorder characterized by bilateral cerebral calcification with diverse neurologic or psychiatric symptoms. Recently, XPR1 variation has accounted for PFBC as another new causative gene. However, little is known about the distribution and basic function of XPR1 and its interaction with the other three pathogenic genes for PFBC (SLC20A2, PDGFRB and PDGFB). The aim of this study was to further clarify the role of XPR1 in PFBC brain pathology. As a result, gene expression profiles showed that XPR1 mRNA was widely expressed throughout the mouse brain. Cerebellum and striatum, most commonly affected in PFBC, contained a higher level of XPR1 protein than other brain regions. Additionally, XPR1 deficiency seriously affected Pi efflux and XPR1 mutations seemed to have an effect through haploinsufficiency mechanism. The immunoprecipitation and immunohistochemical studies demonstrated that XPR1 could interact with PDGFRB and might form a complex on the cell membrane. These results suggested that XPR1 played a fundamental role in the maintenance of cellular phosphate balance in the brain. This provided us with a novel perspective on understanding the pathophysiology of PFBC. The expression networks and interaction with the known pathogenic genes could shed new light on additional candidate genes for PFBC.

Novel mutations of PDGFRB cause primary familial brain calcification in Chinese families.

Four causative genes, including solute carrier family 20 member 2 (SLC20A2), platelet-derived growth factor receptor b (PDGFRB), platelet-derived growth factor b (PDGFB)and xenotropic and polytropic retrovirus receptor 1 (XPR1), have been identified to cause primary familial brain calcification (PFBC). However, PDGFRB mutations seem to be quite rare and no PDGFRB mutations have been reported in Chinese PFBC patients. A total of 146 PFBC patients including 12 families and 134 sporadic patients were recruited in this study. All of them were previously tested negative for the SLC20A2. Mutational analyses of the entire exons and exon-intron boundaries of PDGFRB were carried out by direct gene sequencing. In silico analyses of the identified variants were conducted using Mutation Taster, PolyPhen-2 and Sorts Intolerant From Tolerant. Two heterozygous variants, c.3G>A and c.2209G>A, of the PDGFRB gene were revealed in two PFBC families, respectively. These two variants were not observed in 200 healthy controls. The variant c.3G>A was located in exon 2 and affected the initiation codon of the PDGFRB gene. The variant c.2209G>A resulted in amino-acid substitutions of aspartic acid to asparagine at position 737. Both of these two variants co-segregated with the disease phenotype (variant carriers in Family 1: I1, II2 and II3; variant carriers in Family 2: I2 and II8), suggesting a pathogenic impact of these variants. The prevalence of PDGFRB mutations in Chinese PFBC patients seems to be quite low, indicating that PDGFRB is not a major causative gene of PFBC in Chinese population.

[Effects of simulated nitrogen-oxygen saturation exposure at a water depth of 50m on expression of inflammatory mediators in external auditory canal of rabbits].

OBJECTIVE: To investigate the effects of simulated nitrogen-oxygen saturation exposure at a water depth of 50 m on the expression of inflammatory mediators including interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α) in the external auditory canal (EAC) of rabbits. METHODS: Two batches of New Zealand rabbits were exposed to nitrogen-oxygen saturated at a water depth of 50 m. After exposure, the epithelial tissue in the EAC was analyzed using hematoxylin-eosin (HE) staining, and the changes in expression of inflammatory mediators including IL-6, IL-10, and TNF-α in the EAC of rabbits were determined by real-time polymerase chain reaction (PCR). RESULTS: According to the result of HE staining, more inflammatory cell infiltration, small vascular congestion, and mucosal edema in the EAC of rabbits were observed in the exposure group than in the control group. Additionally, compared with the control group, the exposure group had increased expression of IL-6 and TNF-α and reduced expression of IL-10 in the EAC of rabbits according to the result of real-time PCR. CONCLUSION: The nitrogen-oxygen saturation exposure at a water depth of 50 m can cause inflammatory injuries in the EAC of rabbits. The mechanism may be associated with increased expression of IL-6 and TNF-α and reduced expression of IL-10.

