Sarcanoids A and B, two new lindenane-type sesquiterpenoid dimers from the aerial parts of Sarcandra glabra.

Sarcanoids A and B (1 and 2), two new lindenane-type sesquiterpenoid dimers with a γ-hydroxysenecioate moiety at C-15', were isolated from the ethyl acetate extract of Sarcandra glabra. The structures were elucidated by extensive analysis of spectroscopic data, and their absolute configurations were determined by single-crystal X-ray crystallography. Compounds 1 and 2 showed moderate inhibitory activities on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages.

Analgesia efficacy of lidocaine transfused by a novel disposable injectable cervical dilator during intrauterine device removal procedure: A randomized clinical trial.

OBJECTIVE: The majority of intrauterine devices (IUDs) inserted in China are tailless, requiring intrauterine manipulations for removal and causing pain. This study aimed to investigate the analgesic efficacy of lidocaine injection into a novel disposable injectable cervical dilator for IUD removal procedures. STUDY DESIGN: A double-blinded, placebo-controlled, randomized clinical trial was conducted with women aged 18-65 years old requesting outpatient IUD removal. The study randomly assigned participants to either lidocaine (injecting 5 ml of 2% lidocaine into the injectable cervical dilator) or placebo (injecting 5 ml of normal saline into the device) group. All participants received a standardized paracervical block. The primary outcome was pain reported during IUD removal on a 100 mm Visual Analog Scale (VAS). Intention-to-treat were conducted to evaluate the analgesic effectiveness of injecting lidocaine into the injectable cervical dilators. RESULTS: We enrolled seventy-four eligible participants (37 in lidocaine group and 37 in placebo group). The results showed that the median intraoperative VAS score in the lidocaine group was lower than the placebo group (30.0 mm [IQR 20.0-46.0, n = 37] vs 46.0 mm [IQR 30.0-55.0, n = 37], p = 0.01. In subgroup analyses, among participants with IUD removal and without uterine manipulation and additional procedures, there was no statistically significant disparity observed in intraoperative VAS scores between the lidocaine and placebo group (15.0 mm [IQR 10.0-27.5, n = 8] vs 20.0 mm [IQR 20.0-40.0, n = 6]), p = 0.28). Among participants with an IUD removal necessitating intrauterine manipulations and without additional procedures, showing lower intraoperative VAS scores in lidocaine group (25.0 mm [IQR 15.0-40.5, n = 17]) compared to placebo group (46.0 mm [IQR 38.5-50.0, n = 23]), p < 0.01. Among participants with additional procedures in addition to IUD removal, there was no statistically significant disparity observed in intraoperative VAS scores between the lidocaine and placebo group (41.0 mm [IQR 32.5-57.5, n = 12] vs 45.0 mm [IQR 22.5-69.0, n = 8]), p = 0.97). CONCLUSIONS: Injecting lidocaine into the novel disposable injectable cervical dilator for cervix dilation can significantly reduce pain during an IUD removal, particularly in patients necessitating intrauterine manipulations during IUD removal. IMPLICATIONS: When we have to perform intrauterine manipulations to remove an IUD, surgical pain and narrow cervical canal undoubtedly affect the implementation of the procedure. Injecting lidocaine into the injectable cervical dilator can achieve local anesthesia while dilating the cervix, and might reduce the choice of general anesthesia for IUD removal.

Feasibility and Effectiveness of Hysteroscopic Suture Fixation of the Levonorgestrel-Releasing Intrauterine System in the Treatment of Adenomyosis.

