A Real-World Retrospective Study to Evaluate the Reliability of Cetuximab plus Capecitabine versus Capecitabine as Maintenance Therapy in Patients with RAS and BRAF Wild-Type Metastatic Colorectal Cancer.

BACKGROUND: The optimal maintenance therapy for rat sarcoma (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) metastatic colorectal cancers (mCRCs) remains unclear. It is critical to evaluate the reliability of cetuximab-capecitabine (the observation group) relative to capecitabine alone (control group). PATIENTS AND METHODS: In this retrospective analysis, patients with RAS and BRAF mCRC admitted to Huizhou Municipal Central Hospital, between January 2016 and October 2020 were enrolled and treated with cetuximab plus 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as an initial therapy. Patients whose disease was controlled after at least six cycles of treatment were administered a maintenance therapy until disease progression. We also analyzed the prognosis of patients according to clinicopathological features. Altogether, 39 RAS and BRAF mCRC patients were recruited from January 2016 to October 2020, with 18 cases in the treatment group and 21 cases in the control group. The difference in baseline clinicopathological features between the two treatments is not obvious. RESULTS: The median progression-free survival after maintenance treatment in observation group (9.5 months [95% confidence interval (CI) = 6.4-12.6]), was significantly better than the control group (7.3 months [95% CI = 5.8-8.8]). During maintenance treatment, there were no deaths caused by treatment-related adverse events, and the overall incidence of rash acne was different between the observation and control groups (p < 0.05). Most adverse events were mild and easily controlled. Primary tumor site, baseline carcinoembryonic antigen levels, and microsatellite instability status were independent prognostic factors. CONCLUSION: Maintenance therapy using cetuximab plus capecitabine improved survival in patients with mCRC and was well tolerated by patients.

Circ_CSPP1 Regulates the Development of Non-small Cell Lung Cancer via the miR-486-3p/BRD9 Axis.

In this study, we explored the role of circ_CSPP1 in non-small cell lung cancer (NSCLC) using NSCLC cell lines (A549 and H1299) and human bronchial epithelioid cells (16HBE). The differential expression of circ_CSPP1, miR-486-3p and BRD9 in NSCLC by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot in A549 cells, H1299 cells, 16HBE cells, NSCLC tissues and healthy lung tissues. Dual-luciferase reporter assay was conducted to verify the interaction between circ_CSPP1 and miR-486-3p or miR-486-3p and BRD9. The effect of circ_CSPP1/miR-486-3p/BRD9 axis on NSCLC cell proliferation was evaluated using cell counting kit-8 assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine assay. Additionally, transwell assays were performed to evaluate the effect of circ_CSPP1/miR-486-3p/BRD9 axis on A549 and H1299 cell migration and invasion. The effect of circ_CSPP1 on tumor tumorigenesis of A549 cells in vivo was determined by xenograft tumor model and immunohistochemistry assay. Circ_CSPP1 and BRD9 expression were upregulated, while miR-486-3p expression was downregulated in tumor tissues of NSCCL patients and A549 and H1299 cells. Circ_CSPP1 specifically bound miR-486-3p, and miR-486-3p could target BRD9. Circ_CSPP1 upregulation promoted proliferation, invasion and migration of NSCLC cells, circ_CSPP1 knockdown or miR-486-3p upregulation had the opposite effects. Circ_CSPP1 knockdown-induced effects were reverted by miR-486-3p inhibition. Similarly, the effects of miR-486-3p upregulation on NSCLC cell proliferation, invasion and migration were reversed by BRD9 overexpression. In addition, circ_CSPP1 silencing inhibited tumor growth in nude mice. Circ_CSPP1 promoted A549 and H1299 cell malignancy by competitively inhibiting BRD9 and binding to miR-486-3p.

Integrated Metabolome and Lipidome Strategy to Reveal the Action Pattern of Paclobutrazol, a Plant Growth Retardant, in Varying the Chemical Constituents of Platycodon Root.

