Harnessing cGAS-STING axis for therapeutic benefits in systemic lupus erythematosus.

The cyclic GMP-AMP synthase (cGAS), a prominent intracellular DNA sensor in mammalian cells, controls the innate immune response and the stimulator of interferon genes (STING)-mediated synthesis of pro-inflammatory cytokines, such as type-I interferon (IFN-I). For decades, IFN-I has been hypothesized to be essential in the development of systemic lupus erythematosus (SLE), a chronic multisystem autoimmunity characterized by immune complex (IC) deposition in small vessels. Recent findings revealed that the activation of the cGAS-STING pathway by self-DNA would propagate the autoimmune responses via upregulating IFN-I production in SLE. In this review, we aimed to provide a comprehensive outlook of the role of the cGAS-STING pathway in SLE pathobiology, as well as, a better understanding of current therapeutic opportunities targeting this axis.

Study on the dynamic response and roadways stability during mining under the disturbance of hard roof break.

Under the condition that the working face was directly covered with hard roof, the abrupt breaking of hard roof release significant amount of energy, thus prone to triggering dynamic disasters such as roadway instability or rockburst. This paper based on the engineering background of the Xieqiao Coal Mine's 11,618 working face, a numerical simulation method was put forward to study the dynamic response of roadway under the disturbance of hard roof breaking and proposed an evaluation index IC for roadway stability. Research indicates that the elastic energy released during the periodic weighting of the hard roof is higher than that released during the first weighting. Under the dynamic disturbance caused by hard roof breaking, the peak stresses of the roadway was slight decreased, accompanied by a significant increase in the range of stress concentration and plastic zone expansion. Roadway deformation patterns are significantly influenced by hard roof breaking, with noticeable increases in deformation on the roof and right side. During the period of hard roof breaking, the possibility of instability of the roadway increase significantly due to the disturbance caused by the dynamic load. The research results reveal the instability mechanism of roadway under the condition of hard roof, and provide a more reliable basis for evaluating the stability of roadway.

Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives.

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Fossil and Nonfossil Sources of Winter Organic Aerosols in the Regional Background Atmosphere of China.

Carbonaceous aerosols (CA) from anthropogenic emissions have been significantly reduced in urban China in recent years. However, the relative contributions of fossil and nonfossil sources to CA in rural and background regions of China remain unclear. In this study, the sources of different carbonaceous fractions in fine aerosols (PM2.5) from five background sites of the China Meteorological Administration Atmosphere Watch Network during the winter of 2019 and 2020 were quantified using radiocarbon (14C) and organic markers. The results showed that nonfossil sources contributed 44-69% to total carbon at these five background sites. Fossil fuel combustion was the predominant source of elemental carbon at all sites (73 ± 12%). Nonfossil sources dominated organic carbon (OC) in these background regions (61 ± 13%), with biomass burning or biogenic-derived secondary organic carbon (SOC) as the most important contributors. However, the relative fossil fuel source to OC in China (39 ± 13%) still exceeds those at other regional/background sites in Asia, Europe, and the USA. SOC dominated the fossil fuel-derived OC, highlighting the impact of regional transport from anthropogenic sources on background aerosol levels. It is therefore imperative to develop and implement aerosol reduction policies and technologies tailored to both the anthropogenic and biogenic emissions to mitigate the environmental and health risks of aerosol pollution across China.

Prevalence and influencing factors analysis of the polycystic ovary syndrome among female college students in Fuzhou City， Jiangxi Province / 上海预防医学

