Effects of Aeromonas infection on the immune system, physical barriers and microflora structure in the intestine of juvenile grass carp (Ctenopharyngodon idella).

Grass carp (Ctenopharyngodon idella) is an intensively cultured and economically important herbivorous fish species in China, but its culture is often impacted by Aeromonas pathogens such as Aeromonas hydrophila and Aeromonas veronii. In this study, healthy grass carp were separately infected with A. hydrophila or A. veronii for 12, 24, 48 or 72 h. The results showed that the mRNA expression levels of intestinal inflammatory factors (tnf-α, il-1ß and il-8), complement factors (c3 and c4), antimicrobial peptides (hepcidin, nk-lysin and ß-defensin-1), immunoglobulins (igm and igt), and immune pathway-related signaling molecules (tlr1, tlr2, tlr4, myd88, irak4, irak1, traf6, nf-κb p65 and ap-1) were differentially upregulated in response to A. hydrophila and A. veronii challenge. Additionally, the expression levels of the intestinal pro-apoptotic genes tnfr1, tnfr2, tradd, caspase-8, caspase-3 and bax were significantly increased, whereas the expression of the inhibitory factor bcl-2 was significantly downregulated, indicating that Aeromonas infection significantly induced apoptosis in the intestine of grass carp. Moreover, the expression of intestinal tight junction proteins (occludin, zo-1, claudin b and claudin c) was significantly decreased after infection with Aeromonas. Histopathological analysis indicated the Aeromonas challenge caused severe damage to the intestinal villi with adhesions and detachment of intestinal villi accompanied by severe inflammatory cell infiltration at 12 h and 72 h. The 16S rRNA sequencing results showed that Aeromonas infection significantly altered the structure of the intestinal microflora of the grass carp at the phylum (Proteobacteria, Fusobacteria, Bacteroidetes and Firmicutes) and genus (Proteus, Cetobacterium, Bacteroides, and Aeromonas) levels. Take together, the findings of this study revealed that Aeromonas infection induces an intestinal immune response, triggers cell apoptosis, destroys physical barriers and alters microflora structure in the intestine of juvenile grass carp; the results will help to reveal the pathogenesis of intestinal bacterial diseases in grass carp.

Fish decay-accelerating factor (DAF) regulates intestinal complement pathway and immune response to bacterial challenge.

Decay-accelerating factor (DAF) is an essential member of the complement regulatory protein family that plays an important role in immune response and host homeostasis in mammals. However, the immune function of DAF has not been well characterized in bony fish. In this study, a complement regulatory protein named CiDAF was firstly characterized from Ctenopharyngodon idella and its potential roles were investigated in intestine following bacterial infection. Similar to mammalian DAFs, CiDAF has multiple complement control protein (CCP) functional domains, suggesting the evolutionary conservation of DAFs. CiDAF was broadly expressed in all tested tissues, with a relatively high expression level detected in the spleen and kidney. In vivo immune challenge experiments revealed that CiDAF strongly responded to bacterial pathogens (Aeromonas hydrophila and Aeromonas veronii) and PAMPs (lipopolysaccharide (LPS) or muramyl dipeptide (MDP)) challenges. In vitro RNAi experiments indicated that knockdown of CiDAF could upregulate the expression of complement genes (C4b, C5 and C7) and inflammatory cytokines (TNF-α, IL-1ß and IL-8). Moreover, 2000 ng/mL of CiDAF agonist progesterone effectively alleviated LPS- or MDP-induced intestinal inflammation by regulating expression of complement factors, TLR/PepT1 pathway genes and inflammatory cytokines. Overall, these findings revealed that CiDAF may act as a negative regulator of intestinal complement pathway and immune response to bacterial challenge in grass carp.

A low-cost machine learning framework for predicting drug-drug interactions based on fusion of multiple features and a parameter self-tuning strategy.

