Network pharmacology analysis and experimental validation of Xiao-Qing-Long-Tang's therapeutic effects against neutrophilic asthma.

BACKGROUND: Xiao-Qing-Long-Tang (XQLT), a classical Chinese herbal medicine formula, has been extensively used for allergic asthma treatment. However, there is limited research on its anti-inflammatory effects and mechanisms specifically in neutrophilic asthma (NA). PURPOSE: This study aims to investigate the potential therapeutic effects of XQLT against NA using a combination of network pharmacology and experimental validation. STUDY DESIGN: By utilizing traditional Chinese medicine and disease databases, we constructed an XQLT-asthma network to identify potential targets of XQLT for NA. In the experimental phase, we utilized an ovalbumin (OVA)/lipopolysaccharide (LPS)-induced model for neutrophilic asthma and examined the therapeutic effects of XQLT. RESULTS: Our research identified 174 bioactive components within XQLT and obtained 140 target genes of XQLT against asthma. Functional enrichment analysis revealed that these target genes were primarily associated with inflammation and cytokines. In the experimental validation, mice induced with OVA-LPS showcased eosinophilic and neutrophilic cell infiltration in peri-bronchial areas, elevated levels of IL-4 and IL-17 in both serum and lung, increased percentages of Th2 and Th17 cells in the spleen, as well as elevated levels of CD11b+ and CD103+ dendritic cells (DCs) within the lung. Treatment with XQLT effectively reduced IL-4 and IL-17 levels, decreased the percentages of Th2, Th17, CD11b+, and CD103+ DCs, and improved inflammatory cell infiltrations in lung tissues. These findings serve as a foundation for the potential clinical application of XQLT in neutrophilic asthma.

The protective effects of taurine and fish oil supplementation on PM2.5-induced heart dysfunction among aged mice: A random double-blind study.

As it is nearly impossible to reduce PM2.5 concentrations in most cities to safe limits in a short period of time, dietary supplementation presents a promising approach for mitigating the adverse effects of PM2.5 exposure. A cross-sectional study showed that the elderly population of Linfen (PM2.5: 102 µg/m3) exhibited significantly lower serum taurine levels, as well as higher oxidative stress levels and cardiovascular health risks, than the corresponding population in Guangzhou (PM2.5: 39 µg/m3). We conducted a random double-blind study on aged mice that employed a "real-world" PM2.5 exposure system to simulate the conditions of Linfen with the aim of investigating the protective effects of taurine and fish oil supplementation on PM2.5-induced heart dysfunction. When compared with the placebo group, supplementation with taurine and fish oil not only maintained normal taurine levels, but also suppressed oxidative stress and inflammation in aged mice subjected to high concentrations of PM2.5. Variations in heart rate, contractile function, cardiac oxidative stress, inflammation and fibrosis among different groups of aged mice were used to clarify the beneficial effects of taurine and fish oil supplementation. Our results not only revealed the protective effects of taurine and fish oil supplementation on heart dysfunction induced by PM2.5 exposure from the aged mice experiments and also provided new means for the elderly to resist PM2.5 pollution at the individual level.

Vitamin A supplementation prevents the bronchopulmonary dysplasia in premature infants: A systematic review and meta-analysis.

BACKGROUND: It is necessary to evaluate the effectiveness and safety of vitamin A supplementation on the bronchopulmonary dysplasia (BPD) in premature infants. METHODS: Randomized controlled trials (RCTs) on the role of supplemental vitamin A in preterm infants were searched. The Medline et al databases were manually searched from inception to April 30, 2020. Related outcomes including incidence of BPD, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), sepsis and mortality were assessed with Review Manager 5.3 software, and Random-effect model was applied for all conditions. RESULTS: A total of 9 RCTs with 1409 patients were included. The analyzed results showed that the incidence of BPD in vitamin A group was significantly less than that of control group (OR = 0.67, 95%CI [0.52-0.88]). There was no significant difference in the incidence of ROP (OR = 0.65, 95%CI [0.29-1.48]), NEC (OR = 0.88, 95%CI [0.59-1.30]), IVH (OR = 0.90, 95%CI [0.65-1.25]), sepsis (OR = 0.84, 95%CI [0.64-1.09]) and mortality (OR = 0.98, 95%CI [0.72-1.34]) among two groups. CONCLUSION: Vitamin A supplementation is beneficial to the prophylaxis of BPD in premature infants, further studies on the administration approaches and dosages of vitamin A in premature infants are warranted.

miR-221-5p acts as an oncogene and predicts worse survival in patients of renal cell cancer.

