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Summary: Objective: To explore the role of miR‐181b in alterations of apoptosis and autophagy in the kainic acid (KA)‐induced epileptic juvenile rats via modulating TLR4 and P38/JNK signaling pathway. Methods: Dual‐luciferase reporter assay was performed to testify the targeting relationship between miR‐181b and TLR4. After intracerebroventricular injection (i.c.v.) of KA, rats were injected with miR‐181b agomir and TLR4 inhibitor (TAK‐242). The TLR‐4 activator lipopolysaccharide (LPS) was also administered into rats immediately after injection with miR‐181b agomir. Quantitative real‐time‐polymerase chain reaction (qRT‐PCR) was used for detections of miR‐181b and TLR4 expressions, hematoxylin‐eosin (HE) and Nissl staining for observation of the hippocampus morphological changes, and TUNEL staining for apoptosis analysis. Moreover, western blot was determined to detect TLR4 and P38/JNK pathway proteins, as well as autophagy‐ and apoptosis‐related proteins. Results: TLR4 was identified as a direct target of miR‐181b using Dual‐luciferase reporter assay. KA rats injected with miR‐181b agomir or TAK‐242 had improved learning and memory abilities, reduced seizure severity of Racine's scale, and lessened neuron injury. Additionally, miR‐181b agomir or TAK‐242 could significantly inhibit P38/JNK signaling, decrease LC3II/I, Beclin‐1, ATG5, ATG7, ATG12, Bax, and cleaved caspases‐3, but increase p62 and Bcl‐2 expression. No significances were found between KA group and KA + miR‐181b + LPS group. Conclusion: MiR‐181b could inhibit P38/JNK signaling pathway via targeting TLR4, thereby exerting protective roles in attenuating autophagy and apoptosis of KA‐induced epileptic juvenile rats. [ABSTRACT FROM AUTHOR]

Objectives: To study the clinical features of children with autoimmune encephalitis (AE) secondary to epidemic encephalitis B (EEB)., Methods: A retrospective analysis was performed on the medical data of five children with EEB with "bipolar course" who were treated in Children's Hospital Affiliated to Zhengzhou University from January 2020 to June 2022., Results: Among the five children, there were three boys and two girls, with a median age of onset of 7 years (range 3 years 9 months to 12 years) and a median time of 32 (range 25-37) days from the onset of EEB to the appearance of AE symptoms. The main symptoms in the AE stage included dyskinesia (5/5), low-grade fever (4/5), mental and behavioral disorders (4/5), convulsion (2/5), severe disturbance of consciousness (2/5), and limb weakness (1/5). Compared with the results of cranial MRI in the acute phase of EEB, the lesions were enlarged in 3 children and unchanged in 2 children showed on cranial MRI in the AE stage. In the AE stage, four children were positive for anti-N-methyl-D-aspartate receptor antibody (one was also positive for anti-γ-aminobutyric acid type B receptor antibody), and one was negative for all AE antibodies. All five children in the AE stage responded to immunotherapy and were followed up for 3 months, among whom one almost recovered and four still had neurological dysfunction., Conclusions: EEB can induce AE, with anti-N-methyl-D-aspartate receptor encephalitis as the most common disease. The symptoms in the AE stage are similar to those of classical anti-N-methyl-D-aspartate receptor encephalitis. Immunotherapy is effective for children with AE secondary to EEB, and the prognosis might be related to neurological dysfunction in the acute phase of EEB.

The research selected the Tuojia catchment and Jianshan catchment in Changsha County, Hunan Province, to comparatively study the effects of rice agriculture on the nitrogen and phosphorus concentrations and exports in streams in the typical agricultural catchments of the hilly red soil earth region. The monitoring of 16 months suggested that, there was a moderate stream nutrient pollution in both Tuojia and Jianshan catchments, especially for nitrogen pollution. Comparing the two catchments, the nitrogen and phosphorus concentrations were higher and the water quality was worse in the Tuojia catchment than that in the Jianshan catchment. From the nutrient composition of view, ammonia nitrogen was the main species of total nitrogen in the Tuojia catchment (accounting for 58.5% of total nitrogen), while it was nitrate nitrogen in the Jianshan catchment (accounting for 76. 1% of total nitrogen). The proportion of dissolved phosphorus in total phosphorus was 47. 1% in the Tuojia catchment, higher than the proportion of 37.5% in the Jianshan catchment. From temporal variations of nutrient dynamics of view, concentrations of all forms of nitrogen were higher during January to February and in July, respectively, and total phosphorus and dissolved phosphorus were higher during May to June and during October to December. Since the stream discharge in the catchments concentrated during the rice growing period from April to October, the higher nutrient concentrations during the period suggested potential risks of nitrogen and phosphorus losses. The total nitrogen mass flux was 1.67 kg x (hm2 x month)(-1) and TP was 0.06 kg x (hm2 x month)(-1) in the Tuojia catchment, which were greater than the 0.44 kg x (hm2 x month)(-1) and 0.02 kg x (hm2 x month)(-1) in the Jianshan catchment. Given the similar climate, geomorphology, soil type and cultivation patterns but the different area proportion of rice agriculture between two catchments, results suggested that, under the traditional crop management in hilly red soil earth region of central subtropics, the higher area proportion of rice agriculture has the potential to degrade stream aquatic environment.