STUDY OBJECTIVE: To evaluate the feasibility and effectiveness of hysteroscopic suture fixation of the levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis. DESIGN: A retrospective case series. SETTING: Two teaching hospitals with the technology of hysteroscopic suture fixation of the LNG-IUS. PATIENTS: The study reviewed 79 adenomyosis patients who received the hysteroscopic suture fixation of the LNG-IUS from January 2021 to May 2022. INTERVENTION: Hysteroscopic suture fixation of the LNG-IUS to the posterior uterine wall with nondissolvable suture. MEASUREMENTS AND MAIN RESULTS: All patients underwent one-year postoperative follow-up to evaluate the LNG-IUS expulsion rate, postoperative efficacy, and side effects. Two patients (2.6%) experienced expulsion of the LNG-IUS at 8 months and 12 months postoperatively, respectively. The visual analog pain scale, pictorial blood loss assessment chart score and carbohydrate antigen 125 markedly decreased after the suture fixation of the LNG-IUS compared with baseline in all patients (p <.001). Hemoglobin increased significantly (p <.001). The most common side effect was irregular bleeding, which accounted for 44.3%. The second common side effect was weight gain, which accounted for 29.2%. The composite effectiveness based on pain and bleeding showed that the effective treatment rates at 1, 3, 6, and 12 months after surgery were 92.4%, 97.4%, 96.2%, and 97.4% respectively. CONCLUSIONS: Hysteroscopic suture fixation of the LNG-IUS to the uterine fundus was associated with low expulsion rates and significantly improved dysmenorrhea and bleeding.

Fabrication of carboxymethyl starch/xanthan gum combinations Pickering emulsion for protection and sustained release of pterostilbene.

Carboxymethyl starch (CMS)/xanthan gum (XG) combinations with different ratios (CMS/XG: 1/1, 3/1, 5/1, 7/1, 9/1, w/w) were used as Pickering emulsion delivery systems to encapsulate pterostilbene (PTS) to improve its stability. The results showed that the Pickering emulsion prepared using CMS/XG combinations could effectively encapsulate PTS. When the mass ratio of CMS to XG was 1:1, the encapsulation efficiency reached 91.20 %. The spherical particles in the PTS emulsion were dissociated and homogenous. The results of backscattered light experiments and storage stability studies showed that the PTS emulsion system prepared using CMS/XG was uniform and stable, with no obvious phase separation or emulsion droplet coalescence. With an increase in the mass ratio of XG, the water distribution in the emulsion became more evenly distributed, and the aggregation of droplets was reduced. The PTS emulsion prepared using CMS/XG improved the storage retention percentage of PTS. The cumulative release of PTS in the simulated gastric fluid was significantly lower than that in simulated intestinal fluid. The Pickering emulsion prepared using CMS/XG combinations can be used as a delivery system for functional foods and help to develop an efficient and reliable release system for hydrophobic bioactive substances.

Role of microRNAs in glycolysis in gynecological tumors (Review).

Gynecological malignancies are a leading cause of mortality among females worldwide, and difficulties in early diagnosis and acquired drug resistance constitute obstacles to effective therapies. Ovarian cancer causes more deaths than any other cancer of the female reproductive system. Specifically, in females aged 20 to 39 years, cervical cancer is the third leading cause of cancer­related mortality, and the incidence rates of cervical adenocarcinoma are increasing. Endometrial carcinoma is the most common gynecological cancer in developed countries, such as the United States. Vulvar cancer and uterine sarcomas are considered rare, and therefore require further investigation. Notably, the development of novel treatment options is critical. Previous research has revealed metabolic reprogramming as a distinct feature of tumor cells, which includes aerobic glycolysis. In this instance, cells produce adenosine triphosphate and various precursor molecules through glycolysis, despite oxygen levels being sufficient. This is to meet the energy required for rapid DNA replication. This phenomenon is also known as the Warburg effect. The Warburg effect results in an increased glucose uptake, lactate production and reduced pH values in tumor cells. The results of previous studies have demonstrated that microRNAs (miRNAs/miRs) regulate glycolysis, and participate in tumorigenesis and tumor progression via interactions with glucose transporters, essential enzymes, tumor suppressor genes, transcription factors and multiple cellular signaling pathways that play critical roles in glycolysis. Notably, miRNAs affect the levels of glycolysis in ovarian, cervical and endometrial cancers. The present review article provides a comprehensive overview of the literature surrounding miRNAs in the glycolysis of gynecological malignant cells. The present review also aimed to determine the role of miRNAs as potential therapeutic options rather than diagnostic markers.

Long noncoding RNAs: glycolysis regulators in gynaecologic cancers.