BACKGROUND: Renal cell carcinoma(RCC) is one of the most common malignancies in kidney, and usually leads to poor prognosis. Therefore, identifying novel biomarkers for predicting the progression and prognosis of RCC is essential. The purpose of this study is aimed to evaluate the function of miR-221-5p in RCC and the clinical value of miR-221-5p in RCC prognosis after surgery. MATERIALS AND METHODS: In our study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay, and flow cytometry assay were performed to explore miR-221-5p expression level and its proliferation, migration and apoptosis in clear cell RCC(ccRCC). Besides, we collected 196 formalin-fixed and paraffin-embedded (FFPE) tissue samples of patients who received partial or radical nephrectomy from May 2006 to October 2016 at Shenzhen Traditional Chinese Medicine Hospital and People's Liberation Army 303 Hospital. The relative levels of miR-221-5p from the FFPE tissue samples was detected by RT-qPCR. The Kaplan-Meier method, Cox regression analyses, and ROC curve analysis were performed to approve the effect of the miR-221-5p expression on patient survival. RESULTS: In our study, we found that miR-221-5p is significantly upregulated in ccRCC tissues and ccRCC cell lines. Moreover, miR-221-5p promotes cell proliferation, mobility, and inhibits cell apoptosis in 786-O and ACHN cell lines. The Kaplan-Meier analysis indicated that patients with high expression of miR-221-5p had a significantly poor prognosis (P = 0.013). The Cox regression analyses showed that patients with high expression of miR-221-5p remained to have a shorter overall survival (P = 0.025). The ROC curve of miR-221-5p expression combined with tumor stage showed an area under the curve of 0.658 (P < 0.001). CONCLUSION: Our results indicated that miR-221-5p might not only be an oncogene in ccRCC cells but also might be an independent prognosis factor of ccRCC.

Application of Computer-Aided Tongue Inspection for Preliminary Screening of Esophageal Cancer.

OBJECTIVE: To differentiate patients with esophageal cancer or premalignant lesions from the high-risk population for preliminary screening of esophageal cancer using a feature index determined by a computer-aided tongue information acquisition and processing system (DS01-B). METHODS: Totally, 213 patients diagnosed with esophageal cancer or premalignant lesions and 2,840 normal subjects were collected including primarily screened and reexamined, all of them were confirmed with histological examinations. Their tongue color space values and manifestation features were extracted by DS01-B and analyzed. Firstly, the analysis of variance was performed to differentiate normal subjects from patients with esophageal cancer and premalignant lesions. Secondly, the logistic regression was conducted using 10 features and gender, age to get a predictive equation of the possibility of esophageal cancer or premalignant lesions. Lastly, the equation was tested by subjects undergoing primary screening. RESULTS: Saturation (S) values in the HSV color space showed significant differences between patients with esophageal cancer and normal subjects or those with mild atypical hyperplasia (P<0.05); blue-to-yellow (b) values in the Lab color space showed significant differences between patients with esophageal cancer or premalignant lesions and normal subjects (P<0.05). Logistic regression analysis showed that the computer-aided tongue inspection approach had an accuracy of 72.3% (2008/2776) in identifying patients with esophageal cancer or premalignant lesions for preliminary screening in high-risk population. CONCLUSION: Computer-aided tongue inspection, with descriptive and quantitative profile as described in this study, could be applied as a cost- and timeefficient, non-invasive approach for preliminary screening of esophageal cancer in high-risk population.

Cytisine induces endoplasmic reticulum stress caused by calcium overload in HepG2 cells.

