Aloe-emodin alleviates cerebral ischemia-reperfusion injury by regulating microglial polarization and pyroptosis through inhibition of NLRP3 inflammasome activation.

BACKGROUND: Microglial activation plays a crucial role in injury and repair after cerebral ischemia, and microglial pyroptosis exacerbates ischemic injury. NOD-like receptor protein 3 (NLRP3) inflammasome activation has an important role in microglial polarization and pyroptosis. Aloe-emodin (AE) is a natural anthraquinone compound originated from rhubarb and aloe. It exerts antioxidative and anti-apoptotic effects during cerebral ischemia/reperfusion (I/R) injury. However, whether AE affects microglial polarization, pyroptosis, and NLRP3 inflammasome activation remains unknown. PURPOSE: This study aimed to explore the effects of AE on microglial polarization, pyroptosis, and NLRP3 inflammasome activation in the cerebral infarction area after I/R. METHODS: The transient middle cerebral artery occlusion (tMCAO) and oxygen-glucose deprivation/re-oxygenation (OGD/R) methods were used to create cerebral I/R models in vivo and in vitro, respectively. Neurological scores and triphenyl tetrazolium chloride and Nissl staining were used to assess the neuroprotective effects of AE. Immunofluorescence staining, quantitative polymerase chain reaction and western blot were applied to detect NLRP3 inflammasome activation and microglial polarization and pyroptosis levels after tMCAO or OGD/R. Cell viability and levels of interleukin (IL)-18 and IL-1ß were measured. Finally, MCC950 (an NLRP3-specific inhibitor) was used to evaluate whether AE affected microglial polarization and pyroptosis by regulating the activation of the NLRP3 inflammasome. RESULTS: AE improved neurological function scores and reduced the infarct area, brain edema rate, and Nissl-positive cell rate following I/R injury. It also showed a protective effect on BV-2 cells after OGD/R. AE inhibited microglial pyroptosis and induced M1 to M2 phenotype transformation and suppressed microglial NLRP3 inflammasome activation after tMCAO or OGD/R. The combined administration of AE and MCC950 had a synergistic effect on the inhibition of tMCAO- or OGD/R-induced NLRP3 inflammasome activation, which subsequently suppressed microglial pyroptosis and induced microglial phenotype transformation. CONCLUSION: AE exerts neuroprotective effects by regulating microglial polarization and pyroptosis through the inhibition of NLRP3 inflammasome activation after tMCAO or OGD/R. These findings provide new evidence of the molecular mechanisms underlying the neuroprotective effects of AE and may support the exploration of novel therapeutic strategies for cerebral ischemia.

Biotransformation of Bioactive Metabolites in Cassiae Semen by Endogenous Enzymes and Probiotics.

The present study evaluated the potential of endogenous enzymes and probiotics in transforming bioactive metabolites to reduce the purgative effect and improve the functional activity of Cassiae Semen and verified and revealed the biotransformation effect of endogenous enzymes. Although probiotics, especially Lactobacillus rhamnosus, exerted the transformation effect, the endogenous enzymes proved to be more effective in transforming the components of Cassiae Semen. After biotransformation by endogenous enzymes for 12 h, the levels of six anthraquinones in Cassiae Semen increased by at least 2.98-fold, and free anthraquinones, total phenolics, and antioxidant activity also showed significant improvement, accompanied by an 82.2% reduction in combined anthraquinones responsible for the purgative effect of Cassiae Semen. Further metabolomic analysis revealed that the biotransformation effect of endogenous enzymes on the bioactive metabolites of Cassiae Semen was complex and diverse, and the biotransformation of quinones and flavonoids was particularly prominent and occurred by three primary mechanisms, hydrolyzation, methylation, and dimerization, might under the action of glycosyl hydrolases, SAM-dependent methyltransferases, and CYP450s. Accordingly, biotransformation by endogenous enzymes emerges as a mild, economical, food safety risk-free, and effective strategy to modify Cassiae Semen into an excellent functional food.

