Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence.

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy due to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from AD patients. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and reactive oxygen species (ROS) production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

Identification of Angiogenesis-Related Genes and Molecular Subtypes for Psoriasis Based on Random Forest Algorithm.

Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithms. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis (PCA). A diagnostic model was developed using random forest algorithm (ntree=400) and validated by ROC curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by qRT-PCR. We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P<0.0001) and interleukins pathway (R=0.79, P<0.0001). Furtherer, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes.

Formononetin attenuates psoriasiform inflammation by regulating interferon signaling pathway.

BACKGROUND: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis. OBJECTIVE: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis. MATERIALS AND METHODS: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC). RESULTS: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-ß, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group. CONCLUSIONS: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial.

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. OBJECTIVE: The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). MAIN OUTCOME MEASURES: The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient's and investigator's global evaluations of therapeutic response. RESULTS: The mean reduction in pain was -51.22 mm (95% confidence interval [CI], [-53.42, -49.03] mm) for the HZG and -52.00 mm (95% CI, [-54.06, -49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [-2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). CONCLUSION: HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000036970). Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270-278.

Austin-Type Meroterpenoids from Fungi Reported in the Last Five Decades: A Review.

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.

Oral administration of hyaluronic acid to improve skin conditions via a randomized double-blind clinical test.

OBJECTIVE: To evaluate the impact of oral intake of Hyaluronic Acid (HA) on skin health. BACKGROUND: HA, an endogenous substance in the human body, plays a key role in skin health. However, its concentration in the skin decreases significantly with age. Previous studies suggested that oral intake of HA can supplement the body's HA level, but did not reveal the effects on different age groups and skin types. METHODS: A double-blind, randomized clinical trial with 129 female participants, covering young and elderly groups and differnet skin types, was conducted to assess the efficacy of orally administered HA on skin health. RESULTS: Oral administration of HA significantly promoted skin hydration after 2-8 weeks among both young and elderly groups. Skin tone improvement was observed after 4-8 weeks, while an increase in epidermal thickness was noted after 12 weeks. CONCLUSION: This study provides direct evidence supporting the clinical efficacy of oral intake of HA in promoting skin health.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

Functional Disability After Ischemic Stroke: A Community-Based Cross-Sectional Study in Shanghai, China.

Objective: This study aimed to understand the demographics, functional disabilities, cognitive impairment, and depressive mood among stroke patients and to explore the correlation between functional disability and the other health conditions so as to provide some data for community rehabilitation among stroke patients. Methods: A cross-sectional study was conducted to investigate the functional status of ischemic stroke patients with stroke history between 1 month and 2 years by applying the modified Rankin Scale (mRS). Data were collected during October 2016 and January 2017 from 11 communities in two districts of Shanghai, China. We used face-to-face questionnaire interviews to collect information on sociodemographics, vascular risks associated with stroke, cognitive function [Mini-Mental State Examination (MMSE)], and depression [Patient Health Questionnaire-9 (PHQ-9)]; and we applied SPSS 24.0 for data analysis. Results: In this study, 305 patients with ischemic stroke were finally recruited, including 189 (61.97%) men, with an average age of 67 years. According to the mRS score, ischemic stroke patients were divided into patients without symptoms (controls, mRS = 0), patients without obvious disability (mRS = 1), and patients with mild to severe disability (mRS = 2-5). Ischemic stroke patients with different mRS levels demonstrated significant differences in age, tobacco smoke exposure, previous stroke history, cognitive function, and depression status. Compared with patients without symptoms (mRS = 0), patients with mRS = 1 had a lower MMSE score [odds ratio (OR): 0.48, 95% confidence interval (CI): 0.26-0.90]; and patients with mRS = 2-5 had a lower MMSE score [OR = 0.16, 95% CI: 0.08-0.33], had a higher PHQ-9 score [OR = 5.36, 95% CI: 2.19-13.11], and were more likely to have previous stroke history [OR = 2.18, 95% CI: 1.01-4.79]. Conclusion: Lower degrees of functional independence are related to cognitive impairment, as well as the previous stroke history and depression status.