Cytisine, a quinolizidine alkaloid, is one of the major bioactive components found in the small tree Sophora Alopecuraides L., and is a traditional Chinese medicine that is used for treating hepatitis and liver cancer. In the 1960s, quinolizidine alkaloids were reported to exhibit inhibitory effects on tumour cell proliferation in several types of cancer cells. However, few studies have investigated the effect of cytisine on liver cancer. Our team confirmed that cytisine induced apoptosis in HepG2 cells via a mitochondrial pathway. The primary aim of the present study was to evaluate the endoplasmic reticulum (ER) stress caused by calcium overload in cytisine­induced apoptosis in HepG2 cells and the molecular mechanisms of this phenomenon. In addition, the present study was undertaken to evaluate the expression of α7­nAChR when apoptosis was induced by cytisine in HepG2 cells. In the present study, transmission electron microscopy was used to observe the morphological appearance of HepG2 cells. The apoptosis of the cells with cytoplasmic vacuolization was significant under electron microscopy. Apoptotic bodies, the expansion of the ER, and swelling of mitochondria were observed in the HepG2 cells after cytisine treatment. Flow cytometric analysis demonstrated that the apoptosis rate of HepG2 cells was upregulated. In addition, the intracellular calcium concentration was detected by laser confocal fluorescence microscopy. The laser confocal fluorescence microscopy showed that the calcium concentration was increased in a dose­dependent manner. The activity of caspase­4 was evaluated by an enzyme­linked analyser, and the expression levels of CHOP, JNK, p­JNK and α7­nAChR were assessed via western blot analysis. In the present study, we observed that cytisine induced ER stress­inducing factors and CHOP and p­JNK1/2 protein expression, and it increased the JNK protein expression in the HepG2 cells. Furthermore, α7­nAChR protein expression was promoted in a dose­dependent manner after cytisine treatment. These findings suggest that cytisine induced the ER stress­mediated apoptotic pathway via activation of CHOP, JNK and caspase­4 in HepG2 cells, and cytisine is a potential new target compound for nAchRs (nicotinic acetylcholine receptors) to treat liver cancer.

[Review on skin temperature of acupoints].

We retrieve and analyze the articles on body surface temperature of acupoints in the recent 50 years. Surface temperatures have been compared between acupoints and nonacupoints, and among acupoints in different states. The impacts of interventions for acupoint temperature are explored, including acupuncture,moxibustion and cupping, etc. We summarize the features and the rules of acupoint skin temperature. It is considered that there exists distribution rule for healthy people's acupoint skin temperature. That means acupoints have higher surface temperature than nonacupoints. In the same meridian the nearer acupoints close to the head and trunk, the higher the temperature is. The difference in symmetrical acupoints temperatures between the left and right side is about 0.5℃. In the different meridians the skin temperatures of adjacent acpoints are similar. The changes of acupoint's skin temperature in illness can be used as the auxiliary diagnosis. Acupuncture, moxibustion and cupping can produce acupoints stimulating, metabolism improving, yin-yang balance, acupoint temperature regulating. Thus,diseases are relieved. The specificity and regularity that acupoint's skin temperature presents may be one of the manifestations of the acupoint specificity, also it is an important starting point of the research on acupoint sensitization. The further studies should consider different diseases and modern biological engineering techniques, so that more rules of acupoints temperature can be found by more sensitive and objective temperature measurements as well as experimental and the mathematical models.

Structure-activity relationship study between baicalein and wogonin by spectrometry, molecular docking and microcalorimetry.

Flavones (e.g. baicalein and wogonin) extensively used worldwide in food preparation and traditional medicine. In this study, a systematically comparative study of their structure-activity relationships (SAR) on their interaction with BSA, antioxidant activity and antibacterial activity has been carried out by spectrometry, molecular docking and microcalorimetry. Our results show that the skeleton structure of flavones, the number of hydroxyl groups, the type of functional group, conjugated system and the steric hindrance may be responsible for their different biological activity. These findings not only would lay a scientific foundation for discovering and designing flavones-based food and drug, may also help us to understanding the structure-activity relationship between flavones at the molecular level.

Biocides in the Yangtze River of China: spatiotemporal distribution, mass load and risk assessment.

