Machine learning model based on RCA-PDCA nursing methods and differentiating factors to predict hypotension during cesarean section surgery.

BACKGROUND: Intraoperative hypotension during cesarean section has become a serious complication for maternal and fetal healthy. It is commonly encountered by subarachnoid anesthesia. However, currently used control methods have varying degrees of side effects, such as drugs. The Root Cause Analysis (RCA) - Plan, Do, Check, Act (PDCA) is a new model of care that identifies the root causes of problems. The study aimed to demonstrate the usefulness of RCA-PDCA nursing methods in preventing intraoperative hypotension during cesarean section and to predict the occurrence of intraoperative hypotension through a machine learning model. METHODS: Patients who underwent cesarean section at Traditional Chinese Medicine of Southwest Medical University from January 2023 to December 2023 were retrospectively screened, and the data of their gestational times, age, height, weight, history of allergies, intraoperative vital signs, fetal condition, operative time, fluid out and in, adverse effects, use of vasopressor drugs, anxiety-depression-pain scores, and satisfaction were collected and analyzed. The statistically different features were screened and five machine learning models were used as predictive models to assess the usefulness of the RCA-PDCA model of care. RESULTS: (1) Compared with the general nursing model, the RCA-PDCA nursing model significantly reduces the incidence of intraoperative hypotension and postoperative complications in cesarean delivery, and the patient experience is comfortable and satisfactory. (2) Among the five machine learning models, the RF model has the best predictive performance, and the accuracy of the random forest model in preventing intraoperative hypotension is as high as 90%. CONCLUSION: Through computer machine learning model analysis, we prove the importance of the RCA-PDCA nursing method in the prevention of intraoperative hypotension during cesarean section, especially the Random Forest model which performed well and promoted the application of artificial intelligence computer learning methods in the field of medical analysis.

Prediction of viral pneumonia based on machine learning models analyzing pulmonary inflammation index scores.

OBJECT: To obtain Pulmonary Inflammation Index scores from imaging chest CT and combine it with clinical correlates of viral pneumonia to predict the risk and severity of viral pneumonia using a computer learning model. METHODS: All patients with suspected viral pneumonia on CT examination admitted to The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University from December 2022 to March 2023 were retrospectively selected. The respiratory viruses were monitored by RT-PCR and categorized into patients with viral pneumonia and those with non-viral pneumonia. The extent of lung inflammation was quantified according to the Pulmonary Inflammation Index score (PII). Information on patient demographics, comorbidities, laboratory tests, pathogenetic testing, and radiological data were collected. Five machine learning models containing Random Forest(RF), Radial Basis Function Neural Network (RBFNN), Support Vector Machine (SVM), K Nearest Neighbour Algorithm (KNN), and Kernel Ridge Regression (KRR) were used to predict the risk of onset and severity of viral pneumonia based on the clinically relevant factors or PII. RESULTS: Among the five models, the SVM model performed best in ACC (76.75 %), SN (73.99 %), and F1 (72.42 %) and achieved a better area under the receiver operating characteristic curve (ROC) (0.8409) when predicting the risk of developing viral pneumonia. RF had the best overall classification accuracy in predicting the severity of viral pneumonia, especially in predicting pneumonia with a PII classification of grade I, the RF model achieved an accuracy of 98.89%. CONCLUSION: Machine learning models are valuable in assessing the risk of viral pneumonia. Meanwhile, machine learning models confirm the importance in predicting the severity of viral pneumonia through PII. The establishment of machine learning models for predicting the risk and severity of viral pneumonia promotes the further development of machine learning in the medical field.

The pharmacological mechanism of Abelmoschus manihot in the treatment of chronic kidney disease.

Abelmoschus manihot (A.manihot) is a herbaceous flowering medicinal plant and flavonoids are its main pharmacological active ingredients. A.manihot is listed in the 2020 edition of the Chinese Pharmacopoeia for the treatment of chronic kidney disease (CKD). A.manihot significantly reduces proteinuria in CKD, and the effectiveness and safety of A.manihot in the treatment including primary glomerulonephropathy and diabetic kidney disease (DKD) have been proved by several randomized controlled trials (RCT). Emerging pharmacological studies have explored the potential active small molecules and the underlying mechanisms in A.manihot. The active constituents of A.manihot are mainly seven flavonoids, including hibifolin, hyperoside, isoquercetin, rutin, quercetin, myricetin, and quercetin-3-O-robinobioside. The mechanisms of action mainly include alleviating renal fibrosis, reducing the inflammatory response and decreasing the apoptosis of podocytes. In this review, we summarize the updated information of active components and molecular mechanisms of A.manihot on chronic kidney disease.

Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice.

BACKGROUND: Myricetin (3,5,7-trihydroxy-2-(3,4,5-tri hydroxyphenyl)-4-benzopyrone) is a common flavonol extracted from many natural plants and Chinese herb medicines and has been demonstrated to have multiple pharmacological activities, such as anti-microbial, anti-thrombotic, neuroprotective, and anti-inflammatory effects. Previously, myricetin was reported to target Mpro and 3CL-Pro-enzymatic activity to SARS-CoV-2. However, the protective value of myricetin on SARS-Cov-2 infection through viral-entry facilitators has not yet been comprehensively understood. PURPOSE: The aim of the current study was to evaluate the pharmacological efficacy and the mechanisms of action of myricetin against SARS-CoV-2 infection both in vitro and in vivo. METHODS: The inhibitory effects of myricetin on SARS-CoV-2 infection and replication were assessed on Vero E6 cells. Molecular docking analysis and bilayer interferometry (BLI) assays, immunocytochemistry (ICC), and pseudoviruses assays were performed to evaluate the roles of myricetin in the intermolecular interaction between the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein and angiotensin-converting enzyme 2 (ACE2). The anti-inflammatory potency and mechanisms of myricetin were examined in THP1 macrophages in vitro, as well as in carrageenan-induced paw edema, delayed-type hypersensitivity (DTH) induced auricle edema, and LPS-induced acute lung injury (ALI) animal models. RESULTS: The results showed that myricetin was able to inhibit binding between the RBD of the SARS-CoV-2 S protein and ACE2 through molecular docking analysis and BLI assay, demonstrating its potential as a viral-entry facilitator blocker. Myricetin could also significantly inhibit SASR-CoV-2 infection and replication in Vero E6 cells (EC50 55.18 µM), which was further validated with pseudoviruses containing the RBD (wild-type, N501Y, N439K, Y453F) and an S1 glycoprotein mutant (S-D614G). Moreover, myricetin exhibited a marked suppressive action on the receptor-interacting serine/threonine protein kinase 1 (RIPK1)-driven inflammation and NF-kappa B signaling in THP1 macrophages. In animal model studies, myricetin notably ameliorated carrageenan-induced paw edema in rats, DTH induced auricle edema in mice, and LPS-induced ALI in mice. CONCLUSION: Our findings showed that myricetin inhibited HCoV-229E and SARS-CoV-2 replication in vitro, blocked SARS-CoV-2 virus entry facilitators and relieved inflammation through the RIPK1/NF-κB pathway, suggesting that this flavonol has the potential to be developed as a therapeutic agent against COVID-19.

Fufang Shenhua tablet inhibits renal fibrosis by inhibiting PI3K/AKT.

