Enhancing guided bone regeneration with cross-linked collagen-conjugated xenogeneic bone blocks and membrane fixation: A preclinical in vivo study.

OBJECTIVE: To determine whether combining cross-linked (CL) collagen-integrated xenogeneic bone blocks stabilized with the fixation of resorbable collagen membranes (CM) can enhance guided bone regeneration (GBR) in the overaugmented calvarial defect model. MATERIALS AND METHODS: Four circular defects with a diameter of 8 mm were prepared in the calvarium of 13 rabbits. Defects were randomly assigned to receive one of the following treatments: (i) non-cross-linked (NCL) porcine-derived collagen-embedded bone block covered by a CM without fixation (NCL + unfix group); (ii) NCL bone block covered by CM with fixation using bone-tack (NCL + fix group); (iii) cross-linked (CL) porcine-derived collagen-embedded bone block covered by CM without fixation (CL + unfix group); and (iv) CL bone block covered by CM with fixation using bone-tack fixation (CL + fix group). The efficacy of GBR was assessed through histological and molecular analyses after 2 and 8 weeks. RESULTS: At 2 weeks, there were no significant differences in histologically measured areas of newly formed bone among the groups. At 8 weeks, however, the CL + fix group exhibited a larger area of new bone (5.08 ± 1.09 mm2, mean ± standard deviation) compared to the NCL + unfix (1.62 ± 0.42 mm2; p < .0083), NCL + fix (3.97 ± 1.39 mm2) and CL + unfix (2.55 ± 1.04 mm2) groups. Additionally, the expression levels of tumour necrosis factor-alpha, fibroblast growth factor-2, vascular endothelial growth factor, osteocalcin and calcitonin receptor were significantly higher in the CL + fix group compared to the other three groups (p < .0083). CONCLUSION: Cross-linked bone blocks stabilized with collagen membrane fixation can significantly enhance GBR.

Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases.

BACKGROUND AND AIMS: There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. METHODS: From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. RESULTS: A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. CONCLUSIONS: ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

Systemic inflammation response index as a clinical outcome evaluating tool and prognostic indicator for hospitalized stroke patients: a systematic review and meta-analysis.

BACKGROUND: Stroke, which is the main element of cerebrovascular disease (CVD), has become the foremost reason for death and disability on a global scale. The systemic inflammation response index (SIRI), a newly developed and comprehensive indicator, has demonstrated promise in forecasting clinical results for diverse ailments. Nevertheless, the uncertainty surrounding the assessment and prediction of clinical outcomes for stroke patients by SIRI persists, and the conflicting findings from the limited studies conducted on this matter further complicate the situation. Consequently, we performed a thorough systematic review and meta-analysis to explore the correlation between SIRI and the clinical results in individuals suffering from stroke. METHODS: This research was registered in PROSPERO and carried out following the PRISMA guidelines. A thorough investigation was carried out on PubMed, Embase, the Cochrane Library, Web of Science, and Scopus databases. Furthermore, we conducted a manual search in Chinese databases, such as China national Knowledge Infrastructure (CNKI), WanFang, VIP, and China Biology Medicine (CBM). We assessed the potential for bias in the studies included by utilizing the Newcastle-Ottawa Scale (NOS) tool. Adverse clinical outcomes were the main focus of the study, with secondary endpoints including mortality, the predictive value of SIRI, SIRI values across various endpoints, and clinical parameters associated with subarachnoid hemorrhage (SAH) in relation to low and high SIRI group. RESULTS: Following rigorous evaluation, a grand total of 22 investigations, encompassing a populace of 12,737 individuals, were considered suitable for incorporation in the final analysis. The findings from our meta-analysis indicate a strong and consistent correlation between elevated SIRI levels and adverse functional outcomes, irrespective of the method used to evaluate unfavorable outcomes. Furthermore, increased SIRI values have a strong correlation with mortality rates in both the short and long term. Besides, SIRI is a useful indicator of the severity of SAH. SIRI demonstrates strong predictive ability in identifying unfavorable outcomes and stroke-related pneumonia (SAP), as higher SIRI values are typically linked to negative endpoints. Nevertheless, the meta-analysis indicated that there was no significant increase in the risk of early neurological deterioration (END) and acute hydrocephalus (AHC) in high SIRI group when comparing to low SIRI. CONCLUSION: This study could potentially pave the way for groundbreaking insights into the relationship between SIRI and stroke patient outcomes, as it appears to be the first meta-analysis to explore this association. Given the critical role of the inflammatory response in stroke recovery, closely monitoring patients with high SIRI levels could represent a promising strategy for mitigating brain damage post-stroke. Thus, further investigation into SIRI and its impact on clinical outcomes is essential. While our initial findings offer valuable insights into this area, continued research is necessary to fully elucidate the potential of SIRI, ideally through dynamic monitoring and large-scale, multi-center studies. Ultimately, this research has the potential to inform clinical decision-making and improve patient outcomes following stroke. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/ ; Identifier CRD42023405221.