"Fan-zhen Jie-ci" acupuncture therapy for treatment of discogenic sciatica: protocol for a single-blind, randomized controlled clinical trial.

BACKGROUND: Curative medical treatment for patients with discogenic sciatica is limited. Acupuncture is an important non-pharmacological therapy reported to have positive therapeutic effects on discogenic sciatica. According to traditional Chinese acupuncture theory, discogenic sciatica is a channel tendon disease which can be treated by a special "Fan-zhen Jie-ci (FZJC)" method. Our recent preliminary clinical evidence indicated that the FZJC method had a positive treatment effect on the disease. This study will further evaluate the efficacy and safety of FZJC on patients with discogenic sciatica. METHODS: A single-blind randomized controlled clinical trial will be conducted, assigning 76 participants with discogenic sciatica to a randomly assigned FZJC group or a control group. Acupuncture treatment combined with the FZJC method will be applied in the FZJC group while routine acupuncture treatment only will be applied in the control group. Treatments will be administered three times a week for a total of 3 consecutive weeks. The primary outcome of this trial is change in the visual analogue scale of leg pain (VAS-LP), and the secondary outcomes are changes in the visual analogue scale of back pain (VAS-BP), the Brief Pain Inventory (BPI), the Oswestry Disability Index (ODI), the 36-Item Short Form Health Survey (SF-36), and serum concentrations of mitochondrial DNA (mtDNA) and high sensitivity C reactive protein (hsCRP). DISCUSSION: The results of this study will provide insight into the efficacy and safety of FZJC acupuncture as a treatment for discogenic sciatica. TRIAL REGISTRAION: The trial has been registered at the Chinese Clinical Trial Registry (ChiCTR1900026272) and the Acupuncture-Moxibustion Clinical Trial Registry (AMCTR-IOR-19000275).

A clinical study on the efficacy of Yiqi Huayu Jiedu decoction for reducing the risk of postoperative recurrence and metastasis of gastric cancer: Protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Gastric cancer (GC) is one of the top 10 malignant tumors worldwide and poses a great threat to human life and health, the prevention and treatment of which has become the focus and difficulty of medical research. With its unique advantages, traditional Chinese medicine (TCM) is widely used in the prevention and treatment of postoperative recurrence and metastasis of GC as well as the improvement of patients' quality of life. The aim of this study is to elucidate the curative effect and the underlying mechanism of Yiqi Huayu Jiedu (YQHYJD) decoction. METHODS/DESIGN: This is a prospective, multicenter, randomized controlled trial continuing 3 years. Two hundred ninety-eight eligible patients will be randomly divided into 2 groups, the chemotherapy combined with placebo and the chemotherapy combined with YQHYJD group at a ratio of 1:1. All patients will receive the treatment for 6 months and follow up for 3 years. The primary outcomes are disease-free survival, and 1-year, 2-year, 3-year progression-free survival rate, while the secondary outcomes are tumor makers, TCM syndrome score, quality of life score, overall chemotherapy completion rate, intestinal flora diversity test, immune function (T, B lymphocyte subsets and NK cells) test. The Security index includes blood, urine and stool routine, electrocardiogram, liver function (ALT), and renal function (BUN, Scr). All of these outcomes will be analyzed at the end of the trial. DISCUSSION: This research will provide the valuable evidence for the efficacy and safety of Yiqi Huayu Jiedu decoction in postoperative GC. Furthermore, it will be helpful to form a higher level of evidence-based medical basis for TCM in the treatment of GC recurrence and metastasis. TRIAL REGISTRATION: ChiCTR2000039038.

Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial.

BACKGROUND: Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis. METHODS: Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd. DISCUSSION: It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03953885 . Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome.

Efficacy and Safety of Jueyin Granules for Patients with Mild-to-Moderate Psoriasis Vulgaris: Protocol for a Multicenter Randomized Placebo-Controlled Trial.