The effect and mechanism of novel methoxy curcumin analogs based on network pharmacology.

In this study, a series of novel compounds were synthesized by introducing the 3,4,5-trimethoxyphenyl and isatin groups into the monocarbonyl skeleton of curcumin. The possible biological activities and potential targets for these compounds were explored through network pharmacology. The results revealed that these compounds could significantly inhibit production of the inflammatory factors IL-6 and TNF-α, and suppress phosphorylation of the extracellular signal-regulated kinase (ERK) protein. Moreover, molecular docking experiments showed that the ERK protein was the potential target for these compounds. In summary, this study, through network pharmacology, presents a novel series of methoxy curcumin analogs as potent anti-inflammatory drugs.

Investigation of anti-depression effects and potential mechanisms of the ethyl acetate extract of Cynomorium songaricum Rupr. through the integration of in vivo experiments, LC-MS/MS chemical analysis, and a systems biology approach.

Background: Cynomorium songaricum Rupr. has long been used as an anti-inflammatory, antidepressant, and anti-aging agent in traditional Chinese medicine in Asia. Its ethyl acetate extract (ECS) has been identified as the main antioxidant component with neuroprotective and estrogen-like effects. However, the potential of ECS in treating depression has not been explored yet. Methods: We identified the primary metabolites in ECS in this study using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Network analysis was used to find the potential targets and pathways associated with the anti-neuroinflammatory depression action of the ECS. In addition, we established a corticosterone (CORT)-induced depression mouse model to assess ECS's antidepressant effects by monitoring various behavioral changes (e.g., sucrose preference, forced swimming, tail suspension, and open field tests) and biochemical indices of the hippocampus, and validating the network analysis results. Significant pathways underwent verification through western blotting based on network analysis prediction. Results: Our study demonstrates that ECS possesses significant antidepressant activity. The LC-MS/MS analysis of ECS identified 30 main metabolites, including phloridzin, phlorizin, ursolic acid, and naringenin, as well as other flavonoids, terpenoids, and phenolic acids. These metabolites were found to be associated with 64 candidate target proteins related to neuroinflammatory depression from the database, and ten hub proteins were identified through filtration: CXCL8, ICAM1, NOS2, SELP, TNF, IL6, APP, ACHE, MAOA and ADA. Functional enrichment analyses of the candidate targets revealed their primary roles in regulating cytokine production, inflammatory response, cytokine activity, and tumor necrosis factor receptor binding. In vivo, ECS improved hippocampal neuroinflammation in the mouse model. Specifically, ECS reduced the expression of inflammatory factors in the hippocampus, inhibited M1 microglial cell polarization, and alleviated depression through the regulation of the NF-κB-NLRP3 inflammation pathway. Conclusion: Based on experimental and network analysis, this study revealed for the first time that ECS exerted antidepression effect via anti-neuroinflammation. Our research provides valuable information on the use of ECS as an alternative therapeutic approach for depression.

Exploring the mechanism of ellagic acid against gastric cancer based on bioinformatics analysis and network pharmacology.

Ellagic acid (EA) is a natural polyphenolic compound. Recent studies have shown that EA has potential anticancer properties against gastric cancer (GC). This study aims to reveal the potential targets and mechanisms of EA against GC. This study adopted methods of bioinformatics analysis and network pharmacology, including the weighted gene co-expression network analysis (WGCNA), construction of protein-protein interaction (PPI) network, receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival curve analysis, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics simulations (MDS). A total of 540 EA targets were obtained. Through WGCNA, we obtained a total of 2914 GC clinical module genes, combined with the disease database for screening, a total of 606 GC-related targets and 79 intersection targets of EA and GC were obtained by constructing Venn diagram. PPI network was constructed to identify 14 core candidate targets; TP53, JUN, CASP3, HSP90AA1, VEGFA, HRAS, CDH1, MAPK3, CDKN1A, SRC, CYCS, BCL2L1 and CDK4 were identified as the key targets of EA regulation of GC by ROC and KM curve analysis. The enrichment analysis of GO and KEGG pathways of key targets was performed, and they were mainly enriched in p53 signalling pathway, PI3K-Akt signalling pathway. The results of molecular docking and MDS showed that EA could effectively bind to 13 key targets to form stable protein-ligand complexes. This study revealed the key targets and molecular mechanisms of EA against GC and provided a theoretical basis for further study of the pharmacological mechanism of EA against GC.