Poly-drug therapy is now recognized as a crucial treatment, and the analysis of drug-drug interactions (DDIs) offers substantial theoretical support and guidance for its implementation. Predicting potential DDIs using intelligent algorithms is an emerging approach in pharmacological research. However, the existing supervised models and deep learning-based techniques still have several limitations. This paper proposes a novel DDI analysis and prediction framework called the Multi-View Semi-supervised Graph-based (MVSG) framework, which provides a comprehensive judgment by integrating multiple DDI features and functions without any time-consuming training process. Unlike conventional approaches, MVSG can search for the most suitable similarity (or distance) measurement among DDI data and construct graph structures for each feature. By employing a parameter self-tuning strategy, MVSG fuses multiple graphs according to the contributions of features' information. The actual anticancer drug data are extracted from the authoritative public database for evaluating the effectiveness of our framework, including 904 drugs, 7730 DDI records and 19 types of drug interactions. Validation results indicate that the prediction is more accurate when multiple features are adopted by our framework. In comparison to conventional machine learning techniques, MVSG can achieve higher performance even with less labeled data and without a training process. Finally, MVSG is employed to narrow down the search for potential valuable combinations.

Rituximab may affect T lymphocyte subsets balance in primary membranous nephropathy.

BACKGROUND: The aim of this study was to investigate the effects and significance of rituximab (RTX) on the levels of T lymphocyte subsets in patients diagnosed with primary membranous nephropathy (PMN). METHODS: A total of 58 PMN patients and 25 healthy donors were chosen as the subjects. Among the PMN patients, 40 individuals received RTX treatment and completed at least 6 months of follow-up. All subjects underwent flow cytometry analysis to determine the peripheral blood lymphocyte subsets. The changes in anti-PLA2R antibody titers and 24-hour urinary protein levels were evaluated by ELISA and Biuret method before and after treatment. RESULTS: (1) The PMN group exhibited a significantly greater percentage of peripheral blood CD3-CD19+ B cells than the healthy group, which is consistent with the findings of previous reports. Additionally, compared with those in the peripheral blood of healthy individuals, the numbers of CD4+ central memory T cells, CD4+ effector memory T cells, CD4+/CD8+, and CD4+CD25+ T cells in the PMN peripheral blood were markedly greater. However, the number of peripheral blood Treg cells was reduced in the PMN group. (2) After 6 months of RTX treatment, PMN patients exhibited significant decreases in anti-PLA2R antibody titers, 24-hour urinary protein levels, and peripheral blood CD3-CD19+ B cells. Importantly, RTX administration decreased CD4+CD25+ T cells and CD4+/CD8+ in the peripheral blood of PMN patients and improved Treg cell levels. (3) RTX treatment induced alterations in the CD4+ T lymphocyte subsets in PMN patients, which did not correlate with B lymphocyte counts or anti-PLA2R antibody titers. CONCLUSIONS: RTX treatment might have a beneficial impact on cellular immunity by effectively restoring the balance of CD4+ T lymphocyte subsets in PMN patients, which is beyond its effects on B cells and antibody production. TRIAL REGISTRATION: The research was registered at the First Affiliated Hospital of Soochow University. REGISTRATION NUMBER: MR-32-23-016211. Registration Date: May 31, 2023.

Posterior Hip Pericapsular Block (PHPB) with pericapsular nerve group (PENG) block for hip fracture: a case series.

BACKGROUND: Pain after total hip arthroplasty (THA) for femoral neck fracture (FNF) can be severe, potentially leading to serious complications. PENG block has become an optional local analgesic strategy in hip fracture surgery, but it cannot provide effective pain relief for the posterior capsule of the hip joint. Therefore, we modified the traditional sacral plexus nerve block and named it Posterior Hip Pericapsule Block (PHPB) to complement the blockade of the relevant nerves innervating the posterior hip capsule region. Thereby, we detail the analgesic effect of PHPB combined with PENG block on five hip fracture patients and the effect on their hip motor function. METHODS: This case series was conducted from December 2023 to February 2024. We performed ultrasound-guided PHPB combined with PENG block on five patients with hip fractures. Numerical Rating Scale (NRS) pain scores at rest and maximum NRS pain scores during limb movement of the five patients were recorded within 48 h after surgery. Their hip flexion, abduction, adduction, keen flexion and quadriceps muscle strength were also recorded. Serious postoperative complications, including wound infection, hematoma formation, or nerve injury, were recorded. RESULTS: They experienced effective pain control within 48 h postoperatively, with NRS pain scores at rest decreasing from 3.0 (3.0, 4.5) to 0.0 (0.0, 1.0) and maximum NRS pain scores during limb movement from 8.0 (7.5, 8.5) to 1.0 (0.5, 2.0). They can autonomously perform hip flexion, abduction, adduction, and knee flexion within 48 h postoperatively without any signs of movement disorders or quadriceps muscle weakness. No severe postoperative complications, such as wound infections, hematoma formation or nerve damage, were observed in any of the patients. CONCLUSIONS: Ultrasound-guided PENG block combined with PHPB provided effective analgesia for hip fracture patients in the perioperative period. It maintained hip joint motor function and quadriceps muscle strength within 24 h after THA.