Study on the shielding effect of low resistance body when using transient electromagnetic to detect urban underground space.

Transient electromagnetic Method (TEM) is an efficient geophysical detection technology suitable for detection of urban near-surface space. However, its detection results are well affected by the low resistance anomaly, which interferes with the interpretation of the inversion results. This article used finite element method to simulate the entire process of urban underground pipeline under TEM detection. The causes of interference and the degree of interference under different working conditions were analyzed. The results demonstrate that low resistance anomaly in magnetic field will caused electromagnetic energy absorption and resulting eddy current losses, which lead to a distortion of the primary magnetic field in the vicinity of the pipeline, and formation of a weak field zone beneath the pipeline. The size and shape of the shielding zone are affected by burial depth, transmitter coil diameter, and anomaly size. When the burial depth exceeds 10 times the diameter of the coil or pipeline, the shielding range stabilizes at 1.5-2 times the pipeline's transverse diameter. Moreover, when the pipeline's transverse diameter exceeds twice the transmitter coil diameter, the weak field zone beneath the pipeline will transform into a strong field zone, this is due to the refractive and reflective effects of the electromagnetic field. Finally, experiments were conducted and the inverted results was found to be larger than the actual pipeline diameter, with an error margin similar to that explained by the simulation. These results have implications for high accuracy detecting underground pipelines in urban areas.

Transjugular liver biopsy: enlarge the indications for liver biopsy with reliable diagnostic quality.

BACKGROUND: Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM). METHODS: The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques. RESULTS: 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P < 0.05). Moreover, the median length of sample for TJLBs and PLBs were 10.0 and 16.5 mm (P < 0.05). The diagnostic efficiency of hepatopathy of unknown etiology of TJLB versus PLB groups before and after matching were 96.4% vs. 94.1% and 95.7% vs. 93.2%, respectively (P > 0.05). CONCLUSION: TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality.

The plasma membrane-associated transcription factor NAC091 regulates unfolded protein response in Arabidopsis thaliana.

Adverse environmental stresses may cause the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), and the unfolded protein response (UPR) pathway is initiated to mitigate the ER stress. Previous studies demonstrate that NAC062, a plasma membrane-associated transcription factor, plays important roles in promoting cell survival under ER stress conditions in Arabidopsis thaliana. In this study, we identified another plasma membrane-associated transcription factor, NAC091 (also known as ANAC091/TIP), as an important UPR mediator. ER stress induces the expression of NAC091, which is mainly dependent on the ER stress regulators bZIP60 and bZIP28. In addition, NAC091 has transcriptional activation activity, and the truncated form of NAC091 devoid of the C-terminal transmembrane domain (TMD) forms a homodimer in the nucleus. Under ER stress conditions, NAC091 relocates from the plasma membrane to the nucleus and regulates the expression of canonical UPR genes involved in cell survival. Further, the loss-of-function mutant of NAC091 confers impaired ER stress tolerance. Together, these results reveal the important role of NAC091 in ER stress response in Arabidopsis, and demonstrate that NAC091 relays the ER stress signal from the plasma membrane to the nucleus to alleviate ER stress and promote cell survival in plants.

Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

BACKGROUND: Aberrant cytokeratin 7 expression by hepatocytes (CK7+Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients. METHODS: The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0. RESULTS: Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7+Hs (2 +), CK7+Hs (1 +), and CK7-Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7-Hs and CK7+Hs (2 +) (P < 0.05). The ductopenia grade was also significantly different between patients with CK7+Hs (2 +) and CK7+Hs (1 +) according to sex (P < 0.05). Upon merging the data of CK7+Hs (2 +) and CK7+Hs (1 +) into CK7+Hs, we found significant differences in AMA, AMA-M2, anti-gp210, TB, DB, ALP, TA, IgM, fibrosis, and ductopenia grade between CK7+Hs and CK7-Hs (P < 0.05). The odds ratios (ORs) (and 95% confidence intervals (CIs)) of CK7+Hs according to anti-gp210, ductopenia grade, and interface activity were 6.413 (95% CI 1.363-30.162), 4.145 (95% CI 1.898-9.052) and 3.247 (95% CI 1.556-6.775), respectively (P < 0.05). Spearman's rank correlation according to interface activity and ductopenia grade in patients with CK7+Hs (2 + , 1 + , 0) was r = 0.359 (P = 0.001) and r = 0.396 (P < 0.001), respectively. CONCLUSION: CK7+Hs serves as a cholestasis index of PBC and are associated with the ductopenia grade and interface activity. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

FOXO1 Alleviates Liver Ischemia-reperfusion Injury by Regulating the Th17/Treg Ratio through the AKT/Stat3/FOXO1 Pathway.

Background and Aims: Hepatic ischemic reperfusion injury (IRI) occurring during surgery seriously affects patient prognosis. The specific mechanism of IRI has not been fully elucidated. The study aim was to explore the changes of inflammatory environment, and the relationship of the Th17/Treg cell ratio and FOXO1 expression in hepatic IRI. Methods: Liver samples at different ischemic times were collected from patients and mice. The expression of inflammatory markers and FOXO1 in the liver was detected by western blotting and qPCR. Phenotypic changes of liver lymphocytes were analyzed by flow cytometry. The AKT/Stat3/FOXO1 pathway was verified by targeting AKT with GSK2141795. The role of FOXO1 in liver inflammation and changes in lymphocyte phenotype was confirmed by upregulating FOXO1 with resveratrol. Results: Prolonged ischemic time aggravates liver injury in both humans and mouse models of hepatic IRI. IR-stress caused Th17/Treg imbalance and FOXO1 down-regulation by activating the AKT/Stat3/FOXO1 signaling pathway. Upregulation of FOXO1 reversed the Th17/Treg cytokine imbalance and altered the inflammation environment in the liver. Conclusions: Liver IRI induced Th17/Treg imbalance. Upregulation of FOXO1 reversed the imbalance and alleviated liver inflammation.

Identification and Validation of Long Non-Coding RNA LCIIAR as a Biomarker in LUAD.

Lung cancer is the leading cause of cancer-related death worldwide. Therapies for lung cancer have relatively poor outcomes and need to be improved. Lung cancer immune cell infiltration associated RNA (LCIIAR) is a long noncoding RNA (lncRNA), which is overexpressed in human cancers. However, the clinical significance and functional role of LCIIAR in Lung Adenocarcinoma remain unclear. Here, we identified a novel long non-coding RNA (ENSG00000256802), termed LCIIAR (lung cancer immune cell infiltration associated lncRNA), up-regulated in lung cancer tissue and cell lines. We show that increase LCIIAR expression correlated with poor clinical stage and adverse clinical outcomes and that could also serve as an independent unfavorable prognostic factor in patients with Lung Adenocarcinima. GSEA analysis demonstrated that LCIIAR is mainly involved in the regulation of the immune response. We uncovered that elevate LCIIAR expression positively correlated with immune infiltration and immune modulator in Lung Adenocarcinoma. More importantly, we confirmed that silencing of LCIIAR expression significantly inhibits the proliferation, and migration abilities of these tumour cells. We also demonstrated that the LCIIAR/hsa-miR184/SLC16A3/CDCP1 network regulates SLC16A3/CDCP1 overexpression in and is associated with poor prognosis in this tumour. Therefore our findings revealed the critical role of LCIIAR in Lung Adenocarcinoma progression, which may also serve as a prognostic biomarker and novel therapeutic target.