A new risk predictive scoring system of vasovagal reactions in patients with preoperative autologous blood donation.

BACKGROUND AND OBJECTIVES: Vasovagal response (VVR) is the most common adverse reaction during blood donation and it is the main element for the safety of the patients with preoperative autologous blood donation (PABD). Accurate identification high-risk group is of great significance for PABD. Our study aimed to establish a scoring system based on the nomogram to screen the high-risk population and provide evidence for preventing the occurrence of VVRs. MATERIALS AND METHODS: A number of 4829 patients underwent PABD between July 2017 and June 2020 in the first medical center of Chinese PLA Hospital were recruited, 3387 of whom were included in the training group (70 %; 108 VVRs patients vs 3279 Non-VVRs patients), 1442 were included in the validation group (30 %; 46 VVRs patients vs 1396 Non-VVRs patients). The data were analyzed by univariate and multivariate logistic regression. The nomogram of the scoring system was created by using the RMS tool in R software. RESULTS: Seven variables including BMI, hematocrit, pre-phlebotomy heart rate and systolic blood pressure, history of blood donation, age group and primary disease were selected to build the nomogram, which was shown as prediction model. And the score was 0-1 for BMI, 0-2 for hematocrit, systolic blood pressure, heart rate and no blood donation history, 0-10 for age, 0-3 for primary disease. When the total cutoff score was 11, the predictive system for identifying VVRs displayed higher diagnostic accuracy. The area under the curve, specificity, and sensitivity of the training group were 0.942, 82.41 % and 97.17 %, respectively, whereas those of the validation group were 0.836, 78.26 % and 78.15 %, respectively. CONCLUSION: A risk predictive scoring system was successfully developed to identify high-risk VVRs group form PABD patients that performed well.

The Ka /Ks and πa /πs Ratios under Different Models of Gametophytic and Sporophytic Selection.

Alternation of generations in plant life cycle provides a biological basis for natural selection occurring in either the gametophyte or the sporophyte phase or in both. Divergent biphasic selection could yield distinct evolutionary rates for phase-specific or pleiotropic genes. Here, we analyze models that deal with antagonistic and synergistic selection between alternative generations in terms of the ratio of nonsynonymous to synonymous divergence (Ka/Ks). Effects of biphasic selection are opposite under antagonistic selection but cumulative under synergistic selection for pleiotropic genes. Under the additive and comparable strengths of biphasic allelic selection, the absolute Ka/Ks for the gametophyte gene is equal to in outcrossing but smaller than, in a mixed mating system, that for the sporophyte gene under antagonistic selection. The same pattern is predicted for Ka/Ks under synergistic selection. Selfing reduces efficacy of gametophytic selection. Other processes, including pollen and seed flow and genetic drift, reduce selection efficacy. The polymorphism (πa) at a nonsynonymous site is affected by the joint effects of selfing with gametophytic or sporophytic selection. Likewise, the ratio of nonsynonymous to synonymous polymorphism (πa/πs) is also affected by the same joint effects. Gene flow and genetic drift have opposite effects on πa or πa/πs in interacting with gametophytic and sporophytic selection. We discuss implications of this theory for detecting natural selection in terms of Ka/Ks and for interpreting the evolutionary divergence among gametophyte-specific, sporophyte-specific, and pleiotropic genes.

Exploring the Potential Mechanism of Action of Ursolic Acid against Gastric Cancer and COVID-19 using Network Pharmacology and Bioinformatics Analysis.