Platycodon root, a medicinal food homology species which has been used in Asian countries for hundreds of years, is now widely cultivated in China. Treatment with paclobutrazol, a typical plant growth retardant, has raised uncertainties regarding the quality of Platycodon root, which have been rarely investigated. In the present study, metabolomic and lipidomic differences were revealed by ultra-high performance liquid chromatography coupled to ion mobility-quadrupole time of flight mass spectrometry (UPLC-IM-QTOF-MS). A significant decrease of platycodigenin-type saponins was observed in the paclobutrazol-treated sample. Carrying out a comprehensive quantitative analysis, the contents of total saponins and saccharides were determined to illustrate the mode of action of paclobutrazol on Platycodon root. This study demonstrated an exemplary research model in explaining how the exogenous matter influences the chemical properties of medicinal plants, and therefore might provide insights into the reasonable application of plant growth regulators.

An innovative three-layer strategy in response to a quartan malaria outbreak among forest goers in Hainan Island, China: a retrospective study.

BACKGROUND: An outbreak of Plasmodium malariae infection among forest goers in Sanya City of Hainan Island, China was reported in 2015. In response to this outbreak, an innovative three-layer strategy (TLS) targeted forest goers was adapted based on the 1-3-7 approach. MAIN TEXT: Key elements of TLS are: (i) The village with five malaria cases and adjacent villages were set as the first layer. All residents including forest goers were taken as the high-risk population (HRP). Active case detection (ACD) by blood smear microscopy and PCR was selected as the primary measure, and passive case detection (PCD) as complementary measure. One case was identified under TLS implementation. (ii) The township with cases (Gaofeng Town) and the nearby towns were chosen as the second layer. Only forest goers were screened by ACD, while PCD as a routine screening method. 7831 blood smears collected by ACD and PCD and tested with negative results. (iii) The city with cases (Sanya City) and others 12 counties/county-level cities were selected as the third layer. Malaria cases were monitored passively. A total of 77,555 blood slides were screened by PCD with zero positive sample. For each layer, the malaria vector mosquitoes were monitored using light traps, cattle-baited/human-bait traps. Anopheles minimus (dominant species), An. sinensis and An. dirus were captured. Vector control measures mainly include insecticide residual spraying and long-lasting insecticide nets. The capacity of clinicians, public health practitioners and laboratory technicians has been improved through training. During 2016‒2018, TLS and chemoprophylaxis were implemented in the same areas. In the first layer, all residents were monitored by ACD, and malaria chemoprophylaxis were distributed, 89.5% of forest goers were using chemoprophylaxis against malaria. The blood smears (3126 by ACD plus 1516 by PCD) were with zero positive results. Chemoprophylaxis and ACD were offered to forest goers once a year, and PCD in residents as a complementary measure in the second and third layer, 77.8% and 95.1% of forest goers received chemoprophylaxis. In each layer, vector surveillance and control of malaria and trainings for medical staff were still in place. CONCLUSIONS: TLS was effective in blocking the outbreak by P. malariae among forest goers in Hainan in malaria elimination stage. However, whether it could prevent the malaria resurgence in the post-elimination phase needs to be further assessed.

Discovering a Four-Gene Prognostic Model Based on Single-Cell Data and Gene Expression Data of Pancreatic Adenocarcinoma.

Background: Pancreatic cancer has a 5-year overall survival lower than 8%. Pancreatic adenocarcinoma (PAAD) is the most common type. This study attempted to explore novel molecular subtypes and a prognostic model through analyzing tumor microenvironment (TME). Materials and Methods: Single-cell RNA sequencing (scRNA-seq) data and expression profiles from public databases were downloaded. Three PAAD samples with single-cell data and 566 samples with gene expression data were included. Seurat was used to identify cell subsets. SVA merged and removed batch effects from multichip datasets. CIBERSORT was used to evaluate the components of different cells in transcriptome, ConsensusClusterPlus was used to identify molecular subtypes, and gene set enrichment analysis was used for functional enrichment analysis. LASSO Cox was performed to construct dimensionality reduction and prognosis model. Results: Memory B cells (MBCs) were identified to be significantly with PAAD prognosis. Two immune subtypes (IS1 and IS2) with distinct overall survival were constructed. Forty-one DEGs were identified between IS1 and IS2. Four prognostic genes (ANLN, ARNTL2, SERPINB5, and DKK1) were screened to develop a prognostic model. The model was effective in classifying samples into high-risk and low-risk groups with distinct prognosis. Three subgroups of MBCs were identified, where MBC_0 and MBC_1 were differentially distributed between IS1 and IS2, high-risk and low-risk groups. Conclusions: MBCs were closely involved in PAAD progression, especially MBC_0 and MBC_1 subgroups. The four-gene prognostic model was predictive of overall survival and could guide immunotherapy for patients with PAAD.

