NF‐κB axis

Posted on 7 September 2023 by

Abstract

Inflammatory response induced by biological stress usually occurs in weaning piglets, it reduces the production performance of piglets and even causes death. Tert-butylhydroquinone (TBHQ) is a food additive that has the effect of anti-inflammation and anti-oxidation. However, there are few reports related to the protective mechanisms of TBHQ on lipopolysaccharide (LPS) induced injury in intestinal porcine epithelial (IPEC-J2) cells. Quantitative real-time polymerase chain reaction and western blot analysis, respectively, detected the mRNA levels and protein expressions related to pyroptosis, tight junction (TJ) protein and high-mobility group box 1/toll-like receptor 4/nuclear factor kappa-B (HMGB1/TLR4/NF-κB) axis. Localisation and expression of NOD-like receptor pyrin domain containing 3 (NLRP3), HMGB1 and P-NF-κB proteins detected by immunofluorescence. The results showed that TBHQ (12.5 and 25 μM) can increase cell activity and reduce intracellular lactate dehydrogenase (LDH) levels in a dose-dependent manner. LPS significantly decreases cell viability and increases the LDH level. However, pretreatment with TBHQ evidently increases cell viability and decreases the LDH level of IPEC-J2 cells. In addition, treatment with LPS decreased the mRNA level and protein expression of zonula occludens-1, occludin and claudin-1, and increased the mRNA level and protein expression of pyroptosis and HMGB1/TLR4/NF-κB axis. Interestingly, pretreatment with TBHQ increased the TJ protein expressions as well as decreased the mRNA level and protein expressions of pyroptosis and HMGB1/TLR4/NF-κB axis. Moreover, the results of immunofluorescence showed that TBHQ significantly reduced the expression of NLRP3, HMGB1 and P-NF-κB in LPS-induced injury of IPEC-J2 cells. Therefore, we come to the conclusion that TBHQ attenuates LPS-induced pyroptosis in IPEC-J2 cells through downregulation of the HMGB1/TLR4/NF-κB axis, TBHQ may become a potential feed additive for preventing inflammatory diarrhoea in piglets.

Impact of albumin–lymphocyte–platelet–C‐reactive protein index as a prognostic indicator of hepatocellular carcinoma after resection: Associated with nuclear factor erythroid 2–related factor 2

Posted on 6 September 2023 by

Abstract

Aim

To investigate the prognostic value of the preoperative albumin–lymphocyte–platelet–C-reactive protein (ALPC) index in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. We also evaluated the relationship between the ALPC index and the phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) levels.

Methods

Data were analyzed retrospectively from 256 patients who underwent resection for HCC. For cross-validation, patients were divided into the training and testing cohort. We assessed eight combinations of inflammatory markers for predictive value for recurrence. We examined the associations of the ALPC index with recurrence-free survival and overall survival in univariate and multivariate analyses (Cox proportional hazards model). Immunohistochemical staining of p-Nrf2 was performed on tumor samples of 317 patients who underwent hepatic resection for HCC.

Results

A high preoperative ALPC index correlated with a high serum albumin concentration, small tumor size, low rate of poor differentiation, solitary tumor, early Barcelona Clinic Liver Cancer stage, and low rate of microscopic intrahepatic metastasis in the training dataset. A high preoperative ALPC index correlated with a high serum albumin concentration, high serum alpha-fetoprotein concentration, small tumor size, a low rate of poor differentiation and a low rate of microscopic intrahepatic metastasis in the testing dataset. A higher preoperative ALPC index was an independent predictor of longer recurrence-free survival and overall survival in the training and testing datasets. A high ALPC index was associated with negative p-Nrf2 expression in HCC tumor cells.

Conclusions

We showed that a high ALPC index was an independent prognostic factor for patients with HCC undergoing curative hepatic resection.