Objective: To determine the antitumor effects of the recombinant human RhoB with low-dose cisplatin in lung carcinoma models., Methods: The pVITRO2-RhoB recombinant was constructed and transfected into A549 cells. Its expression and the inhibition effect to the A549 cells were observed models. A549 lung carcinoma mice were treated with either RhoB or cisplatin or both agents together. And the change of tumor size, the survive time of mice, the apoptosis of tumor were also observed., Results: The pVITRO2-RhoB recombinant was constructed successfully. This recombinant could inhibit the growth and promote the apoptosis of A594 in vitro. Mice treated with RhoB or low-dose cisplatin treatment individually resulted in tumor inhibition to a certain extent. Mice treated with combination of RhoB and low-dose cisplatin resulted in synergistic antitumor activity with more effective tumor inhibition (P < 0.05) and longer survival (P < 0.05). TUNEL analysis of tumors exhibited that RhoB in combination with cisplatin led to the increased rate of apoptosis (P < 0.05)., Conclusion: Our data demonstrated that RhoB could increase the sensitivity of lung carcinoma to cisplatin, resulting in enhanced anti-tumor activity. These results suggest that combination with recombinant human RhoB with chemotherapy drugs may be an effective approach in the treatment of lung carcinoma.

Objective: To investigate the therapeutic effect of PI3Kgamma inhibitor AS605240 on cardiac hypertrophy and cardiac fibrosis induced by Isoproterenol in rats., Methods: Wistar rats were randomly divided into three groups (n = 10), control group, ISO group (vehicle group) and AS605240 group. The rats in control group without any treatment. The rats in ISO and AS605240 group were given ISO 10 mg/kg for 3 days and 5 mg/kg for another 11 days by subcutaneous injection to prepare the animal model of cardiac fibrosis. Rats in AS605240 group were given AS605240 50 mg/(kg x d) by intraperitoneal injection continuously for 14 days. The vehicle group received the intraperitoneal injection of an equal volume of 0.5% carboxymethylcellulose. Twenty-four hours after the last treatment, rats were sacrificed. Heart, body weight, cardiac function and the CVF were measured., Results: Compared with the control group, the HW/BW of ISO group was increased significantly (P < 0.05) with a increased collagen inter cardiac muscle cells (P < 0. 05). Compared with ISO group, histological examination of the heart showed that AS605240 significantly relieved the rat cardiac fibrosis and reduced heart/body weight ratios in experimental cardiac fibrosis (P < 0.05)., Conclusion: AS605240 may be an effective antagonist for cardiac hypertrophy and cardiac fibrosis.

A pivotal role of phosphoinositide 3-kinase-gamma (PI3Kgamma) in inflammatory cell activation and recruitment makes it an attractive target for immunomodulatory therapy. In present study we investigated the therapeutic efficiency of AS605240, a selective PI3Kgamma inhibitor, on hepatitis and liver fibrosis in murine models induced by concanavalin A (ConA). Orally administration of AS605240 significantly improved survival, decreased the serum levels of alanine aminotransaminase (ALT), prevented inflammatory infiltration to liver in ConA-induced hepatitis. TNF-alpha and IFN-gamma at protein levels in serum and mRNA levels in liver were markedly reduced. Downregulated phospho-Akt level of inflammatory cells infiltrating the liver by AS605240 treatment was detected by immunohistochemistry analysis in liver and further confirmed by Western blotting analysis in splenocytes. In ConA-induced chronic liver fibrosis model, accumulation of smooth-muscle actin (SMA)-expressing cells was partially inhibited by AS605240 treatment. These observations suggest that AS605240 might be of therapeutic value for the treatment of ConA-induced hepatic injury.

Objective: To investigate the therapeutic effect of PI3Kgamma inhibitor AS605240 on autoimmune myocarditis in mice., Methods: BALB/c mice were randomly divided into three groups, AS605240 group and vehicle group were injected subcutaneously with emulsions containing CFA and 100 ng peptide which derived from murine cardiac alpha-myosin heavy chain on day 0 and 7 while control group were injected with emulsions containing CFA and PBS. AS605240 group received the oral administration of AS605240 50 mg/(kg x d). The vehicle group received the oral administration of an equal volume of 0.5% carboxymethylcellulose. 21 days after the first immunization, mice were sacrificed, heart and body weight were measured. Myocarditis severity was evaluated according to a semi-quantitative scoring system in heart sections. Immunohistochemistry was performed to determine the effect of AS605240 on myocardium macrophage infiltration; TNF-alpha levels in myocardium were determined by ELISA. In vitro and in vivo chemotaxis assays were performed to determine the effect of AS605240 on MCP-1-induced macrophage chemotaxis., Results: Histological examination of the heart showed that AS605240 significantly relieved the murine myocarditis and reduced heart/body weight ratios in experimental autoimmune myocarditis (EAM) (P< 0.01). Immunohistochemical detection showed that AS605240 significantly suppressed macrophage infiltration into the heart with EAM. ELISA demonstrated that AS605240 down-regulated TNF-alpha levels in myocardium (P<0.01). In vitro and in vivo chemotaxis assays indicated that AS605240 significantly suppressed MCP-1-induced macrophage chemotaxis (P<0.01)., Conclusion: AS605240 may be an effective drug for autoimmune myocarditis, of which the mechanism is relating to suppress macrophage chemotaxis and macrophage infiltration into myocardium, and to decrease TNF-alpha levels in myocardium.