Non-contact electrical stimulation as an effective means to promote wound healing.

Electrical stimulation has been demonstrated to have beneficial effects in skin tissue repair. However, most electrical stimulations are applied with percutaneous electrode, which is prone to causing serious trauma. Using non-contact electrical stimulation (NCES) is expected to reduce the potential risk. In this study, NCES was expediently exerted by a self-designed practical device. Electrode plates of 10-cm spacing with appropriate side lengths of 21 and 30 cm were selected by EF distribution analysis for applying NCES to cells and mice, respectively, and the real EF strengths were measured. The change of loading voltage which had no effect on the regular pattern of EF distribution could be used as a single factor to explore the effect of NCES on wound healing. It was subsequently demonstrated that 53 mV mm-1 NCES facilitated the migration and proliferation of HaCaT cells and HDFs in vitro, and the M2-type polarization of macrophages. Moreover, 54 and 84 mV mm-1 NCESs accelerated the wound healing rate of model mice from the perspective of reducing scarring, enhancing collagen synthesis and increasing angiogenesis in vivo. The promoting role of NCES in wound healing showed the potential to initiate new possibilities for the clinical treatment of skin tissue injuries.

Comprehensive profiling of Platycodonis radix in different growing regions using liquid chromatography coupled with mass spectrometry: from metabolome and lipidome aspects.

Platycodon grandiflorus (Jacq.) A. DC. is widely cultivated across the south and north of China. Its root, Platycodonis radix, is commonly used as a vegetable, functional food, and traditional herbal medicine with various biological benefits. It is critical to fully clarify the chemical composition of Platycodonis radix for the sake of the food industry and traditional herb markets. In this study, a strategy of metabolome and lipidome profiling based on ultra-high performance liquid chromatography coupled to ion mobility-quadrupole time of flight mass spectrometry (UPLC-IM-QTOF-MS) was developed to reveal the overall chemical composition of Platycodonis radix. IN particular, comprehensive lipidome profiling was first performed for Platycodonis radix, in which 170 lipid molecular species including 55.9% glycerophospholipids, 31.2% glycerolipids, and 12.9% sphingolipids were identified. Platycodonis radix from two major production regions in China, Inner Mongolia and Anhui province, were collected and analyzed by the MS based approach combined with multivariate statistical analysis from both the metabolome and lipidome aspects. This study threw focus on the profiling investigations of Platycodonis radix from different growing regions and provided new potential in the lipidome analysis of medicinal food.

LncRNA SNHG11 enhances bevacizumab resistance in colorectal cancer by mediating miR-1207-5p/ABCC1 axis.

Long noncoding RNAs (lncRNAs) have been reported to serve as vital regulators in the chemoresistance of human cancers, including colorectal cancer (CRC). In this study, we aimed to explore the functions of lncRNA small nucleolar RNA host gene 11 (SNHG11) in the resistance of CRC to bevacizumab. Quantitative real-time PCR, western blot assay or immunohistochemistry assay were performed to examine the expression of SNHG11, microRNA-1207-5p (miR-1207-5p), ATP binding cassette subfamily C member 1 (ABCC1) and Ki67. Cell Counting Kit-8 assay was conducted to evaluate bevacizumab resistance and cell viability. 5'-ethynyl-2'-deoxyuridine analysis, flow cytometry analysis and wound-healing assay were conducted for cell proliferation, apoptosis and migration, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to analyze the relations among SNHG11, miR-1207-5p and ABCC1. Murine xenograft model assay was employed to analyze bevacizumab resistance in vivo. The exosomes were observed under transmission electron microscopy. SNHG11 was overexpressed in bevacizumab-resistant CRC tissues and cells. Knockdown of SNHG11 restrained bevacizumab resistance, repressed cell proliferation and migration, and promoted apoptosis in bevacizumab-resistant CRC cells. MiR-1207-5p served as the target of SNHG11 and SNHG11 regulated bevacizumab resistance by targeting miR-1207-5p. ABCC1 was the target gene of miR-1207-5p. Overexpression of miR-1207-5p inhibited bevacizumab resistance and cell progression in bevacizumab-resistant CRC cells, with ABCC1 elevation abrogated the impacts. SNHG11 silencing repressed bevacizumab resistance in vivo. In addition, exosomal SNHG11 was upregulated in bevacizumab-resistant CRC cells. SNHG11 contributes to bevacizumab resistance in CRC depending on the modulation of miR-1207-5p and ABCC1.