Vitamin B5 supplementation enhances intestinal development and alters microbes in weaned piglets.

This study explored the effects of different vitamin B5 (VB5) levels on intestinal growth and function of weaned piglets. Twenty-one piglets (7.20 ± 1.11 kg) were included in a 28-day feeding trial with three treatments, including 0 mg/kg (L-VB5), 10 mg/kg (Control) and 50 mg/kg (H-VB5) of VB5 supplement. The results showed that: Large intestine weight/body weight was the highest in H-VB5 group, Control and H-VB5 groups had significantly higher villus height and villus height/crypt depth than the L-VB5 in the ileum (p < .05). Goblet cells (ileal crypt) and endocrine cells (ileal villus) significantly increased in Control and H-VB5 (p < .05). The H-VB5 group exhibited significantly higher levels of ki67 and crypt depth in the cecum and colon, colonic goblet cells and endocrine cells were both rising considerably (p < .05). Isobutyric acid and isovaleric acid were significantly reduced in the H-VB5 group (p < .05), and there was a decreasing trend in butyric acid (p = .073). At the genus level, the relative abundance of harmful bacteria such as Clostridium_Sensu_Structo_1 Strecto_1, Terrisporbacter and Streptococcus decreased significantly and the relative abundance of beneficial bacteria Turicibacter increased significantly in H-VB5 group (p < .05). Overall, the addition of 50 mg/kg VB5 primarily enhanced the morphological structure, cell proliferation and differentiation of the ileum, cecum and colon. It also had a significant impact on the gut microbiota and short-chain fatty acids.

CircRSU1 alleviates LPS-induced human pulmonary microvascular endothelial cell injury by targeting miR-1224-5p/ITGA5 axis.

To investigate the potential functions and regulatory mechanism of circRSU1 on septic acute lung injury (sepsis-ALI) progression. We used lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) to establish the cell model of sepsis-ALI in vitro. qRT-PCR and Western blotting were used for the detection of genes and proteins. The migration and tubulogenesis of HPMECs were assessed by transwell, wound healing, and tube formation assays. Inflammatory factors were detected by ELISA analysis. Cell permeability (PA) was determined by transendothelial resistance (TEER) and fluorescein isothiocyanate (FITC) with transwell assay. The interaction between miR-1224-5p and circRSU1 or ITGA5 (Integrin Subunit Alpha 5) was studied by dual-luciferase reporter and RNA pull-down assays. CircRSU1 expression was decreased after LPS treatment in HPMECs. Functionally, re-expression of circRSU1 in HPMECs could alleviate LPS-induced inflammatory response, the inhibition of cell migration and tube formation and enhancement of cell permeability. Mechanistically, circRSU1 acted as a sponge for miR-1224-5p. LPS treatment enhanced miR-1224-5p expression, and inhibition of miR-1224-5p reversed LPS-evoked HPMEC dysfunction mentioned above. Moreover, miR-1224-5p could abolish the protective effects of circRSU1 on HPMECs. In addition, miR-1224-5p directly targeted ITGA5, and circRSU1 was able to regulate ITGA5 expression via interacting with miR-1224-5p. CircRSU1 could alleviate LPS-induced HPMEC injury by miR-1224-5p/ITGA5 axis, indicating the potential molecular contribution of circRSU1 in sepsis-ALI.

Exploration of the potential common pathogenic mechanisms in COVID-19 and silicosis by using bioinformatics and system biology.

