Combinatorial Chemistry & High Throughput Screening - Volume 26, Issue 1, 2023

Background: The recent outbreak of SARS-CoV-2 has received global attention. Due to a lack of recommended treatment regimens, the world faced various limitations resulting in improper management of the disease. Phytomedicines have played a prominent role in the prevention of various epidemics and pandemics in the past. Objective: Here, we attempt to focus on safe and feasible use of Thuja occidentalis to manage and alleviate the panic of viral respiratory infections, including COVID-19, by strengthening an individual’s immunity. The relevant information was collected from the web-based databases PubMed, Google Scholar, and MEDLINE, as well as other internet sources to review the applicability of T. occidentalis as a phytomedicine in managing respiratory infections and strengthening immunity. Conclusion: As important phytomedicine, and antipsychotic, T. occidentalis possesses a plethora of immunological properties that can be used effectively in the management of viral respiratory infections and has the potential to prevent further progression of the disease. Importantly, this could be only a part of the approach for treatment during the current outbreak that should be considered along with other measures.

Background: The Lingqihuangban Granule (LQHBG), a remarkable Chinese herbal compound, has been used for decades to treat diabetic retinopathy (DR) in the Department of Ophthalmology, Shanghai General Hospital (National Clinical Research Center for Eye Diseases) with obvious effects. Through the method of network pharmacology, the present study constructed bioactive component-relative targets and protein-protein interaction network of the LQHBG and implemented gene function analysis and pathway enrichment of targets, discussing the mechanisms of traditional Chinese medicine LQHBG in treating DR. Materials and Methods: The bioactive ingredients of LQHBG were screened and obtained using TCMSP and ETCM databases, while the potential targets of bioactive ingredients were predicted by SwissTargetPrediction and ETCM databases. Compared with the disease target databases of TTD, Drugbank, OMIM and DisGeNET, the therapeutic targets of LQHBG for DR were extracted. Based on the DAVID platform, GO annotation and KEGG pathway analyses of key targets were explored, combined with the screening of core pathways on the Omicshare database and pathway annotation on the Reactome database. Results: A total of 357 bioactive components were screened from LQHBG, involving 86 possible targets of LQHBG treating DR. In the PPI network, INS and ALB were identified as key genes. The effective targets were enriched in multiple signaling pathways, such as PI3K/Akt and MAPK pathways. Conclusion: This study revealed the possible targets and pathways of LQHBG treating DR, reflecting the characteristics of multicomponent, multitarget and multipathway treatment of a Chinese herbal compound, and provided new ideas for further discussion.

Background: Wu-Mei-Wan (WMW), a traditional Chinese medicine (TCM) formula, has a good effect on the treatment of obesity and has been proven helpful to promote the metabolism of adipose tissue. However, its underlying mechanism remains to be studied. This study aims to explore the potential pharmacological mechanism of WMW in the treatment of obesity. Methods: Network pharmacology was used to sort out the relationship between WMW putative targets and obesity-related drug targets or disease targets, which indicated the mechanism of WMW in treating obesity from two aspects of clinical drugs approved by the Food and Drug Administration (FDA) and obesity-related diseases. Databases such as Traditional Chinese Medicine Systems Pharmacology (TCMSP), PubChem, DrugBank, DisGeNET, and Genecards were used to collect information about targets. String platform was used to convert the data into gene symbol of “homo sapiens”, and perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. With the Human Protein Reference Database (HPRD) as background data, Cytoscape 3.6.0 software was used to construct a new protein-protein interaction (PPI) network. Mechanism diagrams of key pathways were obtained from the KEGG database. AutoDock Vina software was used to conduct molecular docking verification. Results: The number of targets in the overlap between WMW putative targets and obesity-related drug targets accounted for more than 50% of the latter, and HTR3A, SLC6A4, and CYP3A4 were core targets. In obesity-related disease targets-WMW putative targets PPI network, the Th17 cell differentiation pathway, and the IL-17 signaling pathway were key pathways, and the 1st module and the 7th module were central function modules that were highly associated with immunity and inflammation. Molecular docking verified that STAT3, TGFB1, MMP9, AHR, IL1B, and CCL2 were core targets in the treatment of WMW on obesity. Conclusion: WMW has similar effects on lipid and drug metabolism as the current obesity-related drugs, and is likely to treat obesity by inhibiting Th17 cell differentiation and alleviating metabolic inflammation.