Nineteen biocides were investigated in the Yangtze River to understand their spatiotemporal distribution, mass loads and ecological risks. Fourteen biocides were detected, with the highest concentrations up to 166 ng/L for DEET in surface water, and 54.3 ng/g dry weight (dw) for triclocarban in sediment. The dominant biocides were DEET and methylparaben, with their detection frequencies of 100% in both phases. An estimate of 152 t/y of 14 biocides was carried by the Yangtze River to the East China Sea. The distribution of biocides in the aquatic environments was significantly correlated to Gross Domestic Product (GDP), total phosphorus (TP) and total nitrogen (TN), suggesting dominant input sources from domestic wastewater of the cities along the river. Risk assessment showed high ecological risks posed by carbendazim in both phases and by triclosan in sediment. Therefore, proper measures should be taken to reduce the input of biocides into the river systems.

[Cardioprotective Effect and Its Mechanism of Total Saponins of Panacis Majoris Rhizoma in Myocardial Infarction Rats].

OBJECTIVE: To explore the cardioprotective effect and its mechanism of total saponins of Panacis Majoris Rhizoma in myocardial infarction (MI) rats. METHODS: The MI model rats induced by ligating anterior descending branch of coronary artery were randomly divided into four group:model group, total saponins of Panacis Majoris Rhizoma (100 and 200 mg/kg) groups and compound Danshen dripping pills group. The rats were orally administrated with drugs once a day for four weeks. Another rats were selected as sham operation group. After four weeks intervention, cardiac function was examined, the serum levels of TNF-α, IL-1ß, IL-6 and IL-8 were measured by using ELISA, respectively. The myocardial hypertrophy index was investigated, the myocardial infarct size, degree of ventricular dilatation, myocardial interstitial collagen volume fraction and tissue morphology were investigated by HE, Masson, picric acid-sirius red staining and observing with alight microscope and electron microscope. Protein expressions of phosphorylation IκB-α( pIκB-α) and NF-κB p65 in heart tissue were detected by Western blotting. RESULTS: Total saponins of Panacis Majoris Rhizoma might significantly decrease the levels of serum TNF-α, IL-1ß, IL-6 and IL-8; decrease myocardial hypertrophy indexes, myocardial infarct size, degree of ventricular dilatation and myocardial interstitial collagen volume fraction; improve heart tissue morphology and cardiac function; downregulate protein expression of pIκB-α and NF-κBp65; and upregulate protein expression of SIRT1. The aforementioned action effects of total saponins of Panacis Majoris Rhizoma (200 mg/kg) were similar with compound Danshen dripping pills. CONCLUSION: Total saponins of Panacis Majoris Rhizoma possesses cardioprotective effect against ligating left anterior descending branch induced MI in rats. The mechanism may be related to strengthening SIRT1 expression, inhibiting the phosphorylation of IκB-α, and finally inhibiting the activation of NF-κB and proinflammatory production.

Simultaneous removal of inorganic and organic compounds in wastewater by freshwater green microalgae.

Batch experiments were carried out for 7 days to investigate the simultaneous removal of various organic and inorganic contaminants including total nitrogen (TN), total phosphorus (TP), metals, pharmaceuticals and personal care products (PPCPs), endocrine disrupting chemicals (EDCs), and estrogenic activity in wastewater by four freshwater green microalgae species, Chlamydomonas reinhardtii, Scenedesmus obliquus, Chlorella pyrenoidosa and Chlorella vulgaris. After treatment for 7 days, 76.7-92.3% of TN, and 67.5-82.2% of TP were removed by these four algae species. The removal of metals from wastewater by the four algae species varied among the metal species. These four algae species could remove most of the metals efficiently (>40% removal), but showed low efficiencies in removing Pb, Ni and Co. The four algae species were also found to be efficient in removing most of the selected organic compounds with >50% removal, and the estrogenic activity with removal efficiencies ranging from 46.2 to 81.1% from the wastewater. Therefore, algae could be harnessed to simultaneously remove various contaminants in wastewater.

[Evaluation of medicinal reasonableness and resource utilization of Dida (Zang Yin Cheng) commonly used in Tibetan medicine].

OBJECTIVE: To evaluate the medicinal reasonableness and resource utilization of Dida from different species. METHOD: With common characteristic absorption peaks of HPLC fingerprints and SPSS cluster, the composition similarity of Dida from different species was evaluated. RESULT: The composition similarity of HPLC fingerprints of 33 Dida samples from 15 species and 1 variety originated from Swertia, Halenia, Gentianopsis, Lomatogonium was difference. The original species can be clustered into four groups by the relative area of 10 common characteristic peaks of HPLC fingerprints. The compositions of four different genera are quite different. CONCLUSION: Because of containing iridoids, xanthones, and triterpenes which have liver protection and cholagogue functions, all of species from Swertia, Halenia, Gentianopsis and Lomatogonium in Gentianaceae are classified as Dida in Tibetan medicine. According to the composition difference among different species, the HPLC fingerprints established for Dida from different source are an effective means to identify nd control the quality of Dida.