ObjectiveTo investigate the prevalence of polycystic ovary syndrome （PCOS） among female college students at a university in Fuzhou City， Jiangxi Province， and to facilitate early detection and intervention of PCOS. MethodsUsing a stratified sampling method， a total of 450 female freshmen were randomly selected for PCOS screening. A self-designed questionnaire was used for data collection， covering menstrual status， high androgen signs， lifestyle， dietary habits， and awareness of PCOS. Sample t test and χ2 test were used to compare the basic information and dietary habits between PCOS and non-PCOS cases. The correlation between various indicators and the prevalence of PCOS was analyzed by a logistic regression model. ResultsA total of 12 PCOS cases were identified， with a prevalence rate of 2.99%. PCOS cases exhibited statistically significant differences compared to non-PCOS cases in terms of waist-to-hip ratio， waist circumference， abdominal obesity， the proportion of overweight or obese individuals， and a preference for sweet food （all P<0.05）. Multivariate logistic regression analysis revealed a significant correlation between preference for sweet food and the occurrence of PCOS （OR=4.858， 95%CI=1.199‒19.675，P=0.027）， as well as a significant correlation with PCOS accompanied by abdominal obesity （OR=7.083， 95%CI=0.773‒64.937， P=0.048）. Among the female college students surveyed， 37.90% had never heard of PCOS， 51.62% were only familiar with the name of the disease， and 10.47% had attempted to search for PCOS-related information. ConclusionThe prevalence of PCOS among female college students should not be overlooked and unhealthy dietary habits may be a crucial factor contributing to the occurrence of PCOS during this period. Early screening for PCOS during puberty is crucial.

Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats / 中国药理学通报

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients: a single-centre study / 中国天然药物

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.

Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke / 神经科学通报·英文版

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

Analysis of chemical constituents and components absorbed into plasma of Ardisia crenata based on UPLC-QE-HF-MS/MS / 中国药房

OBJECTIVE To analyze the chemical constituents and components absorbed into plasma of the extract of Ardisia crenata and to elucidate its possible pharmacodynamic material basis. METHODS Overall， 12 rats were randomly assigned to the blank group （n＝6） and A. crenata group （n＝6） by the paired comparison method. The drug was administered once daily in the morning and afternoon for three days. Serum samples were prepared from serum after redosing on 4th day. The UPLC-QE-HF-MS/ MS was used to analyze and identify the chemical constituents in A. crenata extract and serum samples. Compound Discoverer 3.0 was employed for retention time correction， peak identification， and peak extraction. According to the secondary mass spectrometry information， the Thermo mzCloud online and Thermo mzVault local databases， referring to the relevant literature and control quality spectrum information were used to preliminarily identify the chemical constituents and components absorbed into plasma of A. crenata. RESULTS A total of 34 compounds were identified from the extract of A. crenata， mainly coumarins， flavonoids， organic acids， amino acids， including bergenin， quercetin， gallic acid， L-pyroglutamic acid， etc. Besides， 5 components absorbed into plasma were identified from serum samples: L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid. CONCLUSIONS L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid may act as the pharmacodynamic material basis of A. crenata.

Reconstruction and analysis of K-Clip surgery process based on finite element method / 中国胸心血管外科临床杂志

@#Objective     To investigate the effects of different types of tricuspid regurgitation, implantation positions, and device models on the treatment outcomes of K-Clip for tricuspid regurgitation using numerical simulations. Methods     Three-dimensional reconstruction of the heart model was performed based on CT images. Two different regurgitation orifices were obtained by modifying the standard parameterized tricuspid valve leaflets and chordae tendineae. The effects of different K-Clip models at different implantation positions (posterior leaflet midpoint, anterior-posterior commissure, anterior leaflet midpoint, posterior septal commissure) were simulated using commercial explicit dynamics software Ls-Dyna. Conclusion     For the two types of regurgitation in this study, clipping at the posterior leaflet midpoint resulted in a better reduction of the regurgitation orifice (up to 75% reduction in area). Higher clamping forces were required for implantation at the anterior leaflet midpoint and posterior septal commissure, which was unfavorable for the smooth closure of the clipping components. There was no statistical difference in the treatment outcomes between the 18T and 16T K-Clip components, and the 16T component required less clamping force. Therefore, the use of the 16T K-Clip component is recommended.

