[Research progress in treatment of chronic prostatitis/chronic pelvic pain syndrome with traditional Chinese medicine].

Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) is a common urological disease with complex etiology. The treatment effect of western medicine is not satisfactory, and the course of the disease is protracted, which brings great trouble to patients. Traditional Chinese medicine(TCM) has a variety of treatment methods based on syndrome differentiation and treatment, including internal treatment with TCM, acupuncture and massage, and other external treatment methods for comprehensive treatment, with significant effect. This study summarized the etiology and pathogenesis of CP/CPPS and found that western medicine cannot fully explain the etiology and pathogenesis of CP/CPPS. It was believed that CP/CPPS was mainly related to many factors such as special pathogen infection, voiding dysfunction, mental and psychological abnormalities, neuroendocrine abnormalities, immune abnormalities, excessive oxidative stress, pelvic diseases, and heredity. TCM believed that CP/CPPS was caused by damp heat, blood stasis, Qi stagnation, and poisoning and was closely related to the organs of the liver, spleen, kidney, lung, stomach, bladder, and meridians of Chong and Ren channels and three yin channels of the foot. In the treatment of TCM, multiple comprehensive treatment plans are currently used, including internal treatment with TCM(decoction, proprietary Chinese medicine, and unique therapies of famous doctors), acupuncture and massage treatment, and other external treatment methods(rectal administration, topical application of TCM, and ear acupoint pressure). Comprehensive regulation has significant clinical efficacy and prominent characteristics of TCM, and it is worth clinical promotion. This study aims to provide a reference for clinical prevention and treatment of CP/CPPS and points out potential directions for future research in this field.

Antimicrobial resistance in E. Coli of animal origin and discovery of a novel ICE mobile element in Northeast China.

BACKGROUND: Multidrug resistance in Enterobacteriaceae including resistance to quinolones is rising worldwide. The development of resistance may lead to the emergence of new transmission mechanisms. In this study, the collection of different E. coli was performed from animals and subjected to subsequent procedures including pulsed-field gel electrophoresis, micro-broth dilution method, polymerase chain reaction. Whole genome sequencing of E. coli C3 was performed to detect the affinity, antimicrobial resistance and major carriers of the isolates. RESULTS: A total of 66 E. coli were isolated and their antibiotic resistance genes, frequency of horizontal transfer and genetic environment of E. coli C3 were determined. The results showed there were both different and same types in PFGE typing, indicating clonal transmission of E. coli among different animals. The detection of antimicrobial resistance and major antibiotic resistance genes and the plasmid transfer results showed that strains from different sources had high levels of resistance to commonly used clinical antibiotics and could be spread horizontally. Whole-genome sequencing discovered a novel ICE mobile element. CONCLUSION: In summary, the antimicrobial resistance of E. coli in northeast China is a serious issue and there is a risk of antimicrobial resistance transmission. Meanwhile, a novel ICE mobile element appeared in the process of antimicrobial resistance formation.

Heterologous expression of a deacetylase and its application in L-glufosinate preparation.

With potent herbicidal activity, biocatalysis synthesis of L-glufosinate has drawn attention. In present research, NAP-Das2.3, a deacetylase capable of stereoselectively resolving N-acetyl-L-glufosinate to L-glufosinate mined from Arenimonas malthae, was heterologously expressed and characterized. In Escherichia coli, NAP-Das2.3 activity only reached 0.25 U/L due to the formation of inclusive bodies. Efficient soluble expression of NAP-Das2.3 was achieved in Pichia pastoris. In shake flask and 5 L bioreactor fermentation, NAP-Das2.3 activity by recombinant P. pastoris reached 107.39 U/L and 1287.52 U/L, respectively. The optimum temperature and pH for N-acetyl-glufosinate hydrolysis by NAP-Das2.3 were 45 °C and pH 8.0, respectively. The Km and Vmax of NAP-Das2.3 towards N-acetyl-glufosinate were 25.32 mM and 19.23 µmol mg-1 min-1, respectively. Within 90 min, 92.71% of L-enantiomer in 100 mM racemic N-acetyl-glufosinate was converted by NAP-Das2.3. L-glufosinate with high optical purity (e.e.P above 99.9%) was obtained. Therefore, the recombinant NAP-Das2.3 might be an alternative for L-glufosinate biosynthesis.