Usefulness of the Fibrosis‐4 index and alanine aminotransferase at 1 year of nucleos(t)ide analog treatment for prediction of hepatocellular carcinoma in chronic hepatitis B patients

Posted on 6 September 2023 by

Nucleos(t)ide analog-treated chronic hepatitis B patients with a higher Fibrosis-4 index (≥1.58) at year 1 after the therapy showed a higher incidence of hepatocellular carcinoma. A fibrosis and alanine aminotransferase-1 (FAL-1) score that can be calculated simply with the Fibrosis-4 index and alanine aminotransferase at year 1 of nucleos(t)ide analog might be useful to predict hepatocellular carcinoma development in the clinical settings.

Abstract

Aim

Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitis B virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development.

Methods

Among a total of 882 chronically hepatitis B virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1 year of treatment was obtained were evaluated for the incidence of HCC.

Results

The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1 year (P < 0.001), but the reduction was small at 2 years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5 years, the area under the curve of FIB-4 at 1 year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10 years, P < 0.001). Additionally, an abnormal alanine aminotransferase (≥31 U/L) at 1 year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1) score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10 years, P < 0.001).

Conclusions

FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1 year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.

Benzoic acid promotes Fusarium wilt incidence by enhancing susceptibility and reducing photosynthesis of faba bean

Posted on 6 September 2023 by nWenhao Yang, nYuting Guo, nYu Li, nJiaxing Lv, nYan Dongn

The cell wall degrading enzymes showed a significant negative correlation with photosynthesis, while they positively related with disease incidence. Photosynthesis also presented a significant negative correlation with disease incidence rate. The incidence and disease index were positively correlated. Biomass positively correlated with leaf length and width, and photosynthesis positively correlated with transpiration rate and stomatal conductance.

Abstract

Continuous faba bean (Vicia faba L.) cropping causes adverse effects, including increased secretion of autotoxic substances (benzoic acid) and incidence of diseases (Fusarium wilt). Fusarium commune infects faba bean seedlings and is treated with different benzoic acid concentrations. Therefore, this investigation analysed the association of benzoic acid with faba bean wilt incidence and the mechanisms involved. Furthermore, seedling growth, tissue structure, Fusarium wilt incidence, cell wall degrading enzymes (CWDEs) activity, lignin levels, and leaf photosynthetic parameters were assessed. The results indicated that fungal infection markedly reduced biomass and photosynthesis in the faba bean. Microscopic analysis showed slightly thickened stems' xylem vessels. Benzoic acid treatment with F. commune infection substantially increased F. commune-mediated CWDEs activity in the faba bean stem and lignin level but reduced photosynthesis and biomass, elevating Fusarium wilt incidence. Furthermore, broken tissues, xylem thickening, and stem cavities were observed. The investigation indicated that benzoic acid treatment and F. commune infection-induced stem lignin might be a resistance response; however, increased pathogenicity and reduced photosynthesis enhanced susceptibility and aggravated Fusarium wilt.

Serum inducible protein 10 kDa/C‐X‐C motif chemokine 10 levels predict regression of M2BPGi‐based liver fibrosis after hepatitis C virus eradication by direct‐acting antiviral agents

Posted on 6 September 2023 by

Abstract

Aim

It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitis C virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10 kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy.

Methods

The study participants were recruited from a historical cohort of 116 chronically hepatitis C virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2 years after the end of treatment (EOT) as the regression (n = 71) and non-regression (n = 45) groups, respectively.

Results

Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24 weeks after the EOT, and serum IP-10 change from baseline to 24 weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline.

Conclusions

Serum IP-10 change from baseline to 24 weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.

Association between age at menarche and cardiometabolic risk among Samoan adults

Posted on 5 September 2023 by

Abstract

Objectives

Recent studies suggest that early menarche may increase cardiometabolic morbidity and mortality. Yet few studies have examined this association in the Pacific Islands, where obesity prevalence is among the highest globally. We sought to examine associations between age at menarche and cardiometabolic risk in Samoa.

Methods

Participants were from the Soifua Manuia study (n = 285, age 32–72 years) conducted in Samoa from 2017 to 2019. Logistic regressions were conducted to estimate odds of obesity, hypertension, diabetes, dyslipidemia, and metabolic syndrome per one-year increase in age at menarche. Linear regressions were conducted to examine associations between age at menarche and continuous measures of adiposity, blood pressure, insulin resistance, and serum lipids.