Silicosis is an occupational lung disease that is common worldwide. In recent years, coronavirus disease 2019 (COVID-19) has provided daunting challenges to public healthcare systems globally. Although multiple studies have shown a close link between COVID-19 and other respiratory diseases, the inter-relational mechanisms between COVID-19 and silicosis remain unclear. This study aimed to explore the shared molecular mechanisms and drug targets of COVID-19 and silicosis. Gene expression profiling identified four modules that were most closely associated with both diseases. Furthermore, we performed functional analysis and constructed a protein-protein interaction network. Seven hub genes (budding uninhibited by benzimidazoles 1 [BUB1], protein regulator of cytokinesis 1 [PRC1], kinesin family member C1 [KIFC1], ribonucleotide reductase regulatory subunit M2 [RRM2], cyclin-dependent kinase inhibitor 3 [CDKN3], Cyclin B2 [CCNB2], and minichromosome maintenance complex component 6 [MCM6]) were involved in the interaction between COVID-19 and silicosis. We investigated how diverse microRNAs and transcription factors regulate these seven genes. Subsequently, the correlation between the hub genes and infiltrating immune cells was explored. Further in-depth analyses were performed based on single-cell transcriptomic data from COVID-19, and the expression of hub-shared genes was characterized and located in multiple cell clusters. Finally, molecular docking results reveal small molecular compounds that may improve COVID-19 and silicosis. The current study reveals the common pathogenesis of COVID-19 and silicosis, which may provide a novel reference for further research.

The high-risk features and effect of postoperative radiotherapy on survival for patients with surgically treated stage IIIA-N2 non-small cell lung cancer.

OBJECTIVES: Although postoperative radiotherapy (PORT) could reduce the incidence of local recurrence in patients with IIIA-N2 non-small cell lung cancer (NSCLC), the role of PORT on survival in patients with surgically treated stage IIIA-N2 NSCLC remains controversial. Therefore, this study was designed to evaluate the effect of PORT on survival for patients with surgically treated stage IIIA-N2 NSCLC. MATERIALS AND METHODS: This study population was chosen from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) and cancer special survival (CSS) outcomes. To balance baseline characteristics between the non-PORT group and PORT group, propensity score matching (PSM) with 1:1 propensity nearest-neighbor match by 0.001 matching tolerance was conducted by R software. Furthermore, a Kaplan-Meier curve was used to visualize the OS and CSS between the PORT group and non-PORT group survival probability. RESULTS: Of all evaluated cases, 4511 with IIIA-N2 NSCLC were eligible for inclusion, of which 1920 were enrolled into the PORT group. On univariate analysis and multivariate analysis, sex, age, year of diagnosis, race, histologic type, T stage, PORT, use of chemotherapy, and positive regional nodes were significantly associated with OS and CSS in IIIA-N2 NSCLC (P < 0.05). However, PORT was not significantly associated with OS (univariate HR = 0.92, 95%CI 0.85-0.99, P = 0.02; multivariate HR = 1.01, 95%CI 0.93-1.08, P = 0.91) and CSS (univariate HR = 0.92, 95%CI 0.85-1.01, P = 0.06; multivariate HR = 1.103 95%CI 0.94-1.12, P = 0.56) in IIIA-N2 NSCLC. Meanwhile, after PSM, neither OS nor CSS did differ significantly between the non-PORT group and PORT group (OS HR = 1.08, 95%CI 0.98-1.19, P = 0.12; CSS HR = 1.10, 95%CI 0.99-1.23, P = 0.07). CONCLUSION: PORT did not contribute to a survival benefit in patients with surgically treated stage IIIA-N2 NSCLC.

Effect of dietary protein on growth performance, and serum biochemical index in late pregnant Hu ewes and their offspring.

The purpose of this study was to investigate the effects of different protein levels in late pregnancy on ewe and lamb growth performance, serum biochemical indexes. Thirty-three ewes (46.4 ± 1.38 kg initial weight) were randomly divided into 3 groups, with 11 ewes in each group. The protein levels of three diets formulated to provide components to meet 10.00 MJ/kg ME requirements diets were: 10.12%, 11.26%, 12.4%. Ewes were raised from the 90th day of pregnancy to the end of delivery, and the lambs were weaned at 60 days. Dietary protein levels had significant effects on blood urea nitrogen, glucose, ammonia nitrogen and triglyceride of ewes (p < 0.05). The height, chest depth, chest circumference, straight crown hip length and curved crown hip length of lambs decreased at first and then increased with the increase of protein. The body length, chest circumference, head width and head length of weaned lambs decreased at first and then increased with the increase of protein. The results showed that when the dietary protein level was increased to 12.4%, the amino acid, glucose and fat metabolism of ewes were affected. The body size development of lambs was better than 10.12% and 11.26% proteins.