Object: This study aims to determine the protective effect and molecular responses of the traditional Chinese medicine Qingchang mixture on intestinal ischemia-reperfusion (IR) injury. Methods: The rat intestinal IR model was prepared. The intestinal ischemic injury was evaluated by HE staining, biochemical assay and western blot. In addition, a human hypoxia-reoxygenation (HR) in vitro model was prepared using intestinal epithelial cells (IEC-6). The viability and apoptosis of IEC-6 cells were measured by CCK8 and apoptosis detection. TAK242 or PDTC was used as a small molecule inhibitor of TLR4 or NF-ΚB, respectively. Results: Compared with the IR group, the pretreatment of the Qingchang mixture reduced the morphological damage, oxidative stress, inflammatory response, and barrier function damage of the small intestine tissue. IR significantly increased the expression of TLR4 and NF-ΚB, while the pretreatment of the Qingchang mixture inhibited the expression of TLR4 and NF-ΚB. Furthermore, the pretreatment of Qingchang mixture, TAK242, or PDTC effectively improved the viability and hindered apoptosis of the HR-induced IEC-6 cells. Conclusions: Traditional Chinese medicine Qingchang mixture prevents intestinal IR injury through TLR4/NF-kB pathway.

Background: Brain development is an extremely complex and precisely regulated process, with about one-third of genes expressed and precisely regulated during brain development. Objective: This study aims to explore the molecular mechanisms involved in brain development. Methods: We first established the expression profile of long non-coding RNAs (lncRNAs) and mRNAs in brain tissues of fetal mice at 12.5d, 14.5d and 16.5d through high-throughput sequencing. Second, the associated functions, pathways, and networks of the co-differentially expressed lncRNAs and mRNAs were identified via Gene Ontology (GO), pathway analysis, and PPI network. After bioinformatic analysis and screening, 8 differentially expressed lncRNAs and mRNAs with the same genetic origin were verified by RT-qPCR analysis in brain tissues of fetal mice at different developmental stages. Results: The data revealed that there were 972 co-differentially expressed lncRNAs and 992 codifferentially expressed mRNAs in brain tissues of fetal mice at 12.5d, 14.5d and 16.5d. And we discovered 125 differentially expressed lncRNAs and mRNAs, which have the same genetic origin, in brain tissues of fetal mice at 12.5d, 14.5d and 16.5d through sequencing results and bioinformatics analysis. Besides, we proved that 8 lncRNAs, which have had the same genetic origin as differentially expressed mRNAs, were prominently downregulated, while their maternal genes were upregulated during brain development in fetal mice. Conclusion: Our results preliminarily illustrated the differentially expressed lncRNAs and mRNAs, both of which were derived from the same parent genes, during brain development in fetal mice, which suggests that alternative splicing of lncRNA exists during brain development. Besides, our study provides a perspective on critical genes for brain development, which might be the underlying therapeutic targets for developmental brain diseases in children.

Background: Pan-cancer analysis is an efficient tool to obtain a panoramic view of cancer- related genes and identify their oncogenic processes, facilitating the development of new therapeutic targets. Lysine methyltransferase 2D (KMT2D), acting as a major enhancer coactivator for mammalian cells, is one of the most frequently mutated genes across various cancer types and is considered an oncogene and a rationale for epigenetic therapeutic targets. Objective: This study was designed to explore the potential role of KMT2D in human cancer through a pan-cancer analysis. Methods: The expression of KMT2D was assessed in normal tissues and cell lines, and pancancers from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTE) datasets were used to explore its correlation with prognosis, immune cell infiltration, tumor mutation burden, microsatellite instability, and mismatch repair. Results: KMT2D expression was heterogeneous across different cancer types. Increased KMT2D indicated a worse prognosis in adrenocortical carcinoma (ACC), brain lower-grade glioma (LGG), and mesothelioma (MESO), while patients with high KMT2D expression showed better outcomes in renal clear cell carcinoma (KIRC). Moreover, KMT2D expression was positively correlated with immune cell infiltration and negative tumor mutation burden in multiple cancers. In addition, a significant correlation between KMT2D and immune checkpoint-related genes or mismatch repair genes was identified. Conclusions: These findings support the hypothesis that KMT2D is not only a potential biomarker for prognosis and immunotherapy response prediction but also an essential immune regulator in human cancer.