Results

Median age at menarche was 14 years (IQR = 2). After controlling for relevant covariates, each one-year increase in age at menarche was associated with a 15% decrease (OR = 0.85, 95% CI: 0.72–1.01, p = .067) in odds of hypertension, but a 21% increase (OR = 1.21, 95% CI: 1.01–1.45, p = .044) in odds of diabetes and 18% increase (OR = 1.18, 95% CI: 0.98–1.42, p = .081) in odds of high total cholesterol. Each additional year in age at menarche was associated with a 1.60 ± 0.52 kg (p = .002) decrease in lean mass and 1.56 ± 0.51 kg (p = .003) decrease in fat-free mass.

Conclusions

Associations between age at menarche and cardiometabolic risk may be population-specific and are likely influenced by both current and historical nutritional and epidemiological contexts. Prospective studies are needed to clarify the role of childhood adiposity and other early life exposures on age at menarche and subsequent cardiometabolic risk.

Reversion of liver cirrhosis after endovascular treatment in Chinese patients with Budd–Chiari syndrome

Posted on 5 September 2023 by

Abstract

Aims

To investigate the impact of endovascular (EV) treatment on liver cirrhosis in Chinese patients with Budd–Chiari syndrome (BCS).

Methods

From September 2011 to March 2022, 97 patients from four hospitals in China who were diagnosed with primary BCS complicated with liver cirrhosis and received EV treatment were retrospectively enrolled in this study for clinical analysis. In addition, liver tissues for basic research were acquired from 25 patients between June 2022 and March 2023, including six with benign liver tumors, 11 with BCS before EV treatment, and eight with EV-treated BCS. Liver cirrhosis was assessed by clinical outcomes, histological studies, and the expression of related genes at the mRNA and protein levels.

Results

The patients with BCS had better liver function after EV treatment, evidenced by an increased albumin level and reduced total bilirubin, ALT, and AST. The imaging findings suggested an amelioration of liver cirrhosis and portal hypertension, including increased portal vein velocity (13.52 ± 8.89 cm/s vs. 17.51 ± 6.67 cm/s, p < 0.001) and decreased liver stiffness (30.37 ± 6.39 kPa vs. 23.70 ± 7.99 kPa, p < 0.001), portal vein diameter (14.97 ± 3.42 mm vs. 13.36 ± 2.89 mm, p < 0.001), and spleen volume (870.00 ± 355.61 cm³ vs. 771.36 ± 277.45 cm³, p < 0.001). Furthermore, histological studies revealed that EV treatment resulted in a restoration of liver architecture with reduced extracellular matrix deposition. Meanwhile, hepatic angiogenesis and inflammation, which have a close relationship with cirrhosis, were also inhibited. In addition, the state of hepatocytes switches from apoptosis to proliferation after EV treatment.

Conclusions

BCS-induced liver cirrhosis could be reversed by EV treatment from macroscopic to microscopic dimensions. Our study may provide further insights into understanding BCS and treating cirrhosis.

Significance of malnutrition defined with Global Leadership Initiative on Malnutrition criteria in patients with hepatocellular carcinoma after hepatic resection

Posted on 5 September 2023 by

Malnutrition defined by the modified Global Leadership Initiative on Malnutrition (GLIM) criteria using both handgrip strength and skeletal muscle area can more accurately predict short- and long-term outcomes compared to malnutrition defined by the GLIM criteria. Nutritional and exercise therapy could become more important in patients with malnutrition and poor liver function.

Abstract

Aim

A recent study reported the utility of the definition of malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) criteria in many types of cancers and chronic inflammatory disease. The present retrospective study aimed to investigate the significance of malnutrition defined with GLIM criteria in patients with hepatic resection for hepatocellular carcinoma (HCC) and also to compare malnutrition using handgrip strength.

Methods

We retrospectively reviewed data from 174 patients who had undergone curative hepatic resection for HCC including both skeletal muscle area and handgrip strength. Patients were divided according to malnutrition defined by GLIM or modified GLIM and clinicopathologic and short- and long-term outcomes were analyzed. The modified GLIM criteria was defined using both handgrip strength and skeletal muscle area.