The three most common gynaecologic cancers that seriously threaten female lives and health are ovarian cancer, cervical cancer, and endometrial cancer. Glycolysis plays a vital role in gynaecologic cancers. Several long noncoding RNAs (lncRNAs) are known to function as oncogenic molecules. LncRNAs impact downstream target genes by acting as ceRNAs, guides, scaffolds, decoys, or signalling molecules. However, the role of glycolysis-related lncRNAs in regulating gynaecologic cancers remains poorly understood. In this review, we emphasize the functional roles of many lncRNAs that have been found to promote glycolysis in gynaecologic cancers and discuss reasonable strategies for future research.

Ginsenoside Rg3, a promising agent for NSCLC patients in the pandemic: a large-scale data mining and systemic biological analysis.

Introduction: Non-small cell lung cancer (NSCLC) patients are particularly vulnerable to the Coronavirus Disease-2019 (COVID-19). Currently, no anti-NSCLC/COVID-19 treatment options are available. As ginsenoside Rg3 is beneficial to NSCLC patients and has been identified as an entry inhibitor of the virus, this study aims to explore underlying pharmacological mechanisms of ginsenoside Rg3 for the treatment of NSCLC patients with COVID-19. Methods: Based on a large-scale data mining and systemic biological analysis, this study investigated target genes, biological processes, pharmacological mechanisms, and underlying immune implications of ginsenoside Rg3 for NSCLC patients with COVID-19. Results: An important gene set containing 26 target genes was built. Target genes with significant prognostic value were identified, including baculoviral IAP repeat containing 5 (BIRC5), carbonic anhydrase 9 (CA9), endothelin receptor type B (EDNRB), glucagon receptor (GCGR), interleukin 2 (IL2), peptidyl arginine deiminase 4 (PADI4), and solute carrier organic anion transporter family member 1B1 (SLCO1B1). The expression of target genes was significantly correlated with the infiltration level of macrophages, eosinophils, natural killer cells, and T lymphocytes. Ginsenoside Rg3 may benefit NSCLC patients with COVID-19 by regulating signaling pathways primarily involved in anti-inflammation, immunomodulation, cell cycle, cell fate, carcinogenesis, and hemodynamics. Conclusions: This study provided a comprehensive strategy for drug discovery in NSCLC and COVID-19 based on systemic biology approaches. Ginsenoside Rg3 may be a prospective drug for NSCLC patients with COVID-19. Future studies are needed to determine the value of ginsenoside Rg3 for NSCLC patients with COVID-19.

Do Deep Regional Trade Agreements Improve Residents' Health? A Cross-Country Study.

The development trend of deepening regional trade agreements (RTAs) is becoming more prominent, traditional RTAs based on border terms continue to shift to deep RTAs based on the high level of border terms and a series of post-border terms, but the relationship between deep RTAs and residents' health has not drawn much attention. Based on Gallup World Poll data from 2009 to 2017 covering 786,040 respondents in 143 countries, this study empirically examined the impact of deep RTAs on the health of residents as well as its influence mechanisms by using the combination of fixed effects and stepwise regression. The results show that deep RTAs have a significantly positive impact on residents' health, which means that an increase in the depth of RTAs can improve residents' health. However, the impact of deep RTAs on residents' health is heterogeneous, caused by the different terms of RTAs, the different income levels of different countries, and the different types of residents. Meanwhile, deep RTAs mainly improve the health of residents through employment effects and environmental effects. This study highlights the importance of deep RTAs for improving the health of residents and provides new ideas for governments to assist in the formulation of policies that can effectively improve their residents' health.

RNA m6A methylation regulators in endometrial cancer (Review).

As one of the three major malignant tumor types of the female reproductive system, endometrial cancer (EC) is the most prevalent gynecologic cancer in developed countries. In recent years, the incidence of EC has increased worldwide, threatening the health and well­being of women. Recent research has indicated that the expression of multiple N6­methyladenosine (m6A) regulators is up­ or downregulated in EC and that abnormalities in m6A methylation and the expression of associated regulators are critical to the pathogenesis and progression of EC. m6A is the most abundant internal modification of mRNA. Several studies have demonstrated a close association between the development and progression of malignant tumors and the epigenetic phenomenon of m6A methylation. In the present study, the current status of research on m6A methylation in EC was reviewed. The mechanisms of methyltransferase, demethylase and m6A binding protein in regulating the development and progression of EC by modifying mRNA were introduced. The related research results will provide novel methods and approaches for the prevention and treatment of EC.