Membrane fixation enhances guided bone regeneration in standardized calvarial defects: A pre-clinical study.

AIM: To determine whether collagen membrane (CM) fixation enhances guided bone regeneration in standardized defects. MATERIALS AND METHODS: Four 8-mm-diameter defects were surgically made in eight rabbit calvaria, and randomly allocated into four groups: control (empty), unfixed-CM, fixed-CM, and unfixed-CM with bone graft (BG + CM) (positive control). After 1- and 4-week healing periods, the animals were sacrificed and quantitative reverse transcription polymerase chain reaction, micro-computed tomography, and histological outcomes were assessed. RESULTS: At week 1, the expression levels of BMP-2, FGF-2, VEGF, and osteocalcin were significantly higher in the fixed-CM group than in the unfixed-CM and control groups (p < .05). Conversely, cathepsin-K was significantly expressed in the unfixed-CM group. No significant differences in expression markers were observed between the fixed-CM and BG + CM groups (p > .05). At week 4, new bone formation was significantly higher in the fixed-CM group than the unfixed-CM and control groups (p < .05), but similar to the BG + CM group (p > .05). CONCLUSIONS: CM fixation enhances the expression of osteogenic factors similar to BG + CM, leading to significantly more new bone formation. This suggests that the osteogenic potential is greater when membranes are fixed, thereby limiting the necessity of membrane-supporting materials to enhance bone formation.

Study on the mechanism of action of Scutellaria barbata on hepatocellular carcinoma based on network pharmacology and bioinformatics.

Background: Hepatocellular carcinoma is one of the most common cancers with the characteristics of invasion and high mortality. Current forms of prevention remain severe. Scutellaria barbata is widely used in traditional Chinese medicine treatment of various tumors. This study explored the mechanism of Scutellaria barbata in the treatment of hepatocellular carcinoma by network pharmacology and bioinformatics. Methods: The active ingredients of Scutellaria barbata and potential targets for the treatment of hepatocellular carcinoma were collected by network pharmacology. The protein interaction network was constructed to screen the core targets, and the association between the core targets and diseases was further verified by bioinformatics methods. Finally, the active ingredients corresponding to the targets closely related to the disease were screened for AMDE characteristics analysis. Molecular docking of drug-like ingredients with corresponding targets was performed. We used CCK-8 kit to determine the effect of active ingredients on cell proliferation. Results: 29 candidate active ingredients and 461 related targets of Scutellaria barbata were screened. A total of 8238 potential therapeutic targets for hepatocellular carcinoma were indentified. Finally, 373 potential targets for the treatment of HCC were obtained. The active ingredients: wogonin, Rhamnazin, eriodictyol, quercetin, baicalein, and luteolin, etc. The core targets were CDK1, CDK4, SRC, and E2F1. A total of 3056 GO enrichment entries were obtained, and 180 enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in PI3K-Akt signaling pathway, IL-17 signaling pathway, TNF signaling pathway, apoptosis pathway, and hepatocellular carcinoma pathway. Molecular docking results showed that the screened compounds had strong binding ability with the corresponding target proteins. CCK8 assays showed that Rhamnazin and Luteolin suppressed the proliferation of HCC cells significantly compared with controls. Conclusion: This study revealed that the mechanism of Scutellaria barbata in the treatment of hepatocellular carcinoma may be that the active ingredients inhibit the expression of core genes and block the PI3K-AKT signaling pathway to inhibit the proliferation, and migration and induce apoptosis of cancer cells.

