Corrigendum: The beneficial effects of traditional Chinese medicine on antioxidative status and inflammatory cytokines expression in the liver of piglets.

[This corrects the article DOI: 10.3389/fvets.2022.937745.].

The beneficial effects of traditional Chinese medicine on antioxidative status and inflammatory cytokines expression in the liver of piglets.

Oxidative stress and inflammation seriously affected the growth and development of piglets. Traditional Chinese medicine (TCM) prescriptions has been used to prevent various diseases of piglets, including anti-inflammatory and antioxidant. Here, we identified the effects of Xiao-Jian-Zhong-Tang (XJZT) and Jingsananli-sepsis (JJS) on the oxidative stress and inflammatory in the liver of piglets. The piglets were fed with the basal diet (Control group), basal diet affixed with 10 g/kg XJZT (TCM I group), and basal diet affixed with 3 g/kg JJS (TCM II group), respectively. The serum was gathered on days 30 and 60 and the liver samples were also collected on day 60. Results showed that the TCM I and TCM II markedly increased the activities of the glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC), and reduced the levels of malonaldehyde (MDA), TNF-α, IL-6, and IL-8 in serum. In addition, compared to the control group, Nrf2, SOD-1, NQO-1, and HO-1 mRNA expression levels and the protein levels of Nrf2 and HO-1 were significantly increased while NF-κB, TNF-α, IL-6, and IL-8 mRNA expression levels and the phosphorylation levels of NF-κB and IκB-α were decreased in TCM I and TCM II groups. Collectively, these findings suggested that TCM I and TCM II could enhance anti-oxidative and anti-inflammatory capabilities in the liver of piglets via the Nrf2/NF-κB pathway, providing a basis for the functional exploration of TCM prescriptions.

Two kinds of traditional Chinese medicine prescriptions reduce thymic inflammation levels and improve humoral immunity of finishing pigs.

In animal husbandry, traditional Chinese medicine (TCM) as a reasonable alternative to antibiotics has attracted more and more concerns to reduce microbial resistance. This study was aimed to investigate the effects of dietary supplementation with TCM prescriptions on serum parameters and thymus inflammation responses in finishing pigs. Thirty finishing pigs were randomly divided into three groups, which included the Con group (basal diet), the TCM1 group (basal diet supplemented with Xiao Jian Zhong prescriptions), and the TCM2 group (basal diet supplemented with Jingsananli-sepsis). The results showed that the contents of C3 and C4 in the serum were significantly increased in both the TCM1 and TCM2 groups compared to the Con group on day 30. Similarly, the levels of IgA, IgG, and IgM were increased in the TCM2 group, and only the level of IgM in TCM1 was increased on day 30. Meanwhile, the levels of classical swine fever virus (CSFV) and respiratory syndrome virus (PRRSV) antibodies had a notable increase in the TCM1 and TCM2 groups. Both TCM1 and TCM2 inhibited the levels of TLR4/MyD88/NF-κB signaling pathway-related mRNA (TLR4, MyD88, NF-κB, IL6, IL8, and TNF-α) and protein (p-IκBα and p-P65) expression levels in the thymus. In conclusion, dietary supplementation with TCM could reduce thymic inflammation levels and improve humoral immunity of finishing pigs.

New sight into interaction between endoplasmic reticulum stress and autophagy induced by vanadium in duck renal tubule epithelial cells.

Vanadium (V) is a common environmental and industrial pollutant that can cause nephrotoxicity in animals in excess. The purpose of this research was to explore the interaction between endoplasmic reticulum (ER) stress and autophagy induced by V in the kidney of ducks. Duck renal tubule epithelial cells were exposed to different concentrations of sodium metavanadate (NaVO3) (0, 100 and 200 µM) and PERK inhibitor (GSK, 1 µM), or autophagy inhibitor (chloroquine, 50 µM) alone for 24 h (chloroquine for the last 4 h). The results showed that exposure to V caused the dilatation and swelling of the ER and intracellular calcium overload, and upregulated PERK, eIF2α, ATF4 and CHOP mRNA levels and p-PERK and CHOP protein levels associated with ER stress in cells. Additionally, V markedly increased the number of autophagosomes, acidic vesicular organelles (AVOs) and LC3 puncta, as well as the mRNA levels of Beclin1, Atg5, Atg12, LC3A and LC3B and protein levels of Beclin1, Atg5 and LC3B-II/LC3B-I, but decreased the imRNA and protein levels of p62. Moreover, treatment with the PERK inhibitor ameliorated the changed factors above induced by V, but the V-induced variation of ER-stress related factors were aggravated after treatment with the autophagy inhibitor. Together, our data suggested that excessive V could induce ER stress and autophagy in duck renal tubular epithelial cells. ER stress might promote V-induced autophagy via the PERK/ATF4/CHOP signaling pathway, and autophagy may play a role in alleviating ER stress induced by V.