Circ_0101802 Facilitates Colorectal Cancer Progression Depending on the Regulation of miR-665/DVL3 Signaling.

Colorectal cancer (CRC) is a common malignancy in both men and women, and the prognosis of CRC patients is still unsatisfactory. We aimed to identify novel effective diagnostic and prognostic targets for CRC. The study design is listed as below: we first confirmed the linear correlation between the expression of disheveled 3 (DVL3) and circular RNA_0101802 (circ_0101802) in CRC tissues, and their functional correlation in CRC cells was verified by rescue assays. Subsequently, bioinformatics databases were used to search the common interacted microRNAs (miRNAs) of DVL3 and circ_0101802, and compensation experiments were conducted to verify the functional correlation between miR-665 and DVL3 in CRC cells. Finally, xenograft tumor model was established to confirm the role of circ_0101802/miR-665/DVL3 axis in tumor growth in vivo. The expression of DVL3 and circ_0101802 was elevated in CRC tissues and cell lines, and high levels of DVL3 and circ_0101802 were closely associated with short survival time of CRC patients. Circ_0101802 silencing restrained the proliferation, migration, and tube formation abilities and induced the apoptosis of CRC cells. Circ_0101802 silencing-induced anti-tumor effects in CRC cells were partly reversed by DVL3 overexpression. miR-665 was an intermediary molecule between circ_0101802 and DVL3, and circ_0101802 could positively regulate DVL3 protein expression by sponging miR-665 in CRC cells. DVL3 overexpression partly overturned miR-665 overexpression-mediated anti-tumor effects in CRC cells. Circ_0101802 knockdown significantly suppressed xenograft tumor growth in vivo. In conclusion, circ_0101802 contributed to CRC progression by targeting miR-665/DVL3 signaling.

Efficacy and safety analysis of bevacizumab combined with capecitabine in the maintenance treatment of RAS-mutant metastatic colorectal cancer.

WHAT IS KNOWN AND OBJECTIVES: The optimal strategy for maintenance therapy in patients with metastatic colorectal cancer (mCRC) remains controversial. Considering that, beyond progression, co-therapy with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate. We aimed to investigate the differences in efficacy and safety between bevacizumab combined with capecitabine maintenance therapy and capecitabine monotherapy for RAS-mutant mCRC （as defined by mutations in KRAS and NRAS exons 2-4）controlled by bevacizumab plus FOLFIRI chemotherapy for at least 12 weeks. METHODS: We retrospectively analysed patients with RAS-mutant mCRC admitted to the Department of Oncology, Huizhou Municipal Central Hospital from December, 2015 to December, 2020. All patients were first treated with bevacizumab combined with FOLFIRI for at least 12 weeks of induction therapy. 154 patients whose disease was brought under control then continued maintenance therapy. 78 patients were in the observation group (bevacizumab plus capecitabine) and 76 patients were in the control group (capecitabine alone). The efficacy and adverse effects of maintenance treatment were compared between the two groups. The clinicopathological characteristics such as sex, age, performance status (PS) score, primary tumour site, degree of pathological differentiation, baseline carcinoembryonic antigen (CEA) level, microsatellite instability (MSI) status, number of metastatic tumour sites and efficacy of induction treatment were compared in terms of prognosis. RESULTS AND DISCUSSION: The median progression-free survival (mPFS)of patients was 9.0 months (95% CI 8.0-10.0) in the observation group and 7.2 months (95% CI 6.0-8.4) in the control group, with a statistically significant difference (p < 0.05). The baseline CEA level was an independent prognostic factor. Both groups tolerated the toxic side effects. WHAT IS NEW AND CONCLUSION: Bevacizumab combined with capecitabine was well tolerated and contributed to a longer PFS time than capecitabine alone, and it is worthy of popularization in clinical practice.

Development and validation of a radiomics-based model to predict local progression-free survival after chemo-radiotherapy in patients with esophageal squamous cell cancer.