The impact of lactating Hu sheep's dietary protein levels on lactation performance, progeny growth and rumen development.

This study aimed to investigate whether lactating Hu sheep's dietary protein levels could generate dynamic effects on the performance of their offspring. Twelve ewes with similar parity were fed iso-energy diets which contained different protein levels (P1: 9.82%, P2: 10.99%) (n = 6), and the corresponding offspring were divided into SP1 and SP2 (n = 12). At 60 days, half of the lambs were harvested for further study: the carcass weight (p = 0.043) and dressing percentage (p = 0.004) in the SP2 group were significantly higher than SP1. The acetic acid (p = 0.007), propionic acid (p = 0.003), butyric acid (p < 0.001) and volatile fatty acids (p < 0.001) in rumen fluid of SP2 were significantly lower than SP1. The expression of MCT2 (p = 0.024), ACSS1 (p = 0.039) and NHE3 (p = 0.006) in the rumen of SP2 was lower than SP1, while the HMGCS1 (p = 0.026), HMGCR (p = 0.024) and Na+/K+-ATPase (p = 0.020) was higher than SP1. The three dominant phyla in the rumen are Bacteroidetes, Proteobacteria and Firmicutes. The membrane transport, amino acid metabolism and carbohydrate metabolism of SP1 were relatively enhanced, the replication and repair function of SP2 was relatively enhanced. To sum up, the increase of dietary protein level significantly increased the carcass weight and dressing percentage of offspring and had significant effects on rumen volatile fatty acids, acetic acid activation and cholesterol synthesis related genes. HIGHLIGHTSIn the early feeding period, the difference in ADG of lambs was mainly caused by the sucking effect.The increase in dietary protein level of ewes significantly increased the carcass weight and dressing percentage of offspring.The dietary protein level of ewes significantly affected the volatile fatty acids (VFAs) and genes related to acetic acid activation and cholesterol synthesis in the rumen of their offspring.The membrane transport, amino acid metabolism and carbohydrate metabolism of the offspring of ewes fed with a low protein diet were relatively enhanced.The replication and repair function of the offspring of ewes fed with a high protein diet was relatively strengthened.

Effect of riboflavin on intestinal development and intestinal epithelial cell function of weaned piglets.

Riboflavin is a water-soluble vitamin involved in the metabolism of protein, fats and carbohydrates as a coenzyme. Pigs, mainly weaned piglets, are prone to riboflavin deficiency. Therefore, this study devoted to explore the effects of riboflavin on intestinal development and function of weaned piglets. A total of 21 piglets, weaned at day 21 of age, were randomly divided into three treatments. The experiment lasted 28 days. The three treatment groups were administered with 0 mg/kg (L_VB2), 3.5 mg/kg (M_VB2) and 17.5 (H_VB2) mg/kg riboflavin by addition into the dry matter basal diets of each group. During the 28-day trial, the feed conversion ratio of the M_VB2 group was lowest (p < 0.05). Duodenum villus height (VH) and the ratio of VH to crypt depth (VH:CD) in L_VB2 group was significantly lower compared with that in M_VB2 group and H_VB2 group (p < 0.05). In the L_VB2 group the number of Ki67 cells in the crypts of the duodenum was increased significantly (p < 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis using transcriptomic data showed that pathways related to apoptosis were significantly enriched in the L_VB2 group (p < 0.01). In addition, pathways related to inflammatory factors were significantly enriched in the H_VB2 group. The total antioxidant capacity (p < 0.05) and glutathione peroxidase (GSH-PX) activity (p < 0.05) of the L_VB2 group were lowest. In summary, riboflavin levels may regulate the intestinal morphology of piglet duodenum by affecting the renewal and differentiation of intestinal epithelial cells.

Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease.

