Peste des petits ruminants virus infection induces endoplasmic reticulum stress and apoptosis via IRE1-XBP1 and IRE1-JNK signaling pathways.

BACKGROUND: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. OBJECTIVES: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. METHODS: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. RESULTS: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly down-regulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. CONCLUSIONS: PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

ST-segment elevations with bradycardia in inferior leads: Acute pulmonary embolism.

Electrocardiographic (ECG) abnormalities are seen in 70%-80% of patients with acute pulmonary embolism (PE). Rarely, acute PE presents with ST-segment elevation (STE) in leads II; III and aVF and V1-3 mimicking ST-segment elevation myocardial infarction (STEMI). Herein, we describe a case of acute PE presenting with STE in II; III and aVF and V1-3.

Preparation of Novel Sea Cucumber Intestinal Peptides to Promote Tibial Fracture Healing in Mice by Inducing Differentiation of Hypertrophic Chondrocytes to the Osteoblast Lineage.

SCOPE: Hypertrophic chondrocytes have a decisive regulatory role in the process of fracture healing, and the fate of hypertrophic chondrocytes is not only apoptosis. However, the mechanism of sea cucumber (Stichopus japonicus) intestinal peptide (SCIP) on fracture promotion is still unclear. This study aims to investigate the effect of sea cucumber intestinal peptide on the differentiation fate of hypertrophic chondrocytes in a mouse tibial fracture model. METHODS AND RESULTS: Mice are subjected to open fractures of the right tibia to establish a tibial fracture model. The results exhibit that the SCIP intervention significantly promotes the mineralization of cartilage callus, decreases the expression of the hypertrophic chondrocyte marker Col X, and increases the expression of the osteoblast marker Col I. Mechanically, SCIP promotes tibial fracture healing by promoting histone acetylation and inhibiting histone methylation, thereby upregulating pluripotent transcription factors induced the differentiation of hypertrophic chondrocytes to the osteoblast lineage in a manner distinct from classical endochondral ossification. CONCLUSION: This study is the first to report that SCIP can promote tibial fracture healing in mice by inducing the differentiation of hypertrophic chondrocytes to the osteoblast lineage. SCIP may be considered raw material for developing nutraceuticals to promote fracture healing.

Association of the dietary copper intake with all-cause and cardiovascular mortality: A prospective cohort study.

BACKGROUND: Copper (Cu) is a component that performs a crucial role in the normal function and development of the human body. Nonetheless, it is still largely unclear how Cu consumption in the diet relates to the risk for all-cause and cardiovascular disease (CVD) mortality. METHODS: Data from the National Health and Nutrition Examination Survey from 2001-2018 were used to conduct a prospective cohort study of individuals between the ages of 20 years and above. Regression coefficients and 95% confidence intervals for the link between dietary Cu consumption and all-cause and cardiovascular-related mortality were computed utilizing univariate and multivariate-adjusted Cox proportional hazards models. RESULTS: A total of 197.9 million non-institutionalized American citizens were represented by the NHANES's 39,784 participants. The link between Cu in the diet and all-cause mortality was discovered to be non-linear in our restricted cubic spline regression models. When comparing the highest with the lowest quartile of Cu consumption in the diet, the weighted multivariate hazard ratios for all-cause mortality were 0.91 (0.83-0.99) for Q2, 0.88 (0.80-0.97) for Q3, and 0.86 (0.76-0.98) for Q4 (P for trend = 0.017). An identical trend was observed for cardiovascular mortality, but the association is not significant. CONCLUSION: The most important discovery was that higher dietary Cu consumption was associated with a lower risk of all-cause mortality. This trend was also consistent with that of cardiovascular-related mortality, but the association is not significant.

Isolation and Identification of a Novel Anti-Dry Eye Peptide from Tilapia Skin Peptides Based on In Silico, In Vitro, and In Vivo Approaches.

