Elucidating the mechanisms of Buyang Huanwu Decoction in treating chronic cerebral ischemia: A combined approach using network pharmacology, molecular docking, and in vivo validation.

OBJECTIVE: This study aimed to explore the potential mechanisms of Buyang Huanwu Decoction (BHD) in regulating the AKT/TP53 pathway and reducing inflammatory responses for the treatment of chronic cerebral ischemia (CCI) using UHPLC-QE-MS combined with network pharmacology, molecular docking techniques, and animal experiment validation. METHODS: Targets of seven herbal components in BHD, such as Astragalus membranaceus, Paeoniae Rubra Radix, and Ligusticum chuanxiong, were identified through TCMSP and HERB databases. CCI-related targets were obtained from DisGeNET and Genecards, with an intersection analysis conducted to determine shared targets between the disease and the herbal components. Functional enrichment analysis of these intersecting targets was performed. Networks of gene ontology and pathway associations with these targets were constructed and visualized. A pharmacological network involving intersecting genes and active components was delineated. A protein-protein interaction network was established for these intersecting targets and visualized using Cytoscape 3.9.1. The top five genes from the PPI network and their corresponding active components underwent molecular docking. Finally, the 2-vessel occlusion (2-VO) induced CCI rat model was treated with BHD, and the network pharmacology findings were validated using Western blot, RT-PCR, behavioral tests, laser speckle imaging, ELISA, HE staining, Nissl staining, LFB staining, and immunohistochemistry and immunofluorescence. RESULTS: After filtration and deduplication, 150 intersecting genes were obtained, with the top five active components by Degree value identified as Quercetin, Beta-Sitosterol, Oleic Acid, Kaempferol, and Succinic Acid. KEGG pathway enrichment analysis linked key target genes significantly with Lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. The PPI network highlighted ALB, IL-6, AKT1, TP53, and IL-1ß as key protein targets. Molecular docking results showed the strongest binding affinity between ALB and Beta-Sitosterol. Behavioral tests using the Morris water maze indicated that both medium and high doses of BHD could enhance spatial memory in 2-VO model rats, with high-dose BHD being more effective. Laser speckle results showed that BHD at medium and high doses could facilitate CBF recovery in CCI rats, demonstrating a dose-response relationship. HE staining indicated that all doses of BHD could reduce neuronal damage in the cortex and hippocampal CA1 region to varying extents, with the highest dose being the most efficacious. Nissl staining showed that nimodipine and medium and high doses of BHD could alleviate Nissl body damage. LFB staining indicated that nimodipine and medium and high doses of BHD could reduce the pathological damage to fiber bundles and myelin sheaths in the internal capsule and corpus callosum of CCI rats. ELISA results showed that nimodipine and BHD at medium and high doses could decrease the levels of TNF-α, IL-6, IL-17, and IL-1ß in the serum of CCI rats (p < 0.05). Immunohistochemistry and immunofluorescence demonstrated that BHD could activate the AKT signaling pathway and inhibit TP53 in treating CCI. Western blot and RT-PCR results indicated that nimodipine and all doses of BHD could upregulate Akt1 expression and downregulate Alb, Tp53, Il-1ß, and Il-6 expression in the hippocampus of CCI rats to varying degrees (p < 0.05). CONCLUSION: BHD exerts therapeutic effects in the treatment of CCI by regulating targets, such as AKT1, ALB, TP53, IL-1ß, and IL-6, and reducing inflammatory responses.

Reveal the correlation between hub hypoxia/immune-related genes and immunity and diagnosis, and the effect of SAP30 on cell apoptosis, ROS and MDA production in cerebral ischemic stroke.

BACKGROUND: Cerebral ischemic stroke (CIS) is a common cerebrovascular disease. The purpose of this study was to investigate the potential mechanism of hypoxia and immune-related genes in CIS. METHODS: All data were downloaded from public databases. Hub mRNAs was identified by differential expression analysis, WGCNA analysis and machine learning. Hub mRNAs were used to construct the classification models. Pearson correlation analysis was used to analyze the correlation between hub mRNAs and immune cell infiltration. Finally, the SAP30 was selected for verification in HMC3 cells. RESULTS: The SVM, RF and DT classification models constructed based on 6 hub mRNAs had higher area under the curve values, which implied that these classification models had high diagnostic accuracy. Pearson correlation analysis found that Macrophage has the highest negative correlation with CCR7, while Neutrophil has the highest positive correlation with SLC2A3. Drug prediction found that ruxolitinib, methotrexate, resveratrol and resatorvid may play a role in disease treatment by targeting different hub mRNAs. Notably, inhibition of SAP30 expression can reduce the apoptosis of HMC3 cells and inhibit the production of ROS and MDA. CONCLUSION: The identification of hub miRNAs and the construction of classification diagnosis models provide a theoretical basis for the diagnosis and management of CIS.