BACKGROUND: A novel and improved methodology is still required for the diagnosis of diabetic kidney disease (DKD). The aim of the present study was to identify novel biomarkers using extracellular vesicle (EV)-derived mRNA based on kidney tissue microarray data. METHODS: Candidate genes were identified by intersecting the differentially expressed genes (DEGs) and eGFR-correlated genes using the GEO datasets GSE30528 and GSE96804, followed by clinical parameter correlation and diagnostic efficacy assessment. RESULTS: Fifteen intersecting genes, including 8 positively correlated genes, B3GALT2, CDH10, MIR3916, NELL1, OCLM, PRKAR2B, TREM1 and USP46, and 7 negatively correlated genes, AEBP1, CDH6, HSD17B2, LUM, MS4A4A, PTN and RASSF9, were confirmed. The expression level assessment results revealed significantly increased levels of AEBP1 in DKD-derived EVs compared to those in T2DM and control EVs. Correlation analysis revealed that AEBP1 levels were positively correlated with Cr, 24-h urine protein and serum CYC and negatively correlated with eGFR and LDL, and good diagnostic efficacy for DKD was also found using AEBP1 levels to differentiate DKD patients from T2DM patients or controls. CONCLUSIONS: Our results confirmed that the AEBP1 level from plasma EVs could differentiate DKD patients from T2DM patients and control subjects and was a good indication of the function of multiple critical clinical parameters. The AEBP1 level of EVs may serve as a novel and efficacious biomarker for DKD diagnosis.

Association between serum elastin-derived peptides and abdominal aortic calcification in peritoneal dialysis patients: a cross-sectional study.

BACKGROUND: Peritoneal dialysis (PD) patients experience accelerated arterial aging, which is characterized by elastin degradation. Elastin-derived peptides (EDPs) are direct products of elastin fragmentation. This study tried to explore the association between serum EDPs and abdominal aortic calcification (AAC) in PD patients. METHODS: Serum levels of EDPs were analyzed in 126 eligible PD patients and 30 controls. PD patients were grouped according to the annularity of AAC evaluated by an abdominal computed tomography (CT) scan. Serum EDPs were analyzed in relation to the presence of AAC or severe AAC in PD patients by logistic regression analysis. RESULTS: Serum EDPs in PD patients were significantly higher than age-matched controls. In 126 PD patients, higher EDPs was associated with greater risk of present AAC (OR = 1.056, 95%CI 1.010-1.103) and severe AAC (OR = 1.062, 95%CI 1.004-1.123). A combination of EDPs substantially improved the accuracy of diagnostic performance for AAC and severe AAC. CONCLUSIONS: EDPs can predict the presence and extent of AAC in PD patients, indicating its possible role to recognize PD patients at risk for AAC and severe AAC.

Effects and interaction of dietary electrolyte balance and citric acid on growth performance, intestinal histomorphology, digestive enzyme activity and nutrient transporters expression of weaned piglets.

Fifty-six piglets were weaned at 21 days and randomly assigned to 1 of 8 dietary treatments with 7 replicate pens for a 14-day experimental period. The eight experimental diets were prepared via a 2 × 4 factorial arrangement with citric acid (CA; 0 and 0.3%) and dietary electrolyte balance (dEB, Na +K - Cl mEq/kg of the diet; -50, 100, 250, and 400 mEq/kg). Varying dEB values were obtained by altering calcium chloride and sodium bicarbonate contents. Dietary CA significantly increased (p < .05) villus height (VH) and villus height:crypt depth (VH:CD) in the jejunum. Piglets fed a 250 mEq/kg diet increased (p < .05) VH and VH:CD values in the duodenum. Jejunal VH and VH:CD increased (quadratic; p < .05), and ileal VH:CD (liner and quadratic; p < .05) decreased as dEB was increased in diets without CA, but no such effect was observed on the diets containing CA (dEB ×CA; p < .05). The CD in jejunum (quadratic; p < .05) increased as dEB was increased in diets containing CA, whereas it was decreased (linear; p < .05) in the diets without CA (dEB ×CA; p < .001). Dietary CA increased maltase activity and reduced the number of Ki67-positive cells (p < .05). Increasing dEB values in diets without CA increased sucrose and lactase activities (quadratic; p < .05), but no such effect was observed in the diets with CA (dEB ×CA; p < .05). An interaction effect between dEB and CA on the number of Ki67-positive cells was observed (p < .001). In conclusion, 250 mEq/kg dEB diet with CA improved piglet intestinal digestion and absorption function by improving intestinal morphology and increasing digestive enzyme activities. However, these improvements were also observed in piglets fed the 100 mEq/kg dEB diet without CA.

