Exploring the Influence of Hepatitis B Immunoglobulin on the Immune Response to the Hepatitis B Vaccine in a Mouse Model.

Background: The extent to which maternal antibodies against the hepatitis B surface antigen (HBsAb) acquired transplacentally affect the immune responses to the hepatitis B vaccine (HBVac) in infants is still uncertain. Objective: To explore the impact of the HBsAb on the immune response to the HBVac in a mouse model. Methods: According to the doses of the HBVac (2, 5 µg) injected, 267 BALB/c mice were divided into two groups. Each group was subdivided into 3 subgroups based on the doses of the hepatitis B immunoglobulin (HBIG) (0, 25, 50 IU) administered. The HBsAb titers were detected 4 weeks after completing the HepB vaccination. Results: Among all the mice, 40 had an HBsAb titer <100 mIU/mL (non- or low-response to the HBVac). The rates of the HBsAb titer <100 mIU/mL in 0, 25 and 50 IU HBIG groups were 1.1%, 23.1%, and 20.7%, respectively. Multivariate logistic regression analysis showed that the risk factors for low- or non-response to the HBVac were injection with the HBIG, low HBVac dose, and hypodermic injection. The mean HBsAb titers (log10) reduced gradually in the 0, 25 and 50 IU HBIG groups (P<0.001). Conclusion: The HBIG administration has negative impacts on the peak level of the HBsAb and the rate of an effective immune response. This implies that the maternal HBsAb acquired transplacentally might inhibit the immune responses to the HBVac in infants.

A Simple Clinical Prediction Tool for COVID-19 in Primary Care with Epidemiology: Temperature-Leukocytes-CT Results.

BACKGROUND Effective identification of patients with suspected COVID-19 is vital for the management. This study aimed to establish a simple clinical prediction model for COVID-19 in primary care. MATERIAL AND METHODS We consecutively enrolled 60 confirmed cases and 152 suspected cases with COVID-19 into the study. The training cohort consisted of 30 confirmed and 78 suspected cases, whereas the validation cohort consisted of 30 confirmed and 74 suspected cases. Four clinical variables - epidemiological history (E), body temperature (T), leukocytes count (L), and chest computed tomography (C) - were collected to construct a preliminary prediction model (model A). By integerizing coefficients of model A, a clinical prediction model (model B) was constructed. Finally, the scores of each variable in model B were summed up to build the ETLC score. RESULTS The preliminary prediction model A was Logit (YA)=2.657X1+1.153X2+2.125X3+2.828X4-10.771, while the model B was Logit (YB)=2.5X1+1X2+2X3+3X4-10. No significant difference was found between the area under the curve (AUC) of model A (0.920, 95% CI: 0.875-0.953) and model B (0.919, 95% CI: 0.874-0.952) (Z=0.035, P=0.972). When ETLC score was more than or equal to 9.5, the sensitivity and specificity for COVID-19 was 76.7% (46/60) and 90.1% (137/152), respectively, and the positive and negative predictive values were 75.4% (46/61) and 90.7% (137/151), respectively. CONCLUSIONS The ETLC score is helpful for efficiently identifying patients with suspected COVID-19.

Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. RESULTS: Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. CONCLUSION: PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.

miR­505 inhibits cell growth and EMT by targeting MAP3K3 through the AKT­NFκB pathway in NSCLC cells.

