Two types of transcriptional controls on polyphosphate kinase (PPK) gene promoters in different bacteria

In bacteria, polyphosphate kinase (PPK) is responsible for the synthesis of polyP from ATP and the reversible conversion of polyP and ADP to ATP. PPK plays a crucial role in the ability of bacteria to adapt to nutritional stringencies and environmental stresses. Bacterial ppk gene expression was tested at the transcriptional level by using a ppk-promoter lacZ fusion reporter system under a variety of stressful conditions. The expression of ppk gene was greatly induced (7-20 fold higher depending on stress or medium) by deficiencies of phosphate, amino acids, or during entry into stationary phase. In this work, evidence was found for two different modes of regulation of ppk transcription in bacteria. In E. coli and S. enterica, ppk expression in response to starvation appears to be dependent on the ppGpp/DksA system and independent of the PhoR/PhoB two-component system under conditions of phosphate starvation. In contrast, increased ppk expression in response to phosphate starvation is dependent on the PhoR/PhoB two-component system in Acinetobacter. sp. ADP1, K. pneumoniae, and V. cholerae. The activity of the ppk promoter is also greatly induced by purine starvation. Purine deficiency seems to be a common stimulus for the induction of ppk expression in both of the above categories of bacteria. However, the induction of ppk transcription by purine starvation seems to be independent of both the ppGpp/DksA system and the PhoR/PhoB two-component system. This result implies the presence of third control system in ppk expression

Inhibitory Effect and Mechanism on Antiproliferation of Isoatriplicolide Tiglate (PCAC) from Paulownia Coreana

Paulownia coreana has traditionally been used as the medicine and health food in the treatment of cancer and infectious diseases. In the present study, a new antiproliferation agent, isoatriplicolide tiglate (PCAC) was isolated from the chloroform soluble fraction of the leaves of Paulownia coreana. The antiproliferation activities of PCAC plant extract was examined in breast and cervical cancer cell lines in a time-and dose-dependent manners. Our in vitro experiments showed that PCAC suppresses the cell growth and proliferation of cancer cells at a relatively low concentration ( 50 µg/mL). Western blot analysis showed that concentration higher than 50 µg/mL induces a time-dependent increase in the percentage of apoptotic cells. In this case, PCAC uses both extrinsic and intrinsic pathways for the apoptosis. PCAC treatment decreased the expression of pro-caspase 8, 9, and 3, the main regulators of apoptotic cell death, in MDA-MB-231 cells, accompanied by the activation of caspase 8, 9, and 3. More importantly, PCAC inhibited the in vitro proliferation of six other human breast and cervical cancer cell lines. In conclusion, our data strongly suggest that PCAC acts as an antiproliferation agents particularly against breast and cervical cancers by inducing cell cycle arrest in the S/G2 phase and caspase dependent apoptosis at relatively low ( 50 µg/mL) concentrations, respectively

Enhancing the Thermo-Stability and Anti-Biofilm Activity of Alginate Lyase by Immobilization on Low Molecular Weight Chitosan Nanoparticles

Bacterial biofilm causes severe antibiotic resistance. An extracellular polymeric substance (EPS) is the main component in the bacterial biofilm. Alginate is a key EPS component in the biofilm of Pseudomonas aeruginosa and responsible for surface adhesion and stabilization of biofilm. Alginate lyase has emerged as an efficient therapeutic strategy targeting to degrade the alginate in the biofilm of P. aeruginosa. However, the application of this enzyme is limited by its poor stability. In this study, chitosan nanoparticles (CS-NPs) were synthesized using low molecular weight chitosan and alginate lyase Aly08 was immobilized on low molecular weight chitosan nanoparticles (AL-LMW-CS-NPs). As a result, the immobilization significantly enhanced the thermal stability and reusability of Aly08. In addition, compared with free Aly08, the immobilized AL-LMW-CS-NPs exhibited higher efficiency in inhibiting biofilm formation and interrupting the established mature biofilm of P. aeruginosa, which could reduce its biomass and thickness confirmed by confocal microscopy. Moreover, the biofilm disruption greatly increased the antibiotic sensitivity of P. aeruginosa. This research will contribute to the further development of alginate lyase as an anti-biofilm agent

An efficient enzyme-triggered controlled release system for colon-targeted oral delivery to combat dextran sodium sulfate (DSS)-induced colitis in mice

