Diffusion MRI marks progressive alterations in fiber integrity in the zQ175DN mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive neurodegenerative disease affecting motor and cognitive abilities. Multiple studies have found white matter anomalies in HD-affected humans and animal models of HD. The identification of sensitive white-matter-based biomarkers in HD animal models will be important in understanding disease mechanisms and testing the efficacy of therapeutic interventions. Here we investigated the progression of white matter deficits in the knock-in zQ175DN heterozygous (HET) mouse model of HD at 3, 6 and 11 months of age (M), reflecting different states of phenotypic progression. We compared findings from traditional diffusion tensor imaging (DTI) and advanced fixel-based analysis (FBA) diffusion metrics for their sensitivity in detecting white matter anomalies in the striatum, motor cortex, and segments of the corpus callosum. FBA metrics revealed progressive and widespread reductions of fiber cross-section and fiber density in myelinated bundles of HET mice. The corpus callosum genu was the most affected structure in HET mice at 6 and 11 M based on the DTI and FBA metrics, while the striatum showed the earliest progressive differences starting at 3 M based on the FBA metrics. Overall, FBA metrics detected earlier and more prominent alterations in myelinated fiber bundles compared to the DTI metrics. Luxol fast blue staining showed no loss in myelin density, indicating that diffusion anomalies could not be explained by myelin reduction but diffusion anomalies in HET mice were accompanied by increased levels of neurofilament light chain protein at 11 M. Altogether, our findings reveal progressive alterations in myelinated fiber bundles that can be measured using diffusion MRI, representing a candidate noninvasive imaging biomarker to study phenotype progression and the efficacy of therapeutic interventions in zQ175DN mice. Moreover, our study exposed higher sensitivity of FBA than DTI metrics, suggesting a potential benefit of adopting these advanced metrics in other contexts, including biomarker development in humans.

Overexpression of OsACL5 triggers environmentally-dependent leaf rolling and reduces grain size in rice.

Major polyamines include putrescine, spermidine, spermine and thermospermine, which play vital roles in growth and adaptation against environmental changes in plants. Thermospermine (T-Spm) is synthetised by ACL5. The function of ACL5 in rice is still unknown. In this study, we used a reverse genetic strategy to investigate the biological function of OsACL5. We generated several knockout mutants by pYLCRISPR/Cas9 system and overexpressing (OE) lines of OsACL5. Interestingly, the OE plants exhibited environmentally-dependent leaf rolling, smaller grains, lighter 1000-grain weight and reduction in yield per plot. The area of metaxylem vessels of roots and leaves of OE plants were significantly smaller than those of WT, which possibly caused reduction in leaf water potential, resulting in leaf rolling with rise in the environmental temperature and light intensity and decrease in humidity. Additionally, the T-Spm contents were markedly increased by over ninefold whereas the ethylene evolution was reduced in OE plants, suggesting that T-Spm signalling pathway interacts with ethylene pathway to regulate multiple agronomic characters. Moreover, the osacl5 exhibited an increase in grain length, 1000-grain weight, and yield per plot. OsACL5 may affect grain size via mediating the expression of OsDEP1, OsGS3 and OsGW2. Furthermore, haplotypes analysis indicated that OsACL5 plays a conserved function on regulating T-Spm levels during the domestication of rice. Our data demonstrated that identification of OsACL5 provides a theoretical basis for understanding the physiological mechanism of T-Spm which may play roles in triggering environmentally dependent leaf rolling; OsACL5 will be an important gene resource for molecular breeding for higher yield.

Resting-state fMRI reveals longitudinal alterations in brain network connectivity in the zQ175DN mouse model of Huntington's disease.