MicroRNAs (miRNAs) are short non­coding RNAs, which generally regulate gene expression at the post­transcriptional level. Dysregulation of miRNAs has been reported in numerous cancer types, including lung cancer. In the present study, the role of miR­505 in non­small cell lung cancer (NSCLC) cells was investigated. miR­505 served a tumor suppressor role in NSCLC cells. By reverse transcriptase­quantitative polymerase chain reaction detection, it was demonstrated that miR­505 was downregulated in NSCLC tissues and cell lines, which is negatively associated with large tumor size, Tumor­Node­Metastasis stage and distant metastasis in patients with NSCLC. Functional studies revealed that miR­505 inhibited cell proliferation, migration, invasion and epithelial­mesenchymal transition progress in vitro and tumor growth in vivo. Mechanically, mitogen­activated protein kinase kinase kinase 3 (MAP3K3) was identified as a direct target of miR­505 by binding to its 3'untranslated region and demonstrated to mediate the tumor suppressor roles of miR­505 in NSCLC cells. The effect of miR­505 on the activation of AKT/nuclear factor­κB (NFκB) pathway, which was downstream targets of MAP3K3, was further analyzed by western blot analysis and immunofluorescence analyses. The data demonstrated the inhibition of the AKT/NFκB pathway upon overexpressing miR­505 and the activation of AKT/NFκB pathway upon silencing miR­505. Collectively, the data revealed the novel role and target of miR­505 in NSCLC cells, which may provide novel insights regarding its role in the carcinogenesis of NSCLC and its potential values for clinical applications.

The effect of trans-resveratrol on post-stroke depression via regulation of hypothalamus-pituitary-adrenal axis.

Post-stroke depression (PSD) occurs about 40% among all stroke survivors, but the effective pharmacotherapy is inadequately understood. The present study investigated the effects of a natural polyphenol trans-resveratrol (RES) on behavioral changes after middle cerebral artery occlusion (MCAO) and examined what its molecular targets may be. RES was shown to decrease the infarct size and neurological scores after MCAO, suggesting the amelioration of brain damage and motor activity. RES also reversed the depressive-like behaviors 13 days after MCAO, both in the forced swimming and sucrose consumption tests. Moreover, MCAO-induced series abnormalities related to depressive-like behaviors, such as an abnormal adrenal gland weight to body weight ratio, an increased expression of the corticotropin-releasing factor (CRF) in the frontal cortex, hippocampus and hypothalamus, the differential expression of glucocorticoid receptor (GR) in these three brain regions, and a decreased brain-derived neurotrophic factor (BDNF) level, were ameliorated after treatment with increasing doses of RES at 10, 20 and 40 mg/kg via gavage. These findings provide compelling evidence that RES protects the brain against focal cerebral ischemia-induced injury, but most of all is its antidepressant-like effect on PSD, which might at least in part be mediated by regulation of hypothalamus-pituitary-adrenal axis function.

Effectiveness of a hydroxynaphthoquinone fraction from Arnebia euchroma in rats with experimental colitis.

AIM: To evaluate the potential effectiveness of hydroxynaphthoquinone mixture (HM) in rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: Colitis was induced by intracolonic administration of TNBS (80 mg/kg, dissolved in 50% ethanol). Rats were treated daily for 7 d with HM (2.5, 5, 10 mg/kg) and mesalazine 100 mg/kg 24 h after TNBS instillation. Disease progression was monitored daily by observation of clinical signs and body weight change. At the end of the experiment, macroscopic and histopathologic lesions of rats were scored, and myeloperoxidase (MPO) activity was determined. We also determined inflammatory cytokine tumor necrosis factor (TNF)-α level by ELISA, Western blotting and immunochemistry to explore the potential mechanisms of HM. RESULTS: After intracolonic instillation of TNBS, animals developed colitis associated with soft stool, diarrhea and marked colonic destruction. Administration of HM significantly attenuated clinical and histopathologic severity of TNBS-induced colitis in a dose-dependent manner. It abrogated body weight loss, diarrhea and inflammation, decreased macroscopic damage score, and improved histological signs, with a significant reduction of inflammatory infiltration, ulcer size and the severity of goblet cell depletion (all P < 0.05 vs TNBS alone group). HM could reduce MPO activity. In addition, it also decreased serum TNF-α level and down-regulated TNF-α expression in colonic tissue. This reduction was statistically significant when the dose of HM was 10 mg/kg (P < 0.05 vs TNBS alone group), and the effect was comparable to that of mesalazine and showed no apparent adverse effect. The underlying mechanism may be associated with TNF-α inhibition. CONCLUSION: These findings suggest that HM possesses favourable therapeutic action in TNBS-induced colitis, which provides direct pharmacological evidence for its clinical application.

