Moxibustion Regulates Gastrointestinal Motility via HCN1 in Functional Dyspepsia Rats.

BACKGROUND Moxibustion therapy has been found to ameliorate clinical symptoms of functional dyspepsia (FD). We aimed to examine the regulatory effect of moxibustion on the gastrointestinal (GI) motility in FD and explore the underlying mechanism based on the hyperpolarization-activated cyclic nucleotide-gated cation channel 1 (HCN1). MATERIAL AND METHODS Moxibustion therapy was used in FD rats induced by using classic tail-pinch and irregular feeding. Weight gain and food intake were recorded weekly, followed by detecting gastric residual rate (GRR) and small intestine propulsion rate (IPR). Next, western blotting was performed to determine the expression levels of HCN1 in the gastric antrum. qRT-PCR was used to detect HCN1 in the small intestine and hypothalamic satiety center. Double immunolabeling was used for HCN1 and ICCs in gastric antrum and small intestine. RESULTS The obtained results suggested that moxibustion treatment could increase weight gain and food intake in FD rats. The GRR and IPR were compared among the groups, which showed that moxibustion treatment could decrease GRR and increase IPR. Moxibustion increased the expression of HCN1 in the gastric antrum, small intestine, and hypothalamic satiety center. Histologically, the co-expressions of HCN1 and ICCs tended to increase in gastric antrum and small intestine. Meanwhile, HCN channel inhibitor ZD7288 prevented the above-mentioned therapeutic effects of moxibustion. CONCLUSIONS The results of the present study suggest that moxibustion can effectively improve the GI motility of FD rats, which may be related to the upregulation of HCN1 expression in gastric antrum, small intestine, and satiety center.

Metabolically healthy obesity is associated with longitudinal changes in high-density lipoprotein cholesterol in Chinese adults.

PURPOSE: Whether metabolically healthy obesity (MHO) is associated with longitudinal changes in high-density lipoprotein cholesterol (HDL-C) remains unclear. METHODS: MHO was defined as participants with overweight and obesity (BMI ≥ 24.0 kg/m2, n = 2921), free of history of metabolic diseases, and without abnormalities of blood pressure, fasting blood glucose, hemoglobin A1c, lipid profile, carotid artery and liver ultrasonographic findings at baseline. Metabolically healthy normal weight (MHN) was defined as participants with normal weight (BMI < 24.0 kg/m2, n = 9578) and without above-mentioned abnormalities. HDL-C, fasting blood glucose, hemoglobin A1c, and blood pressure were assessed annually. Glucose abnormality was considered if either FBG ≥ 5.6 mmol/L or HbA1c ≥ 5.7%; while, high blood pressure (HBP) was considered if either systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg during 5 years of follow-up. RESULTS: Compared with the MHN group, the adjusted mean difference in HDL-C change rate was - 0.005 mmol/L per year [95% confidence interval (CI) - 0.007, - 0.003] for MHO after adjustment for a series of potential confounders. Furthermore, transiting to abnormality of blood glucose, but not high blood pressure, was associated with lower cumulative average of HDL-C in MHN group, compared with those remained in metabolically healthy status. CONCLUSIONS: MHO and transiting from metabolically healthy to abnormality of blood glucose were associated with HDL-C in Chinese adults. LEVEL OF EVIDENCE: III, cohort study.

The experience of patients with cancer on narrative practice: A systematic review and meta-synthesis.