BACKGROUND: Fufang Shenhua tablet (SHT), a traditional Chinese medicine compound, has been utilized in the clinical management of chronic kidney disease (CKD) for a long time. Nevertheless, the fundamental active constituents and potential mechanism of action remain unclear. Thus, the objective of this study was to investigate the renoprotective effect of SHT on residual renal tissue in CKD model rats and to explore its primary efficacious components and their underlying mechanism. METHODS: After a 12-week period of SHT treatment through gavage in a 5/6 nephrectomized animal model of CKD, we evaluated the body weight, renal function, and renal pathological changes. Furthermore, the expression levels of fibronectin (FN), collagen I (COL-1), α-smooth muscle actin (α-SMA), and vimentin in renal tissues were assessed. In addition, network pharmacology analysis and molecular docking were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways through which SHT could potentially exert its anti-kidney fibrosis effects. Subsequently, these predictions were validated in renal tissues of rats with CKD and in transforming growth factor ß1 (TGF-ß1)-induced HK-2 cells. RESULTS: SHT significantly improved renal function and reduced renal pathological damage and fibrosis in CKD model rats. Network pharmacological analysis identified 62 active components in SHT, with quercetin ranked first, and 105 protein targets shared by SHT and CKD. Based on the protein‒protein interaction network (PPI) and the SHT-CKD-pathway network, AKT1, MYC, IL2, and VEGFA were identified as key targets. Furthermore, GO and KEGG pathway enrichment analyses indicated that the renoprotective effect of SHT on CKD was closely associated with the PI3K/AKT signaling pathway. Molecular docking results demonstrated that the main active components of SHT had a strong binding affinity to the hub genes. During experimental validation, SHT hindered the activity of the PI3K/AKT signaling pathway in the renal tissue of CKD model rats. Furthermore, activation of the PI3K/AKT signaling pathway was correlated with a modified fibrotic phenotype in rats with 5/6 nephrectomy-induced CKD and TGF-ß1-induced HK-2 cells. Conversely, SHT and quercetin curtailed the activation of the PI3K/AKT signaling pathway and inhibited the formation of renal fibrosis, thus indicating that the PI3K/AKT signaling pathway is the basis of the antifibrotic effects of SHT. Ultimately, administration of the PI3K/AKT agonist 740Y-P counteracted the fibrotic phenotype of TGF-ß1-induced HK-2 cells induced by SHT. CONCLUSIONS: In this investigation, we employed a fusion of systems pharmacology and in vivo and in vitro experiments to elucidate the mechanism of SHT's antifibrotic properties via obstruction of the PI3K/AKT signaling pathway. Additionally, we surmised that AKT may be the principal target of SHT for the management of CKD and that quercetin may be its efficacious component. We have thus identified SHT as a promising drug for the amelioration of renal fibrosis and the progression of CKD.

Fufang shenhua tablet, astragali radix and its active component astragaloside IV: Research progress on anti-inflammatory and immunomodulatory mechanisms in the kidney.

Background: Given the limited treatment options available for kidney disease, a significant number of patients turn to alternative therapies, including traditional Chinese medicine. Among these therapies, the Fufang Shenhua tablet (SHT) has garnered attention for its effectiveness in addressing the most common deficiency of Qi and Yin in chronic glomerulonephritis. Notably, the sovereign drug of SHT is Astragali Radix (AR), with the most abundant and effective component being Astragaloside IV (AS-IV). AS-IV has been shown to possess anti-inflammatory and immunomodulatory properties, and it is extensively used in treating kidney diseases. Nevertheless, the molecular mechanisms underlying its action are numerous and intricate, and a comprehensive understanding is yet to be achieved. Aim of the review: Thus, we have thoroughly examined the existing research and outlined the advancements made in investigating the anti-inflammatory and immunomodulatory mechanisms of SHT, AR and its active component AS-IV, in relation to kidney health. This serves as a dependable foundation for conducting more comprehensive investigations, evaluating efficacy, and making further improvements in the future. Materials and methods: We conducted a comprehensive literature search utilizing multiple globally recognized databases, including Web of Science, Google Scholar, PubMed, ScienceDirect, Wiley, ACS, Springer, and CNKI. The search keywords used in this study were "Fufang Shenhua tablet," "Astragali Radix," "Astragaloside IV," and "Anti-inflammatory" or "Immunity." Results: The mechanism of inflammation inhibition by SHT, AR and its active component AS-IV is mainly related to the signaling pathways such as NF-κB, TLRs, PI3K/AKT, Wnt/ß-catenin, and JAK-STAT. Immunomodulation exerts not only activating, stimulating, and regulating effects on macrophages and dendritic cells, but also on immune organs, T-lymphocytes, B-lymphocytes, and a myriad of cytokines. Moreover, the SHT, AR and its active component AS-IV also demonstrate regulatory effects on renal cells, including glomerular mesangial cells, tubular epithelial cells, and podocytes. Conclusion: To summarize, SHT, AR and its active component AS-IV, exhibit notable therapeutic effects in kidney-related ailments, and their molecular mechanisms for anti-inflammatory and immunomodulatory effects have been extensively explored. However, further standard clinical trials are necessary to evaluate their safety and efficacy in the adjunctive treatment of kidney-related diseases. Moreover, in-depth studies of unverified chemical components and regulatory mechanisms in SHT are required. It is our belief that with continued research, SHT, AR and its active component AS-IV are poised to pave the way for enhancing therapeutic outcomes in kidney-related ailments.

Sinomenine hydrochloride bidirectionally inhibits progression of tumor and autoimmune diseases by regulating AMPK pathway.

