Preoperatively predicting vessels encapsulating tumor clusters in hepatocellular carcinoma: Machine learning model based on contrast-enhanced computed tomography.

BACKGROUND: Recently, vessels encapsulating tumor clusters (VETC) was considered as a distinct pattern of tumor vascularization which can primarily facilitate the entry of the whole tumor cluster into the bloodstream in an invasion independent manner, and was regarded as an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). AIM: To develop and validate a preoperative nomogram using contrast-enhanced computed tomography (CECT) to predict the presence of VETC+ in HCC. METHODS: We retrospectively evaluated 190 patients with pathologically confirmed HCC who underwent CECT scanning and immunochemical staining for cluster of differentiation 34 at two medical centers. Radiomics analysis was conducted on intratumoral and peritumoral regions in the portal vein phase. Radiomics features, essential for identifying VETC+ HCC, were extracted and utilized to develop a radiomics model using machine learning algorithms in the training set. The model's performance was validated on two separate test sets. Receiver operating characteristic (ROC) analysis was employed to compare the identified performance of three models in predicting the VETC status of HCC on both training and test sets. The most predictive model was then used to constructed a radiomics nomogram that integrated the independent clinical-radiological features. ROC and decision curve analysis were used to assess the performance characteristics of the clinical-radiological features, the radiomics features and the radiomics nomogram. RESULTS: The study included 190 individuals from two independent centers, with the majority being male (81%) and a median age of 57 years (interquartile range: 51-66). The area under the curve (AUC) for the combined radiomics features selected from the intratumoral and peritumoral areas were 0.825, 0.788, and 0.680 in the training set and the two test sets. A total of 13 features were selected to construct the Rad-score. The nomogram, combining clinical-radiological and combined radiomics features could accurately predict VETC+ in all three sets, with AUC values of 0.859, 0.848 and 0.757. Decision curve analysis revealed that the radiomics nomogram was more clinically useful than both the clinical-radiological feature and the combined radiomics models. CONCLUSION: This study demonstrates the potential utility of a CECT-based radiomics nomogram, incorporating clinical-radiological features and combined radiomics features, in the identification of VETC+ HCC.

Associations between the use of red yeast rice preparations and adverse health outcomes: An umbrella review of meta-analyses of randomized controlled trials.

BACKGROUND: Red yeast rice (RYR), a natural lipid-lowering agent, is widely used in clinical practice. However, the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results, and the credibility of the evidence has not been quantified. OBJECTIVE: This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes. SEARCH STRATEGY: Seven literature databases were searched from inception to May 5, 2023, using medical subject headings and free-text terms (e.g., "red yeast rice," "Xuezhikang," and "Zhibitai"). INCLUSION CRITERIA: Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study. DATA EXTRACTION AND ANALYSIS: Two researchers independently extracted data using a standardized data collection table; any disagreements were resolved by consulting a third researcher. Based on the participant, intervention, comparator and outcome (PICO) framework in each eligible meta-analysis, a series of unique associations between the use of RYR preparations and adverse health outcomes were determined. The associations' effect estimates were re-evaluated using random-effect models. RESULTS: Fifteen meta-analyses, comprising 186 (164 unique) randomized controlled trials, were identified. Based on A MeaSurement Tool to Assess Systematic Reviews version 2, 3 (20%) and 12 (80%) of these meta-analyses had low and critically low confidence, respectively. A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible meta-analyses. Based on the random-effect models, 10 (16.4%) associations indicated a significant protective effect of RYR preparations against adverse health outcomes, while 5 (8.2%) indicated an increased risk of adverse health outcomes related to uric acid, alanine transaminase and aspartate transaminase levels. The other 46 (75.4%) associations showed no significant difference between the use of RYR preparations and control treatments. Regarding the credibility of the evidence, 21 (34.4%), 34 (55.7%) and 6 (9.8%) associations showed moderate, low and very low credibility, respectively. CONCLUSION: The evidence examined in this study suggests that RYR preparations are safe; however, the credibility of the evidence was not high. Further high-quality evidence is required. Please cite this article as: Ma ZY, Yang SP, Li Y, Xu TT, Yang YL, Yang HY, Li HB, Zhou LJ, Diao Y, Li SY. Associations between the use of red yeast rice preparations and adverse health outcomes: An umbrella review of meta-analyses of randomized controlled trials. J Integr Med. 2024; 22(2): 126-136.