BACKGROUND: In recent years, narrative practice has been applied in clinical settings to address the relational and psychological concerns that occur in tandem with physical illness. It is an emerging strategy to treat patients as individuals with their own stories, rather than purely based on symptoms. OBJECTIVE: To synthesize the experience of patients with cancer using narrative practice. METHODS: Following a systematic search strategy, a literature search was conducted to identify qualitative studies on the experience of patients with cancer using narrative practice. Nine databases were searched up to April 2018, which included six English databases and three Chinese databases. A meta-synthesis was conducted to synthesize the findings of the included studies. MAIN RESULTS: Seven studies out of 2894 studies were included in this review. Patients with cancer had different preferences on narrative practices. In terms of the impacts of narrative practice on patients with cancer, six themes were identified, which included '(a) reducing the gap between patients and clinicians; (b) healing effect; (c) social connection; (d) facilitating self-reflection, self-recognition and self-realization; (e) risk of negative impacts; and (f) Patients' preference on different approaches of narrative practice'. CONCLUSIONS: Patients with cancer experienced positive effects regarding narrative practice. Although some patients may experience negative effects, narrative practice is a humanized way to provide care for patients with cancer in the clinical settings.

Lack of patient education is risk factor of disease flare in patients with systemic lupus erythematosus in China.

BACKGROUND: To explore the inadequacies of health service and its impact on clinical outcomes of patients with systemic lupus erythematosus (SLE) in China. METHODS: A total of 210 SLE patients were randomly recruited between January 2017 and January 2018. Each patient received self-report questionnaires to assess medication adherence [Compliance Questionnaire for Rheumatology (CQR)], beliefs about medicines [Beliefs about Medicines Questionnaire (BMQ)] and satisfaction about medicine information [the Satisfaction with Information about Medicines Scale (SIMS)]. Associations between SLE disease activity index (SLEDAI-2 K) and observed factors were analyzed by multiple logistic regression. RESULTS: Based on CQR, only 28.10% patients were adherent. The score of BMQ was 2.85 ± 5.42, and merely 32.38% patients were satisfied with the information about their prescribed medicines. Disease activity was associated with SIMS, EuroQol five-dimensions [EQ5D], Systemic Lupus International Collaborating Clinics (SLICC), depression, use of NSAID (P ≤ 0.05). Remission of disease was positively correlated with SIMS (OR = 0.16, 95% CI: [0.06, 0.40]), and BMQ (OR = 0.64, 95%CI: [0.43, 0.94]). CONCLUSION: In this study, the scores of BMQ and SIMS were low, implying defects in the patient education of health service system, which led to disease flare in Chinese SLE patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03024307 . Registered January 18, 2017.

Quality of life and self-care in elderly patients with cardiovascular diseases: The effect of a Traditional Chinese Medicine health educational intervention.

AIMS: To explore the effects of a Traditional Chinese Medicine health educational intervention on the quality of life and self-care agency of elderly patients living with chronic cardiovascular disease. BACKGROUND: Cardiovascular disease is a leading cause of morbidity and mortality worldwide. The secondary prevention and treatment for chronic cardiovascular disease emphasize the importance of lifestyle modification. However, behavior-changing is difficult and individual choices are influenced by broader environmental factors. The lifestyle intervention for the purpose of self-care enhancing should be considered the driving force from the cultural element. METHODS: The study was conducted from April 2014 to October 2014. Ninety-eight community dwelling individuals with chronic cardiovascular disease were recruited from Shaoxing and randomized. 48 participants were in the intervention group with a 6-month Traditional Chinese Medicine health education and 50 participants were in the control group with routine care. The main measurements included health-related quality of life and self-care agency, which was assessed by the Short Form-36 Chinese version and the Exercise of Self-Care Agency Scale respectively, and were measured at the baseline and post intervention (6months after baseline). RESULTS: After 6months of intervention, the quality of life and self-care agency in the intervention group were significantly improved. CONCLUSIONS: The traditional Chinese medicine health education is an effective method for promoting quality of life and self-care agency in cardiovascular disease patients. It could be applied as adjunctive care for cardiovascular disease patients self-care supporting.

Professional quality of life: A cross-sectional survey among Chinese clinical nurses.