BACKGROUND: Chronic diseases such as tumors and autoimmune disorders are closely linked to metabolism and immunity and require conflicting treatment methods. AMPK can regulate cell growth and inflammation through energy metabolism. Sinomenine is a compound extracted from the traditional Chinese herb sinomenium acutum (Thunb.) Rehd. et Wils. It has been used to treat NSCLC (non-small-cell lung cancer) and RA (rheumatoid arthritis) in some studies, but with limited understanding of its mechanisms. OBJECTIVE: This study aims to examine the inhibitory effect of sinomenine hydrochloride (SH) on NSCLC and RA and to understand the underlying joint mechanisms. RESULTS: The results indicate that SH has a cytotoxic effect specifically on tumor cells, but not on normal cells. SH was found to induce cell apoptosis by activating the AMPK-mTOR pathway. Additionally, in autoimmune disease cell models, SH was shown to reduce the growth of RA-FLS cells by inhibiting the phosphorylation of AMPK, while having no effect on normal macrophages. Moreover, in vivo studies also showed that SH could reduce the production of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 and slow the development of adjuvant arthritis in rats. Furthermore, SH was found to significantly suppress tumor growth in a tumor xenograft experiment in mice. CONCLUSIONS: This study provides new insights into the treatment of tumors and autoimmune diseases by demonstrating that SH can selectively inhibit the growth of NSCLC cells and the progression of RA through activation of the AMPK pathway.

Effect of Ginkgo biloba extract on pharmacology and pharmacokinetics of atorvastatin in rats with hyperlipidaemia.

Ginkgo biloba extract (GBE) is a common dietary supplement used by people with dyslipidaemia worldwide to reduce the risk of cardiovascular disease. Many studies have found that GBE itself has a variety of pharmacological activities. However, the role of GBE as an adjunct to conventional therapy with chemical drugs remains controversial. Therefore, this study explored the additional benefits of GBE in the treatment of hyperlipidaemia with statins in terms of both pharmacodynamics and pharmacokinetics. A hyperlipidaemia model was established by feeding rats a high-fat diet for a long time. The animals were treated with atorvastatin only, GBE only, or a combination of atorvastatin and GBE. The results showed that statins combined with GBE could significantly improve the blood lipid parameters, reduce the liver fat content, and reduce the size of adipocytes in abdominal fat. The effect was superior to statin therapy alone. In addition, the combination has shown additional liver protection against possible pathological liver injury or statin-induced liver injury. A lipidomic study showed that GBE could regulate the abnormal lipid metabolism of the liver in hyperlipemia. When statins are combined with GBE, this callback effect introduced by GBE on endogenous metabolism has important implications for resistance to disease progression and statin resistance. Finally, in the presence of GBE, there was a significant increase in plasma statin exposure. These results all confirmed that GBE has incremental benefits as a dietary supplement of statin therapy for dyslipidaemia.

[Evaluation of calcium intake levels and sources among pregnant women in a Chengdu hospital in 2017].

OBJECTIVE: Investigate and evaluate the levels and sources of calcium intake of pregnant women in Chengdu during three trimesters. METHODS: Use the data of a cohort study in Chengdu in 2017. The healthy singleton pregnant women with 8-14 weeks of pregnancy in an obstetrical clinic of a maternal-and-child health care institution in Chengdu were selected as the object of the study. Data on maternal demographic characteristics and the use information of calcium supplements in the past month of each trimester were collected by questionnaire investigation. The dietary intakes data of pregnant women in each trimester was collected by the 3-day 24-hour dietary recall method. The dietary calcium intake and the contribution of calcium from different foods were calculated based on the Chinese Food Composition Table(2018). The total calcium intake was obtained by adding the dietary calcium and supplement calcium intake. The calcium intake was evaluated with reference to the Chinese Dietary Nutrient Reference Intakes(2013). RESULTS: Valid samples of 1653 cases in early pregnancy, 1024 cases in middle pregnancy and 1017 cases in late pregnancy were finally included. The median intake of total calcium was 523.3, 1280.5 and 1491.3 mg/d in three trimesters, respectively. The adequate rate of total calcium intake was 16.3%, 63.2% and 67.1%, the insufficient rate was 69.0%, 15.7% and 11.2%, the excess rate was 0.2%, 9.1% and 14.4%, respectively. The median intake of dietary calcium was 453.0, 613.0 and 723.0 mg/d in three trimesters respectively. The dietary calcium adequate rates were 7.1%, 9.7% and 16.2%, the dietary calcium deficiency rates were 82.0%, 75.0%, 62.6%, respectively. The main food sources of dietary calcium in each pregnancy were dairy foods, vegetables, tubers and grains. The contribution of dairy foods to the dietary calcium was 33.8%, 37.7% and 40.2%, respectively. The median intake of milk was 125.0, 235.3 and 250.0 g/d, respectively. Among all pregnant women, the calcium supplement use in three trimesters was 36.2%, 93.4% and 91.7%, respectively; the median intake of supplement calcium was 0.0, 625.0 and 750.0 mg/d, respectively. Among pregnant women who met the dietary calcium standard, the use of calcium supplements in the three trimesters was 38.1%, 95.0% and 94.5%, respectively; the median intake of supplemental calcium was 0.0, 725.0 and 750.0 mg/d, respectively. CONCLUSION: The insufficient and excessive total calcium intake coexisted among pregnant women in Chengdu, with the insufficient dietary calcium intake prominent in all trimesters. The use of calcium supplements was common in middle and late pregnancy.