Protein-protein interactions and related inhibitors involved in the NLRP3 inflammasome pathway.

NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) receptor serves as the central node of immune sensing in the innate immune system, and plays an important role in the initiation and progression of chronic diseases. Cryo-electron microscopy (cryo-EM) has provided insights into the conformation of various oligomers within the NLRP3 activation pathway, significantly advancing our understanding of the mechanisms underlying NLRP3 inflammasome activation. Despite the extensive network of protein-protein interactions (PPIs) involved in the assembly and activation of NLRP3 inflammasome, the utilization of protein-protein interactions has been relatively overlooked in the development of NLRP3 inhibitors. This review focuses on summarizing PPIs within the NLRP3 inflammasome activation pathway and small molecule inhibitors capable of interfering with PPIs to counteract the NLRP3 overactivation. Small molecule NLRP3 inhibitors have been gained significant attention owing to their remarkable efficacy, excellent safety profiles, and unique mechanisms of action.

Pseudohalogen Resurfaced CsPbBr3 Nanocrystals for Bright, Efficient, and Stable Green-Light-Emitting Diodes.

Lead halide perovskite nanocrystals (LHP NCs) are regarded as promising emitters for next-generation ultrahigh-definition displays due to their high color purity and wide color gamut. Recently, the external quantum efficiency (EQE) of LHP NC based light-emitting diodes (PNC LEDs) has been rapidly improved to a level required by practical applications. However, the poor operational stability of the device, caused by halide ion migration at the grain boundary of LHP NC thin films, remains a great challenge. Herein, we report a resurfacing strategy via pseudohalogen ions to mitigate detrimental halide ion migration, aiming to stabilize PNC LEDs. We employ a thiocyanate solution processed post-treatment method to efficiently resurface CsPbBr3 NCs and demonstrate that the thiocyanate ions can effectively inhibit bromide ion migration in LHP NC thin films. Owing to thiocyanate resurfacing, we fabricated LEDs with a high EQE of 17.3%, a maximum brightness of 48000 cd m-2, and an excellent operation half-life time.

Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance.

Epidemiological characteristics of central nervous system tumors in children: a 5-year review of 3180 cases from Beijing Tiantan Hospital.

BACKGROUND: To describe the epidemiological characteristics of central nervous system (CNS) tumors in children, based on the neurosurgery department of Beijing Tiantan Hospital. METHODS: From January 2015 to December 2019, 3180 children were histopathologically diagnosed with CNS tumors based on the 2016 World Health Organization (WHO) classification of tumors. Patients were 0 to 15 years old. We analyzed age-related gender preferences, tumor locations, and the histological grades of the tumors. In addition, the epidemiological characteristics of the five most common intracranial tumors were compared to the previous studies. RESULTS: In this study, intracranial and spinal tumors account for 96.4% (3066) and 3.6% (114) of all tumors, with a preponderance of supratentorial tumors (57.9%). Among all pediatric patients, low-grade tumors comprise 67.1% (2 135). The integral gender ratio of males to females is 1.47: 1 and the average age of patients is 7.59 years old. The five most common intracranial tumors are craniopharyngioma (15.4%), medulloblastoma (14.3%), pilocytic astrocytoma (11.8%), diffuse astrocytoma (9.8%), and anaplastic ependymoma (4.8%). CONCLUSIONS: Due to the lack of national data on childhood brain tumors, we used a large nationally representative population sample based on the largest pediatric neurosurgery center in China. We analyzed the data of the past 5 years, reflecting the incidence of CNS tumors in Chinese children to a certain extent, and laying a data foundation for subsequent clinical studies.