LncRNA GAS5 suppresses inflammatory responses and apoptosis of alveolar epithelial cells by targeting miR-429/DUSP1.

Acute lung injury (ALI) is a life-threatening syndrome characterized by excessive inflammation and apoptosis of alveolar epithelial cells. This study firstly investigated the role and mechanism of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in regulating lipopolysaccharide (LPS)-induced inflammatory response and apoptosis of murine alveolar epithelial cell line MLE-12. The expression of GAS5, miR-429, and dual-specificity phosphatase 1 (DUSP1) were examined using quantitative Real-Time PCR (qRT-PCR) and western blot. The inflammatory responses were evaluated by detecting the levels of pro-inflammatory cytokines using ELISA. Cell apoptosis was assessed by TUNEL assay. The interactions among GAS5, miR-429, and DUSP1 were examined using luciferase reporter assay. The results showed that GAS5 and DUSP1 expression were decreased, whereas miR-429 was increased in lung tissues from LPS-induced ALI mice and LPS-treated MLE-12 cells. Furthermore, GAS5 overexpression decreased cell inflammatory responses and apoptosis in LPS-treated MLE-12 cells, which was reversed by miR-429 mimic and DUSP1 knockdown. Mechanistically, GAS5 acted as a competitive endogenous RNA by sponging miR-429 to facilitate DUSP1 expression. Our findings suggest that GAS5 suppresses inflammatory responses and apoptosis of alveolar epithelial cell MLE-12 by targeting miR-429/DUSP1 axis.

Endoscopic Variceal Sequential Ligation Does Not Increase Risk of Gastroesophageal Reflux Disease in Cirrhosis Patients.

BACKGROUND: Endoscopic variceal sequential ligation (EVSL) is currently endorsed in our hospital, as the preferred endoscopic treatment for prevention of variceal rebleeding and achieving adequate hemostasis. There is currently a lack of consensus surrounding EVSL-induced changes in esophageal motor function and abnormal reflux. AIMS: To explore alterations in esophageal motor function and risk of abnormal gastroesophageal reflux in liver cirrhosis patients with esophageal varices, after EVSL. METHODS: Twenty-one liver cirrhosis patients with esophageal varices were studied using manometry and 24-h pH monitoring 1 day prior to and 1 month following EVSL. The EVSL consisted of performing esophageal variceal ligation using a multi-band ligator, which was repeated every 4 weeks until the varices were eradicated. RESULTS: The amplitude and duration of peristaltic contraction waves and the percentage of abnormal esophageal contraction waveforms were unaltered in both the proximal (P > 0.05) and the distal (P > 0.05) esophagus after EVSL. However, the lower esophageal sphincter pressure was decreased following EVSL (16.1 ± 7.9 mmHg vs 21.1 ± 6.3 mmHg (P < 0.05)). Various quantitative parameters including percentage of total monitoring time with pH < 4.0, total number of reflux episodes, number of reflux episodes > 5 min, and DeMeester scores were not increased in post-EVSL patients. Abnormal reflux monitored by 24-h pH monitoring occurred in ten (47.6%) pre-EVSL patients and 11 (52.4%) post-EVSL patients. CONCLUSIONS: Although EVSL affects esophageal motility by relatively decreasing LES pressure, it does not induce substantial motor abnormalities nor increase risk of abnormal gastroesophageal reflux disease in cirrhosis patients.

Circular RNA SMARCA5 suppressed non-small cell lung cancer progression by regulating miR-670-5p/RBM24 axis.