Silk-Based Electrochemical Sensor for the Detection of Glucose in Sweat.

The development of reliable glucose sensors for noninvasive monitoring is highly desirable and essential for diabetes detection. As a testing sample, sweat is voluminous and is easy to collect compared to blood. However, the application of sweat glucose sensors is generally limited because of their low stability and sensitivity compared to commercial glucometers. In this manuscript, a silk nanofibril (SNF)/reduced graphene oxide (RGO)/glucose oxidase (GOx) composite was developed as the working electrode of the sweat glucose sensor. The SNF/RGO/GOx composite was prepared via a facile two-step process, which involved the self-assembly of SNF from silk fibroin while reducing graphene oxide to RGO and immobilizing GOx on SNF. The SNF/RGO/GOx glucose sensor exhibited a low limit of detection (300 nM) and high sensitivity (18.0 µA/mM) in the sweat glucose range, covering both healthy people and diabetic patients (0-100 µM). Moreover, the SNF/RGO/GOx glucose sensors showed a long stability for at least 4 weeks. Finally, the SNF/RGO/GOx glucose sensor was applied to test the actual sweat samples from two volunteers and two sweating methods (by dry sauna and exercise). The results indicate the glucose data tested by the SNF/RGO/GOx glucose sensor were reliable, which correlated well to the data obtained from the commercial glucometer. Therefore, the SNF/RGO/GOx glucose sensor developed in this study may have a great potential for glucose control in personalized healthcare monitoring and chronic disease management.

The Influence of Various Role Models on Children's Pro-environmental Behaviours.

Although most schoolchildren can dispose of their own litter, they are typically not sensitive to environmental issues in the school's public areas. How do we improve children's sensitivity to public environments and cultivate pro-environmental behaviours? Based on Bandura's social learning theory, this study explored the effects of various role models (teachers and peers) on the pro-environmental behaviours of children aged 7-13. A field study was conducted in which examples of postprandial garbage disposal behaviours were provided using role models and the subsequent behaviours of the children were observed. We located the experiment in a real educational context and manipulated the type of role model (teacher or peer) and the behaviour being modelled (positive behaviours involving picking up litter or negative behaviours involving littering). The results showed that different role models had different effects on the subjects' pro-environmental behaviours. Only positive demonstration by teachers significantly improved the subjects' pro-environmental behaviours, that is, teachers' picking up of garbage in front of children significantly improved the children's attention to the environment and their adoption of pro-environmental behaviours. Positive demonstration by peers, negative demonstration by teachers and negative demonstration by peers had no impact on the children's pro-environmental behaviours. The results demonstrate that teachers must be mindful of their role as role models in the educational environment and facilitate students' development of pro-environmental behaviours.

Bioinformatics and System Biology Approach to Reveal the Interaction Network and the Therapeutic Implications for Non-Small Cell Lung Cancer Patients With COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the leading cause of coronavirus disease-2019 (COVID-19), is an emerging global health crisis. Lung cancer patients are at a higher risk of COVID-19 infection. With the increasing number of non-small-cell lung cancer (NSCLC) patients with COVID-19, there is an urgent need of efficacious drugs for the treatment of COVID-19/NSCLC. Methods: Based on a comprehensive bioinformatic and systemic biological analysis, this study investigated COVID-19/NSCLC interactional hub genes, detected common pathways and molecular biomarkers, and predicted potential agents for COVID-19 and NSCLC. Results: A total of 122 COVID-19/NSCLC interactional genes and 21 interactional hub genes were identified. The enrichment analysis indicated that COVID-19 and NSCLC shared common signaling pathways, including cell cycle, viral carcinogenesis, and p53 signaling pathway. In total, 10 important transcription factors (TFs) and 44 microRNAs (miRNAs) participated in regulations of 21 interactional hub genes. In addition, 23 potential candidates were predicted for the treatment of COVID-19 and NSCLC. Conclusion: This study increased our understanding of pathophysiology and screened potential drugs for COVID-19 and NSCLC.

Origami Spring-Inspired Shape Morphing for Flexible Robotics.