Tilapia skin is a great source of collagen. Here, we aimed to isolate and identify the peptides responsible for combating dry eye disease (DED) in tilapia skin peptides (TSP). In vitro cell DED model was used to screen anti-DED peptides from TSP via Sephadex G-25 chromatography, LC/MS/MS, and in silico methods. The anti-DED activity of the screened peptide was further verified in the mice DED model. TSP was divided into five fractions (TSP-I, TSP-II, TSP-III, TSP-IV, and TSP-V), and TSP-II exerted an effective effect for anti-DED. A total of 131 peptides were identified using LC/MS/MS in TSP-II, and NGGPSGPR (NGG) was screened as a potential anti-DED fragment in TSP-II via in silico methods. In vitro, NGG restored cell viability and inhibited the expression level of Cyclooxygenase-2 (COX-2) protein in Human corneal epithelial cells (HCECs) induced by NaCl. In vivo, NGG increased tear production, decreased tear ferning score, prevented corneal epithelial thinning, alleviated conjunctival goblet cell loss, and inhibited the apoptosis of corneal epithelial cells in DED mice. Overall, NGG, as an anti-DED peptide, was successfully identified from TSP, and it may be devoted to functional food ingredients or medicine for DED.

Socioeconomic status may affect association of vegetable intake with risk of ischemic cardio-cerebral vascular disease: a Mendelian randomization study.

Background: Previous studies found that increasing vegetable intake benefits are reduced after adjustment for socioeconomic factors. Using genetic variation as an instrumental variable for vegetable intake and socioeconomic status, we investigated the relationship between vegetable intake and ischemic cardio-cerebral vascular diseases and focused on whether socioeconomic status was a possible confounder. Methods: From three independent genome-wide association studies, we extracted instrumental variables reflecting raw and cooked vegetable intake, which were used to perform Mendelian randomization analysis. To evaluate the effects of socioeconomic factors on vegetable intake, univariate and multivariate Mendelian randomization analyses were performed using single nucleotide polymorphisms representing education attainment and household income reported in the literature. We also performed outlier assessment and a series of sensitivity analyses to confirm the results. Results: Genetically predicted raw and cooked vegetable intake were not associated with any ischemic cardio-cerebral vascular diseases and lipid components after Bonferroni correction. Univariate Mendelian randomized analysis revealed that raw vegetable intake was positively correlated with education attainment (ß = 0.04, p = 0.029) and household income (ß = 0.07, p < 0.001). Multivariate Mendelian randomized model showed a positive correlation between household income and raw vegetable intake (ß = 0.06, p = 0.004). Socioeconomic status was closely associated with eating habits and lifestyle related to the risk of cardiovascular diseases. Conclusion: Genetically determined raw and cooked vegetable intake was not associated with significant benefits in terms of ischemic cardio-cerebral vascular diseases while genetically determined socioeconomic status may have an impact on vegetable intake. Socioeconomic status, which was closely associated with other eating habits and lifestyle, may affect the association between vegetable intake and ischemic cardio-cerebral vascular diseases.

Chest Pain With Exercise-Induced Left Bundle-Branch Block-Is There a Connection?

This case report describes a patient in their early 60s with chest pain during exertion.

Clinical and electrocardiographic features in acute total left main coronary artery occlusion without collateral circulation.

BACKGROUNDS: Study concerning the clinical features, electrocardiogram (ECG) findings and outcomes in patients presenting with acute total occlusion of left main coronary artery (LM) without collateral circulation is limited. METHODS: 25 patients with acute total LM occlusion without collateral circulation by emergency coronary angiography, from muti-center registry, were retrospectively studied. The clinical and angiographic characteristics, ECG and in-hospital mortality were reviewed. RESULTS: Nineteen patients (76%) presented with cardiogenic shock. Twelve (60%, 12/20) patients had coronary slow flow or no reflow phenomenon after primary percutaneous coronary intervention (PCI). The in-hospital mortality rate was 88% (n = 22). All the patients presented with ST-segment elevation myocardial ischemia (STEMI) pattern, mostly involving leads I, aVL, V2, V3, V4, V5 and ST-segment depression in leads II, III and aVF. CONCLUSIONS: Acute total LM occlusion without collateral circulation portends high in-hospital mortality. Anterior ST elevation in the precordial leads from V2 to V4 through V6, and ST elevation in leads I and aVL, accompanying with ST depression in the inferior leads is associated with acute total LM occlusion without collateral circulation.