Objective: Pulmonary tuberculosis (PTB) is a significant risk factor for COPD, and Xinjiang, China, has a high incidence of pulmonary tuberculosis. The effects of tuberculosis history on airflow restriction, clinical symptoms, and acute episodes in COPD patients have not been reported in the local population. Besides, the exact relationship between lung function changes in people with a history of tuberculosis and COPD risk is not clear. Methods: This study is based on the Xinjiang baseline survey data included in the Natural Population Cohort Study in Northwest China from June to December, 2018. Subjects' questionnaires, physical examination, and lung function tests were performed through a face-to-face field survey to analyze the impact of previous pulmonary tuberculosis on local COPD. Furthermore, we clarified the specific relationship between pulmonary function decline and the probability of developing COPD in people with a history of tuberculosis. Results: A total of 3249 subjects were eventually enrolled in this study, including 87 with a history of tuberculosis and 3162 non-TB. The prevalence of COPD in the prior TB group was significantly higher than that in the control group (p-value = 0.005). First, previous pulmonary tuberculosis is an essential contributor to airflow limitation in the general population and patients with COPD. In all subjects included, pulmonary function, FEV1% predicted (p-value < 0.001), and FEV1/FVC (%) (p-value < 0.001) were significantly lower in the prior TB group than in the control group. Compared to non-TB group, FEV1% prediction (p-value = 0.019) and FEV1/FVC (%) (p-value = 0.016) were found to be significantly reduced, and airflow restriction (p-value = 0.004) was more severe in prior TB group among COPD patients. Second, COPD patients in the prior TB group had more severe clinical symptoms. Compared with no history of tuberculosis, mMRC (p-value = 0.001) and CAT (p-value = 0.002) scores were higher in the group with a history of tuberculosis among COPD patients. Third, compared with the non-TB group, the number of acute exacerbations per year (p-values = 0.008), the duration of each acute exacerbation (p-values0.004), and hospitalization/ patient/year (p-values<0.001) were higher in the group with a history of tuberculosis among COPD patients. Finally, a dose-response relationship between FEV1/FVC (%) and the probability of developing COPD in people with previous pulmonary TB was observed; when FEV1/FVC (%) was < 80.8, the risk of COPD increased by 13.5% per unit decrease in lung function [0.865(0.805, 0.930)]. Conclusion: COPD patients with previous pulmonary tuberculosis have more severe airflow limitations and clinical symptoms and are at higher risk for acute exacerbations. Furthermore, lung function changes in people with a history of tuberculosis were associated with a dose-response relationship with the probability of developing COPD.

Background: Thrombosis triggered by platelet activation plays a vital role in the pathogenesis of cardiovascular and cerebrovascular diseases. Objective: This study aims to find platelet combined biomarkers for cardiovascular diseases and investigate the possibility of Concanavalin A (ConA) acting on platelets as a new pharmacological target. Methods: High-throughput Technology and bioinformatics analysis were combined and groups of microarray chip gene expression profiles for acute myocardial infarction (AMI) and sickle cell disease (SCD) were obtained using GEO database screening. R language limma package was used to obtain differentially expressed genes (DEGs). GO, KEGG, and other databases were utilized to perform the enrichment analysis of DEGs’ functions, pathways, etc. PPI network was constructed using STRING database and Cytoscape software, and MCC algorithm was used to obtain the 200 core genes of the two groups of DEGs. Core targets were confirmed by constructing an intersection area screening. A type of molecular probe, ConA, was molecularly docked with the above core targets on the Zdock, HEX, and 3D-DOCK servers. Results: We found six core markers, CD34, SOCS2, ABL1, MTOR, VEGFA, and SMURF1, which were simultaneously related to both diseases, and the docking effect showed that VEGFA is the best-performing. Conclusion: VEGFA is most likely to reduce its expression by binding to ConA, which could affect the downstream regulation of the PI3K/Akt signaling pathway during platelet activation. Some other core targets also have the opportunity to interact with ConA to affect platelet-activated thrombosis and trigger changes in cardiovascular events.