Flexible robotics are capable of achieving various functionalities by shape morphing, benefiting from their compliant bodies and reconfigurable structures. In this study, we construct and study a class of origami springs generalized from the known interleaved origami spring, as promising candidates for shape morphing in flexible robotics. These springs are found to exhibit nonlinear stretch-twist coupling and linear/nonlinear mechanical response in the compression/tension region, analyzed by the demonstrated continuum mechanics models, experiments, and finite element simulations. To improve the mechanical performance such as the damage resistance, we establish an origami rigidization method by adding additional creases to the spring system. Guided by the theoretical framework, we experimentally realize three types of flexible robotics-origami spring ejectors, crawlers, and transformers. These robots show the desired functionality and outstanding mechanical performance. The proposed concept of origami-aided design is expected to pave the way to facilitate the diverse shape morphing of flexible robotics.

A Data Mining-Based Analysis of Core Herbs on Different Patterns (Zheng) of Non-Small Cell Lung Cancer.

OBJECTIVE: To explore the role of Chinese prescriptions in non-small cell lung cancer (NSCLC) and provide references for the application of herbs and prescriptions. METHODS: Randomized and quasirandomized controlled clinical trials on Chinese herbal medicine in the treatment of NSCLC were collected from seven databases to establish a database of prescriptions on NSCLC. Data-mining analyses were performed by RStudio (v4.0.3) software. RESULTS: A total of 970 prescriptions were obtained from 945 included studies, involving 7 syndromes and 428 herbs. The main patterns of NSCLC included qi deficiency pattern, yin deficiency pattern, blood deficiency pattern, kidney deficiency pattern, heat toxin pattern, phlegm-dampness pattern, and blood stasis pattern. High-frequency herbs on NSCLC were Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizome (Baizhu), Glycyrrhizae Radix Rhizome (Gancao), Poria (Fuling), Ophiopogonis Radix (Maidong), Hedyotidis Diffusae Herba (Baihuasheshecao), Codonopsis Radix (Dangshen), and Glehniae Radix (Beishashen). The properties of the herbs were mainly cold, warm, and mild. The flavors of the herbs were mainly sweet, bitter, and pungent. The main meridian tropisms were Lung Meridian of Hand-Taiyin, Spleen Meridian of Foot-Taiyin, and Stomach Meridian of Foot-Yangming. CONCLUSION: Applying clearing and tonifying method by targeting the lung and spleen was the most frequently used therapy in the treatment of NSCLC. This study offered a glimpse of unique views of traditional Chinese medicine on NSCLC and may benefit the treatment of NSCLC.

Intelligent Shape-Morphing Micromachines.

Intelligent machines are capable of switching shape configurations to adapt to changes in dynamic environments and thus have offered the potentials in many applications such as precision medicine, lab on a chip, and bioengineering. Even though the developments of smart materials and advanced micro/nanomanufacturing are flouring, how to achieve intelligent shape-morphing machines at micro/nanoscales is still significantly challenging due to the lack of design methods and strategies especially for small-scale shape transformations. This review is aimed at summarizing the principles and methods for the construction of intelligent shape-morphing micromachines by introducing the dimensions, modes, realization methods, and applications of shape-morphing micromachines. Meanwhile, this review highlights the advantages and challenges in shape transformations by comparing micromachines with the macroscale counterparts and presents the future outlines for the next generation of intelligent shape-morphing micromachines.

Structural Changes in Spider Dragline Silk after Repeated Supercontraction-Stretching Processes.

