Artificial neural network-genetic algorithm-based optimization of aerobic composting process parameters of Ganoderma lucidum residue.

The rapid development of traditional Chinese medicine enterprises has put forward higher requirements for the resource utilization of traditional Chinese medicine residues (TCMR). Aerobic composting of TCMR to prepare bio-organic fertilizer is an effective resource utilization method. In this study, a back-propagation artificial neural network (BPNN) model using composting factors as inputs (C/N, initial moisture content, type of inoculant, composting days) and the humic acid content as the output was constructed based on the orthogonal test data. BPNN-GA (a genetic algorithm) was used for extreme value optimization, and the optimal composting process parameter combination was obtained and verified. The results show that the combination of orthogonal testing and BPNN can effectively establish the relationship between the composting process parameters and humic acid content. The R2 value was 0. 9064. The optimized parameter combination is as follows: C/N,37.42; moisture content,69.76%; bacteria,no; and composting time,50 d.

JQ1 inhibits high glucose-induced migration of retinal microglial cells by regulating the PI3K/AKT signaling pathway.

Diabetic retinopathy (DR) is one of the main leading causes of visual impairment worldwide. The current study elucidates the role of JQ1 in DR. A diabetic model was constructed by STZ injection and a high-fat diet. After establishment of the diabetic model, rats were assigned to treatment groups: 1) control, 2) diabetic model, and 3) diabetic+JQ1 model. In vitro Transwell and wound-healing assays were used to measure BV2 cell viability by stimulation with low glucose and high glucose with or without JQ1 and 740Y-P. Pathological methods were used to analyze DR, and Western blotting was used to analyze protein expression. Identification of enriched pathways in DR was performed by bioinformatics. Histopathological examination demonstrated that JQ1 rescued the loss of retinal cells and increased the thickness of retinal layers in diabetic rats. JQ1 attenuated high glucose-stimulated BV2 microglial motility and migration. The bioinformatics analysis implied that the Pl3K-Akt signaling pathway was enriched in DR. JQ1 decreased the phosphorylation of PI3K and AKT as well as the immunostaining of PI3K in BV2 cells. 740Y-P (a PI3K agonist) significantly reversed the decrease in p-PI3K and p-AK in BV2 cells. Additionally, JQ1 decreased the protein expression of p-PI3K, p-AKT, and MMP2/9 and immunostaining of PI3K in retinal tissues of rats. JQ1 suppresses the PI3K/Akt cascade by targeting MMP expression, thus decreasing the viability and invasion capacity of retinal microglia, suggesting an interesting treatment target for DR.

Exercise reduces hyperlipidemia-induced kidney damage in apolipoprotein E-deficient mice.

Hyperlipidemia is a risk factor of kidney damage that can lead to chronic kidney disease. Studies have shown that exercise reduces kidney damage; however, the specific mechanisms underlying the protective effects of exercise remain unclear. For 12 weeks, 8-week-old male apolipoprotein E-deficient (ApoE-/-) mice were randomly divided into four treatment groups (n=7/group) as follows: Mice fed a normal diet (ND group); mice fed a ND and exercised (ND + E group); mice fed a high-fat diet (HD group); and mice fed a HD and exercised (HD + E group). Exercise training consisted of swimming for 40 min, 5 days/week. Metabolic parameters, such as low-density lipoprotein-cholesterol, total cholesterol and creatinine levels were higher in the ApoE-/- HD mice compared with those in the ApoE-/- HD + E mice. Serum levels of glutathione peroxidase and superoxide dismutase were significantly decreased in the HD group compared with those in the HD + E group. Significant pathological changes were observed in the HD + E group compared with in the HD group. Immunohistochemistry and immunoblotting revealed increased levels of oxidative stress (nuclear factor erythroid-2-related factor 2) and fibrosis (Smad3 and TGF-ß) markers in the ApoE-/- HD group; however, the expression levels of these markers were significantly decreased in the ApoE-/- HD + E group. Furthermore, NF-κB expression in the HD + E group was significantly lower compared with that in the HD group. These results suggested that exercise may exert protective effects against kidney damage caused by hyperlipidemia.

Erratum to "Effect of Thymoquinone on Acute Kidney Injury Induced by Sepsis in BALB/c Mice".

[This corrects the article DOI: 10.1155/2020/1594726.].

Effect of Thymoquinone on Acute Kidney Injury Induced by Sepsis in BALB/c Mice.

Acute kidney injury (AKI) is a common complication of sepsis and has also been observed in some patients suffering from the new coronavirus pneumonia COVID-19, which is currently a major global concern. Thymoquinone (TQ) is one of the most active ingredients in Nigella sativa seeds. It has a variety of beneficial properties including anti-inflammatory and antioxidative activities. Here, we investigated the possible protective effects of TQ against kidney damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ+CLP. CLP was performed after 2 weeks of TQ gavage. After 48 h, we measured the histopathological alterations in the kidney tissue and the serum levels of creatinine (CRE) and blood urea nitrogen (BUN). We also evaluated pyroptosis (NLRP3, caspase-1), apoptosis (caspase-3, caspase-8), proinflammatory (TNF-α, IL-1ß, and IL-6)-related protein and gene expression levels. Our results demonstrated that TQ inhibited CLP-induced increased serum CRE and BUN levels. It also significantly inhibited the high levels of NLRP3, caspase-1, caspase-3, caspase-8, TNF-α, IL-1ß, and IL-6 induced by CLP. Furthermore, NF-κB protein level was significantly decreased in the TQ+CLP group than in the CLP group. Together, our results indicate that TQ may be a potential therapeutic agent for sepsis-induced AKI.