Huntington's disease is an autosomal, dominantly inherited neurodegenerative disease caused by an expansion of the CAG repeats in exon 1 of the huntingtin gene. Neuronal degeneration and dysfunction that precedes regional atrophy result in the impairment of striatal and cortical circuits that affect the brain's large-scale network functionality. However, the evolution of these disease-driven, large-scale connectivity alterations is still poorly understood. Here we used resting-state fMRI to investigate functional connectivity changes in a mouse model of Huntington's disease in several relevant brain networks and how they are affected at different ages that follow a disease-like phenotypic progression. Towards this, we used the heterozygous (HET) form of the zQ175DN Huntington's disease mouse model that recapitulates aspects of human disease pathology. Seed- and Region-based analyses were performed at different ages, on 3-, 6-, 10-, and 12-month-old HET and age-matched wild-type mice. Our results demonstrate decreased connectivity starting at 6 months of age, most prominently in regions such as the retrosplenial and cingulate cortices, pertaining to the default mode-like network and auditory and visual cortices, part of the associative cortical network. At 12 months, we observe a shift towards decreased connectivity in regions such as the somatosensory cortices, pertaining to the lateral cortical network, and the caudate putamen, a constituent of the subcortical network. Moreover, we assessed the impact of distinct Huntington's Disease-like pathology of the zQ175DN HET mice on age-dependent connectivity between different brain regions and networks where we demonstrate that connectivity strength follows a non-linear, inverted U-shape pattern, a well-known phenomenon of development and normal aging. Conversely, the neuropathologically driven alteration of connectivity, especially in the default mode and associative cortical networks, showed diminished age-dependent evolution of functional connectivity. These findings reveal that in this Huntington's disease model, altered connectivity starts with cortical network aberrations which precede striatal connectivity changes, that appear only at a later age. Taken together, these results suggest that the age-dependent cortical network dysfunction seen in rodents could represent a relevant pathological process in Huntington's disease progression.

Serum uric acid and outcome in hospitalized elderly patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes.

INTRODUCTION: Elevated serum uric acid (SUA) levels have been associated with poor outcome in patients with heart failure (HF). Uric acid is associated with inflammation and microvascular dysfunction, which may differentially affect left ventricular ejection fraction (EF) phenotypes. We aimed to identify the role of SUA across EF phenotypes in hospitalized elderly patients with chronic HF. METHODS: We analyzed 1355 elderly patients who were diagnosed with chronic HF. All patients had SUA levels measured within the first 24 h following admission. Patients with left ventricle EF were categorized as having HF with reduced EF (HFrEF, EF < 40%), HF with mid-range EF (HFmrEF, 40%≦LVEF ≦ 49%) or HF with preserved EF (HFpEF, LVEF ≥ 50%). Endpoints were cardiovascular death, HF rehospitalization, and their composite. The median follow-up period was 18 months. RESULTS: Compared with the lowest SUA quartile, the highest SUA quartile was significantly associated with the endpoints (adjusted HR: 2.404, 95% CI: 1.178-4.906, P = 0.016; HR: 1.418, 95% CI: 1.021-1.971, P = 0.037; HR: 1.439, 95% CI: 1.049-1.972, P = 0.024, respectively). After model adjustment, a significant association of SUA with cardiovascular death and the composite endpoint persisted among HFrEF and HFmrEF patients in the highest SUA quartile (P < 0.05 for all). CONCLUSIONS: In hospitalized elderly patients with chronic HF, SUA is an independent predictor of adverse outcomes, which can be seen in HFrEF and HFmrEF patients.

The impact and role of identified long noncoding RNAs in nonalcoholic fatty liver disease: A narrative review.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, but its mechanism and pathophysiology remain unclear. Long noncoding RNAs (lncRNAs) may exert a vital influence on regulating various biological functions in NAFLD. METHODS: The databases such as Google Scholar, PubMed, and Medline were searched using the following keywords: nonalcoholic fatty liver disease, nonalcoholic fatty liver disease, NAFLD, nonalcoholic steatohepatitis, nonalcoholic steatohepatitis, NASH, long noncoding RNAs, and lncRNAs. Considering the titles and abstracts, unrelated studies were excluded. The authors evaluated the full texts of the remaining studies. RESULTS: We summarized the current knowledge of lncRNAs and the main signaling pathways of lncRNAs involved in NAFLD explored in recent years. As a heterogeneous group of noncoding RNAs (ncRNAs), lncRNAs play crucial roles in biological processes underlying the pathophysiology of NAFLD. The mechanisms, particularly those associated with the regulation of the expression and activities of lncRNAs, play important roles in NAFLD. CONCLUSION: A better comprehension of the mechanism controlled by lncRNAs in NAFLD is necessary for the identification of novel therapeutic targets for drug development and improved, noninvasive methods for diagnosis.