Addition of autogenous bone chips to deproteinized bovine bone mineral does not have additional benefit in lateral ridge augmentation-A preclinical in vivo experimental study.

OBJECTIVE: To compare the outcome after extensive lateral guided bone regeneration using deproteinized bovine bone mineral (DBBM) with or without autogenous bone chips in a canine model of chronic horizontal alveolar ridge defect. MATERIALS AND METHODS: The second, third and fourth lower premolars of both sides were extracted, and the buccal bone walls were completely removed in five beagle dogs. After 4 weeks, DBBM particles mixed with autogenous bone chips at a ratio of 1:1 were grafted at one side (DBBM/Auto group), while DBBM particles alone were grafted at the contralateral side (DBBM group). The graft materials on both sides were covered by a resorbable collagen membrane and fixation pins. Microcomputed tomographic volume and histomorphometric analyses were performed at 16 weeks post-surgery. RESULTS: The ridges of both groups were recovered horizontally, but new bone formation beyond the original ridge contour at the defect site was not found. The DBBM group exhibited a larger total radiographic augmented volume and new bone volume compared with the DBBM/Auto group, but the differences were minimal (p > .05). Histologically, the regenerated area and new bone area were also slightly larger without any statistical significance in the DBBM group than in the DBBM/Auto group (p > .05). CONCLUSION: The addition of autogenous bone chips to DBBM for lateral ridge augmentation may confer no advantage over grafting DBBM alone with respect to both space maintenance and de novo bone formation in dogs.

Do periodontal defects affect periodontal inflammation and destruction? Histological/microbiological changes and gene expression profiles of a pilot study in beagle dogs.

BACKGROUND: The present study focused on the inflammatory disease progress after periodontal defect induction and aimed to specifically determine periodontal tissue responses following dental plaque accumulation by ligatures on a site with/without standardized periodontal defect induction. METHODS: After 1 month from extraction of the adjacent teeth, semi-circumferential defects were surgically created in the unilateral second and fourth premolars (test group), whereas no defects were being induced at the contralateral sites (control group). One week later, silk was used to ligate the tooth cervix at both sites to encourage the accumulation of dental plaque. Four weeks later, the tissue samples were collected for histological/histomorphometric and microarray analysis. Microbiological analysis was performed before defect induction and at ligatures, and after 4 weeks of dental plaque accumulation. RESULTS: Remarkable inflammation was clinically and histologically observed in both groups after plaque accumulation, and the intrabony type of periodontal defect exaggerated inflammatory cell infiltration into the connective tissue layer. Expression of genes related to inflammation such as IL-1 was highly up-regulated in test sites. However, these inflammatory infiltrations did not invade to a boundary of periodontal ligament and connective tissue attachment in both groups, and histomorphometric results corresponds to these observational results. Bacterial findings also showed no significant differences in detected microbiome compositions between control and test groups at three-time points. CONCLUSION: Intrabony defect might exaggerate the plaque-induced inflammation in the aspect of inflammatory cell infiltration and the related gene expression, but both dental plaque and the pre-existing periodontal defect negligibly disrupt periodontal attachment and the underlying alveolar bone.

The Axin2-snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma.

BACKGROUND: In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC. METHODS: The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo. RESULTS: Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model. CONCLUSIONS: Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.

Protective Properties of FOXO1 Inhibition in a Murine Model of Non-alcoholic Fatty Liver Disease Are Associated With Attenuation of ER Stress and Necroptosis.

