Erratum: [Corrigendum] Changes of type II collagenase biomarkers on IL­1ß­induced rat articular chondrocytes.

[This corrects the article DOI: 10.3892/etm.2021.10014.].

Quercetin alleviates Mycoplasma gallisepticum-induced inflammatory damage and oxidative stress through inhibition of TLR2/MyD88/NF-κB pathway in vivo and in vitro.

Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) in chickens leads to enormous economic damage to the poultry industry yearly. The active components and mechanism of action of the traditional herbal remedy Ephedra houttuynia powder (EHP), which had been approved for clinical treatment against MG infection in China, remain unknown. In this study, the active components of EHP against MG were screened using a network pharmacological method, additionally, we studied the mechanism of action of the screened results (quercetin (QUE)). The findings demonstrated that QUE was an essential element of EHP against MG infection, effectively attenuating MG-induced oxidative stress and activation of the TLR2/MyD88/NF-κB pathway. Following QUE therapy, IL-1, IL-6, and TNF-α content and expression were downregulated, whereas IL-4 and IL-10 expression were upregulated, eventually suppressing the inflammatory response both in vitro and in vivo. Together, this study presents a strong rationale for using QUE as a therapeutic strategy to inhibit MG infection-induced inflammatory damage and oxidative stress.

Curcumin alleviates ketamine-induced oxidative stress and apoptosis via Nrf2 signaling pathway in rats' cerebral cortex and hippocampus.

AIMS: To investigate curcumin's protective effect on nerve damage caused by ketamine anesthesia via the Nrf2 signaling pathway. Rats and PC12 cells were used in this experiment to investigate the mechanism of nerve injury caused by ketamine anesthesia. Furthermore, our findings suggest that curcumin may affect oxidative stress and apoptosis by targeting the Nrf2 pathway, thereby alleviating the nerve injury caused by ketamine. METHODS: The rat cerebral cortex and hippocampus were stained with Nissl and immunohistochemistry to determine the number of neurons and the expression of Caspase-3, Bcl-2, and Bax. CCK-8 assay was used to determine the optimal concentration of ketamine, curcumin, and H2 O2 in PC12 cells. Flow cytometry was used to detect changes in reactive oxygen species and the rate of apoptosis in each group. To determine whether Nrf2 entered the nucleus, immunofluorescence was used. Both tissues and cells were subjected to RT-PCR and Western blotting detection at the same time. The levels of oxidative stress were determined using a malondialdehyde (MDA) and superoxide dismutase (SOD) assay kit. RESULTS: Ketamine reduced the number of neurons in the cortex and hippocampus of rats. The proteins Bax and Caspase-3 were upregulated, while Bcl-2 was down-regulated in the cortex and hippocampus. The viability of PC12 cells has decreased. MDA content increased while SOD activity decreased in cortex, hippocampus, and PC12 cells. Ketamine had an effect on the expression of some genes in the Nrf2 signaling pathway as well as apoptosis. Curcumin pretreatment may be able to prevent ketamine-induced damage. CONCLUSIONS: The oxidative stress and apoptosis caused by ketamine during growth of the cerebral cortex, hippocampus, and PC12 cells may be decreased by curcumin's activation of the Nrf2 signaling pathway. Our research provides a potential strategy for the secure administration of anesthetics in medical settings.

Methylsulfonylmethane ameliorates inflammation via NF-κB and ERK/JNK-MAPK signaling pathway in chicken trachea and HD11 cells during Mycoplasma gallisepticum infection.

Mycoplasma gallisepticum (MG) is an avian pathogen that commonly causes respiratory diseases in poultry. Methylsulfonylmethane (MSM) is a sulfur-containing natural compound that could alleviate inflammatory injury through its excellent anti-inflammatory and antioxidant properties. However, it is still unclear whether MSM prevents MG infection. The purpose of this study is to determine whether MSM has mitigative effects on MG-induced inflammatory injury in chicken and chicken like macrophages (HD11 cells). In this research, White Leghorn chickens and HD11 cells were used to build the MG-infection model. Besides, the protective effects of MSM against MG infection were evaluated by detecting MG colonization, histopathological changes, oxidative stress and inflammatory injury of trachea, and HD11 cells. The results revealed that MG infection induced inflammatory injury and oxidative stress in trachea and HD11 cells. However, MSM treatment significantly ameliorated oxidative stress, partially alleviated the abnormal morphological changes and reduced MG colonization under MG infection. Moreover, MSM reduced the mRNA expression of proinflammatory cytokines-related genes and decreased the number of death cells under MG infection. Importantly, the protective effects of MSM were associated with suppression of nuclear factor-kappa B (NF-κB) and extracellular signal-related kinases (ERK)/Jun amino terminal kinases (JNK)-mitogen-activated protein kinases (MAPK) pathway in trachea and HD11 cells. These results proved that MSM has protective effects on MG-induced inflammation in chicken, and supplied a better strategy for the protective intervention of this disease.

Cardiopulmonary (No Ventilation) and Anesthetic Effects of Dexmedetomidine-Tiletamine in Dogs.