A review on sources of soil antimony pollution and recent progress on remediation of antimony polluted soils.

Antimony (Sb) is a serious toxic and non-essential metalloid for animals, humans, and plants. The rapid increase in anthropogenic inputs from mining and industrial activities, vehicle emissions, and shoot activity increased the Sb concentration in the environment, which has become a serious concern across the globe. Hence, remediation of Sb-contaminated soils needs serious attention to provide safe and healthy foods to humans. Different techniques, including biochar (BC), compost, manures, plant additives, phyto-hormones, nano-particles (NPs), organic acids (OA), silicon (Si), microbial remediation techniques, and phytoremediation are being used globally to remediate the Sb polluted soils. In the present review, we described sources of soil Sb pollution, the environmental impact of antimony pollution, the multi-faceted nature of antimony pollution, recent progress in remediation techniques, and recommendations for the remediation of soil Sb-pollution. We also discussed the success stories and potential of different practices to remediate Sb-polluted soils. In particular, we discussed the various mechanisms, including bio-sorption, bio-accumulation, complexation, and electrostatic attraction, that can reduce the toxicity of Sb by converting Sb-V into Sb-III. Additionally, we also identified the research gaps that need to be filled in future studies. Therefore, the current review will help to develop appropriate and innovative strategies to limit Sb bioavailability and toxicity and sustainably manage Sb polluted soils hence reducing the toxic effects of Sb on the environment and human health.

Evaluation of a PEGylated Fibroblast Growth Factor 21 Variant Using Novel Preclinical Magnetic Resonance Imaging and Magnetic Resonance Elastography in a Mouse Model of Nonalcoholic Steatohepatitis.

BACKGROUND: Treatments for nonalcoholic steatohepatitis (NASH) are urgently needed. Hepatic fat fraction and shear stiffness quantified by magnetic resonance imaging (MRI-HFF) and magnetic resonance elastography (MRE-SS), respectively, are biomarkers for hepatic steatosis and fibrosis. PURPOSE: This study assessed the longitudinal effects of fibroblast growth factor 21 variant (polyethylene glycol [PEG]-FGF21v) on MRI-HFF and MRE-SS in a NASH mouse model. STUDY TYPE: Preclinical. ANIMAL MODEL: This study included a choline-deficient, amino acid-defined, high-fat diet (CDAHFD) model and 6-week-old, male C57BL/6J mice (N = 78). FIELD STRENGTH/SEQUENCE: This study was performed using: 3T: gradient-echo two-point Dixon and spin-echo (SE) echo-planar imaging elastography (200 Hz) and 7T: SE two-point Dixon and SE elastography (200 Hz). ASSESSMENT: MRI and MRE were performed before control diet (CD) or CDAHFD (BD), before PEG-FGF21v dosing (baseline), and after PEG-FGF21v treatment (WK4/8). Regions of interest for MRI-HFF and MRE-SS were delineated by J.L. and H.T. (>5 years of experience each). Fibrosis and steatosis were measured histologically after picrosirius red and H&E staining. Alkaline phosphatase, alanine transaminase, bile acids, and triglycerides (TGs) were measured. STATISTICAL TESTS: Two-tailed Dunnett's tests were used for statistical analysis; untreated CDAHFD or baseline was used for comparisons. Imaging and histology/biochemistry data were determined using Spearman correlations. Bayesian posterior distributions for MRE-SS at WK8, posterior means, and 95% credible intervals were presented. RESULTS: CDAHFD significantly increased baseline MRI-HFF (3T: 21.97% ± 0.29%; 7T: 40.12% ± 0.35%) and MRE-SS (3T: 1.25 ± 0.02; 7T: 1.78 ± 0.06 kPa) vs. CD (3T: 3.45% ± 0.7%; 7T: 12.06% ± 1.4% and 3T: 1.01 ± 0.02; 7T: 0.89 ± 0.06 kPa). At 7T, PEG-FGF21v significantly decreased MRI-HFF (WK4: 28.97% ± 1.22%; WK8: 20.93% ± 1.15%) and MRE-SS (WK4: 1.57 ± 0.04; WK8: 1.36 ± 0.05 kPa) vs. untreated (WK4: 36.36% ± 0.62%; WK8: 30.58% ± 0.81% and WK4: 2.03 ± 0.06; WK8: 2.01 ± 0.04 kPa); 3T trends were similar. WK8 SS posterior mean percent attenuation ratios (RDI ) were -68% (-90%, -44%; 3T) and -64% (-78%, -52%; 7T). MRI-HFF was significantly correlated with H&E (3T, r = 0.93; 7T, r = 0.94) and TGs (both, r = 0.92). DATA CONCLUSIONS: MRI-HFF and MRE-SS showed PEG-FGF21v effects on hepatic steatosis and fibrosis across 3 and 7T, consistent with histological and biochemical data. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Impaired CCR9/CCL25 signalling induced by inefficient dendritic cells contributes to intestinal immune imbalance in nonalcoholic steatohepatitis.