BACKGROUND: Patients with gastric cancer (GC) are more likely to be infected with 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the prognosis is worse. It is urgent to find effective treatment methods. OBJECTIVE: This study aimed to explore the potential targets and mechanism of ursolic acid (UA) on GC and COVID-19 by network pharmacology and bioinformatics analysis. METHODS: The online public database and weighted co-expression gene network analysis (WGCNA) were used to screen the clinical related targets of GC. COVID-19-related targets were retrieved from online public databases. Then, a clinicopathological analysis was performed on GC and COVID-19 intersection genes. Following that, the related targets of UA and the intersection targets of UA and GC/COVID-19 were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome Analysis (KEGG) pathway enrichment analyses were performed on the intersection targets. Core targets were screened using a constructed protein-protein interaction network. Finally, molecular docking and molecular dynamics simulation (MDS) of UA and core targets were performed to verify the accuracy of the prediction results. RESULTS: A total of 347 GC/COVID-19-related genes were obtained. The clinical features of GC/COVID-19 patients were revealed using clinicopathological analysis. Three potential biomarkers (TRIM25, CD59, MAPK14) associated with the clinical prognosis of GC/COVID-19 were identified. A total of 32 intersection targets of UA and GC/COVID-19 were obtained. The intersection targets were primarily enriched in FoxO, PI3K/Akt, and ErbB signaling pathways. HSP90AA1, CTNNB1, MTOR, SIRT1, MAPK1, MAPK14, PARP1, MAP2K1, HSPA8, EZH2, PTPN11, and CDK2 were identified as core targets. Molecular docking revealed that UA strongly binds to its core targets. The MDS results revealed that UA stabilizes the protein-ligand complexes of PARP1, MAPK14, and ACE2. CONCLUSION: This study found that in patients with gastric cancer and COVID-19, UA may bind to ACE2, regulate core targets such as PARP1 and MAPK14, and the PI3K/Akt signaling pathway, and participate in antiinflammatory, anti-oxidation, anti-virus, and immune regulation to exert therapeutic effects.

The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis.

BACKGROUND: Dehydroandrographolide (Deh) from Andrographis paniculata (Burm.f.) Wall has strong anti-inflammatory and antioxidant activities. PURPOSE: To explore the role of Deh in acute lung injury (ALI) of coronavirus disease 19 (COVID-19) and its inflammatory molecular mechanism. METHODS: Liposaccharide (LPS) was injected into a C57BL/6 mouse model of ALI, and LPS + adenosine triphosphate (ATP) was used to stimulate BMDMs in an in vitro model of ALI. RESULTS: In an in vivo and in vitro model of ALI, Deh considerably reduced inflammation and oxidative stress by inhibiting NLRP3-mediated pyroptosis and attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis through the suppression of ROS production by inhibiting the Akt/Nrf2 pathway. Deh inhibited the interaction between Akt at T308 and PDPK1 at S549 to promote Akt protein phosphorylation. Deh directly targeted PDPK1 protein and accelerated PDPK1 ubiquitination. 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP and 223-ASP may be the reason for the interaction between PDPK1 and Deh. CONCLUSION: Deh from Andrographis paniculata (Burm.f.) Wall presented NLRP3-mediated pyroptosis in a model of ALI through ROS-induced mitochondrial damage through inhibition of the Akt/Nrf2 pathway by PDPK1 ubiquitination. Therefore, it can be concluded that Deh may be a potential therapeutic drug for the treatment of ALI in COVID-19 or other respiratory diseases.

Relationship between vitamin D status and cardiac autonomic neuropathy in prediabetes.