Results

Malnutrition defined by GLIM criteria was diagnosed in 47 patients (26.7%) and malnutrition defined by modified GLIM criteria was diagnosed in 21 patients (11.9%). Malnutrition defined by GLIM or modified GLIM criteria was associated with poorer liver function and malignant tumor behavior, but modified GLIM criteria predicted the postoperative complication and recurrence-free survival outcome independently. In patients with poor liver function, malnutrition defined by modified GLIM criteria predicted postoperative complication and overall and recurrence-free survival.

Conclusions

Malnutrition defined by modified GLIM criteria using both handgrip strength and skeletal muscle area can more accurately predict short- and long-term outcomes compared to malnutrition defined by the GLIM criteria. Nutritional and exercise therapy could become more important in patients with malnutrition and poor liver function.

Genetic parameters for carcass and meat quality traits in Jinhua, Duroc, and their crossbred pigs

Posted on 5 September 2023 by nKei Terada, nToshiyuki Ohtani, nShinichiro Ogawa, nHiroyuki Hirookan

Abstract

Jinhua pigs have excellent meat quality and intramuscular fat content (IMF). Crossbreeding of Jinhua with Duroc pigs with high productivity was conducted to develop a new composite breed that possesses the beneficial characteristics of both breeds. The objective of this study was to estimate the crossbreeding parameters (additive breed, dominance, and epistatic loss effects) using the Kinghorn model and genetic parameters (heritability and genetic correlation) for carcass and meat quality traits by analysing the phenotypic data of Jinhua, Duroc, and their crossbred pigs. Backfat thickness at the thinnest point above the 9th to 13th thoracic vertebrae (BF), longissimus muscle area between the 4th and 5th thoracic vertebrae (LMA), meat shear force value (SFV), and IMF were measured. The additive breed effects were significant for all traits: 1.59 cm, −8.30 cm², −6.38 lb/cm², and 1.76% for BF, LMA, SFV, and IMF, respectively. The dominance effect was significant for LMA (7.41 cm²) and IMF (−2.46%), whereas the epistatic loss effect was significant for only LMA (−15.18 cm²). The estimated heritability values were high, ranging from 0.58 for IMF to 0.76 for LMA. A negative but non-significant genetic correlation of −0.11 was estimated between BF and IMF; however, previous studies have reported that the genetic correlation between these traits is moderately positive in modern western pigs. Our results imply that, with the estimation of crossbreeding and genetic parameters, genetic improvement could be implemented to produce a new composite breed with good meat quality and productivity, to meet Japanese market requirements, by crossbreeding Jinhua and Duroc pigs.

Rabbits (Oryctolagus cuniculus) increase caecal calcium absorption at increasing dietary calcium levels

Posted on 4 September 2023 by

Abstract

Hindgut fermenting herbivores from different vertebrate taxa, including tortoises, and among mammals some afrotheria, perissodactyla incl. equids, several rodents as well as lagomorphs absorb more calcium (Ca) from the digesta than they require, and excrete the surplus via urine. Both proximate and ultimate causes are elusive. It was suggested that this mechanism might ensure phosphorus availability for the hindgut microbiome by removing potentially complex-building Ca from the digesta. Here we use Ussing chamber experiments to show that rabbits (Oryctolagus cuniculus) maintained on four different diets (six animals/diet) increase active Ca absorption at increasing Ca levels. This contradicts the common assumption that at higher dietary levels, where passive uptake should be more prevalent, active transport can relax and hence supports the deliberate removal hypothesis. In the rabbits, this absorption was distinctively higher in the caecum than in the duodenum, which is unexpected in mammals. Additional quantification of the presence of two proteins involved in active Ca absorption (calbindin-D9K CB; vitamin D receptor, VDR) showed higher presence with higher dietary Ca. However, their detailed distribution across the intestinal tract and the diet groups suggests that other factors not investigated in this study must play major roles in Ca absorption in rabbits. Investigating strategies of herbivores to mitigate potential negative effects of Ca in the digesta on microbial activity and growth might represent a promising area of future research.