The Professional Quality of Life Scale was adapted to create a Chinese version to investigate the professional quality of life of Chinese nurses and possible risk factors. A cross-sectional survey was conducted among 752 nurses sampled from four general hospitals in Shanghai, China. An expert panel, cognitive review, and pretest were used to ensure cultural adaptability. Psychometric tests included reliability and validity. One-way and multivariate analysis of variance were conducted for statistical analysis. Content validity indexes of all items were over 0.90. Five items were excluded because their item-total correlations and factor loading of exploratory factor analysis were less than 0.3. The 25-item scale revealed acceptable reliability. Confirmatory factor analysis supported its structure. There was variation in the scores between different departments, religions, working positions, nursing experiences, forms of employment, and average working hours (all P < 0.05). This study extended the application of the original scale in Chinese nursing culture. Attention should be paid to risk factors and differences between East and West.

The meaning of life and health experience for the Chinese elderly with chronic illness: a qualitative study from positive health philosophy.

Ageing and the concurrent prevalence of chronic disease in older adults produce a great burden and challenge for family, society and individuals. There is a definite need to build the science about caring for older Chinese adults from their perspective to inform health-care professionals. The aim of the study was to investigate the meaning of life and health experience of Chinese elderly with chronic illness and identify health potential from a positive perspective. A qualitative descriptive study was undertaken to interview 11 older adults ages 64-92 in a day centre. In 2011, the data were collected and analysed by thematic analysis. Four interrelated themes indicated a rich meaning of life and health experience from the older adults: (i) happiness lies in contentment; (ii) sense of responsibility; (iii) letting nature take its course; (iv) and proactive self-balance. These interrelated themes with partial conflict presented a dialectic meaning of life and were interpreted from traditional Chinese culture and compared with positive health philosophy. The significance of finding will encourage nursing practice work with clients and identify the potential and self-help strength of the elderly.

Neighborhood Governance and Happiness during the COVID-19 Pandemic: An Empirical Analysis of Wuhan's Lockdown.

The outbreak of COVID-19 posed a challenge to global governance, residents' happiness, and economic systems around the world. Since the crux of previous research centers on the reactions of both local and national governments, studies on how governance arrangement at the neighborhood level influences people's happiness during the crisis response remain insufficient. This paper aims to explore the relationship between neighborhood governance and residents' happiness based on first-hand data collected during Wuhan's first lockdown. This study highlights the significance of neighborhood governance in crisis response, which includes providing diverse public services, ensuring access to life's necessities, and offering prompt medical treatment. All of these factors are essential for maintaining overall satisfaction with governance and contributing to the happiness of individuals within the community. However, active governance actions do not always lead to favorable results. For example, increased group participation may lead to social conflicts among those involved, ultimately diminishing one's happiness. Furthermore, the COVID-19 pandemic has acted as a risk 'amplifier', exposing and exacerbating pre-existing hukou-based social inequalities in the governance process. The impact of the pandemic on citizen happiness is the cumulative effect of both the immediate social crisis brought on by the pandemic and long-standing structural inequalities. To improve people's happiness and establish inclusive policies, this paper advocates for a 'people-centered' urban governance that enhances public satisfaction and addresses the needs and priorities of migrant populations.

Characterization and functional analysis of the human microRNA let-7a2 promoter in lung cancer A549 cell lines.