Abnormal crosstalk between gut immune and the liver was involved in nonalcoholic steatohepatitis (NASH). Mice with methionine choline-deficient (MCD) diet-induced NASH presented an imbalance of pro-(IL-6 and IFN-γ) and anti-inflammatory cytokines (IL-10) in the intestine. We also clarified that the ratio of CD4+ T cells and found that the NASH mesenteric lymph node (MLN) presents decreased numbers of CD4+Th17 cells but increased numbers of CD4+CD8+FoxP3+ regulatory T cells (Tregs). Furthermore, the intestinal immune imbalance in NASH was attributed to impaired gut chemokine receptor 9 (CCR9)/chemokine ligand 25 (CCL25) signalling, which is a crucial pathway for immune cell homing in the gut. We also demonstrated that CD4+CCR9+ T cell homing was dependent on CCL25 and that the numbers and migration abilities of CD4+CCR9+ T cells were reduced in NASH. Interestingly, the analysis of dendritic cell (DC) subsets showed that the numbers and retinal dehydrogenase (RALDH) activity of CD103+CD11b+ DCs were decreased and that the ability of these cells to upregulate CD4+ T cell CCR9 expression was damaged in NASH. Taken together, impaired intestinal CCR9/CCL25 signalling induced by CD103+CD11b+ DC dysfunction contributes to the gut immune imbalance observed in NASH.

SHIP-1, a target of miR-155, regulates endothelial cell responses in lung fibrosis.

Src Homology 2-containing Inositol Phosphatase-1 (SHIP-1) is a target of miR-155, a pro-inflammatory factor. Deletion of the SHIP-1 gene in mice caused spontaneous lung inflammation and fibrosis. However, the role and function of endothelial miR-155 and SHIP-1 in lung fibrosis remain unknown. Using whole-body miR-155 knockout mice and endothelial cell-specific conditional miR-155 (VEC-Cre-miR-155 or VEC-miR-155) or SHIP-1 (VEC-SHIP-1) knockout mice, we assessed endothelial-mesenchymal transition (EndoMT) and fibrotic responses in bleomycin (BLM) induced lung fibrosis models. Primary mouse lung endothelial cells (MLEC) and human umbilical vein endothelial cells (HUVEC) with SHIP-1 knockdown were analyzed in TGF-ß1 or BLM, respectively, induced fibrotic responses. Fibrosis and EndoMT were significantly reduced in miR-155KO mice and changes in EndoMT markers in MLEC after TGF-ß1 stimulation confirmed the in vivo findings. Furthermore, lung fibrosis and EndoMT responses were reduced in VEC-miR-155 mice but significantly enhanced in VEC-SHIP-1 mice after BLM challenge. SHIP-1 knockdown in HUVEC cells resulted in enhanced EndoMT induced by BLM. Meanwhile, these changes involved the PI3K/AKT, JAK/STAT3, and SMAD/STAT signaling pathways. These studies demonstrate that endothelial miR-155 plays an important role in fibrotic responses in the lung through EndoMT. Endothelial SHIP-1 is essential in controlling fibrotic responses and SHIP-1 is a target of miR-155. Endothelial cells are an integral part in lung fibrosis.