[Analgesic effect of ferulic acid on CCI mice: behavior and neurobiological analysis].

To study the analgesic effect of chronic administration with ferulic acid, and preliminarily discuss its mechanism. Thermal hyperalgesia and mechanical allodynia tests were conducted to observe the analgesic effect of chronic administration with ferulic acid on CCI mice. The neurochemical detection method was applied to observe the effect chronic administration with ferulic acid on monoamine neurotransmitter and monoamine oxidase activity. Compared with the normal group, CCI mice showed notable reduction in heat sensation and nociceptive threshold in and mechanical allodynia. Ferulic acid (10, 20, 40 and 80 mg x kg(-1), po) could significantly reverse the situations. In an in-depth study, we found that the reason for these results was that ferulic acid was dose-dependent in increasing 5-HT and NE levels in hippocampus, frontal cortex and amygdale and could inhibit MAO-A activity in mouse brains. These results showed that ferulic acid has the analgesic effect. Its mechanism may be related to the inhibition of monoamine oxidase activity and the increase in monoamine neurotransmitter in mouse brains.

Puerarin enhances superoxide dismutase activity and inhibits RAGE and VEGF expression in retinas of STZ-induced early diabetic rats.

OBJECTIVE: To investigate the effects of puerarin on the activity of superoxide dismutase (SOD), and expressions of advanced glycation end-product (AGE) receptor (RAGE) and vascular endothelial growth factor (VEGF) in retinas of streptozotocin (STZ)-induced early diabetic rats. METHODS: Diabetic rat models were established by inducing diabetes via intra-peritoneal injection of STZ. Rats were randomly divided into normal (control), diabetic (DM), and DM+ puerarin groups. After intra-gastric administration of puerarin (500 mg/kg/day for 4 weeks), levels of SOD and malondialdehyde (MDA) were determined in serum and retina. mRNA and protein expression levels of RAGE and VEGF in retinas were determined by real-time polymerase chain reaction (RT-PCR) (mRNA) and Western blot analysis (protein levels). RESULTS: There was significantly lower SOD activity and significantly higher MDA in serum and retinas of the DM group compared with the two other groups (P<0.05). After treatment with puerarin, SOD activity increased and MDA content decreased in this group (P<0.05). mRNA and protein expression levels of RAGE and VEGF in the DM group were significantly higher than those of the other groups (P<0.05), and decreased after puerarin treatment (P<0.05). CONCLUSIONS: Puerarin is able to enhance SOD activity, and inhibit RAGE and VEGF expressions in retinas of STZ-induced early diabetic rats.

[Effects of general glycosides in Cynanchum auriculatum of Jiangsu province on liver fibrosis of rats].

OBJECTIVE: To investigate the effect of general glycosides from Cynanchun auriculatum of Jiangsu on liver fibrosis of rats. METHOD: Seventy-two Wistar rats were randomly divided into normal group, model group, BSW three doses treated group and hydrocortisone treated group. CCl4 (50%, 2 mL x kg(-1)) was orally administraeated twice a week for 8 weeks. The liver and spleen indices were observed. The level of serum GPT, GOT, and HA, PCIII and the level of SOD, HyP, MDA in liver homogenates was also measured. The histopathologic change in hepatic of rats was examined. RESULT: The elevation of serum GPT, GOT, HA, PCIll, MDA and HyP and the content of liver homogenates were attanuated remarkably by BSW treatment. BSW groups also increased the level of SOD of liver homogenates, and make the fibrotic liver better. CONCLUSION: The general glycosides in C. auriculatum of jiangsu province have an anti-hepatic fibrosis ettect on CCl4-induced fibrosis rats, the mechanisms might be associated with its anti-oxidative action.