AIM: The pathogenesis of non-alcoholic fatty liver disease is currently unclear, however, lipid accumulation leading to endoplasmic reticulum stress appears to be pivotal in the process. At present, FOXO1 is known to be involved in NAFLD progression. The relationship between necroptosis and non-alcoholic steatohepatitis has been of great research interest more recently. However, whether FOXO1 regulates ER stress and necroptosis in mice fed with a high fat diet is not clear. Therefore, in this study we analyzed the relationship between non-alcoholic steatohepatitis, ER stress, and necroptosis. MAIN METHODS: Male C57BL/6J mice were fed with an HFD for 14 weeks to induce non-alcoholic steatohepatitis. ER stress and activation of necroptosis in AML12 cells were evaluated after inhibition of FOXO1 in AML12 cells. In addition, mice were fed with AS1842856 for 14 weeks. Liver function and lipid accumulation were measured, and further, ER stress and necroptosis were evaluated by Western Blot and Transmission Electron Microscopy. KEY FINDINGS: Mice fed with a high fat diet showed high levels of FOXO1, accompanying activation of endoplasmic reticulum stress and necroptosis. Further, sustained PA stimulation caused ER stress and necroptosis in AML12 cells. At the same time, protein levels of FOXO1 increased significantly. Inhibition of FOXO1 with AS1842856 alleviated ER stress and necroptosis. Additionally, treatment of mice with a FOXO1 inhibitor ameliorated liver function after they were fed with a high fat diet, displaying better liver condition and lighter necroptosis. SIGNIFICANCE: Inhibition of FOXO1 attenuates ER stress and necroptosis in a mouse model of non-alcoholic steatohepatitis.

Prediction of rat liver transplantation outcomes using energy metabolites measured by microdialysis.

BACKGROUND: Warm ischemia jeopardizes graft quality and recipient survival in donation after cardiac death (DCD) transplantation. Currently, there is no system to objectively evaluate the liver quality from DCD. The present study tried to use energy metabolites to evaluate the donor liver quality. METHODS: We divided 195 Sprague-Dawley rats into five groups: the control (n = 39), warm ischemic time (WIT) 15 min (n = 39), WIT 30 min (n = 39), WIT 45 min (n = 39), and WIT 60 min (n = 39) groups. Three rats from each group were randomly selected for pretransplant histologic evaluation of warm ischemia-related damage. The remaining 36 rats were randomly divided into donors and recipients of 18 liver transplantations, and were subjected to postoperative liver function and survival analyses. Between cardiac arrest and cold storage, liver energy metabolites including glucose, lactate, pyruvate, and glycerol were measured by microdialysis. The lactate to pyruvate ratio (LPR) was calculated. RESULTS: The changes in preoperative pathology with warm ischemia were inconspicuous, but the trends in postoperative pathology and aminotransferase levels were consistent with preoperative energy metabolite measurements. The 30-day survival rates of the control and WIT 15, 30, 45, and 60 min groups were 100%, 81.82%, 76.92%, 58.33%, and 25.00%, respectively. The areas under the receiver operating characteristic curves of glucose, lactate, glycerol, and LPR were 0.87, 0.88, 0.88, and 0.92, respectively. CONCLUSION: Glucose, lactate, glycerol, and LPR are predictors of graft quality and survival outcomes in DCD transplantation.

Physiochemical properties and resorption progress of porcine skin-derived collagen membranes: In vitro and in vivo analysis.

The aim of the present study was to evaluate the physiochemical properties and resorption progress of two cross-linked, porcine skin-derived collagen membranes and compare their features with those of a membrane without cross-linking (Bio-Gide® [BG], Geistlich Biomaterials, Wolhusen, Switzerland). Three porcine skin-derived collagen membranes, dehydrothermally (DHT) cross-linked (experimental), DHT and 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (DHT/EDC) cross-linked (experimental) and BG were investigated for their morphology, enzyme resistance, and tensile strength in vitro and biodegradation in vivo. DHT and DHT/EDC membranes exhibited irregular, interconnected macro- and micropores that formed a 3D mesh, whereas BG exhibited individual collagen fibrils interlaced to form coarse collagen strands. In enzyme resistance and tensile strength tests, DHT and DHT/EDC membranes demonstrated good resistance and mechanical properties compared with BG. In vivo, all three membranes were well integrated into the surrounding connective tissue. Thus, the DHT membrane exhibited its potential as a barrier membrane for guided bone and tissue regeneration.