Traditional Herbal Medicine: A Potential Therapeutic Approach for Adjuvant Treatment of Non-small Cell Lung Cancer in the Future.

Lung carcinoma is the primary reason for cancer-associated mortality, and it exhibits the highest mortality and incidence in developed and developing countries. Non-small cell lung cancer (NSCLC) and SCLC are the 2 main types of lung cancer, with NSCLC contributing to 85% of all lung carcinoma cases. Conventional treatment mainly involves surgery, chemoradiotherapy, and immunotherapy, but has a dismal prognosis for many patients. Therefore, identifying an effective adjuvant therapy is urgent. Historically, traditional herbal medicine has been an essential part of complementary and alternative medicine, due to its numerous targets, few side effects and substantial therapeutic benefits. In China and other East Asian countries, traditional herbal medicine is increasingly popular, and is highly accepted by patients as a clinical adjuvant therapy. Numerous studies have reported that herbal extracts and prescription medications are effective at combating tumors. It emphasizes that, by mainly regulating the P13K/AKT signaling pathway, the Wnt signaling pathway, and the NF-κB signaling pathway, herbal medicine induces apoptosis and inhibits the proliferation and migration of tumor cells. The present review discusses the anti-NSCLC mechanisms of herbal medicines and provides options for future adjuvant therapy in patients with NSCLC.

Association between testosterone levels and bone mineral density in females aged 40-60 years from NHANES 2011-2016.

Growing evidence indicates that testosterone is a conspicuous marker for assessing male bone mineral density (BMD). However, research regarding testosterone levels and BMD is sparse and controversial for females. Hence, we aimed to investigate the association between testosterone levels and BMD among adult females aged 40-60 years in the United States. In this cross-sectional study, all participants were part of the National Health and Nutrition Examination Survey (2011-2016). A weighted general linear model was used to estimate the association between testosterone levels and lumbar BMD. Age, race, income level, education level, body mass index (BMI), blood urea nitrogen (BUN) level, serum uric acid (UA) level, serum calcium (Ca) level, serum phosphorus (P) level, the use of oral contraceptive pills, the use of hormone replacement therapy (HRT), smoking status, drinking status, and the use of corticosteroids were adjusted using a weighted multiple regression model. Subgroup analyses were performed using the same regression model. We included 2198 female participants in the study, and testosterone levels were positively associated with lumbar BMD after adjusting for all the covariates (ß = 1.12, 95% CI 0.31, 1.93). In subgroup analyses, the associations in the fourth quartile of testosterone levels were stronger for the participants aged 40-50 years old (quartile 4, ß = 42.92, 95% CI 7.53, 78.30 vs. quartile 1) and 50 to 60-year-old (quartile 4, ß = 32.41, 95% CI 0.14, 64.69 vs. quartile 1). Similar results were found in other subgroups, including subgroups for race (Non-Hispanic Black, Other), income level (income ≤ 1.3, income > 3.5), education level (college or higher), BMI > 25 kg/m2, BUN levels ≤ 20 mg/dL, UA levels ≤ 6 mg/dL, Ca levels ≤ 10.1 mg/dL, P levels ≤ 5 mg/dL, drinking status, never smoker, never taking birth control pills, and HRT user. There was no interaction among the covariates in the association between lumbar BMD and testosterone levels (P for interaction > 0.05). In US adult females aged 40-60 years, the testosterone level was a positive predictor of the lumbar BMD after adjusting for covariates.