PURPOSE: To develop a nomogram model for predicting local progress-free survival (LPFS) in esophageal squamous cell carcinoma (ESCC) patients treated with concurrent chemo-radiotherapy (CCRT). METHODS: We collected the clinical data of ESCC patients treated with CCRT in our hospital. Eligible patients were randomly divided into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) with COX regression was performed to select optimal radiomic features to calculate Rad-score for predicting LPFS in the training cohort. The univariate and multivariate analyses were performed to identify the predictive clinical factors for developing a nomogram model. The C-index was used to assess the performance of the predictive model and calibration curve was used to evaluate the accuracy. RESULTS: A total of 221 ESCC patients were included in our study, with 155 patients in training cohort and 66 patients in validation cohort. Seventeen radiomic features were selected by LASSO COX regression analysis to calculate Rad-score for predicting LPFS. The patients with a Rad-score ≥ 0.1411 had high risk of local recurrence, and those with a Rad-score < 0.1411 had low risk of local recurrence. Multivariate analysis showed that N stage, CR status and Rad-score were independent predictive factors for LPFS. A nomogram model was built based on the result of multivariate analysis. The C-index of the nomogram was 0.745 (95% CI 0.7700-0.790) in training cohort and 0.723(95% CI 0.654-0.791) in validation cohort. The 3-year LPFS rate predicted by the nomogram model was highly consistent with the actual 3-year LPFS rate both in the training cohort and the validation cohort. CONCLUSION: We developed and validated a prediction model based on radiomic features and clinical factors, which can be used to predict LPFS of patients after CCRT. This model is conducive to identifying the patients with ESCC benefited more from CCRT.

Comprehensive characterization of the chemical constituents in Platycodon grandiflorum by an integrated liquid chromatography-mass spectrometry strategy.

Platycodon grandiflorum (PG), as a well-known medicine food homology species, possess various pharmacological effects and health benefits. Aiming to facilitate in-depth and global characterization of the chemical compositions of PG, a profiling method based on ultra-high performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) was conducted. Consequently, as many as 187 compounds were plausibly or unambiguously identified. Most importantly, phospholipids (PLs) were first observed and identified in PG. Due to their widely confirmed bioactivities, an analysis scheme was developed by hydrophilic interaction liquid chromatography and electrospray ionization tandem mass spectrometry combined with the online Paternò-Büchi reaction (HILIC-PB-MS/MS). The fatty acyl chains and C=C locations of 180 PLs molecular species, which fell into four classes, were unprecedently characterized. This exposure strategy of multi-type constituents greatly enriches the chemical profiling of PG, and helps promoting the further development of therapeutic agents and nutraceutical products from PG.

Disruption of the structural and functional connectivity of the frontoparietal network underlies symptomatic anxiety in late-life depression.

The present study investigated functional connectivity and white matter integrity of the fronto-parietal network (FPN) to reveal the neural mechanisms that underlie late-life depression (LLD). Fifty patients with LLD and 40 non-depressed controls were included in the study. A multi-parametric approach was used by applying independent component analysis (ICA) to estimate functional connectivity of the FPN and by applying tract-based spatial statistics to examine white-matter integrity in tracts to the FPN. Patients with LLD exhibited functional abnormalities in the right inferior frontal gyrus, middle frontal gyrus, and inferior parietal gyrus and lower white matter fractional anisotropy in the right inferior fronto-occipital fasciculus, anterior thalamic radiation, and uncinate fasciculus. Alterations of functional connectivity and white matter fractional anisotropy in these regions were negatively correlated with the severity of symptomatic anxiety in LLD patients. The right inferior frontal gyrus might be a crucial hub in transferring information between these abnormal regions. Significant correlations were found between anxiety symptoms and brain alterations, suggesting that impairments in the FPN network might be involved in symptomatic anxiety in elderly individuals with depression.

Psychological impact of the COVID-19 pandemic on healthcare workers: a cross-sectional study in China.