Background: Long non-coding RNAs (lncRNAs) containing microRNA (miRNA) response elements (MREs) can be used as competitive endogenous RNAs (ceRNAs) to regulate gene expression. Objective: The purpose of this study was to investigate the expression profile and role of mRNAs and lncRNAs in unilateral ureteral obstruction (UUO) model rats and to explore any associated competing endogenous (ceRNA) network. Methods: Using the UUO model, the obstructed kidney was collected on the 15th day after surgery. RNA Seq analysis was performed on renal tissues of four UUO rats and four sham rats. Four mRNAs and four lncRNAs of differentially expressed genes were randomly selected for real-time quantitative PCR (RT qPCR) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed, and bioinformatics was used to predict MREs. By screening for ceRNAs combined with target gene prediction, a related ceRNA network was constructed and verified by RT-qPCR. Results: We identified 649 up-regulated lncRNAs, 518 down-regulated lncRNAs, 924 downregulated mRNAs and 2029 up-regulated mRNAs. We identified 30 pathways with the highest enrichment in GO and KEGG. According to the RNA Seq results and the expression of Nr4a1, the network was constructed based on Nr4a1 and included two MREs and ten lncRNAs. Furthermore, lncNONRATT011668.2/miR-361-3p/Nr4a1 was identified and verified according to ceRNA sequencing and target gene prediction. Conclusion: mRNAs and lncRNAs are differentially expressed in UUO model rats, which may be related to the pathogenesis of chronic kidney disease. The lncNONRATT011668.2/miR-361- 3p/Nr4a1 ceRNA network may be involved in the pathogenesis of chronic kidney disease.

Background: The common and divergent genetic mechanisms of hyperandrogen (HA) and normoandrogen (NA) polycystic ovary syndrome (PCOS) are currently unknown. Objective: This study aimed to explore the hub genes and potential mechanisms of HA and NA PCOS through bioinformatics analysis. Methods: The GSE137684 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The co-expressed genes and differentially expressed genes (DEGs) between HA and NA PCOS samples were functionally annotated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The protein-protein interaction (PPI) network of the DEGs was constructed and visualized using STRING and Cytoscape, respectively, and the hub genes were screened using the Cytohubba plug-in. The transcription factors (TFs) of these hub genes were identified with the JASPAR database, and the hub gene-TF regulatory network was constructed. Results: A total of 327 DEGs, including 191 upregulated and 136 downregulated genes, were identified in HA PCOS relative to NA PCOS. Ten hub genes were screened, of which MYC, CAV1, and HGF were mainly enriched in the Proteoglycans in the cancer pathway. In addition, 47 TFs were identified that were found to be involved in the regulation of hub genes. Conclusion: MYC, CAV1, and HGF are potential diagnostic biomarkers and therapeutic targets for HA PCOS.

Background: Osteosarcoma is the most common type of primary malignant bone tumor. Introduction: This study aimed to explore potential key prognostic genes and their roles in osteosarcoma. Methods: Three microarray datasets for osteosarcoma were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened by the Limma package. Functional enrichment analysis was performed based on DAVID, GeneMANIA, and Metascape databases. Prognostic value of DEGs was elevated by survival analysis. CIBERSORT was used to assess the infiltrating abundance of 22 immune cells, followed by the Pearson correlation analysis between immune cells and prognosis-related genes. Gene set enrichment analysis and drug-gene interactions prediction were performed for prognosis-related genes. Results: A total of 8 common up-regulated DEGs and 13 common down-regulated DEGs were screened in the GSE36001 and GSE56001 datasets. Enrichment analysis showed these DEGs were implicated in platelet activation, SMAD protein phosphorylation, lymphocyte/leukocyte/T cells activation, and cell migration. Survival analysis indicated that elevated expression of ADAM19 and TUBB1 were associated with a favorable prognosis. CIBERSORT algorithm revealed the higher infiltrating level of CD8 T cells, macrophages M0, and M2 in osteosarcoma. ADAM19 expression positively correlated with naïve B cells and negatively correlated with activated dendritic cells infiltrating abundance. TUBB1 expression positively correlated with gamma delta T cells while negatively correlated with helper follicular T cells infiltrating abundance. A total of 56 drugs were found to target TUBB1. Conclusion: ADAM19 and TUBB1 could be prognostic biomarkers in osteosarcoma. Both their expression correlates with tumor infiltrating immune cells. TUBB1 was a multi-drug target that might be a therapeutic target in osteosarcoma.