Recent studies have revealed that microRNAs have a strong association with cancer in humans. The miRNA let-7 is highly expressed in normal lung tissue, but frequently expressed at reduced levels in lung cancers. Let-7a2 is a member of the let-7 family. So far, little is known about the transcriptional regulation of let-7a2. Our study is focused on the characterization and functional analysis of the promoter of the human miRNA let-7a2 in A549 cell lines. Firstly, 5' rapid amplification of cDNA ends (5' RACE) was carried out and a 2.8 kb fragment in the upstream of let-7a2 gene was then cloned into pGL3-basic vector. Sequence analysis with the MatInspector database revealed that there were putative binding sites for some important transcriptional factors in the promoter region of let-7a2, such as p53, c-Myc, Ras, CEBPα, RORA, RXR, TCF, and GR. Additionally, a series of transfection and luciferase reporter assays were carried out to test let-7a2 promoter activity. RT-PCR and transfection of let-7a target sequence-reporter plasmid were performed to detect transcription levels of the let-7a2 gene in A549 cells treated with 9-cis-RA, all-trans-RA, lithium chloride or dexamethasone. Our results showed that the recombinant pGL3-p7a2 could acts as a promoter. The promoter activity of the 2.8 kb fragment could be downregulated by transfection with CEBPα or treatment with lithium chloride and enhanced by 9-cis-RA or all-trans-RA treatment. Furthermore, the results of RT-PCR analysis and transfection of let-7a target sequence-reporter plasmid showed that 9-cis-RA and all-trans-RA both upregulated let-7a2 expression, while lithium chloride downregulated its expression. Our results suggest that 9-cis-RA, all-trans-RA,lithium chloride and CEBPα might play important regulatory roles in let-7a2 gene expression in A549 cells.

A theoretical framework of caring in the Chinese context: a grounded theory study.

AIM: This paper is a report of a study describing the components of nurse caring in the Chinese cultural context. BACKGROUND: The expressions, dimensions and patterns of caring vary in different cultures. Caring is deeply embedded in the Chinese culture and nurses are told to care for patients as if they were related by blood. However, to put caring in a professional and practical context, it must extend meaning with a deeper philosophical inspiration that is transcendent and described to guide nursing practices. METHODS: A grounded theory research design and the Delphi method were adopted. First, a total of 16 individual non-structured interviews were conducted with noted scholars on nursing education, clinical nursing, nursing administration, medical education and the humanities between January 2006 and June 2007. All interviews were audio recorded, transcribed and analysed using constant comparative data analysis. Secondly, 20 experts with the same inclusion criteria were recruited to conduct a two-round Delphi study to enrich and validate the theoretical framework of caring. Experts were asked to score 0 = disagree or 1 = agree for each listed item and its description in a scale. Consensus was considered when 90% or more agreement was reached. Data were collected from May 2007 to February 2009 and calculated for the agreement rates using SPSS version 11.0. RESULTS: Four attributes of caring including attitude of caring, knowledge of caring, ability of caring and perceptions of caring were determined, along with 8 associated subcategories and 22 statements. Among them, caring attitude is central for presenting care in daily practice. Professional knowledge of nursing, the humanities and social science give the basic theoretical guidance for nurses to exhibit caring behaviour. In the education process, perceptions of giving and receiving care are the key factors for cultivating care. CONCLUSIONS: The framework could be interpreted as a list of teaching objectives and could contribute to the further development of an integrated approach for teaching care in nursing curricula. It would also be beneficial for applying and evaluating care in the practice of clinical nursing and nursing education in the Chinese culture.

Gene expression profiles in the PC-3 human prostate cancer cells induced by NKX3.1.

NKX3.1, a prostate-specific gene, plays an important role in prostate development and carcinogenesis. However, its precise function has not been established. In present study, we transfected the NKX3.1 eukaryotic expression plasmid (pcDNA3.1-NKX3.1) into human prostate cancer cells PC-3, which lack of NKX3.1 expression, and established stable transfectants. Then, we investigated the influence of NKX3.1 on the cell growth, cell migration and colony formation efficiency. The results showed that restoration of NKX3.1 expression inhibited proliferation and invasion activities of PC-3 cells. Further, a cDNA microarray containing 22,000 human genes was used to identify the gene expression differences. The results showed that there were 1,953 genes showing more than a two-fold difference in expression. Subsequent ontological analysis revealed that a large proportion of the classified genes were related to cell growth, cell signal and cell invasion. Finally, the expression of Caspase-3, Bcl-2, P27, Cdk6 and AMACR, randomly selected genes from microarray data, was validated by RT-PCR and western blot. Collectively, our results first analyzed the gene expression profile in PC-3 cells induced by NKX3.1 and indicated that NKX3.1 might exert its function by regulating the expression of relative genes.