BACKGROUND: Healthcare workers fighting against the coronavirus disease 2019 (COVID-19) pandemic are under tremendous pressure, which puts them at an increased risk of developing psychological problems. AIMS: This study aimed to investigate the prevalence of psychological problems in different healthcare workers (ie, physicians, medical residents, nurses, technicians and public health professionals) during the COVID-19 pandemic in China and explore factors that are associated with the onset of psychological problems in this population during this public health crisis. METHODS: A cross-sectional, web-based survey was conducted in February 2020 among healthcare workers during the COVID-19 pandemic. Psychological problems were assessed using the Generalized Anxiety Disorder Scale, Patient Health Questionnaire and Insomnia Severity Index. Logistic regression analyses were used to explore the factors that were associated with psychological problems. RESULTS: The prevalence of symptoms of anxiety, depression, insomnia and the overall psychological problems in healthcare workers during the COVID-19 pandemic in China was 46.04%, 44.37%, 28.75% and 56.59%, respectively. The prevalence of the overall psychological problems in physicians, medical residents, nurses, technicians and public health professionals was 60.35%, 50.82%, 62.02%, 57.54% and 62.40%, respectively. Compared with healthcare workers who did not participate in front-line work, front-line healthcare workers had a higher risk of anxiety, insomnia and overall psychological problems. In addition, attention to negative or neutral information about the pandemic, receiving negative feedback from families and friends who joined front-line work, and unwillingness to join front-line work if given a free choice were three major factors for these psychological problems. CONCLUSIONS: Psychological problems are pervasive among healthcare workers during the COVID-19 pandemic. Receiving negative information and participating in front-line work appear to be important risk factors for psychological problems. The psychological health of different healthcare workers should be protected during the COVID-19 pandemic with timely interventions and proper information feedback.

Application of Acupuncture Acupoint Visual Teaching System by Neural Regulation.

OBJECTIVES: This thesis uses the traditional Chinese medicine theory as its background. This article analyzes in detail the visual teaching system for acupuncture on the human body to solve the problems of insufficient teaching resources and waste of corpses used in teaching. The dissertation is based on the mobile platform development technology of the Android operating system. Based on this, researchers have developed a visual teaching system for human acupuncture points based on digital platforms and mobile devices. This system presents acupuncture knowledge with mobile learning method. It can be displayed systematically on the selected human acupoint anatomy teaching model for 14 common clinical conditions. This article provides an intuitive and dynamic teaching method by presenting a system should realize modern digital teaching and application of traditional acupuncture theory.

SNHG11 promotes cell proliferation in colorectal cancer by forming a positive regulatory loop with c-Myc.

Dysregulation of long non-coding RNAs (lncRNA) have long been linked to the onset and development of colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Small nucleolar RNA host gene 11 (SNHG11) is a novel lncRNA with few information about its role in development and progression of CRC. Here, we found SNHG11, a highly conserved lncRNA, was commonly overexpressed in various cancer including CRC. High expression of SNHG11 correlated with poor prognosis in patients with CRC. Gain of function and loss-of function experiments showed that SNHG11 visibly promoted proliferation in CRC cells. Mechanistic assays revealed that SNHG11 interacted with Insulin-like growth factor 2 (IGF2) mRNA-binding protein 1 (IGF2BP1), thereby enhancing the interaction between IGF2BP1 and c-Myc mRNA, a well-known target of IGF2BP1. Consequently, c-Myc mRNA expression was stabilized and its downstream targets were significantly upregulated. Further investigation demonstrated that SNHG11 upregulated c-Myc which in turn transcriptionally upregulated SNHG11. Taken together, our findings suggested that reciprocal regulation of SNHG11 and c-Myc promotes cell proliferation in CRC.

l-Menthol alleviates cigarette smoke extract induced lung injury in rats by inhibiting oxidative stress and inflammation via nuclear factor kappa B, p38 MAPK and Nrf2 signalling pathways.

l-Menthol is the main ingredient of peppermint which affects various pharmacological effects such as anti-inflammation and anti-oxidative activity. In this study, we aimed to evaluate the potential effects of l-menthol on cigarette smoke extract (CSE) induced lung injury in rats. Morphology assessment results revealed that administration with l-menthol (5, 10 or 20 mg kg-1 d-1) significantly alleviated CSE-induced lung injury. Besides, l-menthol significantly reduced the inflammatory response by suppressing the production of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) via downregulating nuclear factor kappa B (NF-κB) and p38 MAPK pathways. Meanwhile, l-menthol decreased the levels of oxidative stress markers including malondialdehyde (MDA) and myeloperoxidase (MPO) whereas it increased the amount of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) through activation of the Nrf2 pathway. Furthermore, the expression of MMP-9 and TIMP-1 in lungs was reduced after treatment with l-menthol, and this indicated that l-menthol might have a potential effect on airway remodeling. Moreover, immunohistochemistry analyses indicated that l-menthol could suppress the infiltration of CD4+ and CD8+ T cells in lung tissues and this was probably due to the immune regulation activity of l-menthol. Taken together, our findings support that l-menthol might be a potential candidate for the treatment of CSE-induced lung injury in rats.