Transcriptomic Analysis of Wuzi Yanzongwan on Testicular Spermatogenic Function in Semi-castrated Male Mice / 中国实验方剂学杂志

ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice， and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group， model group， testosterone propionate group（0.2 mg·kg-1·d-1， intramuscular injection） and Wuzi Yanzongwan group（1.56 g·kg-1·d-1， intragastric administration） according to body weight， with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function， while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention， hematoxylin-eosin（HE） staining was used to observe the histopathology of testis， enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of serum testosterone（T）， luteinizing hormone（LH） and follicle stimulating hormone（FSH）. The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group， the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened， and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to verify the transcriptome data. Through the annotation analysis of Gene Ontology（GO） and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes（KEGG）， the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group， the testicular tissue of mice in the model group showed spermatogenic injury， contraction and vacuolization of the seminiferous tubules， reduction of spermatogenic cells at all levels， widening of the interstitial space， obstruction of spermatogonial cell development and other morphological abnormalities， and serum T significantly decreased， LH significantly increased（P<0.01）， and FSH elevated but no statistically significant difference， the count and vitality of epididymal sperm significantly decreased（P<0.01）. There were 882 differentially expressed mRNAs in the testicular tissues， of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group， the damage to testicular tissue in the Wuzi Yanzongwan group was reduced， the structure of the seminiferous tubules was intact， vacuolization was reduced， and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased， LH significantly decreased（P<0.01）， and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased（P<0.01）. Moreover， Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice， of which 32 were up-regulated and 127 were down-regulated， and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis， renewal， differentiation， metabolism， apoptosis and signal transduction of spermatogenic cells， and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function， endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice， and its mechanism may be related to the regulation of testicular transcriptional regulatory network， the synthesis of sex hormones in testicular interstitial cells， the function of spermatogenic stem cells， the whole cell cycle process of spermatogenesis， as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.

Anxiolytic effect of antidiabetic metformin is mediated by AMPK activation in mPFC inhibitory neurons.

Diabetic patients receiving the antidiabetic drug metformin have been observed to exhibit a lower prevalence of anxiety disorders, yet the precise mechanism behind this phenomenon is unclear. In our study, we found that anxiety induces a region-specific reduction in AMPK activity in the medial prefrontal cortex (mPFC). Concurrently, transgenic mice with brain-specific AMPK knockout displayed abnormal anxiety-like behaviors. Treatment with metformin or the overexpression of AMPK restored normal AMPK activity in the mPFC and mitigated social stress-induced anxiety-like behaviors. Furthermore, the specific genetic deletion of AMPK in the mPFC not only instigated anxiety in mice but also nullified the anxiolytic effects of metformin. Brain slice recordings revealed that GABAergic excitation and the resulting inhibitory inputs to mPFC pyramidal neurons were selectively diminished in stressed mice. This reduction led to an excitation-inhibition imbalance, which was effectively reversed by metformin treatment or AMPK overexpression. Moreover, the genetic deletion of AMPK in the mPFC resulted in a similar defect in GABAergic inhibitory transmission and a consequent hypo-inhibition of mPFC pyramidal neurons. We also generated a mouse model with AMPK knockout specific to GABAergic neurons. The anxiety-like behaviors in this transgenic mouse demonstrated the unique role of AMPK in the GABAergic system in relation to anxiety. Therefore, our findings suggest that the activation of AMPK in mPFC inhibitory neurons underlies the anxiolytic effects of metformin, highlighting the potential of this primary antidiabetic drug as a therapeutic option for treating anxiety disorders.

Mechanism of Artemisia annua L. in the treatment of acute myocardial infarction: network pharmacology, molecular docking and in vivo validation.

This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein-protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.

Comparison of Biatain Ag and Biatain Alginate Ag dressings on skin graft donor sites: a prospective clinical trial.

OBJECTIVE: The aim of this study was to compare Biatain Ag and Biatain Alginate Ag (both Coloplast, Denmark) as skin graft donor site dressings. METHOD: A single-centre, prospective, randomised clinical study was conducted. In patients who had undergone a skin graft operation, adjacent split-thickness skin graft donor sites were dressed with Biatain Ag and Biatain Alginate Ag, respectively. The primary outcomes were time to re-epithelialisation and pain score after the operation. The secondary outcomes were scar scores of the donor site after the operation, haematoma rates, infection rates, and exudation rates before wound healing. Results were compared using the Wilcoxon test and the Chi-squared test. RESULTS: A total of 16 paired wounds in 16 patients were studied. The donor sites dressed with Biatain Ag needed more time for >90% re-epithelialisation than those dressed with Biatain Alginate Ag. On day 3 postoperatively, the pain scores with Biatain Ag were significantly less severe than those with Biatain Alginate Ag. On days 6, 9 and 12, the pain scores of both dressings did not differ significantly. The scar scores of the donor site dressed with Biatain Ag were significantly worse than those dressed with Biatain Alginate Ag at 6 months. With respect to infection rates, no significant differences were detected between these two groups. However, the exudation rates of the donor site dressed with Biatain Ag were significantly lower than those dressed with Biatain Alginate Ag. CONCLUSION: As skin graft donor site dressings, both Biatain Ag and Biatain Alginate Ag have advantages.