Adsorptive granulomonocytapheresis alters the gut bacterial microbiota in patients with active ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a refractory disease with unclear etiology. Studies have shown that UC is closely associated with gut microbiota dysbiosis. Adsorptive granulomonocytapheresis (GMA) using an Adacolumn has been found to treat UC effectively, but its underlying mechanism of treatment has not been fully elucidated. In this study, we aimed to investigate the influence of GMA on the gut microbiota in patients with active UC. METHODS: We conducted a single-center prospective analysis of patients with active UC who received GMA therapy and ultimately achieved clinical remission. Stool samples of healthy controls and patients before and after 5 or 10 sessions of GMA therapy were collected. Subsequently, high-throughput sequencing of the 16S rRNA V3 and V4 gene region of the stool was conducted and clustering of operational taxonomic units and species annotation were performed. RESULTS: Gut microbial profiles in patients with UC were characterized by low bacterial diversity. After 5 or 10 sessions of GMA therapy, the gut microbiota diversity in patients with UC increased and was similar to that of healthy controls. UC was further characterized by increased abundances of Proteobacteria and Bacteroides, as well as decreased abundances of Faecalibacterium, Roseburia, Firmicutes, and Dialister; however, after GMA therapy, the abundance of Bacteroides decreased, whereas those of Faecalibacterium, Roseburia, and Firmicutes increased. CONCLUSIONS: Active UC is associated with gut microbiota dysbiosis. GMA therapy exerts a strong regulatory effect on the gut microbiota in patients with UC.

Efficacy and safety of adsorptive granulomonocytapheresis in Chinese patients with ulcerative colitis: A retrospective analysis of 50 cases with focus on factors impacting clinical efficacy.

BACKGROUND: Myeloid-derived leucocytes, a major source of inflammatory cytokines, play an important role in the exacerbation of ulcerative colitis (UC). Selective depletion of myeloid leucocytes by adsorptive granulomonocytapheresis (GMA) with an Adacolumn should alleviate inflammation and promote remission. However, there are discrepancies among the reported efficacy outcomes. This study aimed to evaluate the efficacy and safety of GMA in UC patients with a focus on factors affecting clinical efficacy. METHODS: This was a retrospective analysis of 50 patients with active UC who had received GMA therapy. GMA efficacy was evaluated based on the Rachmilewitz's clinical activity index (CAI) and Mayo endoscopic score for mucosal healing. Laboratory findings were analyzed to demonstrate any relationship with the GMA-responder or nonresponder feature. Adverse events were recorded during and after GMA therapy. RESULTS: The overall clinical remission rate (CAI ≤4) was 79.2%, and among these, the mucosal healing rate was 59.2%. The clinical remission rate was 69.2% in patients who received 5 GMA sessions and 82.3% in patients who received 10 sessions. Significantly higher baseline CAIs and lower albumin and hemoglobin levels were observed in nonremission cases compared with those who achieved remission. Four patients (8%) experienced transient adverse events, but none were severe. CONCLUSIONS: GMA was favored by patients because of its safety and nonpharmacological treatment options. Accordingly, UC patients were spared from pharmaceuticals after applying GMA therapy.

Elevated D-dimer levels predict adverse outcomes in hospitalised elderly patients with chronic heart failure.

BACKGROUND: Elevated D-dimer levels have been associated with poor outcomes in patients with cardiovascular disease. AIM: To study this association in elderly patients with chronic heart failure (CHF). METHODS: We analysed 1355 elderly patients who were admitted with CHF. All patients had D-dimer levels measured within the first 24 h following admission. A multivariate logistic regression model was used to assess the variables associated with chronic kidney disease. We used Cox regression analysis to assess the multivariable relationship between the D-dimer and subsequent all-cause death. RESULTS: In the multiple logistic regression analysis, the D-dimer was identified as a risk factor for chronic kidney disease (odds ratio = 1.278, 95% confidence interval 1.138 to 1.436, P < 0.001). The optimal cut-off level for D-dimer to predict all-cause death was found to be >885 ng/mL. In the multivariate Cox proportional-hazards model, a D-dimer level >885 ng/mL remained significantly associated with all-cause death (hazard ratio = 2.003, 95% confidence interval 1.334 to 3.010, P = 0.001). Additional analyses revealed that higher D-dimer levels were associated with an increased risk of all-cause death irrespective of the subtype of heart failure (including heart failure with reduced ejection fraction and heart failure with preserved ejection fraction). CONCLUSION: In elderly patients with CHF, measurement of D-dimer levels may help to risk stratify these patients, and high D-dimer levels might be regarded as a warning sign to intensify therapy.