Background: Bone fracture healing is a time-consuming and high-priority orthopedic problem worldwide. Objective: Discovering the potential mechanism of bone healing at a time course and transcriptional level may better help manage bone fracture. Methods: In this study, we analyze a time-course bone fracture healing transcriptional dataset in a rat model (GSE592, GSE594, and GSE1371) of Gene Expression Omnibus (GEO). RNA was obtained from female Sprague-Dawley rats with a femoral fracture at the initial time (day 3) as well as early (week 1), middle (week 2), and late (week 4) time periods, with nonfracture rats used as control. Gene Ontology (GO) functional analysis and pathway examinations were performed for further measurements of GSEA and hub genes. Results: Results indicated that the four stages of bone fracture healing at the initial, early, middle, and late time periods represent the phases of hematoma formation, callus formation, callus molding, and mature lamellar bone formation, respectively. Extracellular organization was positively employed throughout the four stages. At the hematoma formation phase, the muscle contraction process was downregulated. Antibacterial peptide pathway was downregulated at all phases. The upregulation of Fn1 (initial, early, middle, and late time periods), Col3a1 (initial, early, and middle time periods), Col11a1 (initial and early time periods), Mmp9 (middle and late time periods), Mmp13 (early, middle, and late time periods) and the downregulation of RatNP-3b (initial, early, middle, and late time periods) were possible symbols for bone fracture healing and may be used as therapeutic targets. Conclusion: These findings suggest some new potential pathways and genes in the process of bone fracture healing and further provide insights that can be used in targeted molecular therapy for bone fracture healing.

Background: RNA-binding proteins (RBPs) are crucial factors that function in the posttranscriptional modification process and are significant in cancer. Objective: This research aimed for a multigene signature to predict the prognosis and immunotherapy response of patients with colon adenocarcinoma (COAD) based on the expression profile of RNA-binding proteins (RBPs). Methods: COAD samples retrieved from the TCGA and GEO datasets were utilized for a training dataset and a validation dataset. Totally, 14 shared RBP genes with prognostic significance were identified. Non-negative matrix factorization clusters defined by these RBPs could stratify COAD patients into two molecular subtypes. Cox regression analysis and identification of 8-gene signature categorized COAD patients into high- and low-risk populations with significantly different prognosis and immunotherapy responses. Results: Our prediction signature was superior to another five well-established prediction models. A nomogram was generated to quantificationally predict the overall survival (OS) rate, validated by calibration curves. Our findings also indicated that high-risk populations possessed an enhanced immune evasion capacity and low-risk populations might benefit immunotherapy, especially for the joint combination of PD-1 and CTLA4 immunosuppressants. DHX15 and LARS2 were detected with significantly different expressions in both datasets, which were further confirmed by qRTPCR and immunohistochemical staining. Conclusion: Our observations supported an eight-RBP-related signature that could be applied for survival prediction and immunotherapy response of patients with COAD.

Background: The essential oils isolated from several medicinal plants have been reported to possess anticancer activities. Both the essential oil and extracts of many Piper species (Piperaceae) possess potential cytotoxic effects against cancer cell lines and are being used in traditional systems of medicine for the treatment of cancer. There is a need to evaluate and validate the anticancer properties of essential oils extracted from other wild species of Piper. Objective: The current research was undertaken to determine the chemical composition and investigate the anti-proliferative activity of wild-growing Piper trioicum leaf essential oil. The selected five major constituents were subjected to molecular docking to identify possible modes of binding against serine/threonine-protein kinase (MST3) protein. Methods: The essential oil of leaf of P. trioicum was extracted by hydrodistillation method, and its chemical composition was evaluated by GC-FID and GC-MS. The anti-proliferative activity of the essential oil was evaluated by the MTT assay against normal (3T3-L1) and various cancer (HCT 116, HT-29, PC-3 and HepG2) cell lines. Molecular docking analysis was performed using the AutoDock 4.2 software. The pharmacokinetic and pharmacodynamic properties of the major constituents were determined using absorption, distribution, metabolization, excretion and toxicity (ADMET) analysis. Results: The GC-MS analysis revealed the identification of 45 constituents with δ-cadinene (19.57%), germacrene-D (8.54%), β-caryophyllene (6.84%), 1-epi-cubenol (4.83%) and α-pinene (4.52%) being predominant constituents in the leaf essential oil of P. trioicum. The highest cytotoxicity of essential oil was observed against HT-29 cells (IC50 value of 33.14 μg/ml). 1-epi-cubenol and δ-cadinene exhibited low binding energy values of -6.25 and -5.92 kcal/mol, respectively. For prediction of in silico pharmacokinetic and drug-like properties of the major compounds, the ADMET prediction tool was used, the results of which were observed to be within the ideal range. Conclusion: The present findings demonstrate that P. trioicum essential oil possesses significant anti-proliferative activity and could be effective against cancer treatment.