Selenium alleviates cadmium-induced aging via mitochondrial quality control in the livers of sheep.

Cadmium (Cd) is a heavy metal with toxicity that induces mitochondrial dysfunction and aging, and selenium (Se) can alleviate its toxicity. However, the underlying mechanism of Se alleviating Cd-induced aging in sheep livers deserves further study. This study was to explore the protective mechanism of Se on the Cd-induced aging in the livers of sheep. A total of forty-eight sheep weighing about 10 kg were randomly divided into four groups: control group, Se group [0.34 mg Se·kg-1·body weight (BW)], Cd group (1 mg Cd·kg-1·BW), and Se + Cd group (0.34 mg Se·kg-1·BW +1 mg Cd·kg-1·BW). The results showed that Cd caused vacuolization, granule denaturation, and mitochondrial vacuolization in hepatocytes. Furthermore, the levels of catalase (CAT), total superoxide dismutase (T-SOD), glutathione (GSH) and adenosine triphosphate (ATP) in liver mitochondria were down-regulated, but the levels of hydrogen peroxide (H2O2) and malonaldehyde (MDA) were up-regulated under Cd treatment. Besides, the cyclin-dependent kinase inhibitor 1 (P21) immunohistochemistry positive signal and the puncta of immunofluorescence co-locations of E3 ubiquitin ligase Parkin (Parkin)/ cytochrome c oxidase IV (COX IV) and light chain 3B (LC3B)/COX IV were increased under Cd stress. Moreover, Cd exposure decreased the levels of mitochondrial biogenesis and fusion related factors and minichromosome maintenance protein 2 (MCM2), but increased the levels of mitochondrial fission, mitophagy, and cell aging related factors. However, the variations mentioned above caused by Cd were effectively ameliorated by Se co-treatment. In conclusion, Se might alleviate Cd-induced aging via regulating mitochondrial quality control in sheep livers.

MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway.

BACKGROUND: Ischemic stroke is a devastating disease with very limited therapeutics. Although miR-101 has been reported to play crucial roles in various human diseases, its role in ischemic stroke remains unclear. METHODS: Ischemia-reperfusion (I/R) injury neuronal cells and rat model with I/R injury were constructed. Viability and apoptosis of I/R model cells with miR-101 overexpression or downregulation were evaluated. Potential targets of miR-101 were predicted using miRNA database microRNA.org and confirmed using luciferase reporter assays. Meanwhile, JAK2 and p-STAT3 protein levels were evaluated by Western blot. In addition, rescue experiments (silencing of JAK2) were applied to determine the role of miR-101 in cerebral I/R injury. RESULTS: MiR-101 was significantly downregulated in OGD/R-induced neuronal cells and brain tissues with I/R injury. MiR-101 overexpression (miR-101 mimics) significantly promoted viability and inhibited apoptosis of OGD/R-induced neuronal cells in vitro and efficiently protected rats from ischemic brain injury in vivo. By contrast, miR-101 inhibitor exacerbated growth defect, apoptosis, and ischemic brain injury. Luciferase reporter assay indicated that JAK2 was a direct target of mIR-101, and JAK2 silencing effectively reversed the miR-101 inhibitor-induced neuronal cell apoptosis in vitro and reduced cerebral infarction volume in vivo. CONCLUSION: Our study demonstrated that miR-101 efficiently protected neuronal cells from apoptosis and ischemic brain injury through regulating the JAK2/STAT3 signaling pathway, suggesting that miR-101 might be a potential target for treatment of ischemic stroke.

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

Volume-sensitive outwardly rectifying chloride channel blockers protect against high glucose-induced apoptosis of cardiomyocytes via autophagy activation.