DHA- and EPA-Enriched Phosphatidylcholine Suppress Human Lung Carcinoma 95D Cells Metastasis via Activating the Peroxisome Proliferator-Activated Receptor γ.

The antineoplastic effects of docosahexaenoic acid-containing phosphatidylcholine (DHA-PC) and eicosapentaenoic acid-containing phosphatidylcholine (EPA-PC) were explored, and their underlying mechanisms in the human lung carcinoma 95D cells (95D cells) were investigated. After treatment of 95D cells with DHA-PC or EPA-PC, cell biological behaviors such as growth, adhesion, migration, and invasion were studied. Immunofluorescence and western blotting were carried out to assess underlying molecular mechanisms. Results showed that 95D cells proliferation and adherence in the DHA-PC or EPA-PC group were drastically inhibited than the control group. DHA-PC and EPA-PC suppressed the migration and invasion of 95D cells by disrupting intracellular F-actin, which drives cell movement. The protein expression of PPARγ was induced versus the control group. Furthermore, critical factors related to invasion, including matrix metallopeptidase 9 (MMP9), heparanase (Hpa), and vascular endothelial growth factor (VEGF), were drastically downregulated through the PPARγ/NF-κB signaling pathway. C-X-C chemokine receptor type 4 (CXCR4) and cofilin were significantly suppressed via DHA-PC and EPA-PC through the PPARγ/phosphatase and tensin homolog (PTEN)/serine-threonine protein kinase (AKT) signaling pathway. DHA-PC and EPA-PC reversed the PPARγ antagonist GW9662-induced reduction of 95D cells in migration and invasion capacity, suggesting that PPARγ was directly involved in the anti-metastasis efficacy of DHA-PC and EPA-PC. In conclusion, DHA-PC and EPA-PC have great potential for cancer therapy, and the antineoplastic effects involve the activation of PPARγ. EPA-PC showed more pronounced antineoplastic effects than DHA-PC, possibly due to the more robust activation of PPARγ by EPA-PC.

Albumin infusion in hospitalized patients with acute heart failure: a retrospective cohort study.

BACKGROUND: Heart failure is frequently associated with hypoalbuminaemia and poor prognosis. Acute heart failure (AHF) patients are commonly treated with intravenous albumin to improve osmotic pressure and haemodynamics. However, the effects of exogenous albumin supplementation on the fatality rate of AHF patients have not yet been demonstrated. Therefore, the present study strived to examine the impacts of albumin injections on the mortality rate of patients with AHF. METHODS: This retrospective cohort study evaluated the clinical outcomes of all consecutive hospitalized patients. Data were collected from medical records. The primary end-point was a composite of intubation, emergency renal replacement, or mortality in a time-to-event analysis. An inverse probability-weighted multivariable Cox model was used to compare outcomes between patients who were treated with albumin and those who were not based on the propensity score. RESULTS: Among the 1420 consecutive patients hospitalized in our hospital with acute decompensated heart failure between 1 January 2017 and 27 February 2021, 382 were excluded, 337 (32.5%) were administered albumin (median treatment dose of 29.0 g), and 701 (67.5%) were not. The albumin exposure varied by body mass index, age group, previous diagnoses, clinical signs and symptoms, laboratory tests, and use of other drugs in the unmatched sample. The patients receiving albumin exhibited a lower serum albumin level at baseline in contrast with those who were not treated with albumin (median, 37.3 g/L vs. 31.7 g/L, respectively). Overall, primary end-point events occurred in 357 patients (34.4%) (79 died without being intubated or during an emergency renal replacement therapy, 118 were intubated and 160 had an emergency renal replacement therapy). In the inverse probability weighted multivariable analysis based on the propensity score, albumin use was not significantly associated with the composite primary end-point (hazard ratio, 1.05; 95% confidence interval, 0.75-1.47). CONCLUSION: In this observational study of AHF patients hospitalized in our hospital, the administration of albumin did not show a relationship with either a greatly reduced or aggregated risk of the composite end-point of intubation, emergency renal replacement therapy, or death. Therefore, randomized controlled trials of albumin administration are needed for patients with AHF.