Metformin alleviates lead-induced mitochondrial fragmentation via AMPK/Nrf2 activation in SH-SY5Y cells.

As a widely acknowledged environmental pollutant, lead (Pb) exhibits neurological toxicity primarily due to the vulnerability of neural system. It is suggested that Pb could perturb mitochondrial function, triggering the following disturbance of cellular homeostasis. Here, we focused on the role of mitochondrial dynamics in Pb-induced cell damage. Pb exposure enhanced mitochondrial fragmentation and elevated p-Drp1 (s616) level in a reactive oxygen species (ROS) dependent manner, leading to cell death and energy shortage. By applying metformin, an AMP-activated protein kinase (AMPK) activator, these impairments could be alleviated via activation of AMPK, validated by experiments of pharmacological inhibition of AMPK. Further investigation confirmed that nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor managing antioxidative function, and its downstream antioxidant detoxifying enzyme were activated by metformin, resulting in the inhibition of the Pb-caused oxidative stress. Moreover, Nrf2 mediated the protection of metformin against mitochondrial fragmentation induced by Pb exposure, while knockdown of Nrf2 abrogated the protective effect. Finally, the treatment of Mdivi-1, a mitochondrial fission inhibitor, reversed Pb-triggered cell death, revealing that excessive mitochondrial fission is detrimental. To conclude, metformin could ameliorate Pb-induced mitochondrial fragmentation via antioxidative effects originated from AMPK/Nrf2 pathway activation, promoting energy supply and cell survival.

CypD deficiency confers neuroprotection against mitochondrial abnormality caused by lead in SH-SY5Y cell.

Mitochondrial permeability transition (MPT), which is mainly regulated by cyclophilin D (CypD) encoded by ppif gene, is an early event that occurs during mitochondrial stimuli exposure. Lead (Pb) induces MPT and subsequently causes mitochondrial abnormality, followed by events, including oxidative stress and cell death. Here, we generated a ppif-/- SH-SY5Y cell line to determine the role of CypD in Pb-induced mitochondrial abnormality. CypD deficiency significantly blocked mitochondrial permeability transition pore (MPTP) opening and inhibited mitochondrial membrane potential (MMP) collapse, as well as mitochondrial structure damage and fragmentation caused by Pb. Mitochondria fragmentation and MMP collapse, accompanying with Pb-induced downregulation of Glut1 and Glut3 and inactivation of AMPK signaling pathway, could impair the energy supply in wildtype cells. Meanwhile, ppif knockout can alleviate these impairments and maintain the energy supply. In addition, reactive oxygen species accumulation and cell death caused by Pb can also be attenuated by ppif knockout, thereby promoting cell survival. Our study tends to identify CypD as an important contributor to Pb-induced mitochondrial abnormality and provides a potential strategy to inhibit Pb neurotoxicity.

Identification of Sp1-elements in the promoter region of human homeobox gene NKX3.1.

NKX3.1 is a prostate-specific homeobox gene related strongly to prostate development and prostate cancer. However, little is known about the mechanism for regulation of NKX3.1 in prostate cancer. With RT-PCR and western blot, we found that NKX3.1 expression was enhanced by over-expression of Sp1 at both the mRNA and protein levels in prostate cancer LNCaP cells. To identify the Sp1-elements in the promoter region of NKX3.1, a 521 bp-promoter of human NKX3.1 gene containing three possible Sp1-elements was cloned into the upstream of the luciferase reporter gene in pGL(3)-basic plasmid. With deletion mutation analysis, plasmid construction, EMSA and oligonucleotide decoy technique, two Sp1-elements which located between ?29 to ?43 and -60 to -46 of NKX3.1 gene were identified and proven to be functional elements. It will be important to further study on the functions and the regulatory mechanisms of Sp1 element in NKX3.1 gene expression.

Characterization of two functional NKX3.1 binding sites upstream of the PCAN1 gene that are involved in the positive regulation of PCAN1 gene transcription.