Circular RNAs (circRNAs) have good stability and long half-life in blood and other body fluid, and possess regulatory effects on various biological processes as miRNA/RNA-binding protein sponges, or by competing endogenous RNA, indicating their great potential as biomarkers or targets of cancer therapy. In this study, we mainly explored the role and mechanism of circular RNA SMARCA5 (circsSMARCA5) in non-small cell lung cancer (NSCLC). Quantitative RT-PCR was applied to measure the expression levels of genes, and then, the relationships among circsSMARCA5, microRNA-670-5p (miR-670-5p), and RBM24 were further analyzed. Animal and cell experiments were performed to explore the functions of circsSMARCA5 in NSCLC cells. The results showed that circsSMARCA5 was expressed at low level in NSCLC tissues and cells, while miR-670-5p had high level in NSCLC tissues. Dual luciferase reporter assay verified that miR-670-5p was the target of circsSMARCA5, and RBM24 has the binding site of miR-670-5p. Further analysis showed that circsSMARCA5 could negatively regulate miR-670-5p and had positive relationship with RBM24. Moreover, circsSMARCA5 obviously inhibited tumor growth in vivo, reduced cell proliferation and increased cell apoptosis in vitro, while miR-670-5p mimic or RBM24 knockdown could reverse these effects. Thus, circsSMARCA5 may serve as an NSCLC suppressor by regulating the miR-670-5p/RBM24 axis, and it may have the potential to be a biomarker or therapeutic target for NSCLC.

Modeling pesticides toxicity to Sheepshead minnow using QSAR.

Nowadays, the environmental risk caused by the widespread use of pesticides and their ubiquitous residuals has received more and more attention in academia and regulatory agencies. Due to the large number of pesticides used in agriculture and their adverse effects on all living organisms and the numerous end-points, it is necessary to employ the in silico tools to quickly highlight hazardous pesticides. In this study, we have evaluated the toxicity of pesticides against Sheepshead minnow with the Quantitative Structure-Activity Relationship (QSAR) approach. The models for the specific-type (insecticides, herbicides and fungicides) as well as the general-type (combing all the specific-type pesticides and some microbicides, nematicides, etc.) pesticides were developed using the Genetic Algorithm and the Multiple Linear Regression method, subsequently validated with various metrics. The validation results suggested that the obtained models were highly robust, externally predictive and characterized by a broad applicability domain. Considering the modeling descriptors, the toxicity of pesticides would increase with the lipophilicity and decrease with the polarity and hydrophilicity. Most electrotopological state descriptors contribute negatively to the toxicity, while the influence of topological structure descriptors mainly depends on the physiochemical information they encode. The models proposed in this paper would be useful in filling the data gaps, prioritizing and then focusing experiments on more hazardous pesticides.

The relationship between villous height and growth performance, small intestinal mucosal enzymes activities and nutrient transporters expression in weaned piglets.

Intestinal villi are important structures for digesting and absorbing nutrients. It was hypothesized that intestinal villous height (VH) is related to growth performance, and that VH is associated with digestive and absorptive capabilities in piglets. Sixty 21-d-old weaned piglets were fed identical diets for 28 days. The piglets were grouped according to jejunal or ileal VH at the end of the experiment, including short, middle and high VH groups. The final BW (quadratic, p = .003), ADG (liner, p = .052; quadratic, p = .030) and G: F (liner, p = .074; quadratic, p = .005) were greater in higher VH piglets compared with the shorter VH piglets. Significant linear relationships were recorded between jejunal VH and maltase (linear, p = .003) and sucrase (linear, p = .004) activities. Besides, jejunal VH was significantly associated with maltase (r = 0.357, p = .007), sucrase (r = 0.394, p = .003) and alkaline phosphate (r = 0.288, p = .033) activities. Jejunal Slc1a1 (linear, p = .004) mRNA expression increased as VH increased, while Slc7a1 (linear, p = .007) expression decreased as VH increased, and Slc1a1 (r = 0.292, p = .031) expression was positively related to VH. In the ileum, Slc5a1 (linear, p = .002) and Slc1a1 (linear, p < .001) expression increased as VH increased, whereas Slc7a1 (linear, p = .045) expression decreased as VH increased. A positive relationship between ileal VH and Slc5a1 (r = 0.331, p = .018), Slc1a1 (r = 0.444, p = .001) and Slc6a19 (r = 0.314, p = .026), respectively, was established. Additionally, Slc7a9 (r = 0.0271, p = .057) expression tended to be positively associated with VH in ileum. In conclusion, the growth performance of piglets increased with increasing VH, which may via affecting mucosal enzymes activities and nutrient transporters' mRNA expression.