Oral route colon-targeted drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC). However, CDDSs are challenging owing to the physiological and anatomical barriers associated with the gastrointestinal tract (GIT). In this study, we developed an effective enzyme-triggered controlled release system using curcumin–cyclodextrin (CD–Cur) inclusion complex as core and low molecular weight chitosan and unsaturated alginate resulting nanoparticles (CANPs) as shell. The formed CD–Cur–CANPs showed a narrow particle-size distribution and a compact structure. In vitro drug release determination indicated that CD–Cur–CANPs showed pH-sensitive and α-amylase-responsive release characteristics. Furthermore, in vivo experiments demonstrated that oral administration of CD–Cur–CANPs had an efficient therapeutic efficacy, strong colonic biodistribution and accumulation, rapid macrophage uptake, promoted colonic epithelial barrier integrity and modulated production of inflammatory cytokines, reshaped the gut microbiota in mice with dextran sodium sulfate (DSS)-induced colitis. Taken together, our synthetic CD–Cur–CANPs are a promising synergistic colon-targeted approach for UC treatment

Prognostic and Clinicopathological Significance of SERTAD1 in Various Types of Cancer Risk: A Systematic Review and Retrospective Analysis

SERTAD/TRIP-Br genes are considered as a key nuclear transcriptional player in diverse mechanisms of cell including carcinogenesis. The Oncomine™-Online Platform was used for differential expression and biological insights. Kaplan-Meier survival estimated by KM-plotter/cBioPortal/PrognoScan with 95% CI. SERTAD1 was found significantly elevated levels in most of tumor samples. Kaplan-Meier Plotter results distinctly showed the SERTAD1 over-expression significantly reduced median overall-survival (OS) of patients in liver (n = 364/Logrank-test p = 0.0015), ovarian (n = 655/Logrank-test p = 0.00011) and gastric (n = 631/Logrank-test p = 0.1866). Increased level of SERTAD1 has a significantly higher survival rate in the initial time period, but after 100 months slightly reduced OS (n = 26/Logrank-test p = 0.34) and RFS in HER2 positive breast cancer patients. In meta-analysis, cancer patients with higher SERTAD1 mRNA fold resulted worse overall survival than those with lower SERTAD1 levels. Heterogeneity was observed in the fixed effect model analysis DFS [Tau2 = 0.0.073, Q (df = 4) = 15.536 (p = 0.004), I2 = 74.253], DSS [Tau2 = 1.015, Q (df = 2) = 33.214, (p = 0.000), I2 = 93.973], RFS [Tau2 = 0.492, Q (df = 7) = 71.133 (p = 0.000), I2 = 90.159] (Figure 5). OS [Tau2 = 0.480, Q (df = 17) = 222.344 (p = 0.000), I2 = 92.354]. Lastly, SERTAD1 involved in several signaling cascades through interaction and correlation with many candidate factors as well as miRNAs. This meta-analysis demonstrates a robust evidence of an association between higher or lower SERTAD1, alteration and without alteration of SERTAD1 in cancers in terms of survival and cancer invasiveness

Inhibitory Effect and Mechanism on Antiproliferation of Isoatriplicolide Tiglate (PCAC) from <em>Paulownia Coreana</em>

<em>Paulownia coreana</em> has traditionally been used as the medicine and health food in the treatment of cancer and infectious diseases. In the present study, a new antiproliferation agent, isoatriplicolide tiglate (PCAC) was isolated from the chloroform soluble fraction of the leaves of <em>Paulownia coreana</em>. The antiproliferation activities of PCAC plant extract was examined in breast and cervical cancer cell lines in a time-and dose-dependent manners. Our <em>in vitro</em> experiments showed that PCAC suppresses the cell growth and proliferation of cancer cells at a relatively low concentration ( < 10 µg/mL) and induces apoptosis at a high concentration ( > 50 µg/mL). Western blot analysis showed that concentration higher than 50 µg/mL induces a time-dependent increase in the percentage of apoptotic cells. In this case, PCAC uses both extrinsic and intrinsic pathways for the apoptosis. PCAC treatment decreased the expression of pro-caspase 8, 9, and 3, the main regulators of apoptotic cell death, in MDA-MB-231 cells, accompanied by the activation of caspase 8, 9, and 3. More importantly, PCAC inhibited the <em>in vitro</em> proliferation of six other human breast and cervical cancer cell lines. In conclusion, our data strongly suggest that PCAC acts as an antiproliferation agents particularly against breast and cervical cancers by inducing cell cycle arrest in the S/G2 phase and caspase dependent apoptosis at relatively low ( < 10 μg/mL) and high ( > 50 µg/mL) concentrations, respectively