The role of imaging features and resection status in the survival outcome of sporadic optic pathway glioma children receiving different adjuvant treatments.

Optic pathway glioma (OPG) is a rare brain tumor affecting children, with no standard treatment strategy. This study described the sporadic OPG survival outcomes after surgical treatment and analyzed the role of imaging features and resection status in children receiving different adjuvant treatments. This retrospective study included 165 OPG patients whose clinical information were obtained from the hospital record system. Tumor volume and residual tumor volume were calculated by delineating the lesion area. Kaplan-Meier method and Cox proportional hazards model were conducted to analyze the independent prognosis factor. A total of 165 patients were included in this study. Respectively, the 5-year overall survival (OS) and progression-free survival (PFS) were 87.58% and 77.87%. Residual tumor size and first adjuvant treatment (AT) after surgery were both associated with PFS. In patients with small-size residual tumors, there was no significant difference in PFS between the AT treatment groups. Moreover, age, exophytic cystic components, leptomeningeal metastases, and AT were associated with OS. In patients with exophytic cystic components and those with leptomeningeal metastases, there was no significant difference in OS. Our results revealed that OPG patients could avoid or defer AT by maximized resection. Age ≤ 2 years was a disadvantageous factor for OS. Patients with exophytic cystic components were more likely to benefit from primary surgery, and CT or RT was not beneficial for these patients. Patients with leptomeningeal metastases had a poor prognosis regardless of the treatment they received. Future prospective clinical studies are needed to develop more effective treatment regimens.

High Color Purity and Efficient Green Light-Emitting Diode Using Perovskite Nanocrystals with the Size Overly Exceeding Bohr Exciton Diameter.

Lead halide perovskite nanocrystals (PNCs) are emerging as promising light emitters to be actively explored for high color purity and efficient light-emitting diodes. However, the most reported lead halide perovskite nanocrystal light-emitting diodes (PNCLEDs) encountered issues of emission line width broadening and operation voltage elevating caused by the quantum confinement effect. Here, we report a new type of PNCLED using large-size CsPbBr3 PNCs overly exceeding the Bohr exciton diameter, achieving ultranarrow emission line width and rapid brightness rise around the turn-on voltage. We adopt calcium-tributylphosphine oxide hybrid ligand passivation to produce highly dispersed large-size colloidal CsPbBr3 PNCs with a weak size confinement effect and also high photoluminescence quantum yield (∼85%). Utilizing these large-size PNCs as emitters, we manifest that the detrimental effects caused by the quantum confinement effect can be avoided in the device, thereby realizing the highest color purity in green PNCLED, with a narrow full width at half-maximum of 16.4 nm and a high corrected maximum external quantum efficiency of 17.85%. Moreover, the operation half-life time of the large-size PNCLED is 5-fold of that based on smaller-size PNCs. Our work provides a new avenue for improving the performance of PNCLEDs based on unconventional large-size effects.

Completed Suicide With Violent and Non-violent Methods by the Elderly in Rural China: A Psychological Autopsy Study.