MicroRNA-222-3p associated with Helicobacter pylori targets HIPK2 to promote cell proliferation, invasion, and inhibits apoptosis in gastric cancer.

Gastric cancer ranks as the second leading cause of malignancy-related death worldwide, and always diagnosed at advanced stage. MicroRNA-222-3p (miR-222-3p) is aberrantly upregulated in various malignant tumors including gastric cancer, but its role and underlying molecular mechanisms in gastric cancer remain largely unknown. Helicobacter pylori (H. pylori) infection acts as a trigger in the development of gastric cancer, and increasing evidence suggests that H. pylori affects microRNA expression. In this study, gastric cancer tissue samples were divided into H. pylori positive group (+) and negative group (-). QRT-PCR showed that miR-222-3p was significantly upregulated in H. pylori (+) group compared with H. pylori (-) group, and luciferase reporter assays identified homeodomain-interacting protein kinase 2 (HIPK2) as a novel target of miR-222-3p in gastric cancer. Immunohistochemistry revealed that HIPK2 levels were decreased in H. pylori (+) group compared with H. pylori (-). After that, functional experiments indicated that miR-222-3p overexpression promoted the proliferation and invasion, while inhibiting apoptosis of SGC7901 gastric cancer cells, but miR-222-3p knockdown exhibited the opposite effects. Also, HIPK2 knockdown induced similar effects as miR-222-3p overexpression in SGC7901 cells. Nude mouse experiments further suggested that HIPK2 overexpression signally attenuated the enhancing effect of miR-222-3p overexpression on cell proliferation, indicating that the effect of miR-222-3p on gastric cancer progression depends on HIPK2, at least in part. Overall, our results demonstrated that miR-222-3p/HIPK2 signal pathway regulated gastric cancer cell proliferation, apoptosis, and invasion, provided a novel therapeutic target for the treatment of gastric cancer infected by H. pylori.

PPARγ alleviated hepatocyte steatosis through reducing SOCS3 by inhibiting JAK2/STAT3 pathway.

Peroxisome proliferator-activated receptor gamma (PPARγ) participates in the process of insulin resistance (IR), a crucial pathophysiology in non-alcoholic fatty liver disease (NAFLD). Meanwhile, suppressor of cytokine signaling3 (SOCS3) also regulates IR in NAFLD. Both PPARγ and SOCS3 play a role in NAFLD through regulating IR, while it is unclear whether these two proteins interact to regulate hepatic steatosis. PPARγ, SOCS3 and its associated JAK2/STAT3 pathway were analyzed using Kuppfer cells (KCs) treatment with LPS and BRL-3A cells treatment with palmitic acid, KC-conditioned medium (KCCM), PPARγ agonist rosiglitazone (ROZ) or JAK2 inhibitor AG490 to demonstrate the role of PPARγ and SOCS3 in hepatocytes steatosis. As LPS concentration increasing, phagocytosis activity of KCs decreased; but releasing of TNF-α and IL-6 increased. After treatment with KCCM, mRNA level of SOCS3, JAK2 and STAT3 as well as protein expression of SOCS3, p-JAK2 and p-STAT3 in steatosis BRL-3A cells increased significantly, which were inhibited by AG490 or ROZ treatment. Taken together, these results indicated that KCCM attributed to KCs dysfunction facilitated hepatocyte steatosis through promoting expressing SOCS3; but PPARγ agonist ROZ alleviated steatosis through reducing SOCS3 expression by inhibiting JAK2/STAT3 in hepatocytes.