BACKGROUND AND OBJECTIVES: Studies have suggested that vitamin D deficiency is associated with impaired cardiac autonomic nerve function. This study explores the correlation between serum vitamin D and cardiac autonomic neuropathy (CAN) in prediabetes and reveals the protective effect of vitamin D against CAN. METHODS AND STUDY DESIGN: In total, 113 patients with prediabetes and definite CAN and 180 with prediabetes but without CAN were enrolled on the basis of their standard cardiovascular autonomic reflex test results. Chemiluminescence was used to measure 25(OH)D, the patients with CAN were divided into four groups, and the heart rate variability (HRV) of the study groups were compared. RESULTS: Relative to the 50≤25(OH)D<75-nmol/L group, the 25≤25(OH)D<50-nmol/L and 25(OH)D<25-nmol/L groups exhibited significant differences in the time and frequency domains of HRV (p< 0.05). Furthermore, we discovered that 25(OH)D is positively correlated with standard deviation of normal-to-normal RR intervals (SDNN) (ß=0.566, p<0.05) and negatively correlated with low-to-high frequency ratio (LF/HF) (ß=-0.199, p<0.05). A logistic regression reveals that CAN in prediabetes is significantly correlated with the 25(OH)D concentrations of <25 nmol/L (OR, 2.380 [1.208-4.691]; p<0.05) and 25≤25(OH)D<50 nmol/L (OR, 1.875 [1.064-3.751]; p<0.05). CONCLUSIONS: Serum 25(OH)D is significantly correlated with CAN in prediabetes, especially in the 25(OH)D <25-nmol/L group. Therefore, vitamin D deficiency may be related to the occurrence of CAN in prediabetes, and appropriate supplementation may provide protection against CAN.

Effects on neuromodulation, acupuncture, and aerobic exercises on migraine and tension-type headache outcomes: A systematic review and meta-analysis.

BACKGROUND: Headache disorders are common diseases that cause a social burden. This systematic review and meta-analysis aimed to evaluate the effects of various non-pharmacological treatments to address or prevent acute headaches, including neuromodulation, acupuncture, and aerobic exercises in patients with episodic migraine and tension-type headache (TTH). METHODS: We performed a systematic search of the electronic databases PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, WANFANG MEDICINE ONLINE, and Chinese Medical Journal database using Stata/SE 14.0 to obtain weighted mean differences (WMDs). The outcomes included monthly headache days, headache intensity, headache duration, days per month of acute medication use, and the Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Of 872 identified articles, 27 were included in the meta-analysis. Neuromodulation was associated with reduced headache days (WMD: -1.274, 95% CI [-1.914, -0.634], P < .001), duration (WMD: -2.2, 95% CI [-3.32, -0.107], P < .001) and medication consumption (WMD: -1.808, 95% CI [-2.546, -1.071], P < .001) in cases of migraine. Acupuncture was associated with the alleviation of headache days (WMD: -0.677, 95% CI [-0.932, -0.422], P < .001) and intensity (WMD: -0.893, 95% CI [-1.573, -0.212], P = .01) in cases of migraine and acute medication use (WMD: -3.29, 95% CI [-4.86, -1.72], P < .001) in cases of TTH. Aerobic exercise was associated with reduced headache duration (WMD: -5.1, 95% CI [-8.97, -1.22], P = .01) in cases of TTH. The risk of bias for included articles was moderate. CONCLUSIONS: There is low- and moderate-quality evidence that neuromodulation, acupuncture, and aerobic exercises are associated with attenuated headache symptoms in patients with episodic migraine or TTH. However, high-quality studies are needed to draw more detailed conclusions.

[Soil nematode community characteristics of alfalfa field with different growing ages in the semi-arid Loess Plateau of Central Gansu, Northwest China]. / 陇中黄土高原半干旱区不同种植年限紫花苜蓿土壤线虫群落分布特征.

To clarify the impacts of long-term alfalfa plantation on the soil nematode community, soil samples were collected from different alfalfa growing ages (2 a, 9 a, 18 a) in the semi-arid area of Loess Plateau in Central Gansu by Illumina Miseq sequencing technology. The main controlling factors affecting its community change were also explored. The results showed that soil nematode belongs to 2 classes, 7 orders, 16 families and 21 genera. Among them, Chromadorea was the dominant group (44.6%-81.4%), the relative abundance of which decreased with alfalfa growing ages. Paratylenchus, Helicotylenchus, Xiphinema, Pristionchus, Ditylenchus, Panagrolaimus, Longidorus, Aprutides, Isolaimium and Aglenchus were the special nematode species of alfalfa, among which Paratylenchus (54.1%), Helicotylenchus (23.9%) and Xiphinema (21.9%) were the dominant nematodes in 2 a, 9 a and 18 a alfalfa soil respectively. Plant-parasitic nematode was the dominant group in alfalfa soil (31.8%-67.1%), and its relative abundance decreased at first and then increased with alfalfa growing ages. Results of redundancy analysis showed that soil available phosphorus and total nitrogen were the dominant environmental factors affecting community structure of soil nematodes in the region.