Background: Late-life suicide is a severe public health problem in rural China; however, knowledge regarding the specific characteristics and risk factors for completed suicide via violent and non-violent methods among elderly individuals in rural China is limited. Methods: Subjects aged 60 years or older were selected from rural areas in Shandong, Hunan, and Guangxi provinces in China. This study was a 1:1 matched case-control design conducted by using the psychological autopsy method. Results: According to the univariate analyses, the presence of mental disorder, higher degree of depression, loneliness, lack of social support, hopelessness, impulsivity, and increased quantity of life events were associated with suicide in both violent and non-violent methods. For violent suicide, another risk factor was the lack of pesticides at home. For non-violent suicide, other risk factors were not currently married, family suicide history, and alcohol use disorder (P < 0.05). Variables that remained in the logistic regression model were the severity of depressive symptoms for both violent and non-violent suicide. For non-violent suicide, the degree of hopelessness was another independent risk factor. In addition, violent suicides were more likely to lack pesticides at home, choose the spring season and have an increased quantity of life events than those who died by suicide via non-violent methods. Conclusion: The major risk factor for both violent and non-violent suicide was the severity of depressive symptoms. Suicide prevention measures that focus on depression among this vulnerable population are urgently needed. Moreover, the characteristics of suicides via violent methods differed from those via non-violent methods among elderly individuals. Suicide prevention efforts should be tailored to the specific characteristics of the different suicide methods utilized by older adults in rural areas.

Left Hepatic Vein Preferential Approach Based on Anatomy Is Safe and Feasible for Laparoscopic Living Donor Left Lateral Sectionectomy.

We assess the safety and feasibility of the left hepatic vein preferential approach (LHVPA) based on left hepatic vein (LHV) anatomy for living donor laparoscopic left lateral sectionectomy (LLLS). Data from 50 donors who underwent LLLS in Huashan Hospital from October 2016 to November 2019 were analyzed retrospectively. On the basis of the classification of the LHV anatomy, the vein was defined as the direct import type, upper branch type, or indirect import type. A subgroup analysis was performed to compare the outcomes between the LHVPA and non-LHVPA groups. All 50 patients underwent pure LLLS. The mean operative duration was 157.5 ± 29.7 minutes. The intraoperative blood loss was 160.4 ± 97.5 mL. No complications more severe than grade 3 occurred. LHVPA was applied in 13 patients, whereas non-LHVPA was applied in 10 patients with the direct import type and upper branch type anatomy. The operative duration was shorter in the LHVPA group than the non-LHVPA group (142.7 ± 22.0 versus 173.0 ± 22.8 minutes; P = 0.01). Intraoperative blood loss was reduced in the LHVPA group compared with the non-LHVPA group (116.2 ± 45.6 versus 170.0 ± 63.3 mL; P = 0.02). The length of the LHV reserved extrahepatically in the LHVPA group was longer than in the non-LHVPA group (4.3 ± 0.2 versus 3.3 ± 0.3 mm; P = 0.01). Fewer reconstructions of the LHV in the direct import type anatomy were required for the LHVPA group than for the non-LHVPA group (0/8 versus 4/6). LHVPA based on the LHV anatomy is recommended in LLLS because it can further increase the safety and the efficiency of surgery for suitable donors.

Psychometric Characteristics of Duke Social Support Index Among Elderly Suicide in Rural China.

We recruited 242 elderly suicides and 242 controls above 60 years to conduct face-to-face interviews by psychological autopsy to examine the psychometric characteristics of the Duke Social Support Index (DSSI) in rural China. DSSI had high internal consistency, with Cronbach's αs of .89 and .90 in suicides and controls, respectively. DSSI was significantly and negatively correlated to loneliness in both samples. Confirmatory factor analysis basically supported the original structure of DSSI, but Item 4 had low factor loading in controls. In conclusion, DSSI has satisfactory reliability and acceptable validity in evaluating social support in the elderly suicide study in China.

Family Functioning and Suicide Among the Elderly in Rural China: A Case-Control Psychological Autopsy Study.

This study aimed to examine the association between family functioning and suicide among the elderly in rural China. This 1:1 paired case-control psychological autopsy study included 242 suicides at age 60 or more and an equal number of controls matched on age (±3 years), gender, and residency. Family functioning was assessed by the Family Adaptation Partnership Growth Affection Resolve Index. Family dysfunction was reported more frequently in suicides than in paired controls. Severe family dysfunction denoted a significant risk factor for suicide only in women after adjusting for potential confounding factors. Suicides with family dysfunction were prone to have unstable marital status, physical illness, mental disorders, family suicide history, and more stressful life events than those with good family functioning. The findings suggest that the intervention enhancing family functioning may be effective in decreasing suicide among the elderly in rural China.

miR-15b-5p targeting amyloid precursor protein is involved in the anti-amyloid eflect of curcumin in swAPP695-HEK293 cells.