[Effect of Xijiao Dihuang Combined Prescription on Human Dendritic Cell Function Induced by Lipopolysaccharide].

OBJECTIVE: To observe the effects of drug-containing serum of Xijiao Dihuang combined prescription(XJDH) on the related functions of dendritic cells(DCs) induced in vitro, and to explore the mechanisms underlying the effectiveness of XJDH treatment on primary immune thrombocytopenia(ITP). METHODS: Peripheral blood samples were colle-ted from 6 healthy volunteers. Mononuclear cells were isolated by density gradient centrifugation, and CD14+ mononuclear cells were collected by the magnetic separation technique. CD14+ mononuclear cells were induced into immature DCs by recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant human interleukin 4 (IL-4). Immature DCs were divided into three groups: control group, model group and XJDH group. CCK-8 assay was used to determine the intervention concentration and time of drug-containing serum. Lipopolysaccharide(LPS) with the final concentration of 1 µg/ml was added to model group and XJDH group respectively for 24 h to induce DCs maturation. Normal rat serum was added to control group and model group, and XJDH was added to XJDH group for 24 h. Flow cytometry was used to detect the levels of CD80, CD83 and HLA-DR on the surface of DCs. Western blot was used to detect the expression of TLR4 and NF-κB, and levels of IL-6, IL-12 and TNF-α in cell supernatant was detected by ELISA. RESULTS: Compared with the control group, LPS stimulation increased the expression of CD80, CD83 and HLA-DR, with subsequent increasing expression of TLR4 and NF-κB, as well as IL-6, IL-12 and TNF-α increased(P<0.05). In comparison with model group, the expression of DCs surface molecules CD80, CD83 and HLA-DR, DCs' expression of TLR4 and NF-κB protein, and the levels of IL-6, IL-12 and TNF-α in the cell supernatant of XJDH group decreased after the intervention of XJDH (P<0.05). CONCLUSION: Drug containing serum of Xijiao Dihuang combined prescription can down-regulate TLR4/NF-κB signaling pathway related protein expression, inhibit DCs maturation, and reduce proinflammatory factor secretion, which may be one of the mechanisms of drug-containing serum of Xijiao Dihuang combined prescription in the treatment of immune thrombocytopenia.

A method establishment and comparison of in vivo lung cancer model development platforms for evaluation of tumour metabolism and pharmaceutical efficacy.

BACKGROUND: Currently, the identification of accurate biomarkers for the diagnosis of patients with early-stage lung cancer remains difficult. Fortunately, metabolomics technology can be used to improve the detection of plasma metabolic biomarkers for lung cancer. In a previous study, we successfully utilised machine learning methods to identify significant metabolic markers for early-stage lung cancer diagnosis. However, a related research platform for the investigation of tumour metabolism and drug efficacy is still lacking. HYPOTHESIS/PURPOSE: A novel methodology for the comprehensive evaluation of the internal tumour-metabolic profile and drug evaluation needs to be established. METHODS: The optimal location for tumour cell inoculation was identified in mouse chest for the non-traumatic orthotopic lung cancer mouse model. Microcomputed tomography (micro-CT) was applied to monitor lung tumour growth. Proscillaridin A (P.A) and cisplatin (CDDP) were utilised to verify the anti-lung cancer efficacy of the platform. The top five clinically valid biomarkers, including proline, L-kynurenine, spermidine, taurine and palmitoyl-L-carnitine, were selected as the evaluation indices to obtain a suitable lung cancer mouse model for clinical metabolomics research by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: The platform was successfully established, achieving 100% tumour development rate and 0% surgery mortality. P.A and CDDP had significant anti-lung cancer efficacy in the platform. Compared with the control group, four biomarkers in the orthotopic model and two biomarkers in the metastatic model had significantly higher abundance. Principal component analysis (PCA) showed a significant separation between the orthotopic/metastatic model and the control/subcutaneous/KRAS transgenic model. The platform was mainly involved in arginine and proline metabolism, tryptophan metabolism, and taurine and hypotaurine metabolism. CONCLUSION: This study is the first to simulate clinical metabolomics by comparing the metabolic phenotype of plasma in different lung cancer mouse models. We found that the orthotopic model was the most suitable for tumour metabolism. Furthermore, the anti-tumour drug efficacy was verified in the platform. The platform can very well match the clinical reality, providing better lung cancer diagnosis and securing more precise evidence for drug evaluation in the future.

Emodin induces apoptosis and suppresses non-small-cell lung cancer growth via downregulation of sPLA2-IIa.

BACKGROUND: Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development. PURPOSE: This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC). METHODS: MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model. RESULTS: Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle. CONCLUSION: Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC.

Immune checkpoints and immunotherapy in non-small cell lung cancer: Novel study progression, challenges and solutions.

Lung cancer is the most common type of cancer with the highest mortality rate worldwide. Non-small cell lung cancer (NSCLC) accounts for ~85% of the total number of lung cancer cases. In the past two decades, immunotherapy has become a more promising treatment method than traditional treatments (surgery, radiotherapy and chemotherapy). Immunotherapy has been shown to improve the survival rate of patients and to have a superior effect when controlling lung cancer than traditional therapy. However, only a small number of patients can benefit from immunotherapy, and not all patients who qualify experience long-term benefits. In the clinic, the objective response rate of programmed cell death protein 1 treatment without the prior screening of patients is only 15-20%. Immunotherapy is associated with both opportunities and challenges for patients with NSCLC. The current challenges of immunotherapy include the lack of accurate biomarkers, inevitable resistance and insufficient understanding of immune checkpoints. In previous years, several methods for overcoming the challenges posed by immunotherapy have been proposed, but combination therapy is the most suitable choice. A large number of studies have shown that the combination of drugs can significantly improve their efficacy, compared with monotherapy, and that some therapeutic combinations have been approved by the Food and Drug Administration for the treatment of NSCLC. Traditional Chinese medicine (TCM) is a traditional medical practice in China that can play an important role in immunotherapy. Most agents used in TCM originate from plants, and have the advantages of low toxicity and multiple targets. In addition, TCM includes a unique class of drugs that can improve autoimmunity. Therefore, TCM may be a promising treatment method for all types of cancer.

Metabolomics and integrated network pharmacology analysis reveal Tricin as the active anti-cancer component of Weijing decoction by suppression of PRKCA and sphingolipid signaling.

Currently, conventional methods of treating non-small cell lung cancer (NSCLC) have many disadvantages. An alternative effective therapy with minimal adverse reactions is urgently needed. Weijing decoction (WJD), which is a classic ancient Chinese herbal prescription, has been used successfully to treat pulmonary system diseases containing lung cancer in the clinic. However, the key active component and target of Weijing decoction are still unexplored. Therefore, for the first time, our study aims to investigate the pharmacological treatment mechanism of Weijing decoction in treating NSCLC via an integrated model of network pharmacology, metabolomics and biological methods. Network pharmacology results conjectured that Tricin is a main bioactive component in this formula which targets PRKCA to suppress cancer cell growth. Metabolomics analysis demonstrated that sphingosine-1-phosphate, which is regulated by sphingosine kinase 1 and sphingosine kinase 2, is a differential metabolite in plasma between the WJD-treated group and the control group, participating in the sphingolipid signaling. In vitro experiments demonstrated that Tricin had vital effects on the proliferation, pro-apoptosis, migration and colony formation of Lewis lung carcinoma cells. Through a series of validation assays, Tricin inhibited the tumor growth mainly by suppressing PRKCA/SPHK/S1P signaling and antiapoptotic signaling. On the other hand, Weijing formula could inhibit the tumor growth and prolong the survival time. A high dosage of Tricin was much more potent in animal experiments. In conclusion, we confirmed that Weijing formula and its primary active compound Tricin are promising alternative treatments for NSCLC patients.

Loganin Inhibits Angiotensin II-Induced Cardiac Hypertrophy Through the JAK2/STAT3 and NF-κB Signaling Pathways.

Loganin is an iridoid glycoside extracted from Cornus officinalis, which is a traditional oriental medicine, and many biological properties of loganin have been reported. Nevertheless, it is not clear whether loganin has therapeutic effect on cardiovascular diseases. Hence, the aim of the present study was to investigate the effect of loganin on Ang II-induced cardiac hypertrophy. In the present study, we reported for the first time that loganin inhibits Ang II-provoked cardiac hypertrophy and cardiac damages in H9C2 cells and in mice. Furthermore, loganin can achieve cardioprotective effects through attenuating cardiac fibrosis, decreasing pro-inflammatory cytokine secretion, and suppressing the phosphorylation of critical proteins such as JAK2, STAT3, p65, and IκBα. Besides, the outstanding findings of the present study were to prove that loganin has no significant toxicity or side effects on normal cells and organs. Based on these results, we conclude that loganin mitigates Ang II-induced cardiac hypertrophy at least partially through inhibiting the JAK2/STAT3 and NF-κB signaling pathways. Accordingly, the natural product, loganin, might be a novel effective agent for the treatment of cardiac hypertrophy and heart failure.

A Combined Phytochemistry and Network Pharmacology Approach to Reveal Potential Anti-NSCLC Effective Substances and Mechanisms in Marsdenia tenacissima (Roxb.) Moon (Stem).

Marsdeniae tenacissimae Caulis is a traditional Chinese medicine, named Tongguanteng (TGT), that is often used for the adjuvant treatment of cancer. In our previous study, we reported that an ethyl acetate extract of TGT had inhibitory effects against adenocarcinoma A549 cells growth. To identify the components of TGT with anti-tumor activity and to elucidate their underlying mechanisms of action, we developed a technique for isolating compounds, which was then followed by cytotoxicity screening, network pharmacology analysis, and cellular and molecular experiments. We isolated a total of 19 compounds from a TGT ethyl acetate extract. Two novel steroidal saponins were assessed using an ultra-performance liquid chromatography-photodiode array coupled with quadrupole time-of-flight mass (UPLC-ESI-Q/TOF-MS). Then, we screened these constituents for anti-cancer activity against non-small cell lung cancer (NSCLC) in vitro and obtained six target compounds. Furthermore, a compound-target-pathway network of these six bioactive ingredients was constructed to elucidate the potential pathways that controlled anticancer effects. Approximately 205 putative targets that were associated with TGT, as well as 270 putative targets that were related to NSCLC, were obtained from online databases and target prediction software. Protein-protein interaction networks for drugs as well as disease putative targets were generated, and 18 candidate targets were detected based on topological features. In addition, pathway enrichment analysis was performed to identify related pathways, including PI3K/AKT, VEGF, and EGFR tyrosine kinase inhibitor resistance, which are all related to metabolic processes and intrinsic apoptotic pathways involving reactive oxygen species (ROS). Then, various cellular experiments were conducted to validate drug-target mechanisms that had been predicted using network pharmacology analysis. The experimental results showed the four C21 steroidal saponins could upregulate Bax and downregulate Bcl-2 expression, thereby changing the mitochondrial membrane potential, producing ROS, and releasing cytochrome C, which finally activated caspase-3, caspase-9, and caspase-8, all of which induced apoptosis in A549 cells. In addition, these components also downregulated the expression of MMP-2 and MMP-9 proteins, further weakening their degradation of extracellular matrix components and type IV collagen, and inhibiting the migration and invasion of A549 cells. Our study elucidated the chemical composition and underlying anti-tumor mechanism of TGT, which may be utilized in the treatment of lung cancer.

Protective effects of total flavonoids from Qu Zhi Qiao (fruit of Citrus paradisi cv. Changshanhuyou) on OVA-induced allergic airway inflammation and remodeling through MAPKs and Smad2/3 signaling pathway.

Allergic asthma is one of the inflammatory diseases, which has become a major public health problem. Qu zhi qiao (QZQ), a dry and immature fruit of Citrus paradisi cv. Changshanhuyou, has various flavonoids with pharmacological properties. However, there is a knowledge gap on the pharmacological properties of QZQ on allergic asthma. Therefore, here, we explored the efficacy and mechanism of total flavonoids from QZQ (TFCH) on allergic asthma. We extracted and purified TFCH and conducted animal experiments using an Ovalbumin (OVA)-induced mice model. Bronchoalveolar lavage fluid and Swiss-Giemsa staining were used to count different inflammatory cells in allergic asthma mice. We conducted histopathology and immunohistochemistry to evaluate the changes in the lungs of allergic asthma mice. Moreover, we used ELISA assays to analyze chemokines and inflammatory cytokines. Furthermore, western blot analyses were conducted to elucidate the mechanism of TFCH on allergic asthma. We established that TFCH has anti-inflammatory effects and inhibits airway remodeling, providing a potential therapeutic strategy for allergic asthma.

Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.

BACKGROUND: Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection. PURPOSE: To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection. METHODS: Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed. RESULTS: TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model. CONCLUSION: TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.