Alcelaphine herpesvirus 1 genes A7 and A8 regulate viral spread and are essential for malignant catarrhal fever.

Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus that is carried asymptomatically by wildebeest. Upon cross-species transmission to other ruminants, including domestic cattle, AlHV-1 induces malignant catarrhal fever (MCF), which is a fatal lymphoproliferative disease resulting from proliferation and uncontrolled activation of latently infected CD8+ T cells. Two laboratory strains of AlHV-1 are used commonly in research: C500, which is pathogenic, and WC11, which has been attenuated by long-term maintenance in cell culture. The published genome sequence of a WC11 seed stock from a German laboratory revealed the deletion of two major regions. The sequence of a WC11 seed stock used in our laboratory also bears these deletions and, in addition, the duplication of an internal sequence in the terminal region. The larger of the two deletions has resulted in the absence of gene A7 and a large portion of gene A8. These genes are positional orthologs of the Epstein-Barr virus genes encoding envelope glycoproteins gp42 and gp350, respectively, which are involved in viral propagation and switching of cell tropism. To investigate the degree to which the absence of A7 and A8 participates in WC11 attenuation, recombinant viruses lacking these individual functions were generated in C500. Using bovine nasal turbinate and embryonic lung cell lines, increased cell-free viral propagation and impaired syncytia formation were observed in the absence of A7, whereas cell-free viral spread was inhibited in the absence of A8. Therefore, A7 appears to be involved in cell-to-cell viral spread, and A8 in viral cell-free propagation. Finally, infection of rabbits with either mutant did not induce the signs of MCF or the expansion of infected CD8+ T cells. These results demonstrate that A7 and A8 are both essential for regulating viral spread and suggest that AlHV-1 requires both genes to efficiently spread in vivo and reach CD8+ T lymphocytes and induce MCF.

Autophagy-related signaling pathways in non-small cell lung cancer.

Lung cancer is one of the most prevalent causes of morbidity and mortality in both men and women across the globe. The disease has a quiet phenotype at first, which leads to chronic tumor development. Non-small cell lung cancer (NSCLC) is the most common kind of lung cancer, accounting for 85 percent of all lung malignancies. Autophagy has been described as an intracellular "recycle bin" where damaged proteins and molecules are degraded. Autophagy regulation is mainly dependent on signaling pathways such as phosphoinositide 3-kinases (PI3K), AKT, and the mammalian target of rapamycin (mTOR). In the context of NSCLC, studies on these signaling pathways are inconsistent, but our literature review suggests that the inhibition of mTOR, PI3K/AKT, and epidermal growth factor receptor signaling pathways by different medications can active autophagy and inhibit NSCLC progression. In conclusion, signaling pathways related to autophagy are effective therapeutic approaches for the treatment of NSCLC.

TAG, a splice variant of the adaptor TRAM, negatively regulates the adaptor MyD88-independent TLR4 pathway.

Toll-like receptor 4 (TLR4) signals the induction of transcription factor IRF3-dependent genes from the early endosome via the adaptor TRAM. Here we report a splice variant of TRAM, TAG ('TRAM adaptor with GOLD domain'), which has a Golgi dynamics domain coupled to TRAM's Toll-interleukin 1 receptor domain. After stimulation with lipopolysaccharide, TRAM and TAG localized to late endosomes positive for the GTPase Rab7a. TAG inhibited activation of IRF3 by lipopolysaccharide. Knockdown of TAG with small interfering RNA enhanced induction of the chemokine CCL5 (RANTES), but not of interleukin 8, by lipopolysaccharide in human peripheral blood mononuclear cells. TAG displaced the adaptor TRIF from TRAM. TAG is therefore an example of a specific inhibitor of the adaptor MyD88-independent pathway activated by TLR4. Targeting TAG could be useful in the effort to boost the immunostimulatory effect of TLR4 without causing unwanted inflammation.

Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds.

BACKGROUND: Molecular targeted therapy for non-small cell lung carcinoma (NSCLC) is restricted due to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This study evaluated the effects of dual targeting of MEK and PI3K in human EGFR-TKI resistant NSCLC cell lines. METHODS: EGFR-TKI resistant NSCLC cell lines H1975, H460, and A549, with different mutation and amplification status in EGFR, K-RAS, PIK3CA, and MET genes, were treated with a MEK162 (MEK inhibitor) and BKM120 (PI3K inhibitor) combination or a BIBW2992 (EGFR inhibitor) and ARQ197 (MET inhibitor) combination and assayed for cell proliferation, apoptosis, and cell cycle distribution. RESULTS: Dual targeting of MEK and PI3K efficiently inhibited the cell proliferation, induced apoptosis and the G0/G1 cell cycle, and decreased the phosphorylation of ERK1/2, AKT, S6, and 4E-BP1. H460 cells with K-RAS and PIK3CA mutation were most sensitive to MEK162 and BKM120 combinations. H1975 cells with EGFR and PIK3CA mutation and MET amplification were sensitive to BIBW2992 and ARQ197 combinations. CONCLUSION: Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics.

[Relationship of ADC histogram parameters with pathological grade and lymph node metastasis of prostate cancer].

OBJECTIVE: To investigate the relationship between the apparent diffusion coefficient (ADC) histogram parameters based on the whole tumor and the pathological grade and lymph node metastasis (LNM) of PCa. METHODS: This retrospective study included 82 cases of PCa confirmed pathologically and subjected to MRI preoperatively. We obtained a series of ADC histogram parameters, such as ADCmean, ADCmedian, ADC25%, ADC75%, entropy, and histogram width, by processing the ADC images via the Firevoxel Post-Processing and the SPSS24 software. We compared the parameters between the high-risk and low- or moderate-risk groups as well as between the LNM-positive and LNM-negative groups of the patients, and analyzed the diagnostic performance of the parameters with statistically significant differences. RESULTS: The high-risk group, compared with the low- or moderate-risk one, showed a significantly lower ADCmean (ï¼»590 ± 120ï¼½ vs ï¼»837 ± 142ï¼½ ×10－6 mm2/s, P < 0.01), ADCmedian (ï¼»560 ± 117ï¼½ vs ï¼»804 ± 139ï¼½ ×10－6 mm2/s, P < 0.01), ADC25% (ï¼»446.5 ± 98ï¼½ vs ï¼»717 ± 118ï¼½ ×10－6 mm2/, P < 0.01) and ADC75% (ï¼»667 ± 132ï¼½ vs ï¼»931 ± 167ï¼½ ×10－6 mm2/s, P < 0.01). The ADCmean manifested the highest diagnostic performance, with an AUC of 0.907, a sensitivity of 0.933 and a specificity of 0.796. No statistically significant difference was found between the high-risk and the low- or moderate-risk one in entropy (3.58 ± 0.39 vs 3.63 ± 0.42, P = 0.238) or the histogram width (ï¼»540 ± 73ï¼½ vs ï¼»520 ± 65ï¼½ ×10－6 mm2/s, P = 0.086). Both entropy and the histogram width were remarkably higher in the LNM-positive than in the LNM-negative group (3.95 ± 0.41 vs 3.12 ± 0.45, P < 0.01; ï¼»578 ± 59ï¼½ vs ï¼»455 ± 68ï¼½ ×10－6 mm2/s, P < 0.01), and the former had an even higher diagnostic performance, with an AUC of 0.836, a sensitivity of 0.887 and a specificity of 0.781. There were no statistically significant differences between the LNM-positive and LNM-negative groups in the ADCmean (ï¼»768 ± 135ï¼½ vs ï¼»790±128ï¼½ ×10－6 mm2/s, P = 0.402), ADCmedian (ï¼»759 ± 110ï¼½ vs ï¼»775 ± 121ï¼½ ×10－6 mm2/s, P = 0.225), ADC25% (ï¼»643 ± 91ï¼½ vs ï¼»657 ± 89ï¼½ ×10－6 mm2/s, P = 0.654) or ADC75% (ï¼»895 ± 127ï¼½ vs ï¼»872 ± 129ï¼½ ×10－6 mm2/s, P = 0.926). CONCLUSIONS: ADC histogram parameters are related to pathological grade and LNM of PCa, and the analysis of the ADC histogram based on the whole tumor has an important value for preoperative evaluation and prognostic estimation of the malignancy.