Curcumin exerts a neuroprotective effect on Alzheimer's disease; however, it is not known whether microRNAs are involved in this protective effect. This study was conducted using swAPP695-HEK293 cells as an Alzheimer's disease cell model. swAPP695-HEK293 cells were treated with 0, 0.5, 1, 2, 5, and 10 µM curcumin for 24 hours. The changes in miR-15b-5p, miR-19a-3p, miR-195-5p, miR-101-3p, miR-216b-5p, miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain reaction. The mRNA and protein levels of amyloid precursor protein, amyloid-ß40 and amyloid-ß42 were evaluated by quantitative real-time polymerase chain reaction, western blot assays and enzyme-linked immunosorbent assays. swAPP695-HEK293 cells were transfected with miR-15b-5p mimic, or treated with 1 µM curcumin 24 hours before miR-15b-5p inhibitor transfection. The effects of curcumin on amyloid precursor protein, amyloid-ß40 and amyloid-ß42 levels were evaluated by western blot assays and enzyme-linked immunosorbent assay. Luciferase assays were used to analyze the interaction between miR-15b-5p and the 3'-untranslated region of amyloid precursor protein. The results show that amyloid precursor protein and amyloid-ß expression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental cells. Curcumin suppressed the expression of amyloid precursor protein and amyloid-ß and up-regulated the expression of miR-15b-5p in swAPP695-HEK293 cells. In addition, we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-ß levels in the curcumin-treated cells. Luciferase assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3'-untranslated region of amyloid precursor protein. These findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-ß in swAPP695-HEK293 cells, which was partially mediated by miR-15b-5p via targeting of the 3'-untranslated region of amyloid precursor protein.

MicroRNA-144 suppresses the expression of cytokines through targeting RANKL in the matured immune cells.

To investigate whether the microRNA-144 (miR-144) had immune regulation effect on matured immune cells, we firstly used quantitative RT-PCR (qRT-PCR) to detect the expression changes of miR-144 between the matured and immature dendritic cells (DCs), macrophages, and the peripheral blood mononuclear cells (PBMCs). Then we went on inspecting the expression changes of TNF-α, IL-1ß, IL-6 and IL-23 in the matured DCs treated with miR-144 mimics or inhibitors using qRT-PCR, and also performed western blot to test phosphorylation state of ERK, JNK, p38 and p65 in these cells. Next, TargetScan was conducted to forecast the target gene of miR-144, receptor activator for nuclear factor-κB ligand (RANKL), and double luciferase reporter system was applied to research their banding sites. We also determined the expression changes of RANKL in the DCs treated with miR-144 mimics or inhibitors using qRT-PCR and ELISA, respectively. The siRNA of RANKL was synthesized and transfected into DCs to inspect how the immune regulation effect of miR-144 was conducted to inhibit the expression of TNF-α using qRT-PCR, and lastly we used flow cytometry to investigate whether this effect applied to Th17 cells. As results, we found that miR-144 was down-regulated in the matured DCs, macrophages and PBMCs of liver transplantation patients, and the miR-144 mimics could inhibit the expression levels of TNF-α, IL-1ß, IL-6 and IL-23 in the matured DCs. Furthermore, miR-144 interacted with RANKL at position 679-685 of RANKL 3'UTR, and suppressed the translation of RANKL mRNA to realize the negative-regulation. Besides, the silence of RANKL enhanced the suppression effect of miR-144 on TNF-α and this immune regulation effect was applied to Th17 cells, too. In conclusion, this study clearly illustrated that miR-144 could inhibit the expression of cytokine in matured immune cells through suppressing the translation of RANKL mRNA.

p63 inhibits CD44+/CD24- cell proliferation and chemoresistance in papillary thyroid carcinoma cells.