Dehydrothermally Cross-Linked Collagen Membrane with a Bone Graft Improves Bone Regeneration in a Rat Calvarial Defect Model.

In this study, the bone regeneration efficacy of dehydrothermally (DHT) cross-linked collagen membrane with or without a bone graft (BG) material was evaluated in a critical-sized rat model. An 8-mm-diameter defect was created in the calvaria of 40 rats, which were randomized into four groups: (1) control; (2) DHT; (3) BG; and, (4) DHT + BG. Evaluations were made at 2 and 8 weeks after surgery using micro-computed tomographic (micro-CT), histological, and histomorphometric analyses. Micro-CT analysis showed an increase in the new bone volume (NBV) of the BG and DHT + BG groups at 2 weeks after surgery, representing a significant difference (p < 0.05). At 8 weeks after surgery, the NBV increased in all four groups. However, larger NBVs were observed in the BG and DHT + BG groups, and a significant difference was no longer observed between the two groups. Histologic analysis demonstrated that the graft materials sustained the center of the defect in the BG and DHT + BG groups, which was shown in histomorphometric analysis as well. These results suggest that DHT membrane is a safe biomaterial with adequate tissue integration, and has a positive effect on new bone formation. Moreover, the best effects were achieved when DHT was used in conjunction with BG materials.

Surgical Treatment of Severe Peri-Implantitis Using a Round Titanium Brush for Implant Surface Decontamination: A Case Report With Clinical Reentry.

The most common cause of peri-implantitis is the accumulation of plaque and the formation of a biofilm on the implant surface. Terminating the development of the disease requires the biofilm to be removed from the implant surface. This paper describes 2 cases of severe peri-implantitis lesions treated through surgical approaches. Complete mechanical debridement with a round titanium brush was mainly performed to detoxify and modify the affected implant surface. A regenerative approach was then performed. In both cases, the surgical procedure was effective in arresting the peri-implantitis, and clinical reentry revealed uneventful healing of the existing bone defect. No further radiographic bone loss was observed over the 2-year follow-up period. This technique has the advantage of effective cleaning the contaminated implant surface, producing positive clinical and radiological results. However, further studies involving more cases are necessary to verify the reliability and validity of this technique.

Evaluating the trans fatty acid, CLA, PUFA and erucic acid diversity in human milk from five regions in China.

Human milk was obtained from 97 healthy lactating women from five different regions in China. Twenty-four hour dietary questionnaire identified the foods consumed that showed distinct differences in food types between cities. The southern and central regions had higher levels of total trans fatty acids (TFA) and conjugated linoleic acids (CLA) in human milk than the northern region. The major isomers in human milk from the northern region were vaccenic and rumenic acids, whereas the other regions had a random distribution of these isomers. This was consistent with the isomer distribution in the refined vegetable oils used and their increased formation during high temperature stir-frying. The human milk composition showed little evidence that partially hydrogenated fats were consumed, except eight mothers in Guangzhou who reported eating crackers, plus four other mothers. The TFA concentration in these human milk samples was higher (2.06-3.96%). The amount of n-6 (1.70-2.24%) and n-3 (0.60-1.47%) highly unsaturated fatty acids (HUFA) in human milk and the resultant ratio (1.43-2.95) showed all mothers in China had an adequate supply of HUFA in their diet. Rapeseed oil was consumed evidenced by erucic acids in human milk. The levels of erucic acid were below internationally accepted limits for human consumption. The levels of undesirable TFA and CLA isomers in human milk are a concern. Efforts to decrease the practice of high temperature stir-frying using unsaturated oils, and a promotion to increase consumption of dairy and ruminant products should be considered in China.