MiR-19b-3p attenuates IL-1ß induced extracellular matrix degradation and inflammatory injury in chondrocytes by targeting GRK6.

Osteoarthritis (OA) is characterized by degradation of articular cartilage. MiRNAs are involved in the regulation of chondrogenesis and OA. We aimed to investigate effects and mechanisms of miR-19b-3p in regulating chondrocytes viability, cartilage degradation and inflammatory response. Primary chondrocytes were isolated from cartilages in control subjects and patients with OA. Murine ATDC5 cells were pre-conditioned with IL-1ß in vitro. Expressions and interaction of miR-19b-3p with G protein-coupled receptor kinase 6 (GRK6), and their effects on inflammation, chondrocytes viability and cartilage degradation were determined after miR-19b-3p mimic or GRK6 siRNA transfection. MiR-19b-3p was significantly decreased in OA chondrocytes and IL-1ß-stimulated ATDC5 cells, in paralleled with the elevated type-II-collagen, aggrecan, MMP13 and GRK6 expression. MiR-19b-3p mimic dramatically increased the viability of chondrocytes and suppressed cell apoptosis. It also increased type-II-collagen, aggrecan expression and glycosaminoglycan (sGAG) content, and decreased the expression of MMP-1 and MMP-13 that controlled by IL-1ß. Overexpression of miR-19b-3p inhibited the production of IL-6 and IL-8 in ATDC5 cells. However, the protective effects of miR-19b-3p mimic on IL-1ß induced cell death; IL-8 production and sGAG decrease were greatly discounted by GRK6 lentiviral vectors. Luciferase reporter assay confirmed that GRK6 gene was a direct target ofmiR-19b-3p. GRK6 siRNA transfection antagonized the IL-1ß-induced chondrocytes injury, extracellular matrix degradation and inflammatory response. MiR-19b-3p mimic and GRK6 siRNA showed comparable inhibitory effect on IL-1ß-provoked NF-κB as reflected by the expression of p-p65. NF-κB translocation inhibition with PS1154 reversed the effects of IL-1ß on IL-8 and sGAG. Collectively, miR-19b-3p attenuated OA by targeting GRK6-NF-κB pathway.

Role of Thymoquinone in Cardiac Damage Caused by Sepsis from BALB/c Mice.

Sepsis is a major health complication causing patient mortality and increased healthcare costs. Cardiac dysfunction, an important consequence of sepsis, affects mortality. We previously reported that thymoquinone (TQ) protected against hyperlipidemia and doxorubicin-induced cardiac damage. This study investigated the possible protective effects of TQ against cardiac damage in septic BALB/c mice. Eight-week-old male BALB/c mice were divided into four groups: control, TQ, cecal ligation and puncture (CLP), and TQ + CLP. CLP was performed after 2-week TQ gavage. After 48 h, we measured the histopathological alterations of the cardiac tissue and the plasma levels of troponin-T (cTnT) and ATP. We evaluated autophagy (p62 and beclin 1), pyroptosis (NLRP3, caspase-1, interleukin [IL]-1ß, and IL-18) at the gene and protein levels and IL-6 and tumor necrosis factor-α (TNF-α) at the gene level. Our results demonstrated that TQ administration significantly reduced intestinal histological alterations. TQ inhibited plasma cTnT levels; improved ATP; significantly inhibited p62, NLRP3, caspase-1, IL-1ß, IL-18, IL-6, TNF-α, and MCP-1expressions; and increased beclin 1 and IL-10 level. The phosphatidylinositide 3-kinase level was significantly decreased in the TQ + CLP group versus the CLP group. These results suggest that TQ effectively modulates autophagy, pyroptosis, and pro-inflammatory, making it important in the treatment of sepsis-induced cardiac damage.

Coenzyme Q10 protects against hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient mice.

BACKGROUND: Hyperlipidemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that Coenzyme Q10(CoQ10) protects against cardiac damage in vivo. The aim of this study was to investigate the possible protective effects of CoQ10 against cardiac damage in apolipoprotein E-deficient (ApoE-/-) mice. METHODS: Eight-week-old male C57BL/6 and ApoE-/- mice were randomly divided into four groups: C57BL/6 mice fed a normal diet (C57BL/6 group); C57BL/6 mice fed a normal diet + CoQ10 (C57BL/6 + CoQ10 group); ApoE-/- mice fed a high-fat diet (ApoE-/- HD group), and ApoE-/- mice fed a high-fat diet + CoQ10 (ApoE-/- HD + CoQ10 group). All groups were fed the different diets for 16 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at - 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. RESULTS: The metabolic parameters such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglycerides (TG) levels were lower in ApoE-/-HD + CoQ10 mice than in ApoE-/- HD mice. There were significant pathophysiological changes (H&E, PAS, Masson and CD68 staining) in ApoE-/- mice in the HD group compared with those in the HD + CoQ10 group. CoQ10 reduced HD-induced cardiac tissue damage via autophagy (p62 and LC3), as evidenced by immunoblotting, immunohistochemistry, and RT-qPCR. CoQ10 also inhibited inflammation (IL-6 and TNF-α) gene expression in ApoE-/- mice. CONCLUSIONS: These results indicate that CoQ10 is a potential therapeutic target for cardiac damage caused by hyperlipidemia.