Thyroid cancer typically has a good prognosis; however, the risks of recurrence and chemoresistance associated with thyroid cancer remain a cause for concern. Papillary thyroid carcinoma (PTC) comprises 80% of all cases of thyroid carcinoma. A previous study reported that cluster of differentiation (CD) 44+/CD24- PTC cells may contribute to PTC recurrence and chemoresistance; however, the underlying molecular mechanisms remain elusive. In the present study, CD44+/CD24- cells were isolated from the TPC-1 PTC cell line and biological function assays revealed that CD44+/CD24- cells were significantly more proliferative and chemoresistant compared with CD44-/CD24- cells. Furthermore, the expression level of p63 was demonstrated to be negatively correlated with the expression of CD44 in PTC cells. The role of p63 in CD44+/CD24- cell proliferation and chemoresistance was investigated and, the ectopic expression of p63 was observed to significantly inhibit CD44+/CD24- cell proliferation and chemoresistance in vitro and in vivo. In conclusion, the present study indicated that CD44+/CD24- cells contribute to PTC proliferation and chemoresistance and that the suppression of p63 in CD44+/CD24- cells contributes to these effects.

Comparisons of presentations and outcomes of neuromyelitis optica patients with and without Sjögren's syndrome.

Patients with neuromyelitis optica (NMO) often have an accompanying autoimmune disease, most commonly, but not limited to Sjögren's syndrome (SS). The aim of this study was to compare clinical and laboratory features between NMO patients with and without SS and to investigate the prognosis of NMO in patients with and without SS. Twenty-three NMO patients with SS and 42 NMO patients without SS were included. Clinical and laboratory profiles were compared, including annual relapse rate and time from onset of NMO to Expanded Disability Status Scale (EDSS) scores of 4.0 and 6.0. More NMO patients with SS than those without SS had anti-nuclear antibody, anti-SS-A/Ro and anti-SS-B/La antibodies (91.3 vs. 35.7%, p < 0.001, 87.0 vs. 2.3%, p < 0.001, and 34.8 vs. 0.0%, p < 0.001, respectively). Serum immunoglobulins (IgA, IgM and IgG) were markedly increased in NMO patients with SS in comparison with those without SS. Annual relapse rate and the time from disease onset to an EDSS score of 4.0 and 6.0 were not significantly different between the two groups. No differences between the two groups were found for the other parameters, including AQP-4 antibody status, length of spinal cord lesion and brain lesions. These results imply that NMO in SS more likely represents coexistence with SS rather than representing the result of direct central nervous system involvement in SS. Autoimmune response appears to be more intense in the NMO group with SS, but did not cause a more severe prognosis in comparison with the group without SS, indicating that we should pay attention to the potential benefit of the antinuclear antibodies in NMO.

TGF-ß1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro.

Activated fibroblasts continue to proliferate at injury sites, leading to progressive muscular fibrosis in Duchenne muscular dystrophy (DMD). TGF-ß1 is a dominant profibrotic mediator thought to play a critical role in muscle fibrosis; however, the implicated mechanisms are not fully understood. Here we showed that TGF-ß1 increased the resistance to apoptosis and stimulated cell cycle progression in dystrophic muscle fibroblasts under serum deprivation conditions in vitro. TGF-ß1 treatment activated the canonical NF-κB pathway; and we found that pharmacological inhibition of IKKß with IMD-0354 and RelA gene knockdown with siRNA attenuated these effects of TGF-ß1 on dystrophic muscle fibroblasts. Collectively, our data suggest that TGF-ß1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway.

Butyrate protects rats from hepatic ischemia/reperfusion injury.