Tri-zone flame spatial structure imaging combined with endogenic polarized scattering.

We propose a multi-mode optical imaging method to retrieve the 2D and 3D spatial structures of the preheating, reaction, and recombination zones of an axisymmetric steady flame. In the proposed method, an infrared camera, a visible light monochromatic camera, and a polarization camera are triggered synchronously to capture 2D flame images, and their corresponding 3D images are reconstructed by combining different projection position images. The results of the experiments conducted indicate that the infrared and visible light images represent the flame preheating and flame reaction zones, respectively. The polarized image can be obtained by computing the degree of linear polarization (DOLP) of raw images captured by the polarization camera. We discover that the highlighted regions in the DOLP images lie outside the infrared and visible light zones; they are insensitive to the flame reaction and have different spatial structures for different fuels. We deduce that the combustion product particles cause endogenic polarized scattering, and that the DOLP images represent the flame recombination zone. This study focuses on the combustion mechanisms, such as the formation of combustion products and quantitative flame composition and structure.

Probing Individual Particles in Aquatic Suspensions by Simultaneously Measuring Polarized Light Scattering and Fluorescence.

Suspended particles play a significant role in aquatic systems. However, existing methods to probe suspended particles have several limitations. In this paper, we present a portable prototype to in situ probe individual particles in aquatic suspensions by simultaneously measuring polarized light scattering and fluorescence, aiming to obtain an effective classification of microplastics and microalgae. Results show that the obtained classification accuracy is significantly higher than that for either of these two methods. The setup also successfully measures submicron particles and discriminates two species of Synechococcus. Our study demonstrates the feasibility of simultaneously measuring polarized light scattering and fluorescence, and the promising capability of our method for further aquatic environmental monitoring.

Lipid peroxidation of kidney of the turtle Mauremys reevesii caused by cadmium.

This research was designed to investigate lipid peroxidation of the kidney of turtle (Mauremys reevesii) caused by cadmium. Turtles were injected intraperitoneally with cadmium at the concentration of 0 (control), 7.5, 15, and 30 mg/kg, and 5 turtles were taken from each group after exposure for 1 week (1 w), 2 weeks (2 w), and 3 weeks (3 w). Superoxide dismutase (SOD) and catalase (CAT) activities as well as glutathione (GSH) and malonyldialdehyde (MDA) contents in the homogenate of kidney tissue were analyzed. The results demonstrated that a short time of low dose of cadmium could stimulate the increase of SOD activity in the kidney of turtles, but a long time of high dose of cadmium could induce the decrease of SOD activity in the kidney of turtles. Cadmium could decrease CAT activity and GSH content in turtle kidney, but increased MDA content in turtle kidney. There were some other effects on the turtles, such as depression and diarrhea. The experimental results indicate that cadmium causes temporary oxidative stress on the kidney of turtles.

Astragaloside IV Attenuates Lipopolysaccharides-Induced Pulmonary Epithelial Cell Injury through Inhibiting Autophagy.

BACKGROUND: Astragaloside IV has shown its promising effect on acute respiratory distress syndrome (ARDS). OBJECTIVES: We aim to explore whether astragaloside IV is effective for ARDS treatment in a lipopolysaccharides (LPS)-induced cell model and whether autophagy is involved in the therapeutic function of astragaloside IV. METHODS: MLE-12 cells were induced by LPS to construct an ARDS model in vitro. Cell viability was estimated by cell counting kit-8 and cell apoptosis by flow cytometry. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by enzyme-linked immunosorbent assay kit. The expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, zonula occludens (ZO)-1, Beclin-1 and autophagy-related (atg) 5 mRNA was evaluated by quantitative PCR, and the expression of ZO-1, microtubule-associated proteins 1A/1B light chain 3B (LC3B) I and, LC3B II protein by Western blot. RESULTS: LPS effectively inhibited cell viability and LC3B I expression and enhanced LC3B II, Beclin-1 and atg5 expressions in MLE-12 cells. In LPS-induced ARDS cell model, astragaloside IV up-regulated cell viability, SOD activity and ZO-1 and LC3B I expressions but down-regulated cell apoptosis, TNF-α, IL-6, LC3B II, Beclin-1 and atg5 expressions and LDH and MDA levels. 3-methyladenine promoted cell viability and ZO-1 expression, down-regulated Beclin-1 and atg5 expression, while Rapamycin (Rap) had an opposite effect. Astragaloside IV suppressed cell viability and ZO-1 expression after the Rap treatment. CONCLUSIONS: Astragaloside IV might suppress autophagy initiation directly or indirectly through suppressing the oxidative stress and inflammatory response, which further enhances the cell viability and tight junction and reduces apoptosis in LPS-stimulated pulmonary endothelial ARDS cell model, thus exerting its therapeutic function in ARDS.