Introduction. The etiology and pathogenesis of psoriasis are complex. Blood-heat syndrome is the core pathogenesis of psoriasis. Based on theories of Chinese medicine (CM), heat-clearing and blood-cooling (HCBC) are the primary treatment. Very few studies have investigated the pharmacological mechanism of the CM HCBC method for treating psoriasis. This multicenter randomized controlled trial will focus on treating psoriasis blood-heat syndrome with the HCBC method using Jueyin granules (JYKL). This will be an objective and standardized evaluation of the efficacy, safety, and reproducibility of the HCBC method to obtain objective evidence meeting international standards that aim to establish a clinical standard suitable for the popular application of CM for treating psoriasis. Methods and Analysis. A five-center randomized double-blind placebo-controlled clinical design will be used in this study. At least 196 participants will be randomly assigned to receive either JYKL or placebo treatment approximately 30 minutes after meals in the morning and evening (one sachet per time, twice daily for 8 consecutive weeks). The study duration will be 17 weeks, including 1 week of screening, 8 weeks of intervention, and 8 weeks of follow-up. The patients will be evaluated every 2 weeks, and the measures will be compared with baseline values. The primary outcome measure will be the psoriasis lesion area severity index. We will also observe the recurrence rate, body surface area, physician global assessment, dermatology life quality index, quality of life index, visual analogue scale score, CM symptom score, combined drug use, and adverse events. This trial is registered with NCT03961230.

Oral Taodan granules for mild-to-moderate psoriasis vulgaris: protocol for a randomized, double-blind, multicenter clinical trial.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease with high recurrence rates and increasing incidence. Patients require long-term medication to reduce symptoms and prevent disease progression. Therefore, the development of treatments with high efficiency and low rate of adverse events is of utmost importance. Traditional Chinese medicine (TCM) plays an outstanding role in reducing disease symptoms and improving quality of life. The aim of this trial is to clarify the treatment efficacy, safety, and control of disease recurrence in patients with psoriasis with blood-stasis syndrome treated with Taodan granules (TDKL). METHODS: This trial is a five-center, randomized, double-blind, placebo-controlled study planned to transpire between September 1, 2019, and December 31, 2021. A sample size of 216 participants (108 per group) with mild-to-moderate psoriasis will be randomly assigned to receive TDKL or placebo twice per day, 7 days per week, for 8 weeks. The study duration will be 17 weeks, including a 1-week screening period, 8 weeks of intervention, and another 8 weeks of follow-up. The primary outcomes are improvement in the Psoriasis Area and Severity Index score and recurrence rate after 8 weeks of treatment. Secondary outcomes include body surface area affected and the scores for the Physician Global Assessment, Dermatology Life Quality Index, pain-related quality of life, pain on the visual analogue scale, and TCM syndromes. The number, nature, and severity of adverse events will be carefully recorded. DISCUSSION: The study results will help clarify the safety and efficacy of TDKL as treatment for psoriasis with respect to both disease regression and recurrence rate. We expect that this study will provide high-quality evidence with important public health implications that may alter the approach to psoriasis management in China. TRIAL REGISTRATION: The trial has been registered at ClinicalTrials.gov (ID: NCT03942198).

Cinnamaldehyde enhances apoptotic effect of oxaliplatin and reverses epithelial-mesenchymal transition and stemnness in hypoxic colorectal cancer cells.

Oxaliplatin has been widely applied in clinical tumor chemotherapy, the treatment failure of which mainly blames on low susceptibility resulted from intrinsic or acquired drug resistance in tumor cells. Microenvironmental hypoxia is one of the important pathological features of solid tumors, which is closely related to the radiochemotherapy tolerance and poor prognosis. Cinnamaldehyde is extracted from Cinnamomum cassia with inhibiting effect against kinds of tumors. In this study, we demonstrated that hypoxia reduced the sensitivity to oxaliplatin in colorectal cancer (CRC) cells via inducing EMT and stemness. Nonetheless, cinnamaldehyde increased the curative effect of oxaliplatin by promoting apoptosis both in vitro and in vivo. Mechanistically, cinnamaldehyde and oxaliplatin synergistically reversed hypoxia-induced EMT and stemness of CRC cells and suppressed hypoxia-activated Wnt/ß-catenin pathway synergistically. These consequences uncovered the potential therapeutic value of cinnamaldehyde and provided novel ideas on improving the sensitivity of oxaliplatin in CRC therapy.