Knowledge domain and emerging trends in diabetic cardiomyopathy: A scientometric review based on CiteSpace analysis.

Objective: To review the literature related to diabetic cardiomyopathy (DCM), and investigate research hotspots and development trends of this field in the relevant studies based on CiteSpace software of text mining and visualization in scientific literature. Methods: The relevant literature from the last 20 years was retrieved from the Web of Science (WoS) Core Collection database. After manual selection, each document record includes title, authors, year, organization, abstract, keywords, citation, descriptors, and identifiers. We imported the downloaded data into CiteSpace V (version 5.8.R2) to draw the knowledge map and conduct cooperative network analysis, cluster analysis, burst keyword analysis, and co-citation analysis. Results: After manual screening, there were 3,547 relevant pieces of literature published in the last 18 years (from 2004 to 2021), including 2,935 articles and reviews, which contained 15,533 references, and the number was increasing year by year. The publications of DCM were dedicated by 778 authors of 512 institutions in 116 countries. The People's Republic of China dominated this field (1,117), followed by the USA (768) and Canada (176). In general, most articles were published with a focus on "oxidative stress," "heart failure," "diabetic cardiomyopathy," "dysfunction," "cardiomyopathy," "expression," "heart," "mechanism," and "insulin resistance." Then, 10 main clusters were generated with a modularity Q of 0.6442 and a weighted mean silhouette of 0.8325 by the log-likelihood ratio (LLR) algorithm, including #0 heart failure, #1 perfused heart, #2 metabolic disease, #3 protective effect, #4 diabetic patient, #5 cardiac fibrosis, #6 vascular complication, #7 mitochondrial dynamics, #8 sarcoplasmic reticulum, and #9 zinc supplementation. The top five references with the strongest citation bursts include "Boudina and Abel", "Jia et al.", "Fang et al.", "Poornima et al.", and "Aneja et al.". Conclusion: The global field of DCM has expanded in the last 20 years. The People's Republic of China contributes the most. However, there is little cooperation among authors and institutions. Overall, this bibliometric study identified the hotspots in DCM research, including "stress state," "energy metabolism," "autophagy," "apoptosis," "inflammation," "fibrosis," "PPAR," etc. Thus, further research focuses on these topics that may be more helpful to identify, prevent DCM and improve prophylaxis strategies to bring benefit to patients in the near future.

Molecular mechanisms of Biyu decoction as treatment for psoriasis: A network pharmacology and molecular docking study.

BACKGROUND: The therapeutic effects of a combination of Chinese medicines called Biyu decoction have been clinically verified, although its molecular targets in psoriasis remain unknown. AIM: To explore the molecular mechanisms of Biyu decoction for psoriasis treatment. METHODS: In this network pharmacology and molecular docking study, the Traditional Chinese Medicine Systems Pharmacology database was searched for Biyu decoction active ingredients. GeneCards, Online Mendelian Inheritance in Man, PharmGkb, Therapeutic Target Database, and DrugBank databases were searched for psoriasis-related genes. The genes targeted by the decoction's active ingredient and disease genes were intersected to obtain predictive targets of the drug during psoriasis treatment. Cytoscape 3.8.0 was used to construct a drug component/ target disease network. The The functional protein association networks database and Cytoscape were used to construct a protein-protein interaction network and streamline the core network. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for pathway enrichment analysis. Molecular docking technology was used to verify the drug component/target disease network. RESULTS: We screened 117 major active ingredients, including quercetin, kaempferol, naringenin, and acetyl-shikonin, and identified 213 gene targets, such as MAPK3, JUN, FOS, MYC, MAPK8, STAT3, and NFKBIA. Using a molecular docking analysis, the main active ingredients demonstrated good binding to the core targets. The Gene Ontology analysis showed that these ingredients were significantly associated with biological activities, such as transcription factor DNA binding, RNA polymerase II-specific DNA binding of transcription factors, and cytokine receptor binding; responses to lipopolysaccharides, molecules of bacterial origin, and oxidative stress; and were mainly distributed in membrane rafts, microdomains, and regions. The Kyoto Encyclopedia of Genes and Genomes analysis showed that decoction ingredients act on Th17 cell differentiation, tumor necrosis factor and mitogen-activated protein signaling pathways, the interleukin-17 signaling pathway, and the PI3K-Akt signaling pathway. CONCLUSION: Biyu decoction may be effective against psoriasis through multi-component, multi-target, and multi-channel synergy.