Tilapia Skin Peptides Ameliorate Cyclophosphamide-Induced Anxiety- and Depression-Like Behavior via Improving Oxidative Stress, Neuroinflammation, Neuron Apoptosis, and Neurogenesis in Mice.

Anxiety- and depression-like behavior following chemotherapy treatment occurs in cancer patients with high probability and no specific therapeutics are available for treatment and prevention of this complication. Here, tilapia skin peptides (TSP), a novel enzymatically hydrolyzed bioactive peptide mixture, obtained from tilapia (Oreochromis mossambicus) scraps, were studied on cyclophosphamide (CP)-induced anxiety- and depression-like behavior in mice. Mice were received intraperitoneal injection of CP for 2 weeks, while TSP was administered for 4 weeks. After the end of the animal experiment, behavioral, biochemical, and molecular tests were carried out. The mice decreased preference for sugar water, increased immobility time in the forced swimming and tail suspension test, and decreased travel distance in the open field test in the Model group, compared with the Control group. Abnormal changes in behavioral tests were significantly improved after the TSP treatment. Additionally, abnormalities on superoxide dismutase, malondialdehyde, glutathione peroxidase were rescued by administration of 1000 mg/kg/d TSP in mice than that of the Model group. TSP has normalized the expression of Iba-1 and the levels of TNF-α and IL-1ß in the hippocampus of mice, which indicated that TSP could observably ameliorate neuroinflammatory response in the hippocampus of mice. TSP ameliorated the apoptosis of hippocampal neurons of CA1 and CA3 regions in the TSP group vs. the Model group. The number of doublecortin positive cells was drastically increased by administering 1000 mg/kg/d TSP in mice vs. the Model group. Furthermore, TSP reversed the Nrf2/HO-1 signaling pathway, BDNF/TrkB/CREB signaling pathway, and reduced the Bcl-2/Bax/caspase-3 apoptosis pathway. In conclusion, TSP could restore CP-induced anxiety- and depression-like behavior via improving oxidative stress, neuroinflammation, neuron apoptosis, and neurogenesis in mice hippocampus.

Immobilization on magnetic PVA/SA@Fe3O4 hydrogel beads enhances the activity and stability of neutral protease.

Enzyme immobilization technology has a key role in improving the stability of enzyme reaction systems and biocatalyst utilization rates. In this study, polyvinyl alcohol/sodium alginate@Fe3O4 (PVA/SA@Fe3O4) magnetic immobilized-enzyme hydrogel beads were prepared. Their structure and morphology were characterized by scanning electron microscopy, surface area and porosity analyses, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and a vibrating sample magnetometer. The capability of PVA/SA@Fe3O4 to adsorb neutral protease was investigated with variations in composition, temperature, pH, stirring speed, enzyme concentration, and crosslinking concentration. The optimal parameters of the immobilization process were determined by response surface methodology (3% neutral protease, 4% crosslinking at 200 rpm, 45 °C and pH 7.2), under which an immobilization rate of 41.98 mg/g was obtained. The thermal stability, acid-base stability, and reusability of the immobilized enzyme were improved significantly. After seven cycles, the immobilized enzyme activity remained at 30.8% that of the initial enzyme activity. The results indicate that the immobilization of NP onto magnetic PVA/SA@Fe3O4 hydrogel beads improves enzyme efficiency, giving this process potential industrial applications.