Cervical lymphadenitis caused by Mycobacterium avium in a patient treated with Janus kinase inhibitors.

A woman diagnosed with rheumatoid arthritis and treated with Janus kinase (JAK) inhibitors presented with a gradually enlarging bilateral submandibular lymph nodes swelling that had lasted several weeks. A lymph node biopsy showed epithelioid granulomatous lymphadenitis with caseous necrosis. Mycobacteria grew in acid-fast bacteria culture and were identified as Mycobacterium avium by polymerase chain reaction. The patient was diagnosed with cervical lymphadenitis caused by M. avium. A computed tomography scan showed no evidence of a mass or infection at other sites, including the lungs; therefore, the mass was excised without any antimicrobial treatments. Her neck mass had not recurred at 9 months after the excision. JAK inhibitors have emerged as an important new class of oral therapy for rheumatoid arthritis and other diseases. Physicians should be aware of the relatively rare complications, such as cervical lymphadenitis caused by nontuberculous mycobacteria, when using JAK inhibitors.

[Composition Characteristics and Sources of Non-polar Organic Compounds in PM2.5 in the Background Atmosphere of Yangtze River Delta].

In order to explore the composition and source characteristics of non-polar organic compounds (NPOCs) in atmospheric fine particulate matter in the Yangtze River Delta region, 129 PM2.5 samples were collected at the Regional Atmospheric background station in Lin'an from December 2019 to November 2020. Including polycyclic aromatic hydrocarbons (PAHs), n-alkanes, and hopanes, the main sources of organic aerosols were investigated using molecular tracers, eigen ratios, and orthogonal matrix factorization models. The results showed that the average annual mass concentration of PM2.5 in Lin'an was approximately (32.36±20.44) µg·m-3, and the average annual mass concentration of NPOCs was approximately (59.05±40.39) ng·m-3, showing the seasonal characteristics of being high in winter and low in summer. n-alkanes mainly came from fossil fuels and biomass (grass, wood, etc.) burning, followed by cuticle wax emission from higher plants. PAHs mainly came from the mixed contribution of non-fossil sources such as coal burning motor vehicle emissions and biomass combustion. Hopanes were mainly derived from motor vehicle emissions, which were also affected by coal burning in winter. Backward trajectory cluster analysis and potential source analysis showed that Lin'an was mainly affected by external air mass transport. Combined with the orthogonal matrix-factor decomposition model, NPOCs observed during the sampling period were analyzed, and non-fossil sources such as coal burning sources, transportation emission sources, and biomass combustion were obtained. In winter, transportation sources were the main source, accounting for 59%. In spring and summer, coal burning was the main source, accounting for 58% and 57%, respectively. In autumn, biomass combustion and other non-fossil sources dominated, accounting for 64%.

Pathogenic mechanism and research progress of adipocytokines in endometrial cancer / 中国临床药理学与治疗学

Endometrial carcinoma (EC) is one of the most common gynecologic tumors, and its incidence and mortality are increasing.The prognosis is usually favorable when the disease is diagnosed at an early stage. However, the prognosis for patients with recurrence and metastasis is relatively poor. As one of the risk factors for EC, the complex and widespread oncogenic role of obesity in EC has been validated, then the oncogenic and pro-carcinogenic mechanisms of adipocytokines secreted by adipose tissue in EC have attracted continuous attention. This review highly summarizes and concludes the previous relevant literature on the role of adipocytokines in endometrial cancer and the progress of research，and elucidates the correlation between adipocytokines and the occurrence risk, stage grading, and long-term prognosis of EC, as well as their signaling pathways and mechanisms of action in the development of EC. All this information will likely contribute to the development of novel molecular markers in EC, the discovery of new therapeutic targets, and the study of related targeted drugs, which may in turn break the current dilemma of early screening, early diagnosis, and treatment of recurrent and metastatic patients in EC in the future, resulting in an improvement of the long-term prognosis of patients with EC.