Background Gastrointestinal cancer (GIC) is a prevalent and lethal malignant tumor. It is obligatory to investigate innovative biomarkers for the diagnosis and prognosis. Proteins play a crucial role in regulating the occurrence and progression of GIC. However, the prognostic value of proteins is unclear in GIC. Objective: This paper aims to identify the hub prognosis-related proteins (PAPs) and construct a prognosis model for GIC patients for clinical application. Methods: Protein expression data of GIC was obtained from The Cancer Proteome Atlas (TCPA) and downloaded the clinicopathological data from The Cancer Genome Atlas database (TCGA). Besides, hub proteins were filtrated via univariate and multivariate Cox regression analysis. Moreover, survival analysis and nomogram were used to predict overall survival (OS). We used the calibration curves to assess the consistency of predictive and actual survival rates. The consistency index (C-index) was used to evaluate the prognostic ability of the predictive model. Furthermore, functional enrichment analysis and protein co-expression of PAPs were used to explore their roles in GIC. Results: Finally, a prognosis model was conducted based on ten PAPs (CYCLIND1, DVL3, NCADHERIN, SYK, ANNEXIN VII, CD20, CMET, RB, TFRC, and PREX1). The risk score calculated by the model was an independent prognostic predictor. Compared with the high-risk subgroup, the low-risk subgroup had better OS. In the TCGA cohort, the area under the curve value of the receiver operating characteristic curve of the prognostic model was 0.692. The expression of proteins and risk score had a significant association with the clinicopathological characteristics of GIC. Besides, a nomogram based on GIC clinicopathological features and risk scores could properly predict the OS of individual GIC patients. The C-index is 0.71 in the TCGA cohort and 0.73 in the GEO cohort. Conclusion: The results indicate that the risk score is an independent prognostic biomarker and is related to the malignant clinical features of GIC patients. Besides, several PAPs associated with the survival and clinicopathological characteristics of GIC might be potential biomarkers for GIC diagnosis and treatment.

Background: Traditional Chinese medicine (TCM) is widely used to treat allergic rhinitis (AR) in China, especially in children. However, due to the complicated composition rules and unclear underlying mechanisms, effective herbal prescriptions’ popularization and application are limited. Purpose: This study tried to detect the core prescription of herbs in treating AR in children, reveal its mechanism based on the ingredients’ network, and explore the main signaling pathways. Methods: We screened medical records of children patients with AR who were treated by TCM in DongZhiMen Hospital from Aug 2009 to Jan 2020 and adopted a descriptive analysis method on herbal characteristics. We used association rules to mine core prescriptions and used network pharmacology to establish the ingredient-target-pathway network through online databases and TCMSP, Genecards, KEGG pathway, Excel, R-Studio, and Cytoscape software. Results: The analysis of 1,092 clinical visits highlighted that the principle of formulating prescription was as follows: ‘pungent and warm herbs were used more frequently while cold-natured herbs were paid equal attention as warm-natured herbs.’ The core prescription was formed by FangFeng, BaiZhi, CangErzi, and ChanTui. These herbs covered 130 underlying targets and 141 signaling pathways of AR, which mainly had an effect on signal transduction and immunoregulation. Conclusion: The core prescription based on these real-world clinical records includes FangFeng, BaiZhi, CangErzi, and ChanTui. It principally acts on targets of signal transduction pathways and immune pathways.