[Effect of intraoperative warming on patient undergoing Le Fort I osteotomy].

PURPOSE: To investigate the effect of intraoperative warming on temperature and blood loss of the patient undergoing Le Fort I osteotomy. METHODS: Forty ASA I patients undergoing Le Fort I osteotomy operation under general anesthesia were randomly allocated into two groups (n=20 in each group): control group and warming group. Rectal temperature was measured during the operation in all patients. Patients in warming group were warmed by using circulating-water mattress during operation and the temperature was set at 37 degrees centigrade. Patients in the control group did not receive the circulating-water mattress. Rectal temperature measurement was started after induction of anesthesia and recorded every thirty minutes afterwards. Blood loss, blood transfusion during the operation, extubation time and rate of keeping intubation after operation were recorded. SPSS13.0 software package was used to analyze the date. RESULTS: There was no difference on the temperature of anesthesia induction between the two groups, the temperature of the patients in the control group at other measure time was significantly lower than that in warming group. The temperature after operation in the control group was significantly lower than the temperature of anesthesia induction, and there was no difference in warming group. During the operation, there were (1095 + or - 473 )mL blood loss in the control group and (831 + or - 291)mL in warming group. There was significant difference between the two group. There were no difference in extubation time and rate of keeping intubation after operation between the two groups. CONCLUSIONS: Intraoperative warming for the patient undergoing Le Fort I osteotomy can prevent hypothermia and reduce blood loss during the operation.

Enzymatic properties of a new peptide deformylase from pathogenic bacterium Leptospira interrogans.

Peptide deformylase (LiPDF), a target protein for antibacterial agents from pathogenic bacteria Leptospira interrogans was identified and purified. Enzymatic studies including kinetics and inhibition revealed new inspiring highlights. The purified active enzyme was a dimer and showed a hyperbolic progress plot when the substrate was low but an excess substrate inhibition effect in higher substrate concentration. Variants on the metal-binding ligand-Cys102 were constructed to verify the indispensable attribute. Also the variant, LiPDF with the insertion residues (R(70)Y(71)P(72)G(73)T(74) P(75)D(76)V(77)) between the conserved motif 1 and motif 2 excised, was constructed and displayed no marked changes on enzymatic features. The results of atom absorbance proved that it contains a tightly bound Zn2+ rather than Fe2+ in E. coliPDF that is an essential cofactor for its high catalytic activity.

Field population-based blocking treatment of esophageal epithelia dysplasia.

AIM: To confirm the value of blocking treatment by zenshengping (ZSP), a Chinese herb composite, and Riboflavin for esophageal epithelia dysplasia cases screened out in high risk area in northern china by exfoliative balloon cytology (EBC), so to reduce the incidence rate of esophageal cancer(EC). METHODS: Esophageal epithelium dysplasia cases including mind esophageal epithelium dysplasia (MEED), stage one severe esophageal epithelium dysplasia (SEED I), and stage two severe esophageal epithelium dysplasia (SEED II) were screened out from people aged 40 years and older in the high risk area of Chixian. These cases were randomly divided into a treatment and control group. Subjects in the treatment and control groups took ZSP, riboflavin, and placebo daily for three years. EC cases registered by cancer registry and identified by EBC re-screening in the treatment and control groups were used to calculate incidence and blocking rates to demonstrate the effects of blocking medication. RESULTS: It was found that 31.92% and 24.15% of people aged 40 years and older in Cixian could been diagnosed as MEED and SEED cases. The severity of dysplasia increased with age. ZSP had blocked EC occurrence by 47.79% after 3 year medication among the SEED cases. CONCLUSION: ZSP can block the development from SEED I and SEED II to EC by 47.79%. Efforts should be made to screen and treat dysplasia cases in people aged 40 years and older in high risk areas to reduce the mortality figures.