Antiviral activity of porcine interferon omega 7 against foot-and-mouth disease virus in vitro.

Foot-and-mouth disease (FMD) is a disease of worldwide economic importance, and vaccines play an important role in preventing FMDV outbreaks. However, new control strategies are still needed since FMDV outbreaks still occur in some disease-free countries. Currently, interferon (IFN)-based strategies have been demonstrated to be an efficient biotherapeutic option against FMDV; however, interferon omega (IFN-ω) has not yet been assessed in this capacity. Thus, this study evaluated the antiviral activity of porcine IFN omega 7 (PoIFN-ω7) against FMDV. After the PoIFN-ω7 was expressed and purified, cell proliferation assays and quantitative real-time reverse transciption-polymerase chain reaction were used to evaluate the effective anti-cytopathic concentration of PoIFN-ω7 and its effectiveness pre- and post-infection with FMDV in swine kidney cells (IBRS-2). Results showed the rHis-PoIFN-ω7 fusion protein was considerably expressed using Escherichia coli BL21 (DE3) strain, and the recombinant protein exhibited significant in vitro protection against FMDV, including two strains belonging to type O and A FMDV, respectively. In addition, PoIFN-ω7 upregulated the transcription of Mx1, ISG15, OAS1, and PKR genes. These findings indicated that IFN-ω has the potential for serving as a useful therapeutic agent to prevent FMDV or other viral outbreaks in pigs.

Inhibitory effects of homoharringtonine on foot and mouth disease virus in vitro.

Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoof animals including cattle, swine, sheep, goats, and lots of wild species. Effectively control measures are urged needed. Here, we showed that homoharringtonine treatment exhibited a strong inhibitory effect against two different strains of FMDVs (O/MYA98/BY/2010 and A/GD/MM/2013) in swine kidney (IBRS-2) cells. Further experiments demonstrated that homoharringtonine did not affect virus attachment or entry. Using time-of-addition assays, we found that the antiviral activity of homoharringtonine occurred primarily during the early stage of infection. These results demonstrated that homoharringtonine might be an effective anti-FMDV drug. Further studies are required to explore the antiviral activity of homoharringtonine against FMDV replication in vivo.

Antiviral effect of amiloride on replication of foot and mouth disease virus in cell culture.

Recently, amiloride was shown to potently suppress Coxsackievirus B3 (CVB3) replication. In the current study, we investigated whether amiloride could also exhibit antiviral activity against foot-and-mouth disease virus (FMDV), which belongs to the same family (Picornaviridae) as CVB3. We found that amiloride exerted antiviral activity in a dose-dependent manner against two strains of FMDV in IBRS-2 cells, with slight cytotoxicity at 1000 µM. Besides, amiloride did not inhibit the attachment and entry of FMDV in IBRS-2 cells, but prevented early viral replication. These data implied that amiloride could be a promising candidate for further research as a potential antiviral drug against FMDV infection.

A novel type I interferon, interferon alphaomega, shows antiviral activity against foot-and-mouth disease virus in vitro.

Recently, a novel type I interferon alphaomega (IFN-αω), also known as IFN-µ, was identified. However, the biological activity of IFN-αω remain poorly understood. In this study, the porcine IFN-αω (PoIFN-αω) was expressed, purified, and its antiviral activities assessed by its ability to inhibit the cytopathic effect caused by FMDV on IBRS-2 cells. In addition, q-PCR was used to evaluate the expression of IFN-stimulated genes induced by PoIFN-αω. It was found that PoIFN-αω exerted effective antiviral activity against FMDV pre- and post-infection. Additionally, PoIFN-αω induced the transcription of IFN-stimulated genes, including Mx1, ISG15, OAS1, and PKR genes. Our study reported a new indication of PoIFN-αω as an effective anti-FMDV agent for the first time.

Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells.

Despite the impressive rates of clinical response to programmed death 1 (PD-1) blockade in multiple cancers, the majority of patients still fail to respond to this therapy. The CT26 tumor in mice showed similar heterogeneity, with most tumors unaffected by anti-PD-1. As in humans, response of CT26 to anti-PD-1 correlated with increased T- and B-cell infiltration and IFN expression. We show that intratumoral injection of a highly interferogenic TLR9 agonist, SD-101, in anti-PD-1 nonresponders led to a complete, durable rejection of essentially all injected tumors and a majority of uninjected, distant-site tumors. Therapeutic efficacy of the combination was also observed with the TSA mammary adenocarcinoma and MCA38 colon carcinoma tumor models that show little response to PD-1 blockade alone. Intratumoral SD-101 substantially increased leukocyte infiltration and IFN-regulated gene expression, and its activity was dependent on CD8+ T cells and type I IFN signaling. Anti-PD-1 plus intratumoral SD-101 promoted infiltration of activated, proliferating CD8+ T cells and led to a synergistic increase in total and tumor antigen-specific CD8+ T cells expressing both IFN-γ and TNF-α. Additionally, PD-1 blockade could alter the CpG-mediated differentiation of tumor-specific CD8+ T cells into CD127lowKLRG1high short-lived effector cells, preferentially expanding the CD127highKLRG1low long-lived memory precursors. Tumor control and intratumoral T-cell proliferation in response to the combined treatment is independent of T-cell trafficking from secondary lymphoid organs. These findings suggest that a CpG oligonucleotide given intratumorally may increase the response of cancer patients to PD-1 blockade, increasing the quantity and the quality of tumor-specific CD8+ T cells.

In Vitro and in Vivo Antiviral Activity of Mizoribine Against Foot-And-Mouth Disease Virus.

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4-7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.

Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection.

The interferons (IFNs) are a primary defense against pathogens because of the strong antiviral activities they induce. IFNs can be classified into three groups: type I, type II and type III, according to their genetic, structural, and functional characteristics and their receptors on the cell surface. The type I IFNs are the largest group and include IFN-α, IFN-ß, IFN-ε, IFN-ω, IFN-κ, IFN-δ, IFN-τ and IFN-ζ. The use of IFNs for the treatment of viral infectious diseases on their antiviral activity may become an important therapeutic option, for example, IFN-α is well known for the successful treatment of hepatitis B and C virus infections, and interest is increasing in the antiviral efficacy of other novel IFN classes and their potential applications. Therefore, in this review, we summarize the recent progress in the study of the biological activities of all the type I IFN classes and their potential applications in the treatment of infections with immunodeficiency virus, hepatitis viruses, and influenza viruses.

A large family of antivirulence regulators modulates the effects of transcriptional activators in Gram-negative pathogenic bacteria.

We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44-100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family.

TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus.

Glucocorticoids are widely used to treat patients with autoimmune diseases such as systemic lupus erythematosus (SLE). However, regimens used to treat many such conditions cannot maintain disease control in the majority of SLE patients and more aggressive approaches such as high-dose methylprednisolone pulse therapy are used to provide transient reductions in disease activity. The primary anti-inflammatory mechanism of glucocorticoids is thought to be NF-kappaB inhibition. Recognition of self nucleic acids by toll-like receptors TLR7 and TLR9 on B cells and plasmacytoid dendritic cells (PDCs) is an important step in the pathogenesis of SLE, promoting anti-nuclear antibodies and the production of type I interferon (IFN), both correlated with the severity of disease. Following their activation by self-nucleic acid-associated immune complexes, PDCs migrate to the tissues. We demonstrate, in vitro and in vivo, that stimulation of PDCs through TLR7 and 9 can account for the reduced activity of glucocorticoids to inhibit the IFN pathway in SLE patients and in two lupus-prone mouse strains. The triggering of PDCs through TLR7 and 9 by nucleic acid-containing immune complexes or by synthetic ligands activates the NF-kappaB pathway essential for PDC survival. Glucocorticoids do not affect NF-kappaB activation in PDCs, preventing glucocorticoid induction of PDC death and the consequent reduction of systemic IFN-alpha levels. These findings unveil a new role for self nucleic acid recognition by TLRs and indicate that inhibitors of TLR7 and 9 signalling could prove to be effective corticosteroid-sparing drugs.