BACKGROUND: NKX3.1 and PCAN1 are both prostate-specific genes related to prostate development and prostate cancer. So far, little is known about the regulatory mechanisms of the expression of these two genes. In the present study, we found that NKX3.1 upregulated PCAN1 gene transcription in LNCaP prostate cancer cells. To understand the regulatory mechanisms, our work focused on identifying the functional NKX3.1 binding sites upstream of the PCAN1 gene, which might be involved in the positive regulation of PCAN1 expression by NKX3.1. RESULTS: We cloned and characterized a 2.6 kb fragment upstream of the PCAN1 gene. Analysis of the 2.6 kb sequence with MatInspector 2.2 revealed five potential binding sites of NKX3.1 transcription factor. Luciferase reporter assays, electrophoretic mobility shift assays, chromatin immunoprecipitation and RNA interference were performed to study the effects of NKX3.1 on PCAN1 gene expression in prostate cancer cells. Our results showed that PCAN1 promoter activity and mRNA expression were increased by transfection with the NKX3.1 containing plasmid (pcDNA3.1-NKX3.1) and that PCAN1 mRNA expression was decreased by RNA interference targeting human NKX3.1 in LNCaP prostate cancer cells. The results of electrophoretic mobility shift assays and chromatin immunoprecipitation showed that NKX3.1 bound to NBS1 (-1848 to -1836) and NBS3 (-803 to -791) upstream of the PCAN1 gene. The luciferase reporter assays showed that NBS1 and NBS3 enhanced the promoter activity in pGL3-promoter vector with cotransfection of the NKX3.1 containing plasmid. Furthermore, the deletion of NBS1 or both NBS1 and NBS3 reduced PCAN1 promoter activity and abolished the positive regulation of PCAN1 expression by NKX3.1. CONCLUSION: Our results suggested that two functional NKX3.1 binding sites located at -1848 to -1836 and -803 to -791 upstream of the PCAN1 gene were involved in the positive regulation of PCAN1 gene transcription by NKX3.1.

Overexpression of the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1 is associated with the poor prognosis of patients with colorectal cancer.

Tumor necrosis factor receptor-associated protein-1 (TRAP-1), a mitochondrial chaperone, contributes significantly to the progression of cancer. However, the understanding of its involvement in the clinicopathological characteristics and prognosis of colorectal cancer (CRC) remains limited. The aim of the present study was to assess the significance of TRAP-1 expression in CRC. The expression of TRAP-1 was evaluated in corresponding cancerous, paracancerous, lymph node and distant metastatic tissues of 256 cases of CRC by immunohistochemistry. The associations between TRAP-1 expression and the clinicopathological parameters and survival rates of patients was assessed. Out of 256 patients with CRC, TRAP-1 expression was detected in 203 (79.3%). TRAP-1 expression was significantly increased in cancerous tissue compared with that in corresponding paracancerous tissues (P<0.001). Overexpression of TRAP-1 was significantly associated with differentiation (P=0.011), depth of invasion (P=0.006), lymph node metastasis (P<0.001) and tumor-node-metastasis stage (P<0.001). In patients with high TRAP-1 expression, the 5-year overall survival (OS) rate was 38.0%, in contrast to 56.5% in patients with low TRAP-1 expression (P=0.003). Similarly, the 5-year progression-free survival (PFS) was 26.6% for patients with high TRAP-1 expression and 53.3% for patients with low TRAP-1 expression (P<0.001). Multivariate analyses indicated the TRAP-1 expression is an independent prognostic factor for poorer OS [P=0.015; hazard ratio (HR), 1.914] and PFS (P<0.001; HR, 2.534). Thus, TRAP-1 may serve as a potential biomarker for predicting the prognosis of patients with CRC. Specifically, overexpression of TRAP-1 may predict progression and poor survival in cases of CRC.

Molecular cloning and analysis of the human PCAN1 (GDEP) promoter.