Spider dragline silk is well-known for its excellent combination of strength and extensibility as well as another unique property called supercontraction. In our previous work, the changes in conformations of the Nephila edulis spider dragline silk when subjected to different supercontraction processes were extensively investigated. When a native spider dragline silk had free supercontraction, and then restretched to its original length, the content and molecular orientation of different conformations (ß-sheet, helix, and random coil) changed but the mechanical properties remained almost the same. Therefore, herein, further supercontraction-stretching treatment was performed up to three cycles, and the corresponding structural changes were investigated. In addition to the synchrotron radiation FTIR (S-FTIR) microspectroscopy employed in our previous study, synchrotron radiation small-angle X-ray scattering (S-SAXS) and atomic force microscopy (AFM) were also used in this work to determine the structural changes of spider dragline silk in different scales. The results show that by repeating the supercontraction-stretching treatment, the ß-sheet structure content in spider dragline silk was slightly increased, but its orientation degree remained almost the same. Also, with the increase in cycle of supercontraction-stretching treatments, a 10.5 nm long period perpendicular to the silk fiber axis gradually appeared, endowing the spider dragline silk with periodic structure both along (6.6 nm, already existed in native silk and did not change with the supercontraction-stretching treatment) and perpendicular to the silk fiber axis. After the third supercontraction-stretching cycle, the AFM images displayed a clear 210 nm × 80 nm corn kernel-like structure on the surface of nanofibrils in spider dragline silks, which may be related to the aggregation of 10.5 nm × 6.6 nm periodic structure observed via S-SAXS. Finally, although the structure of spider dragline silk became increasingly regular with the rise in supercontraction-stretching cycles, mechanical properties remained constant after every cycle of the supercontraction-stretching treatment. These findings can aid in further understanding the structural changes that are related to the supercontraction of spider dragline silk and provide useful guidance in fabrication of high-performance regenerated or artificial silk fibers.

Bmapaf-1 is Involved in the Response against BmNPV Infection by the Mitochondrial Apoptosis Pathway.

Discovery of the anti-BmNPV (Bombyx mori nuclearpolyhedrovirus) silkworm strain suggests that some kind of antiviral molecular mechanism does exist but is still unclear. Apoptosis, as an innate part of the immune system, plays an important role in the response against pathogen infections and may be involved in the anti-BmNPV infection. Several candidate genes involved in the mitochondrial apoptosis pathway were identified from our previous study. Bombyx mori apoptosis protease-activating factor-1 (Bmapaf-1) was one of them, but the antiviral mechanism is still unclear. In this study, sequences of BmApaf-1 were characterized. It was found to contain a unique transposase_1 functional domain and share high CARD and NB-ARC domains with other species. Relatively high expression levels of Bmapaf-1 were found at key moments of embryonic development, metamorphosis, and reproductive development. Further, the significant difference in expression of Bmapaf-1 in different tissues following virus infection indicated its close relationship with BmNPV, which was further validated by RNAi and overexpression in BmN cells. Briefly, infection of budded virus with enhanced green fluorescent protein (BV-EGFP) was significantly inhibited at 72 h after overexpression of Bmapaf-1, which was confirmed after knockdown of Bmapaf-1 with siRNA. Moreover, the downstream genes of Bmapaf-1, including Bmnedd2-like caspase (BmNc) and Bmcaspase-1 (Bmcas-1), were upregulated after overexpression of Bmapaf-1 in BmN cells, which was consistent with the RNAi results. Furthermore, the phenomenon of Bmapaf-1 in response to BmNPV infection was determined to be related to apoptosis using the apoptosis inducer NSC348884 and inhibitor Z-DEVD-FMK. Therefore, Bmapaf-1 is involved in the response against BmNPV infection by the mitochondrial apoptosis pathway. This result provides valuable data for clarifying the anti-BmNPV mechanism of silkworms and breeding of resistant silkworm strains.

A Comprehensive Network Pharmacology-Based Strategy to Investigate Multiple Mechanisms of HeChan Tablet on Lung Cancer.

BACKGROUND: HeChan tablet (HCT) is a traditional Chinese medicine preparation extensively prescribed to treat lung cancer in China. However, the pharmacological mechanisms of HCT on lung cancer remain to be elucidated. METHODS: A comprehensive network pharmacology-based strategy was conducted to explore underlying mechanisms of HCT on lung cancer. Putative targets and compounds of HCT were retrieved from TCMSP and BATMAN-TCM databases; related genes of lung cancer were retrieved from OMIM and DisGeNET databases; known therapeutic target genes of lung cancer were retrieved from TTD and DrugBank databases; PPI networks among target genes were constructed to filter hub genes by STRING. Furthermore, the pathway and GO enrichment analysis of hub genes was performed by clusterProfiler, and the clinical significance of hub genes was identified by The Cancer Genome Atlas. RESULT: A total of 206 compounds and 2,433 target genes of HCT were obtained. 5,317 related genes of lung cancer and 77 known therapeutic target genes of lung cancer were identified. 507 unique target genes were identified among HCT-related genes of lung cancer and 34 unique target genes were identified among HCT-known therapeutic target genes of lung cancer. By PPI networks, 11 target genes AKT1, TP53, MAPK8, JUN, EGFR, TNF, INS, IL-6, MYC, VEGFA, and MAPK1 were identified as major hub genes. IL-6, JUN, EGFR, and MYC were shown to associate with the survival of lung cancer patients. Five compounds of HCT， quercetin, luteolin, kaempferol, beta-sitosterol, and baicalein were recognized as key compounds of HCT on lung cancer. The gene enrichment analysis implied that HCT probably benefitted patients with lung cancer by modulating the MAPK and PI3K-Akt pathways. CONCLUSION: This study predicted pharmacological and molecular mechanisms of HCT against lung cancer and could pave the way for further experimental research and clinical application of HCT.