Robotic-assisted vs. laparoscopic and abdominal myomectomy for treatment of uterine fibroids: a meta-analysis.

Uterine fibroids are extremely common uterine neoplasms. However, whether robotic-assisted laparoscopic myomectomy (RALM) is superior to laparoscopic myomectomy (LM) or abdominal myomectomy (AM) is still debatable. Consequently, we aimed to compare the three currently major surgical techniques used in patients with uterine fibroids. We searched the PubMed, the Cochrane Library, MEDLINE, Embase, and Web of Science databases up to April 22, 2017. The meta-analysis included 20 studies involving 2852 patients. The number of complications [odd ratio (OR) 0.52, p = 0.009], estimated blood loss (EBL) [weighted mean difference (WMD) -33.03, p = 0.02], conversions (OR 0.34, p = 0.03), and postoperative bleeding (OR 0.18, p = 0.03) in RALM cases was significantly less than that for LM. The numbers of complications (OR 0.56, p = 0.03), length of hospital stay (WMD -1.74, p < 0.00001), EBL (WMD -77.74, p < 0.00001), and numbers of transfusions (OR 0.25, p < 0.0001) were significantly decreased, and the operative time (WMD 84.88, p < 0.00001) was significantly prolonged in RALM cases when compared to AM cases. Compared with LM and AM, RALM is associated with significantly fewer complications, significantly lower EBL, significantly fewer conversions than both LM and AM, and significantly less bleeding than LM.

Tanshinone IIA ameliorates bleomycin-induced pulmonary fibrosis and inhibits transforming growth factor-beta-ß-dependent epithelial to mesenchymal transition.

BACKGROUND: Epithelial to mesenchymal transition (EMT) of alveolar epithelial cells occurs in lung fibrotic diseases. Tanshinone IIA (Tan IIA) has been reported to exert anti-inflammatory effects in pulmonary fibrosis. Nonetheless, whether Tan IIA affects lung fibrosis-related EMT remains unknown and requires for further investigations. MATERIALS AND METHODS: A single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg body weight) was performed to induce pulmonary fibrosis in Sprague-Dawley rats. Rats receiving an instillation of equivoluminal normal saline served as controls. Then, these rats were given a daily intraperitoneal administration of Tan IIA (15 mg/kg body weight) for 28 d before sacrifice. In vitro, recombinant transforming growth factor-beta 1 (TGF-ß1; 10 ng/mL) was used to treat human alveolar epithelial A549 cells for 48 h. Tan IIA (10 µM) or control DMSO was used to pretreat cells for 2 h before TGF-ß1 stimulation. Rat lung tissue samples and A549 cells were then subjected to further assessments. RESULTS: Tan IIA was noted to alleviate BLM-induced pulmonary collagen deposition and macrophage infiltration in rats. Epithelial-cadherin expression was decreased after BLM stimulation, whereas α-smooth muscle actin, fibronectin, and vimentin were increased. These expression alterations were partially reversed by Tan IIA. Moreover, Tan IIA suppressed BLM-induced increases in TGF-ß1, phosphorylated Smad-2, and -3 in rats. Additionally, pretreatment of Tan IIA inhibited TGF-ß1-triggered EMT, reduced collagen Ⅰ production, and blocked TGF-ß signal transduction in A549 cells. CONCLUSIONS: Our research suggests that Tan IIA mitigates BLM-induced pulmonary fibrosis and suppresses TGF-ß-dependent EMT of lung alveolar epithelial cells.

MR characterization of hepatic storage iron in transfusional iron overload.

PURPOSE: To quantify the two principal forms of hepatic storage iron, diffuse, soluble iron (primarily ferritin), and aggregated, insoluble iron (primarily hemosiderin) using a new MRI method in patients with transfusional iron overload. MATERIALS AND METHODS: Six healthy volunteers and 20 patients with transfusion-dependent thalassemia syndromes and iron overload were examined. Ferritin- and hemosiderin-like iron were determined based on the measurement of two distinct relaxation parameters: the "reduced" transverse relaxation rate, RR2 , and the "aggregation index," A, using three sets of Carr-Purcell-Meiboom-Gill (CPMG) datasets with different interecho spacings. Agarose phantoms, simulating the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron, were used for validation. RESULTS: Both phantom and in vivo human data confirmed that transverse relaxation components associated with the dispersed and aggregated iron could be separated using the two-parameter (RR2 , A) method. The MRI-determined total hepatic storage iron was highly correlated (r = 0.95) with measurements derived from biopsy or biosusceptometry. As total hepatic storage iron increased, the proportion stored as aggregated iron became greater. CONCLUSION: This method provides a new means for noninvasive MRI determination of the partition of hepatic storage iron between ferritin and hemosiderin in iron overload disorders.