Relationship between serum inflammatory cytokines and lifestyle factors in gastric cancer.

Chronic inflammation is associated with increased risk of gastric cancer (GC), and GC risk is significantly associated with lifestyle. The aim of the present study was to explore the association between serum inflammatory cytokines and lifestyle factors in GC. A total of 20 serum inflammatory cytokines were measured in a hospital-based case-control population with 142 GC patients and 98 healthy controls. Controls without the selected healthy lifestyle factors were regarded as baseline, and correlation analysis was conducted to establish the association between serum inflammatory cytokines and lifestyle factors. The results demonstrated that several lifestyle factors (including eating fried and salty foods, eating quickly, smoking and drinking) could increase the risk of GC, while only eating fresh fruits could decrease the risk of GC. Correlation analysis revealed that increased serum interleukin (IL)-12/IL-23P40 levels was associated with GC risk as significant differences were observed in all lifestyle factors. Increased serum IL-8 was closely associated with smoking in GC patients, while increased IL-17α and IL-8 levels were associated with GC patients who ate salty foods. Increased IL-10 and decreased TGF-ß levels were also associated with GC patients who ate fresh fruits. In conclusion, GC risk was strongly affected by lifestyle factors, which may regulate the expression of inflammatory cytokines and promote gastric carcinogenesis.

Nm23-H1 inhibits hypoxia induced epithelial-mesenchymal transition and stemness in non-small cell lung cancer cells.

The Nm23 gene has been acknowledged to play a crucial role in lung cancer metastasis inhibitory cascades controlled by multiple factors. Low expression or allelic deletion of nm23-H1 is strongly linked to widespread metastasis and poor differentiation of non-small cell lung cancer (NSCLC). In this study, nm23-H1 was down regulated in epithelial-mesenchymal transition (EMT) and stemness enhancement under cobalt chloride (CoCl2)-induced hypoxia in NSCLC cells. Moreover, knocking down of nm23-H1 by shRNA apparently promoted hypoxia induced EMT and stemness, which was entirely suppressed via over expression of nm23-H1. Mechanistically, the Wnt/ß-catenin signaling pathway was found to participate in the nm23-H1-mediated process. Besides, XAV939 prohibited cell EMT and stemness which could be impaired by knocking down of nm23-H1, while stable transfection of nm23-H1 attenuated hypoxia phonotype induced by lithium chloride (LiCl). Generally, our experiment provided evidence that nm23-H1 can reverse hypoxia induced EMT and stemness through the inhibition of the Wnt/ß-catenin pathway, which may furnish a deeper perspective into the better treatment or prognosis for NSCLC.

'Outbreak Gold Standard' selection to provide optimized threshold for infectious diseases early-alert based on China Infectious Disease Automated-alert and Response System.

The China Infectious Disease Automated-alert and Response System (CIDARS) was successfully implemented and became operational nationwide in 2008. The CIDARS plays an important role in and has been integrated into the routine outbreak monitoring efforts of the Center for Disease Control (CDC) at all levels in China. In the CIDARS, thresholds are determined using the "Mean+2SD? in the early stage which have limitations. This study compared the performance of optimized thresholds defined using the "Mean +2SD? method to the performance of 5 novel algorithms to select optimal "Outbreak Gold Standard (OGS)? and corresponding thresholds for outbreak detection. Data for infectious disease were organized by calendar week and year. The "Mean+2SD?, C1, C2, moving average (MA), seasonal model (SM), and cumulative sum (CUSUM) algorithms were applied. Outbreak signals for the predicted value (Px) were calculated using a percentile-based moving window. When the outbreak signals generated by an algorithm were in line with a Px generated outbreak signal for each week, this Px was then defined as the optimized threshold for that algorithm. In this study, six infectious diseases were selected and classified into TYPE A (chickenpox and mumps), TYPE B (influenza and rubella) and TYPE C [hand foot and mouth disease (HFMD) and scarlet fever]. Optimized thresholds for chickenpox (P55), mumps (P50), influenza (P40, P55, and P75), rubella (P45 and P75), HFMD (P65 and P70), and scarlet fever (P75 and P80) were identified. The C1, C2, CUSUM, SM, and MA algorithms were appropriate for TYPE A. All 6 algorithms were appropriate for TYPE B. C1 and CUSUM algorithms were appropriate for TYPE C. It is critical to incorporate more flexible algorithms as OGS into the CIDRAS and to identify the proper OGS and corresponding recommended optimized threshold by different infectious disease types.