Background: cGAS-STING signaling has been primarily discovered as an important DNA sensing machinery, bridging innate immunity and adaptive immunity. Beyond its antiviral response, recent evidence expanded its complicated role in cancer therapy. Methods: UALCAN, The TCGA Wander, GEPIA, SMART, TIMER, Kaplan-Meier plotter, TCGA Data, and cBioPortal were utilized in the investigation. Results: We evaluated the expression of four key molecules (MB21D1, TMEM173, TBK1, and IRF3) in the cGAS-STING pathway and found that the TMEM173 gene was significantly downregulated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Not only immunostimulatory cells but also regulatory T cells were triggered by the DNA sensing pathway. With gene enrichment analysis, we revealed that cell cycle and mechanotransduction/cytoskeleton signals were most closely connected with cGAS-STING signal alterations in non-small-cell lung cancer (NSCLC). cGAS-STING signaling was robustly correlated with methylation changes, especially histone H3K4 lysine demethylase KDM5s. Transient activation of cGAS-STING was found to exert tumor surveillance effect, and inhibition of STING signaling co-opt elevated KDM5 demethylases might inadvertently worsen clinical outcomes. Conclusion: cGAS-STING signaling and KDM5 demethylases have the potential to be used as targets for evaluating an effective immune response in the tumor microenvironment.

Aims and Objectives: In our previous study, 21 sesquiterpenoids with different skeleton types were isolated from the radix of Curcuma aromatica Salisb., a traditional Chinese medicine used for treating depression and qi and blood stasis. C. aromatica enhanced PC12 cell viability upon damage by H2O2. The aim of this study was to elucidate the antioxidation capability of these sesquiterpenoids using a model of H2O2-induced PC12 cells and analyze the correlation between their structure and bio-activity. Materials and Methods: PC12 cells were simultaneously treated with 400 μM H2O2 and sesquiterpenoid compounds or vitamin E (used as a positive control) for 24 h. The activities of GSH-Px, LDH, CAT, and SOD were detected by ELISA kits. The reactive oxygen species (ROS) level in the cells was determined by the fluorescence probe DCFH-DA. [Ca²⁺]i was detected based on the Fluo 2-AM fluorescence labeling assay. The structures of sesquiterpenoids were featured with 41 selected molecular descriptors, and the relationship between active parameters and structural features was determined by the partial least squares (PLS) analysis. Results: All twenty-one sesquiterpenoids from the radix of C. aromatica increased the activities of GSH-Px, CAT, and SOD, and decreased the LDH leakage, and levels of ROS level and [Ca²⁺]i to different degrees. Some relationships were observed between the molecular descriptors featured by the sesquiterpenoids and GSH-Px, CAT, SOD, LDH, ROS, and [Ca²⁺]i by PLS analysis. Conclusions: Twenty-one sesquiterpenoids showed different antioxidation abilities as measured by a model of H2O2-induced PC12 cells. Five molecular descriptors were positively correlated with GSH-Px, CAT, SOD, and were negatively correlated with LDH and [Ca²⁺].

Background: Glanders is a rare zoonotic disease caused by Burkholderia mallei. Humans can be infected by B. mallei, which causes cutaneous lymphadenitis and pneumonia, leading to sepsis and death in severe cases. Case Presentation: We report a case of a 60-year-old male who was diagnosed with glanders. The patient who had a history of diabetes presented with cough, expectoration, and fever. Computed tomography (CT) imaging showed B. mallei infection in the right upper lobe of the lung with mediastinal lymph node involvement and the lingual segment of the left lung. Moreover, the posterior basal segment of the lower lobe of both lungs had inflammation. Subsequently, B. mallei infection was confirmed by lymph node biopsy and bronchoalveolar lavage multiplex PCR-based targeted gene sequencing. After meropenem treatment, the patient was discharged, and CT imaging showed reduced absorption of pulmonary inflammatory lesions. Conclusions: Glanders is a rare disease that can cause skin infection, lymphadenitis, and pneumonia, and in severe cases, it can be life-threatening. The diagnosis of this disease mainly relies on microbiological culture and pathological biopsy. Diagnosis is also facilitated by multiplex PCRbased targeted gene sequencing. Glanders is treated with cephalosporins, carbapenems, and other sensitive antibiotics.