Linear brain measurement: a new screening method for cognitive impairment in elderly patients with cerebral small vessel disease.

Background: The old adults have high incidence of cognitive impairment, especially in patients with cerebral small vessel disease (CSVD). Cognitive impairment is not easy to be detected in such populations. We aimed to develop clinical prediction models for different degrees of cognitive impairments in elderly CSVD patients based on conventional imaging and clinical data to determine the better indicators for assessing cognitive function in the CSVD elderly. Methods: 210 CSVD patients were screened out by the evaluation of Magnetic Resonance Imaging (MRI). Then, participants were divided into the following three groups according to the cognitive assessment results: control, mild cognitive impairment (MCI), and dementia groups. Clinical data were collected from all patients, including demographic data, biochemical indicators, carotid ultrasound, transcranial Doppler (TCD) indicators, and linear measurement parameters based on MRI. Results: Our results showed that the brain atrophy and vascular lesions developed progressive worsening with increased degree of cognitive impairment. Crouse score and Interuncal distance/Bitemporal distance (IUD/BTD) were independent risk factors for MCI in CSVD patients, and independent risk factors for dementia in CSVD were Crouse Score, the pulsatility index of the middle cerebral artery (MCAPI), IUD/BTD, and Sylvian fissure ratio (SFR). Overall, the parameters with high performance were the IUD/BTD (OR 2.28; 95% CI 1.26-4.10) and SFR (OR 3.28; 95% CI 1.54-6.91), and the AUC (area under the curve) in distinguishing between CSVD older adults with MCI and with dementia was 0.675 and 0.724, respectively. Linear brain measurement parameters had larger observed effect than other indexes to identify cognitive impairments in CSVD patients. Conclusion: This study shows that IUD/BTD and SFR are good predictors of cognitive impairments in CSVD elderly. Linear brain measurement showed a good predictive power for identifying MCI and dementia in elderly subjects with CSVD. Linear brain measurement could be a more suitable and novel method for screening cognitive impairment in aged CSVD patients in primary healthcare facilities, and worth further promotion among the rural population.

Silicon a key player to mitigate chromium toxicity in plants: Mechanisms and future prospective.

Chromium is a serious heavy metal (HM) and its concentration in plant-soil interface is soaring due to anthropogenic activities, unregulated disposals, and lack of efficient treatments. High concentration of Cr is toxic to ecosystems and human health. Cr stress also diminishes the plant performance by changing the plant's vegetative and reproductive development that ultimately affects sustainable crop production. Silicon (Si) is the second-most prevalent element in the crust of the planet, and has demonstrated a remarkable potential to minimize the HM toxicity. Amending soils with Si mitigates adverse effects of Cr by improving plant physiological, biochemical, and molecular functioning and ensuring better Cr immobilization, compartmentation, and co-precipitation. However, there is no comprehensive review on the role of Si to mitigate Cr toxicity in plants. Thus, in this present review; the discussion has been carried on; 1) the source of Cr, 2) underlying mechanisms of Cr uptake by plants, 3) how Si affects the plant functioning to reduce Cr toxicity, 4) how Si can cause immobilization, compartmentation, and co-precipitation 5) strategies to improve Si accumulation in plants to counter Cr toxicity. We also discussed the knowledge gaps and future research needs. The present review reports up-to-date knowledge about the role of Si to mitigate Cr toxicity and it will help to get better crop productivity in Cr-contaminated soils. The findings of the current review will educate the readers on Si functions in reducing Cr toxicity and will offer new ideas to develop Cr tolerance in plants through the use of Si.