Hyperglycemia is a well-characterized contributing factor for cardiac dysfunction and heart failure among diabetic patients. Apoptosis of cardiomyocytes plays a major role during the onset and pathogenesis of diabetic cardiomyopathy (DCM). Nonetheless, the molecular machinery underlying hyperglycemia-induced cardiac damage and cell death remains elusive. In the present study, we found that chloride channel blockers, 4,4'-diisothiocya-natostilbene-2,2'- disulfonic acid (DIDS) and 4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-on-5-yl) oxybutyric acid (DCPIB), inhibited high glucose-activated volume-sensitive outwardly rectifying (VSOR) Cl- channel and improved the viability of cardiomyocytes. High glucose induced cardiomyocyte apoptosis by suppressing the autophagic stress, which can be reversed via blockade of VSOR Cl- channel. VSOR activation in high glucose-treated cardiomyocytes was attributed to increased intracellular levels of reactive oxygen species (ROS). Taken together, our study unraveled a role of VSOR chloride currents in impaired autophagy and increased apoptosis of high glucose-exposed cardiomyocyte, and has implications for a therapeutic potential of VSOR chloride channel blockers in DCM.

A novel endoplasmic reticulum stress­induced apoptosis model using tunicamycin in primary cultured neonatal rat cardiomyocytes.

Endoplasmic reticulum (ER) stress is key in the development of cardiovascular diseases. However, there is a lack of a systemic ER stress­induced cardiomyocyte apoptosis model. In the present study, primary cultured neonatal rat cardiomyocytes were exposed to tunicamycin. Cell viability was determined by an MTT assay, and cell damage was detected by a lactose dehydrogenase assay. Flow cytometry was used and the activity of caspase­3 was analyzed in order to measure apoptosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to examine the expression of glucose­regulated protein 78­kDa (GRP78) and C/EBP homologous protein (CHOP). As a result, tunicamycin significantly increased cardiomyocyte injury, which occurred in a time- and concentration­dependent manner. In addition, tunicamycin treatment resulted in apoptosis of cardiomyocytes. Molecularly, tunicamycin (100 ng/ml) increased the levels of GRP78 and CHOP 6 h after administration. In addition, GRP78 and CHOP reached maximum mRNA and protein levels 24 h after administration. In conclusion, the results implicate that the tunicamycin­induced ER stress­induced apoptotic model was successfully constructed in cultured neonatal rat cardiomyocytes. A 100 ng/ml concentration of tunicamycin was selected, and MTT, LDH release and flow cytometry assay was at 72 h. In addition, GRP78 and GRP94 were detected 24 h following administration. The results of the present study indicate a novel experimental basis for the investigation of ERS-induced cardiac apoptosis.

Baicalin protects the cardiomyocytes from ER stress-induced apoptosis: inhibition of CHOP through induction of endothelial nitric oxide synthase.

Baicalin, the main active ingredient of the Scutellaria root, exerts anti-oxidant and anti-apoptotic effects in cardiovascular diseases. However, the therapeutic mechanism of baicalin remains unknown. Cultured neonatal rat cardiomyocytes were pre-treated with baicalin (0-50 µM) for 24 h, and subsequently treated with tunicamycin (100 ng/ml). Cell viability was detected by MTT assay, and cell damage was determined by LDH release and TUNEL assay. The expression of CHOP, JNK, caspase-3, eNOS was analyzed by western blot. NO was measured by DAF-FM staining. As a result, treatment with baicalin significantly reduced apoptosis induced by ER stress inducer tunicamycin in cardiomyocytes. Molecularly, baicalin ameliorated tunicamycin-induced ER stress by downregulation of CHOP. In addition, baicalin inverted tunicamycin-induced decreases of eNOS mRNA and protein levels, phospho eNOS and NO production through CHOP pathway. However, the protective effects of baicalin were significantly decreased in cardiomyocytes treated with L-NAME, which suppressed activation of nitric oxide synthase. In conclusion, our results implicate that baicalin could protect cardiomyocytes from ER stress-induced apoptosis via CHOP/eNOS/NO pathway, and suggest the therapeutic values of baicalin against ER stress-associated cardiomyocyte apoptosis.