Triptolide, A Potential Autophagy Modulator.

As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic process involved in cytoplasmic materials degradation. Autophagic dysfunction contributes to the pathologies of many human diseases, which makes it a promising therapeutic target. Recent studies have shown that triptolide exerts neuroprotection, anti-tumor activities, organ toxicity, and podocyte protection by modulating autophagy. This article highlights the current information on triptolide-modulated autophagy, analyzes the possible pathways involved, and describes the crosstalk between autophagy and apoptosis modulated by triptolide, in hope of providing implications for the roles of autophagy in pharmacological effects of triptolide and expanding its novel usage as an autophagy modulator.

Wuzi Yanzong pill, a Chinese polyherbal formula, alleviates testicular damage in mice induced by ionizing radiation.

BACKGROUND: Chinese medicine Wuzi Yanzong pill (WZYZP) was firstly documented in ancient Chinese medical works "She Sheng Zhong Miao Fang" by Shi-Che Zhang in 1550 AD. The traditional herbal formula is widely used in treating nephrasthenia lumbago, prospermia, erectile dysfunction and male sterility. The present study was to explore the effects of WZYZP on ionizing irradiation-induced testicular damage in mice. METHODS: The pelvic region of male mice was exposed to X-rays for inducing testicular damage. The effects of WZYZP on testicular damage were evaluated in terms of testes weight, sperm quantity and motility, testes oxidative status and serum hormone levels. The alterations in testicular structure were examined by hematoxylin-eosin staining. Additionally, changes in proliferating cell nuclear antigen (PCNA) expression of testes were explored by western blot. RESULTS: Pelvic exposure to x-ray induced reduction in testes weight and sperm quality, along with oxidative stress and abnormal testicular architecture in testes. Oral administration of WZYZP for 3 weeks markedly increased testes weight, sperm quantity and motility, and attenuated testicular architecture damage. Meanwhile, WZYZP treatment significantly reversed the reduction of serum testosterone, and decreased testes malondialdehyde (MDA) and Oxidative stress index (OSI) relative to the radiated mice. Additionally, WZYZP effectively prevented the downregulation of PCNA expression in testes induced by x-ray irradiation. CONCLUSION: These findings suggest WZYZP exhibits ameliorating effects against ionizing irradiation-induced testicular damage in mice, which may be related to its antioxidation.

GS/DBM/PLA porous composite biomaterial for the treatment of infective femoral condyle defect in rats.

A bone defect resulting from open bone trauma may easily become infected; however, the administration of efficacious systemic antibiotics cannot be performed at safe levels. Previous studies have investigated anti-infective biomaterials that incorporate into bone and facilitate the direct application of high-concentration local antibiotics. In the present study, the effect of a novel porous composite with gentamicin sulfate (GS) in treating infected femoral condyle defects was investigated using a rat model. A novel porous composite biomaterial was prepared based on a supercritical carbon dioxide fluid technique that combined GS, demineralized bone matrix (DBM) and polylactic acid (PLA). A rat femoral condyle fracture model of infection was established. The GS/DBM/PLA composite biomaterial was implanted and its physicochemical characteristics, biocompatibility and ability to facilitate repair of infected bone defect were assessed. The GS/DBM/PLA composite biomaterial maintained the antibiotic activity of GS, with good anti-compression strength, porosity and biocompatibility. The results of the animal experiments indicated that the GS/DBM/PLA composite biomaterial exerted marked anti-infective effects and facilitated bone defect repair, while simultaneously controlling infection. Porous GS/DBM/PLA is therefore a promising composite biomaterial for use in bone tissue engineering.

[The FTIR spectral characteristics and comparison study of Astragalus menbranceus soil].

To study the genuine soil of Astragalus menbranceus grows, FTIR spectrometry was used, which is accurate, simple and efficient and has high resolution. The genuine soils include six areas in Hunyuan of Shanxi province, three areas in Yingxian of Shanxi province, Fansi of Shanxi province, and Guyang of Inner Mongolia. Different growth years of two to five for each area were also studied. The results show that there are significant differences between Astragalus menbranceus soil FTIR spectrometry and general soil's, between soil of Astragalus menbranceus growth and radix codonopsitis growth, between different soil of Astragalus menbranceus growth, providing useful information for the area chose of Chinese herb cultural and transplantation.