Mechanism of Sophorae tonkinensis radix et rhizome-induced nephrotoxicity in rats based on network toxicology and experimental validation / 中国药理学通报

Aim To investigate the mechanism of Sophorae tonkinensis radix et rhizome (ST) induced nephrotoxicity based on network toxicology and experimental verification. Methods Through network toxicology the target of toxic components of ST was predicted, nephrotoxicity-related target genes were located, the intersection of targets was taken, the STRING platform was imported to map the target protein interactions, MetaScape database was used for GO and KEGG analysis, BioGPS database for screening the key expressed genes in rat nephrotoxicity and the component-target-pathway network was constructed. The mechanism of ST induced nephrotoxicity was verified through animal experiments, and qRT-PCR was applied to detect mRNA expression level of key genes in kidney tissue. Results Twenty toxic components of ST were screened from network toxicology, mainly including matrine, sophoridine, maackiain. A total of 135 targets were involved, and HSP90AA1, SRC, MAPK1, MAPK3, AKT1 were the main targets. A total of 169 related signaling pathways were yielded by KEGG analysis, and the mechanism of nephrotoxicity might be related to cancer pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway. PPARA, RAF1, MAP2K1, SRC, AKT1 and MAPK3 were screened from BioGPS database. The results of animal experiments showed that BUN and SCr level increased (P <0. 01) in rats with high-dose group, and the kidney tissue was significantly damaged. qRT-PCR results indicated that the expression of PPARA, RAF1, MAP2K1, MAPK3 mRNA increased, the expression of AKT1 mRNA decreased in the high-dose group of ST (P <0. 05). Conclusions The mechanism of Sophorae tonkinensis radix et rhizome induced nephrotoxicity is found to be related to the combined action of multiple components, multiple targets and multiple pathways, which also provides a theoretical basis for the in-depth exploration of the toxicology.

Mechanism of Sophora tonkinensis Gagnep regulating leukocyte transendothelial migration pathway in improving acute pharyngitis based on network pharmacology / 中国药理学通报

Aim To elucidate the molecular mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis based on network pharmacology, animal experiments and quantitative real-time PCR.Methods The active components and targets of Sophora tonkinensis Gagnep were collected from the database of traditional Chinese medicinal systems databases and analysis platform(TCMSP). Targets related to acute pharyngitis were acquired through GeneCards, OMIM, DrugBank and Disgenet databases. After the common targets of the two were screened, the STRING database was used to construct the protein interaction network, and the Metascape platform was used for pathway analysis. At the same time, Cytoscape software was used to construct a network of "herbal-disease-component-target" and "herbal-disease-component-target-pathway" network. The acute pharyngitis models in rats were established to study the effect of water extract of Sophora tonkinensis Gagnep on acute pharyngitis in rats. Quantitative real-time PCR technology was used to study the effect of Sophora tonkinensis Gagnep on key gene targets in key pathways of pharyngeal tissues in rats with acute pharyngitis. Results In this experiment, 509 related targets of 21 active components of Sophora tonkinensis Gagnep were obtained, 2 167 related targets of acute pharyngitis were obtained, and 194 common targets of Sophora tonkinensis Gagnep and acute pharyngitis were obtained. KEGG pathway analysis screened 344 related signaling pathways, indicating that IL-17 signaling pathway, NF-kappa B signaling pathway and leukocyte transendothelial migration pathway might play a key role in the improvement of acute pharyngitis by Sophorae tonkinensis Gagnep. Animal experiments showed that the low dose group of Sophora tonkinensis Gagnep water extract had better therapeutic effect on acute pharyngitis. The results of quantitative real-time PCR showed that the low-dose group of Sophora tonkinensis Gagnep significantly down-regulated the expression levels of ITGB2, PIK3CA, PIK3CD and PTPN11 genes in leukocyte transendothelial migration pathway(P<0.05). Conclusions The above results show that Sophora tonkinensis Gagnep has the characteristics of multi-component, multi-target and multi-pathway synergy in improving acute pharyngitis, which provides a theoretical basis for further study on the complex mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis.