Molecular Mechanism of the Asarum-Angelica Drug Pair in the Treatment of Periodontitis Based on Network Pharmacology and Experimental Verification.

(1) To examine the potential mechanism of the Asarum-Angelica drug pair against periodontitis and provide an experimental basis for the treatment of periodontitis with herbal medicine. (2) The core components and core targets of the Asarum-Angelica drug pair in the treatment of periodontitis were detected according to network pharmacology methods. Finally, the effect of the Asarum-Angelica drug pair on osteogenic differentiation was observed in mouse embryonic osteoblast precursor cells. (3) According to the results of network pharmacology, there are 10 potential active ingredients in the Asarum-Angelica drug pair, and 44 potential targets were obtained by mapping the targets with periodontitis treatment. Ten potential active ingredients, such as kaempferol and ß-sitosterol, may play a role in treating periodontitis. Cell experiments showed that the Asarum-Angelica drug pair can effectively promote the expression of osteoblast markers alkaline phosphatase (ALP), Runt-related Transcription Factor 2 (RUNX2), and BCL2 mRNA and protein in an inflammatory environment (p < 0.05). (4) Network pharmacology effectively analyzed the molecular mechanism of Asarum-Angelica in the treatment of periodontitis, and the Asarum-Angelica drug pair can promote the differentiation of osteoblasts.

Intelligent analysis of excitation-emission matrix fluorescence fingerprint to identify and quantify adulteration in camellia oil based on machine learning.

Camellia oil (CAO) is a premium edible vegetable oil with medical value and biological activity, but it is susceptible to adulteration. Therefore, the demand for intelligent analysis to decipher the category and proportion of adulterated oil in CAO was the main driver of this work. Excitation-emission matrix fluorescence (EEMF) spectra of 933 vegetable oil samples were characterized by a chemometric method to obtain chemically meaningful information. Authenticity identification models were constructed using four machine learning methods to realize the discrimination of oil species adulterated in CAO mixtures. Meanwhile, quantitative models were established aiming at the fraud of CAO proportion in blended oil. Results showed that the specially constructed CNN obtained the optimal performance when evaluating unseen real-world samples, with a classification accuracy of 95.8% and 92.2%, and mean-absolute quantitative errors between 2.6 and 6.7%. Therefore, EEMF fingerprints coupled with machine learning are expected to provide intelligent and accurate analysis for authenticity detection of CAO.

The T stage of esophageal cancer can be effectively predicted by muscularis propria thickness and muscularis propria + mucosa thickness under ultrasonic gastroscopy.

OBJECTIVES: The latest version of the National Comprehensive Cancer Network recommends neoadjuvant therapy followed by surgical treatment or radical chemoradiotherapy for patients with cT3N0M0. Neoadjuvant therapy can improve the prognosis of patients with locally advanced esophageal cancer. Therefore, the evaluation or prediction of T stage is particularly important because the treatment could differently affect the prognosis. Here, we establish a model to predict the T stage of patients with T2-3N0M0 to help choose the best treatment strategy. METHODS: From 1637 patents with esophageal cancer, we enrolled 48 patients and performed least absolute shrinkage and selection operator regression to screen for independent factors influencing pathological T stage. We, then, trained the decision tree to obtain the decision tree diagram and divided the T stages obtained by different methods into two categories, T2 and T3, for survival analysis. RESULTS: A total of 21 and 27 cases were predicted to be T2 and T3, respectively, under ultrasonic gastroscopy, 19 and 29 under magnetic resonance imaging, and 22 and 26 under pathological examination. Multivariate logistic regression analysis revealed that the muscularis propria thickness (MPT) (p = 0.0097) and the muscularis propria + mucosa thickness (MPMT) in the largest tumor cross-section (p = 0.0239) were independent influencing factors. We plotted a decision tree diagram with these two factors. MPT in the largest tumor cross-section >1.3 mm could be judged as pT3; if ≤1.3 mm, MPMT should be considered a thickness ≥1.7 mm could be judged as pT2 (otherwise pT3). Corresponding survival analysis was performed according to the T stage under different examination modalities. CONCLUSION: MPT in the largest tumor cross-section and MPMT in the largest tumor cross-section are independent predicting factors of pathological T stage.

Chemometrics-enhanced high-performance liquid chromatography-diode array detection strategy to quantify protoberberine alkaloids in varying Coptidis Rhizoma-related medicines.

Quantitation of protoberberine alkaloids is an essential guarantee for efficacy control and medication safety of Coptidis Rhizoma (CR) related medicines. Traditional univariate chromatography faced challenges with co-elution, unknown interferences, and retention time shift when analyzing isomeric analytes in varying sample matrices. We presented a chemometrics-enhanced high-performance liquid chromatography-diode array detection (HPLC-DAD) strategy for simultaneous quantification of six protoberberine alkaloids and processed multi-channels chromatographic-spectral data with four second-order calibration algorithms. Chromatographic conditions were firstly optimized. Four groups of predicted samples were modeled individually with the designed calibration set. Mathematical resolutions were then obtained, and pseudo-univariate regression gave the quantitative concentration of each analyte. Four models were scored on fit, linearity, recovery, and robustness, where alternating trilinear decomposition assisted multivariate curve resolution (ATLD-MCR) exhibited an optimal and stable performance. Besides, the resolved spectra presented high consistency with the actual spectra (r≥0.9993). Limits of quantification (LOQ) fully met the pharmacopoeia stipulation and were 0.17, 0.60, 0.19, 0.74, 0.15, and 0.38 µg mL-1 for columbamine, epiberberine, jatrorrhizine, coptisine, palmatine, and berberine, respectively. The importance of this strategy is to exploit collinearity resolution and additional selectivity that permit accurate quantitation at poor chromatographic resolutions, avoiding individual pretreatment and HPLC optimizations for different samples. This study provides a universal alternative for routine quality assessment of protoberberine alkaloids in CR-related medicines.

A clinical nomogram for predicting tumor regression grade in esophageal squamous-cell carcinoma treated with immune neoadjuvant immunotherapy.

Background: There are various treatment options for esophageal squamous cell cancer. including surgery, peri-operative chemotherapy, and radiation. More recently, neoadjuvant immunotherapy has also been shown improve outcomes. In this study, we addressed the question, "Can we predict which patients with esophageal squamous cell cancer will benefit from neoadjuvant immunotherapy?". Methods: All patients with thoracic esophageal squamous-cell carcinoma (T2N+M0-T3-4N0/+M0) (according to the eighth edition of the National Comprehensive Cancer Network guidelines) who underwent immune neoadjuvant immunochemotherapy with programmed cell death protein 1 (PD-1) combined with paclitaxel plus cisplatin or nedaplatin in the Affiliated Cancer Hospital of Zhengzhou University, China, between November 2019 and August 2021 were included in this study. All patients underwent surgical resection. We developed a response [tumor regression grade (TRG)] prediction model using the least absolute shrinkage and selection operator (LASSO) regression incorporating factors associated with response. The accuracy of the prediction model was then validated. Results: We included 79 patients who underwent neoadjuvant immunotherapy combined with chemotherapy, aged 48-78 years (62.05±6.67), including 21 males and 58 females. There were five cases of immune-related pneumonia, of which three cases were diagnosed as immune-related pneumonia during the perioperative period, and one case of immune-related thyroid dysfunction changes. After LASSO regression, the factors that were independently associated with TRG were clinical T stage before neoadjuvant therapy, clinical N stage before neoadjuvant therapy, albumin level difference from before to after neoadjuvant therapy, white blood cell (WBC) count before neoadjuvant therapy, and T stage before surgery. We constructed a prediction model, plotted the nomogram, and verified its accuracy. Its Brier score was 0.13, its calibration slope was 0.98, and its C-index was 0.90 (95% CI: 0.82-0.97). Conclusions: Our prediction model can predict the likelihood of TRG in patients with esophageal squamous cell cancer after immunotherapy combined with neoadjuvant chemotherapy. Using this prediction model, we plan to conduct a subsequent neoadjuvant radiotherapy in patients with of TRG 2-3 patients with neoadjuvant radiotherapy.

[Swimming plus medication reduces the expressions of cytokines in rats with chronic abacterial prostatitis].