The aim of the present study was to evaluate the anesthetic and cardiopulmonary effects of dexmedetomidine in combination with tiletamine (without zolazepam) as a general anesthetic. The study was divided into two phases. In Phase 1, 18 adult healthy mixed-breed dogs were randomly allocated into three groups: Group TD8 (4.5 mg kg-1 tiletamine and 8 µg kg-1 dexmedetomidine), Group TD10 (4.5 mg kg-1 tiletamine and 10 µg kg-1 dexmedetomidine), or Group TD12 (4.5 mg kg-1 tiletamine and 12 µg kg-1 dexmedetomidine). After drug administration, the heart rate (HR), respiratory rate (f R), mean arterial pressure (MAP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), peripheral hemoglobin oxygen saturation (SpO2), behavioral score, quality of induction and recovery, extent of ataxia, the time taken for induction, and the duration of anesthesia were recorded. The recovery time and quality were recorded after administration of atipamezole (50 µg kg-1) after 60 min. In phase 2, the feasibility of combining dexmedetomidine (10 µg kg-1) and tiletamine (4.5 mg kg-1) as general anesthetics for orchiectomy was evaluated in dogs (n = 6). HR, f R, MAP, SAP, DAP, temperature, SpO2, behavioral scores, and adverse reactions were recorded during each surgical procedure. In phase 1, the dogs were anesthetized for 5 min after administration of drugs and achieved a maximum behavioral score in TD10 and TD12 after 10 min. Although HR, MAP, SAP, DAP, and NIBP decreased in all three groups, they still maintained within the normal range. In phase 2, orchiectomy was completed smoothly in all dogs with little fluctuation in the physiological variables. We found that a combination of tiletamine (4.5 mg kg-1) and dexmedetomidine (10 µg kg-1) intramuscularly induced moderate anesthesia in dogs and could be utilized for short-term anesthesia and minor surgery.

Changes of type II collagenase biomarkers on IL-1ß-induced rat articular chondrocytes.

Osteoarthritis (OA) is characterized by progressive degeneration of cartilage, formation of cartilage at the cartilage edge, and remodeling of the subchondral bone. Pro-inflammatory cytokines [e.g., interleukin (IL)-1ß] that induce inflammation and promote chondrocyte damage induce OA. Currently, the diagnosis of OA is commonly based on imaging examinations (e.g., X-ray) and evaluations of clinical symptoms; however, biomarkers that can effectively diagnose OA are currently not available. By studying the mechanism underlying OA cartilage injury and changes in the concentrations of the biomarkers procollagen type II carboxy-terminal propeptide (PIICP), collagen type-II C-telopeptide fragments (CTX-II), and type II collagen cleavage neoepitope (C2C) during pathogenesis, the present study established a theoretical basis for the evaluation and early diagnosis of OA. In an experiment, 10 ng/ml IL-1ß was used to the treat chondrocyte-induced OA models in vitro for 0, 12, 24 and 48 h. Western blotting was used to detect the expression levels of matrix metalloproteinase (MMP)-3, MMP-13, and inducible nitric oxide synthase (iNOS) protein at each time-point. The concentrations of CTX-II, C2C, and PIICP in the cell culture supernatant were detected by ELISA kit. A biochemical kit was used to detect changes of nitric oxide (NO) in the cell culture supernatant. In addition, chondrocytes were treated with 10 ng/ml IL-1ß for 0, 30, 60 and 90 min and the translocation and phosphorylation of the NF-κB pathway were investigated by western blotting. Following IL-1ß stimulation, the NF-κB pathway was activated to increase the expression levels of MMPs and iNOS synthesis downstream of the pathway, resulting in an increased degradation of type II collagen (Col II). To sum up, pro-inflammatory IL-1ß induced an OA chondrocyte model. During the development of OA, the expression of MMPs and NO increased and Col II was degraded.

Protective Effect of GM1 Attenuates Hippocampus and Cortex Apoptosis After Ketamine Exposure in Neonatal Rat via PI3K/AKT/GSK3ß Pathway.

Ketamine is a widely used analgesic and anesthetic in obstetrics and pediatrics. Ketamine is known to promote neuronal death and cognitive dysfunction in the brains of humans and animals during development. Monosialotetrahexosyl ganglioside (GM1), a promoter of brain development, exerts neuroprotective effects in many neurological disease models. Here, we investigated the neuroprotective effect of GM1 and its potential underlying mechanism against ketamine-induced apoptosis of rats. Seven-day-old Sprague Dawley (SD) rats were randomly divided into the following four groups: (1) group C (control group: normal saline was injected intraperitoneally); (2) group K (ketamine); (3) group GM1 (GM1 was given before normal saline injection); and (4) GM1+K group (received GM1 30 min before continuous exposure to ketamine). Each group contained 15 rats, received six doses of ketamine (20 mg/kg), and was injected with saline every 90 min. The Morris water maze (MWM) test, the number of cortical and hippocampal cells, apoptosis, and AKT/GSK3ß pathway were analyzed. To determine whether GM1 exerted its effect via the PI3K/AKT/GSK3ß pathway, PC12 cells were incubated with LY294002, a PI3K inhibitor. We found that GM1 protected against ketamine-induced apoptosis in the hippocampus and cortex by reducing the expression of Bcl-2 and Caspase-3, and by increasing the expression of Bax. GM1 treatment increased the expression of p-AKT and p-GSK3ß. However, the anti-apoptotic effect of GM1 was eliminated after inhibiting the phosphorylation of AKT. We showed that GM1 lessens ketamine-induced apoptosis in the hippocampus and cortex of young rats by regulating the PI3K/AKT/GSK3ß pathway. Taken together, GM1 may be a potential preventive treatment for the neurotoxicity caused by continuous exposure to ketamine.