[Synergistic Effects of Clopidogrel and Xuesaitong Dispersible Tablet by Modulating Plasma Protein Binding].

Objective: The ginsenoside Rb1,which account for platelet aggregation of Xuesaitong dispersible tablet, was selected to investigate the synergistic effects of clopidogrel( CPG) and Xuesaitong dispersible tablet drug by modulating plasma protein binding rate aspect. Methods: The HPLC and equilibrium dialysis were employed to determine the concentration of Rb1 both in dialysate( PBS) and blank plasma from healthy volunteer blood donors. The differences in protein-binding rate between Xuesaitong dispersible tablet alone( the concentration of ginsenoside Rb1 were 5. 0,1. 0,0. 4 µg / m L,respectively) and combined with CPG( each add CPG 2 µg / m L) were then compared. The three-dimensional spatial structure of the blank plasma albumin( HSA) in the subjects was construct by rabbit plasma albumin( PDB ID 3V09) template and evaluated by PRO-CHECK and ERRAT methods. Molecular simulation technique was used to display the competition mechanism with human plasma protein. Results: The protein binding rate of Xuesaitong dispersible tablet alone group in plasma PBS and human plasma at high( the concentration of ginsenoside Rb1 were 5. 0 µg / m L),middle( the concentred of ginsenoside Rb1 were 1. 0 µg / m L) and low( the concentration of ginsenoside Rb1 were 0. 4 µg / m L) concentrations were( 58. 17 ±3. 82) %,( 57. 43 ± 3. 21) %,( 55. 63 ± 3. 42) % respectively. When combined with CPG( each add CPG 2 µg / m L),the protein binding rate value were decline to( 46. 54 ± 3. 35) %,( 49. 25 ± 3. 56) %,( 48. 15 ± 3. 76) %,respectively. The molecular simulation results suggested that the two compounds have competitive synergistic effects with human plasma protein. Conclusion: The present investigation suggestes that there are synergistic effects of CPG and Xuesaitong dispersible tablet by modulating plasma protein binding rate of ginsenoside Rb1.

Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum.

Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti-metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells.

[Gynecologic cancers in a hospital: a retrospective analysis of admission data over ten years].

OBJECTIVE: To investigate admission patterns of patients with gynecologic cancers over a ten year period, which will provide a basis for further epidemiological studies. METHODS: We reviewed medical records of patients with gynecologic cancers who were admitt d to the West China Second University Hospital of Sichuan University from 2003 to 2012. Their clinicopathological data were extracted and analysed. RESULTS: The number of admitted patients increased over the years, with cervical, uterine and ovary cancers as the top three gynaecological cancers. They accounted for 92.13% of total gynaecological cancers. The peak age of gynaecological cancers was 40-49 years, which accounted for 34.02% (3132/9207) of all patients, followed by 50-59 years (26.64%, 2453/9207). Most (72.46%, 3062/4226) cervical cancer patients aged 30-49 years, compared with 40-59 years for uterine cancers (69.77%, 1768/2534) and 40-59 years for ovarian cancers (58.30%, 1004/1722). Patients in their 20th account for 4.43% (408/9 207) of total cancers, with in which cervical and ovarian cancers as the most common pathological type. Patients under 20 years of age accounted for only 0.98% (90/9207) of total cancers, with ovarian cancers as the most common pathological type. Patients over 60 years accounted for 12.90% (1188/9207) of total cancers, with uterine and ovarian cancers as the most common pathological type. Most patients were at an early stage of cancers when they were admitted to the hospital. CONCLUSION: Hospitalized patients with gynecologic cancers increase over years. Cervical, uterine and ovary cancers remain to be a focus of treatment. Peak age of those cancers varies.