[Regulation of antigen specific Th17 cells differentiation in experimental autoimmune uveitis].

OBJECTIVE: To assess the regulation of antigen specific Th17 cells differentiation in experimental autoimmune uveitis (EAU). METHODS: A randomized controlled trials research. EAU model was made through subcutaneous injection of interphotoreceptor retinoid-binding protein (IRBP) at backs and bellies. Mouse splenic CD4 T cells were collected on the fourteenth day and cultured in vitro in the cell culture plates containing IRBP antigen for 72 hours under different conditions: control group, TGF-beta group, IL-6 group, IL-23 group, TGF-beta + IL-6 group, TGF-beta + IL-6 + IL-23 group, IL-27 group, all transretinoic acid (ATRA) group. Cells and the clear liquid were collected. Then Th17 cells, IL-17 and other cells, cytokines were assessed by flow cytometry and ELISA. All data were analyzed by Student's t test. RESULTS: Flow cytometric detection and ELISA experimental results showed:IRBP polypeptide alone mainly induced Th17 and Th1 response. Addition of TGF-beta and IL-6 induced the differentiation of antigen specific Th17 cells. Percentage of Th17 cells increased from 7.55% to 13.08% (t = -2.842, P = 0.048), and the concentration of IL-17 in cell culture fluid increased from 50.66 microg/L to 164.12 microg/L (t = -9.493, P = 0.009). Percentage of Th1 cells reduced from 6.33% to 3.43% (t = 6.059, P = 0.004). Percentage of Treg cells reduced from 4.96% to 1.52% (t = 5.683, P = 0.005); Furthermore, addition of IL-23 could enhance Th17 cells differentiation induced by TGF-beta and IL-6. Compared with IRBP polypeptide alone group, percentage of Th17 cells increased from 7.55% to 18.37% (t = -3.329, P = 0.029), and percentage of Th1 and Th2 cells reduced obviously (t = 7.410, P = 0.002; t = -3.863, P = 0.018). While IL-27 suppressed the differentiation of Th17 cells. Percentage of Th17 cells reduced from 7.55% to 1.92% (t = 4.425, P = 0.041), while percentage of Treg cells increased from 4.96% to 9.98% (t = -5.073, P = 0.015); In ATRA group, percentage of Th17 cells reduced from 7.55% to 4.06% (t = 2.163, P = 0.099). CONCLUSIONS: Antigen specific Th17 differentiation is distinct from Th1 and Th2 cells. TGF-beta, IL-6 and IL-23 are the factors responsible for promoting the differentiation and development of Th17 subset, whereas IL-27 has inhibitory effects.

[Determination of polycyclic aromatic hydrocarbons in thermoplastic elastomer by gas chromatography-mass spectrometry].

A simple and accurate method for the determination of 16 polycyclic aromatic hydrocarbons (PAHs) in thermoplastic elastomer by gas chromatography-mass spectrometry (GC-MS) has been developed. The effects of various operational parameters (e. g. sample pretreatment, extraction solvent, extraction method, extraction temperature, extraction time, etc) on the extraction efficiency were carefully investigated by analyzing different kinds of positive PAHs thermoplastic elastomer samples made by the manufacturer. The samples were extracted ultrasonically with toluene, concentrated to about 1 mL and then redissolved by cyclohexane. After being purified by dimethyl sulfoxide liquid-liquid extraction, 16 PAHs in the sample were analyzed by GC-MS and quantified by internal standard method. Different kinds of thermoplastic elastomer materials and products were analyzed by this method with the recoveries ranged from 70% to 117% and the relative standard derivations between 0.2% and 10.8%. The method is acceptable for the determination of PAHs in thermoplastic elastomer materials and products.