OBJECTIVE: To observe the effects of swimming plus medication on the expressions of cytokines in rats with chronic abacterial prostatitis (CAP). METHODS: Forty healthy adult male SD rats were randomly divided into five groups of equal number, normal control, CAP model control, medication, exercise therapy, and exercise + medication. The CAP model was made by Xiaozhiling injection, and at 7 days after modeling, the rats in the medication and exercise + medication groups were treated intragastrically with Qianlie Shutong Capsules (0.016 g/ml) at 20 ml per kg of the body weight qd, those in the exercise therapy and exercise + medication groups were made swim at a regular time once a day, 35 minutes on the first day and 5 minutes more on the second until 50 minutes once, for 4 successive weeks, and those in the normal control, model control and exercise therapy groups received normal saline only. After 14 and 28 days of treatment, all the rats were killed and their prostates harvested for observation of histopathological changes and determination of the expressions of TNF- α, IL-1ß and IL-6 in the prostatic tissue homogenate by ELISA. RESULTS: After 14 days of treatment, the expression levels of TNF-α, IL-1ß and IL-6 were significantly elevated in the groups of CAP model control (ï¼»183.08±8.07ï¼½ pg/ml, ï¼»57.55±3.53ï¼½ pg/ml and ï¼»256.15±13.95ï¼½ ng/L), medication (ï¼»118.49±8.06ï¼½ pg/ml, ï¼»42.64±4.64 ï¼½ pg/ml and ï¼»200.74±9.33ï¼½ ng/L), exercise therapy (ï¼»169.63±10.64ï¼½ pg/ml, ï¼»50.45±5.71ï¼½ pg/ml and ï¼»245.23±6.49ï¼½ ng/L), and exercise + medication (ï¼»107.82±7.81ï¼½ pg/ml, ï¼»40.35±6.93ï¼½ pg/ml and ï¼»187.04±10.85ï¼½ ng/L) as compared with those in the normal control (ï¼»20.36±1.82ï¼½ pg/ml, ï¼»14.64±1.91ï¼½ pg/ml and ï¼»70.58±2.09ï¼½ ng/L) (P<0.05). At 28 days, the levels of TNF- α, IL-1ß, IL-6 were remarkably lower in the exercise + medication group (ï¼»29.30±3.78ï¼½ pg/ml, ï¼»16.91±1.24ï¼½ pg/ml and ï¼» 88.65±6.74ï¼½ ng/L) than in the medication group (ï¼»39.67±3.19ï¼½ pg/ml, ï¼»26.27±3.49ï¼½ pg/ml and ï¼»110.26±6.33ï¼½ ng/L) (P<0.05) and close to those of the normal control group (ï¼»19.34±1.76ï¼½ pg/ml, ï¼»13.68±1.06ï¼½ pg/ml and ï¼»71.34±2.50ï¼½ ng/L). During the treatment, no obvious pathological changes were found in the prostate tissue of the normal control rats, while significant chronic prostatic inflammation was observed in the CAP models, and the inflammation was relieved in different degrees after intervention, most significantly in the exercise + medication group. CONCLUSIONS: Swimming can relieve prostatic inflammation and swimming plus medication can effectively reduce the expressions of cytokines and alleviate histological damage in the prostatic tissue of CAP rats.

Regulation of demethylation and re-expression of RASSF1A gene in hepatocellular carcinoma cell lines treated with NCTD in vitro.

BACKGROUND: Hepatocellular carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. Norcantharidin (NCTD), the demethylated analog of cantharidin derived from a traditional Chinese medicine, Mylabris, has been used in the treatment of cancer. However, the detailed mechanisms underlying this process are generally unclear. PURPOSE: The aim of this study was to investigate the mechanism of NCTD-induced apoptosis in HepG2 cells. MATERIALS AND METHODS: Human HepG2 cell lines were treated with NCTD at different concentrations (2.50, 5.00, 10.00, 20.00, 40.00 µg/mL) for 24 hours. Cell proliferation was evaluated by measurement of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The methylation levels of RASSF1A (Ras-association domain family 1 A) in HepG2 cells were detected by methylation-specific PCR (MSP). The mRNA levels of RASSF1A in HepG2 cells were detected by real-time fluorescent quantitative PCR (RT-PCR). The levels of RASSF1A protein expression of HepG2 cells were detected by Western blotting assay. RESULTS: The inhibition of cell proliferation was observed when treated with NCTD at concentrations (2.5 µg/mL), and as concentration increased, the proliferation of HepG2 cells was markedly inhibited by NCTD in dose-dependent manners. The levels of methylation of RASSF1A decreased at the increasing concentration of 10, 20 and 40 µg/mL. The levels of RASSF1A mRNA and protein were decreased when treated with NCTD at the concentrations of 10, 20 and 40 µg/mL, which were also in a dose-dependent manner. CONCLUSION: NCTD can reverse the methylation state of RASSF1A gene and induce its re-expression, which will provide the theoretical basis for the clinical practice.