Protective Effect of Flavonoids from Ziziphus jujuba cv. Jinsixiaozao against Acetaminophen-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation in Mice.

This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity. Pretreatment with ZJF significantly decreased APAP-elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TB). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced with ZJF administration, while malondialdehyde (MDA) level and glutathione (GSH) depletion were reduced. Meanwhile, ZJF reversed the suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and up-regulated the protein expression of NAD(P)H: quinone oxidoreductase 1(NQO1) in liver damage mice. Furthermore, ZJF attenuated APAP-induced inflammatory mediator production, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). Expression of p65 showed that ZJF dampened nuclear factor-κB (NF-κB) activation. The results strongly indicate that the hepatoprotective role of ZJF in APAP-induced hepatotoxicity might result from its induction of antioxidant defense via activation of Nrf2 and reduction of inflammation via inhibition of NF-κB.

The long non-coding RNA SNHG3 functions as a competing endogenous RNA to promote malignant development of colorectal cancer.

Accumulating evidence has revealed that aberrantly expressed long non-coding transcripts are involved in the development and progression of colorectal cancer (CRC). Small nucleolar RNA host gene 3 (SNHG3) is a newly identified lncRNA, and little is known about its clinical significance and biological functions in the development of CRC. In the present study, we found that the expression of SNHG3 was significantly upregulated in CRC, and upregulation of SNHG3 predicted poor prognosis for patients with CRC as determined through analysis of the data obtained from TCGA database. Gain-of function and loss-of function assays revealed that SNHG3 markedly promoted cellular proliferation of CRC cells. Gene Set Enrichment Analysis (GSEA) suggested that high expression of SNHG3 was positively associated with c-Myc and its targets genes. Furthermore, ectopic overexpression of SNHG3 increased the expression of c-Myc and its target genes, whereas inhibition of SNHG3 had opposite effect on the expression of c-Myc and its targets. Mechanistic investigations demonstrated that SNHG3 functioned as a competing endogenous RNA (ceRNA) to 'sponge' miR-182-5p, thus leading to the release of c-Myc from miR-182-5p and modulating the expression of c-Myc. In conclusion, SNHG3 promoted CRC progression via sponging miR-182-5p and upregulating c-Myc and its target genes.

Garlic-derived organosulfur compound exerts antitumor efficacy via activation of MAPK pathway and modulation of cytokines in SGC-7901 tumor-bearing mice.

Diallyl trisulfide (DATS), a natural agent derived from garlic, has been tested for its antigastric cancer activities in various preliminary studies. However, more systematic pharmacodymatic (PD) and mechanistic evaluations are clearly needed. The aim of this study was to investigate the antitumor effects of DATS in the treatment of human gastric cancer cell SGC-7901 both in vitro and in vivo using widely recommended study procedures. DATS suppressed cancer cells proliferation and induced cell cycle arrest accompanied by an increase in the expressions of cyclin A2 and cyclin B1 in SGC-7901 cancer cells. DATS also caused an increase in apoptotic cell death, which involved in accumulations of bax, p53, and cytochrome C and reduction of Bcl-2 expressions. Besides, activation of JNK, ERK and p38 phosphorylation in DATS-treated cells suggested that mitogen-activated protein kinase (MAPKs) pathways were involved in DATS-induced apoptosis. Meanwhile, DATS significantly inhibited tumor growth and promoted tumor apoptosis in a xenograft model of gastric cancer cell SGC-7901. DATS inhibited tumor migration and invasion by modulating MMP9 and E-cadherin protein expressions. In addition, DATS treatment evidently increased the cytokine secretions of IL-12, TNF-α and IFN-γ (p<0.05). Biochemical serum analysis and histopathological examination indicated no obvious side effects in major mouse organs. Therefore, our findings provide a framework for further exploration of DATS as a novel chemotherapeutic for human gastric cancer.