Human PCAN1 (prostate cancer gene 1) is a prostate-specific gene that is highly expressed in prostate epithelial tissue, and frequently mutated in prostate tumors. To better understand the regulation of the PCAN1 gene, a 2.6-kb fragment of its 5' flanking region was obtained by PCR. Its promoter activity was examined via the dual-luciferase reporter assay after it had been cloned into a pGL(3)-basic vector generating pGL(3)-p2.6 kb and transfected into LNCaP cells. pGL(3)-basic and pGL(3)-control were respectively used as the negative and positive controls. Sequence analysis with the MatInspector database showed that some possible binding sites for the transcriptional factors, NKX3.1, P53, SP1, cEBP and the PPAR/RXR heterodimers may locate on a 2.6-kb region upstream of the PCAN1 gene. To examine the relevant regulation of PCAN1, pGL(3)-p2.6 kb was transfected into the prostate cancer cell line LNCaP, which was treated with R1881 (10(-7) approximately 10(-9) mol/l), 17beta-estradiol (17beta-E(2), 10(-7) approximately 10(-9) mol/l), all-trans-retinoic acid (all-trans-RA, 10(-5) approximately 10(-7) mol/l) or 9-cis-retinoic acid (9-cis-RA, 10(-5) approximately 10(-7) mol/l), and eukaryotic expression plasmids of NKX3.1, p53, Sp1, Pten, PPARgamma or cEBPalpha were cotransfected with pGL(3)-p2.6 kb into LNCaP cells. pRL-TK, a Renilla luciferase reporter vector, was cotransfected into all the transfection lines as an internal control. The activities of pGL(3)-p2.6 kb (PCAN1 promoter) were analyzed via the dual-luciferase reporter assay 48 h after transfection. The results showed that 9-cis-RA enhanced the PCAN1 promoter activity in a dose-dependent manner, while R1881, 17beta-E(2) and all-trans-RA had no significant effect on PCAN1 promoter activities. Cotransfection with pGL(3)-p2.6kb and the expression plasmids of NKX3.1, p53, Sp1 or Pten respectively resulted in 1.66-, 2.48-, 2.00-and 1.72-fold 2.6 kb PCAN1 promoter activity increases relative to the controls, which were cotransfected with pcDNA3.1(+), while cotransfection of PPARgamma and cEBPalpha yielded no significant effect on PCAN1 promoter activities. These results could be applied for further study of the function and transcription regulation of the PCAN1 gene in prostate development and carcinogenesis.

Inhibition of beta-amyloid precursor protein gene in SK-N-SH cells by piperlonguminine/dihydropiperlonguminine components separated from Chinese herbal medicine Futokadsura stem.

Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by progressive cognitive and memory decline. Amyloid precursor protein (APP) is a transmembrane protein, it has been known to play an important role in AD pathogenesis. Previous studies have shown that a Chinese herb Futokadsura stem can selectively inhibit the expression of amyloid precursor protein (APP) gene. We want to find the effective components in Futokadsura stem which have the inhibitory effect. Futokadsura stem was separated and purified with chemical methods, and then different separation components were added on SK-N-SH cells in different concentrations. Using MTT methods, we detected proliferation activity of SK-N-SH cells which were treated with different separation components of Futokadsura stem. Using RT-PCR, Western blot methods, we detected APP gene expression in SK-N-SH cells after they are treated with different Futokadsura stem separation components. We found that piperlonguminine/dihydropiperlonguminine components (1:0.8) separated from Futokadsura stem acetic ether extracts could selectively inhibit the expression of APP gene in SK-N-SH cells in mRNA and protein levels. This inhibition effect is concentration-dependent. Under experimental concentrations, the components did not affect the proliferation activity of SK-N-SH cells. These data suggest that piperlonguminine/dihydropiperlonguminine components are the effective components in Futokadsura stem which can inhibit the expression of APP gene.

A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer.

C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.