Loureirin A Exerts Antikeloid Activity by Antagonizing the TGF-ß1/Smad Signalling Pathway.

It has been recently shown that loureirin A (LA), a major active component of resina draconis, might be effective in the prevention and treatment of liver fibrosis. We examined whether LA could inhibit the formation of keloids. To investigate the pharmacological effects of loureirin A on keloid formation and the underlying mechanisms. CellTiter-Blue viability assays were used to examine the proliferation of keloid fibroblasts (KFs) that were treated with LA. Fibroblast migration was evaluated using a cell migration assay. Immunofluorescence staining was used to measure the expression of α-SMA in KFs. RT-qPCR was used to evaluate the mRNA expression of Col-I, Col-III, α-SMA, Bax, and Caspase-3, while Western blotting was used to evaluate the protein expression of Col-I, Col-III, α-SMA, Bax, Caspase-3, p-Smad2, and p-Smad3. LA inhibited the proliferation of KFs and suppressed the migration and TGF-ß1-induced myofibroblast differentiation of KFs. In addition, LA downregulated the mRNA and protein levels of Col-I, Col-III, and α-SMA while promoting the mRNA and protein levels of Bax and Caspase-3. Moreover, LA downregulated the protein levels of p-Smad2 and p-Smad3 in cultured TGF-ß1-treated KFs ex vivo. These results show that LA has an antikeloid effect on KFs by suppressing the TGF-ß1/Smad signalling pathway. Our findings suggest that LA may be a potential candidate drug for the prevention and treatment of keloids.

[Screening and identification of a Burkholderia strain and optimization of its phosphate solubilizing capacity]. / ä¸€æ ªä¼¯å ‹éœå°”å¾·èŒçš„ç­›é€‰é‰´å®šåŠæº¶ç£·æ€§èƒ½ä¼˜åŒ–.

In order to solve the problem that soil soluble phosphorus content in most cultivated land in China is insufficient and the plant growth is inhibited, a phosphate solubilizing microorganism (PB) was screened and identified, and its phosphate solubilizing performance was optimized. The results showed that the PB strain was belonged to Burkholderia stabilis. It had the ability of nitrogen fixation and indole-3-acetic acid (IAA) secretion, as well as a certain inhibitory effect on Escherichia coli. It could maintain high activity and phosphorus solubilizing ability at pH 8.0-10.0, indicating good alkali resistance. The results of phosphorus dissolving performance optimization showed that the phosphate solubilizing capacity of strain PB reached the best at 30℃, pH 7.0, 180 r·min-1, using glucose as carbon source, ammonium sulfate as nitrogen source, tricalcium phosphate as phosphorus source and adding 50 µmol·L-1 lysine. The amount of dissolved phosphorus was 569.33 mg·L-1, which was 1.9 times of that before optimization. The strain mainly secreted citric acid, malonic acid, and glucuronic acid during metabolism. After adding lysine, the type of organic acids secreted by the strain did not change, but the content increased significantly. Results from pot experiments showed that the application of PB bacterial fertilizer could significantly improve the growth and physiological indicators of garlic seedlings, and that the promotion effect was more obvious after adding lysine. Compared with the control, the height of seedling was increased by 18.6%, seedling diameter was increased by 16.7%, aboveground fresh and dry weight were increased by 22.1% and 15.7%, and belowground fresh and dry weight were increased by 22.0% and 28.7%, respectively in PB with lysine treatment. Soil available phosphorus content was 2.1 and 2.3 times of the control in PB and PB+lysine treatments, indicating that PB could improve soil available phosphate content. Adding lysine could strengthen such function.