BACKGROUND: Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock and trauma. The use of butyrate, which acts as a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, provides anti-oxidant and anti-apoptotic effects. METHODS: Male Sprague-Dawley (SD) rats model of HI/R were subjected to a partial (70%) hepatic ischemia for 45 minutes (min) after pretreatment with either saline or butyrate, followed reperfusion. 30 rats were randomly allocated to three main experimental groups (n = 10 each): (1) The sham-operated group underwent laparotomy without hepatic ischemia. (2) Butyrate was injected into the tail vein in the butyrate group 30 min before HI/R. (3) The control group underwent the same procedure as the butyrate group but with administration of physiological saline. Rats from each group were randomly euthanized to collect blood and liver samples. RESULTS: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. SD rats that received butyrate displayed reduced HI/R injury compared with controls. Use of butyrate reduced the histologic injury and significantly decreased serum Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. In addition, butyrate decreased myeloperoxidase (MPO) activity and malondialdehyde (MDA) tissue contents. Apoptotic cells in I/R rats were also significantly reduced after butyrate treatment. Furthermore, butyrate also decreased the mean number of apoptotic cells (positively stained for TUNEL) and increased the mean number of proliferating cells (positively stained for Ki-67). The expression levels of TNF-α and IL-6 were attenuated after butyrate treatment. CONCLUSIONS: Our results suggest that butyrate attenuated I/R-induced liver injury through upregulation of intracellular anti-oxidant stress and anti-apoptotic signaling pathways.

Correlation between calcification and bone sialoprotein and osteopontin in papillary thyroid carcinoma.

The correlation between calcification and papillary thyroid carcinoma has received increasing attention. We investigated the ability of bone sialoprotein (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid carcinoma (PTC), and explored the correlation between BSP and OPN protein levels and calcification in PTC. Archival PTC specimens from patients with PTC with calcification and lateral cervical lymph node metastasis (LNM) were included in this retrospective immunohistochemical study. The protein levels of BSP and OPN were analysed immunohistochemically using routinely prepared tissue sections. PTC specimens from 66 patients with PTC were reviewed retrospectively (25 patients with histological calcification seen in paraffin sections, 41 patients without calcification; 35 patients with lateral cervical LNM, 31 patients without LNM). The percentage of samples that had cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules, and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%, respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a significant difference in the immunohistochemical score (IHS) for BSP and OPN protein staining between PTC specimens with and without calcification (P < 0.05). The level of BSP protein staining was found to be significantly correlated with the level of OPN protein staining in PTC specimens. We conclude that the strong correlation between BSP and OPN and PTC suggests a role for BSP and OPN in calcification and tumor progression of PTC. BSP and OPN might be useful tumour markers for the diagnosis of PTC with limited value, because both of them had low specificity.

Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear factor kappa B activation in Kupffer cells.

BACKGROUND: The inflammatory response after hepatic ischemia reperfusion (I/R) contributes to liver dysfunction and failure after transplantation. Butyrate is a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, with anti-inflammatory activities. The purpose of the present study was to investigate the protective effect of butyrate preconditioning, if any, against hepatic I/R injury in rats and the underlying mechanisms involved. METHODS: Male Sprague-Dawley rats were subjected to a partial (70%) hepatic ischemia for 60 min after pretreatment with either vehicle or butyrate, followed by 3, 6, and 24 h of reperfusion. Hepatic injury was evaluated by biochemical and histopathologic examinations. Neutrophil infiltration was measured by myeloperoxidase (MPO) activity. The expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (Elisa) and Real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-κB) p65 was determined by immunohistochemistry and Western blot analysis. RESULTS: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. The expression of tumor necrosis factor-alpha, interleukin-6, and myeloperoxidase activity was attenuated by butyrate. Butyrate also reduced I/R-induced nuclear translocation of NF-κB p65 in Kupffer cells. CONCLUSION: Our results suggest that butyrate alleviates I/R-induced liver injury, possibly by suppressing inflammatory factors production and preventing NF-κB activation in Kupffer cells.