Effect of interleukin-22 on osteogenic differentiation and the osteoclastogenic response of human periodontal ligament fibroblasts in vitro.

BACKGROUND: Interleukin-22 (IL-22) exerts extensive biological effects, playing both protective and pathological roles in autoimmune and infectious diseases. However, the specific role and mechanism of IL-22 in the pathogenesis of periodontitis have not been clarified. The aim of this study was to analyze the possible roles of IL-22 in the osteoclastogenesis and osteogenesis of periodontitis. METHODS: Human periodontal ligament fibroblasts (hPDLFs) were treated with IL-22 and/or lipopolysaccharide from Porphyromonas gingivalis (Pg-LPS), and the mRNA and protein expression of RANKL and OPG were measured by qRT-PCR and Western blotting, respectively. Western blotting was also used to examine the phosphorylated and total protein expression of MAPK signaling molecules. The role of the MAPK pathway in osteoclastogenesis marker expression was further confirmed by inhibition assays. For osteogenic assays, the mRNA expression of osteoblastic markers was quantified by qRT-PCR, the alkaline phosphatase (ALP) activity of hPDLFs was measured by an ALP assay, and the mineralized nodules formed by hPDLFs were determined by Alizarin Red S staining. RESULTS: IL-22 promoted the expression of RANKL in hPDLFs via the MAPK signaling pathway and further upregulated RANKL expression together with Pg-LPS via the p38 MAPK pathway. IL-22 could enhance the ALP activity and mineralized nodule formation of hPDLFs in the early period of osteogenic induction, while exhibiting no profound effect on the expression of osteoblastic markers. CONCLUSION: IL-22 plays regulatory roles in bone homeostasis, and it is likely to contribute to osteoclastogenesis as a proinflammatory cytokine in the pathogenesis of periodontitis.

Research on the roles of genes coding ATP-binding cassette transporters in Porphyromonas gingivalis pathogenicity.

Porphyromonas gingivalis, as a major pathogen of periodontitis, could rapidly adhere to and invade host gingival epithelial cells (GECs) for the induction of infection. One ATP-binding cassette (ABC) transporter gene was found to be upregulated during this infection process, however, the molecular mechanisms remain unclear. In this study, we systemically investigated the messenger RNA level changes of all ABC transporter family genes in P. gingivalis while being internalized within GECs by real-time polymerase chain reaction. We identified that two ABC transporter genes, PG_RS04465 (PG1010) and PG_RS07320 (PG1665), were significantly increased in P. gingivalis after coculturing with GECs. Mutant strains with knockout (KO) of these two genes were generated by homogenous recombination. PG_RS04465 and PG_RS07320 KO mutants showed no change in the growth of bacteria per se. Knockdown of PG_RS07320, but not PG_RS04465, caused decreased endotoxin level in the bacteria. In contrast, both mutant strains showed decreased Arg- and Lys-gingipains activities, with significantly reduced adhesion and invasion capabilities. Secreted interleukin-1ß (IL-1ß) and IL-6 levels in GECs cocultured with PG_RS04465 or PG_RS07320 KO mutants were also decreased, whereas, only the cells cocultured with PG_RS07320 KO mutants showed significant decrease. In addition, virulence study using mouse revealed that both KO mutant strains infection caused less mouse death than wild-type strains, showing reduced virulence of two KO strains. These results indicated that ABC transporter genes PG_RS04465 and PG_RS07320 are positive regulators of the virulence of P. gingivalis.