Characterization, expression, and functional analysis of the pathogenesis-related gene PtDIR11 in transgenic poplar.

Lignins and lignans are important for plant resistance to pathogens. Dirigent (DIR) proteins control the regio- and stereo-selectivity of coniferyl alcohol in lignan and lignin biosynthesis. DIR genes have been implicated in defense-related responses in several plant species, but their role in poplar immunity is unclear. We cloned PtDIR11 from Populus trichocarpa; we found that overexpression of PtDIR11 in poplar improved the lignan biosynthesis and enhanced the resistance of poplar to Septotis populiperda. PtDIR11 has a typical DIR domain; it belongs to the DIR-b/d family and is expressed in the cell membrane. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis showed that PtDIR11 expression was highest in stems, followed by leaves and roots. Furthermore, PtDIR11 expression was induced by S. populiperda, salicylic acid (SA), jasmonate (JA), and ethylene (ET) stresses. The recombinant PtDIR11 protein inhibited the growth of S. populiperda in vitro. Overexpressing (OE) PtDIR11 in "Nanlin 895" poplar enhanced growth. The OE lines exhibited minimal changes in lignin content, but their total lignan and flavonoid contents were significantly greater than in the wild-type (WT) lines. Overexpression of PtDIR11 affected multiple biological pathways of poplar, such as phenylpropanoid biosynthesis. The methanol extracts of OE-PtDIR11 lines showed greater anti-S. populiperda activity than did lignin extracts from the WT lines. Furthermore, OE-PtDIR11 lines upregulated genes that were related to phenylpropanoid biosynthesis and genes associated with the JA and ET signal transduction pathways; it downregulated genes that were related to SA signal transduction compared with the WT line under S. populiperda stress. Therefore, the OE transgenic plants analysis revealed that PtDIR11 is a good candidate gene for breeding of disease resistant poplar.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes.

OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes

SUMMARY OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Cerebral perfusion mediated by thalamo-cortical functional connectivity in non-dominant thalamus affects naming ability in aphasia.

Naming is a commonly impaired language domain in various types of aphasia. Emerging evidence supports the cortico-subcortical circuitry subserving naming processing, although neurovascular regulation of the non-dominant thalamic and basal ganglia subregions underlying post-stroke naming difficulty remains unclear. Data from 25 subacute stroke patients and 26 age-, sex-, and education-matched healthy volunteers were analyzed. Region-of-interest-wise functional connectivity (FC) was calculated to measure the strength of cortico-subcortical connections. Cerebral blood flow (CBF) was determined to reflect perfusion levels. Correlation and mediation analyses were performed to identify the relationship between cortico-subcortical connectivity, regional cerebral perfusion, and naming performance. We observed increased right-hemispheric subcortical connectivity in patients. FC between the right posterior superior temporal sulcus (pSTS) and lateral/medial prefrontal thalamus (lPFtha/mPFtha) exhibited significantly negative correlations with total naming score. Trend-level increased CBF in subcortical nuclei, including that in the right lPFtha, and significant negative correlations between naming and regional perfusion of the right lPFtha were observed. The relationship between CBF in the right lPFtha and naming was fully mediated by the lPFtha-pSTS connectivity in the non-dominant hemisphere. Our findings suggest that perfusion changes in the right thalamic subregions affect naming performance through thalamo-cortical circuits in post-stroke aphasia. This study highlights the neurovascular pathophysiology of the non-dominant hemisphere and demonstrates thalamic involvement in naming after stroke.