Autophagy Protects from Raddeanin A-Induced Apoptosis in SGC-7901 Human Gastric Cancer Cells.

Raddeanin A (RA) is an extractive from Anemone raddeana Regel, a traditional Chinese medicine. The aim of this study is to assess the efficacy of RA against human gastric cancer (GC) cells (SGC-7901) and explore its mechanism. MTT assay showed that RA inhibition of proliferation of SGC-7901 cells increased in a dose-dependent manner. Flow cytometry analysis and Hoechst 33258 staining showed that RA induced apoptosis on SGC-7901 cells. Meanwhile, it induced autophagy. Western blotting analysis showed that the RA induces apoptosis and autophagy by activating p38 MAPK pathway and inhibiting mTOR pathway. Further studies showed that autophagy inhibition could protect from RA-induced apoptosis in SGC-7901 cells. In conclusion, RA can induce SGC-7901 cell apoptosis and autophagy by activating p38 MAPK pathway. And autophagy can protect SGC-7901 cells from apoptosis induced by RA.

Dioscin inhibits gastric tumor growth through regulating the expression level of lncRNA HOTAIR.

BACKGROUND: As a member of non-coding RNAs family, long non-coding RNAs' functions in cancer needs to be further investigated. It has been indicated that the functions of Hox transcript antisense intergenic RNA (lncRNA: HOTAIR) include reprogramming chromatin organization and promoting tumor metastasis such as breast and colorectal tumor. The aim of this study is to investigate the functions of Hox in gastric cancer. METHODS: In the present study, the expression level of HOTAIR was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), 20 gastric cancer tissues and 20 normal tissues was included. All clinical data were analyzed retrospectively. The CCK-8 and colony formation assay was used to identify if the knockdown of HOTAIR have an influence on gastric cancer cell lines. RESULTS: Compared with normal tissues, higher expression level of HOTAIR was found in gastric cancer tissues. Dioscin inhibits proliferation of the three gastric cancer cell lines and decrease HOTAIR expression. CONCLUSIONS: The expression of HOTAIR is up regulated in gastric cancer and gastric cancer cell lines, dioscin inhibits the proliferation of three gastric cancer cell lines and the anti-tumor effect of dioscin may partly depend on the down regulation of HOTAIR.

Tounong Powder () extracts induce G1 cell cycle arrest and apoptosis in LoVo cells.

OBJECTIVE: To further explore the anti-cancer effect of Tounong Powder () extracts (TNSEs) on human colon cancer LoVo cells and examine the possible molecular mechanisms. METHODS: The contents of TNSEs were determined by liquid chromatograph-mass spectrometer (LC-MS) analysis after extraction with water and methanol. Variations of cell morphological features were observed using fluorescence microscopy. Cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution and apoptosis were analyzed using flow cytometry at different TNSE doses (0, 62.5, 125, or 250 µg/mL). Protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphate protein kinase B (p-AKT), phosphate mammalian target of rapamycin (p-mTOR), p-p70s6k1, cleaved caspase-9 and -3 were detected using Western blot analysis. RESULTS: TNSEs induced cell growth inhibition in a concentration- and time-dependent manner. Flow cytometric analysis showed apoptotic cells and cell cycle arrest at the G phase after TNSEs treatment compared with controls. Furthermore, TNSEs significantly down-regulated the proteins PI3K, p-AKT, p-mTOR, and p-p70s6k1, and up-regulated the proteins cleaved caspase-9 and -3 dosedependently, as determined by Western blot. CONCLUSIONS: TNSEs reduced LoVo cell proliferation, and caused apoptosis and cell-cycle arrest in LoVo cells. This effect might be associated with regulation of the PI3K/AKT signaling pathway.