Anti Bacterial Activity of Ethanolic Extract of Zingiber Officinale and Pipper Nigrum against Some Clinical Isolates

Ethanolic extract of Zingiber officinale and Pipper nigrum were evaluated by testing in vitro antimicrobial activity on clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli, and proteus specie using Agar diffusion method. Proteus specie showed sensitivity to Z. officinale at disc concentration range of 50 to 800µg/ml, Staphylococcus aureus also showed sensitivity to z. officinale at concentration of 100 to 800 µg/ml and Klebsiella pneumonia showed sensitivity at disc concentration of 100 to 800 µg/ml likewise proteus specie showed sensitivity to p. nigrum at disc concentration range of 100 to 800µg/ml and staphylococcus aureus also showed sensitivity to p. nigrum at disc concentration range of 100 to 800µg/ml. However, the Ethanolic extract of z. officinale and p. nigrum showed no lethal or inhibitory effects on Pseudomonas aeruginosa and Escherichia coli at all concentration. The observed minimum inhibitory concentration (MIC) of the Ethanolic extraction for proteus species, Staphylococcus aureus and Klebsiella pneumonia were 50, 100,200µglml respectively for Z. officinale, while for P. nigrum, the minimum inhibitory concentration (MIC) were 100 and 200µg/ml for Proteus specie and staphylococcus aureus respectively. The extracts were further subjected to phytochemical tests for the presence of secondary metabolites using standard procedures. The results of phytochemical screening indicated the presence of alkaloids, Flavonoid, reducing sugar, saponins and steroids in Z. officinale, and alkaloids, Flavonoid, saponins, steroids and tannin in P. nigrum. This indicates that both Z. officinale and piper nigrum has the potential for the production of drugs against pathogenic organisms

Chronic Hepatitis B Virus Infection and Rubella Susceptibility Among Obstetric Population in Metropolis Antenatal Centre Kano, Nigeria

It is well known that hepatitis B virus (HBV) infection is endemic in Nigeria. However, increased rubella susceptibility has been shown in patients from the Asian pacific region where chronic HBV infection is endemic. This study was carried out to assess the relationship between chronic HBV infection and rubella susceptibility in obstetric population aged 15–47 years attending Antenatal Clinic at Muhammad Abdullahi Wase Specialist Hospital Kano, Nigeria. From a total of 288 patients screened, 31 (10.76%) were reactive for HBsAg, meanwhile 50 (17.36%) were reactive to rubella IgM. Among the 31 infected patients 15 (48.39%) were from 20 – 24 years age bracket representing the most  susceptible age group while the infection rate was lowest (0.35%) in 45 – 49  age group (P = 0.00). The results of serological markers shows that HBsAg (+) was found in all 31 subjects (100%), anti HBs (+) 0 (0.00%), HBeAg (+) 3 (9.68%); anti HBe (+) and anti HBc (+) 24 (77.42%) respectively (P = 0.09). The study of liver enzymes activity among the HBV positive patients shows abnormal Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) among HBsAg (+) and HBeAg (+) group. However, abnormal Alkaline phospatase (ALP) was found to be non-significantly different between HBsAg (+) and HBeAg (+) vsHBsAg (+) and HBeAg (-) groups (P=0.00). Moreover, obstetric histories such as abortion still birth and neonatal deaths among various age groups with respect to rubella was also studied, it implies that  out of the 50 reactive patients, 35(12.15%) had a previous abnormal obstetric history (P=0.02). In a comparative study conducted, it was observed that HBV carriers were (25.81%) susceptible to rubella as against (12.91%) observed in HBV free subjects (positive correlation). The study demonstrates strong associations between chronic HBV infection and rubella susceptibility among the studied population

HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress

Background Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER) stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC. Methodology and Principal Findings HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R), were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1), as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase. Conclusion and Significance HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC

Protein-Binding Microarray Analysis of Tumor Suppressor AP2α Target Gene Specificity

Cheap and massively parallel methods to assess the DNA-binding specificity of transcription factors are actively sought, given their prominent regulatory role in cellular processes and diseases. Here we evaluated the use of protein-binding microarrays (PBM) to probe the association of the tumor suppressor AP2α with 6000 human genomic DNA regulatory sequences. We show that the PBM provides accurate relative binding affinities when compared to quantitative surface plasmon resonance assays. A PBM-based study of human healthy and breast tumor tissue extracts allowed the identification of previously unknown AP2α target genes and it revealed genes whose direct or indirect interactions with AP2α are affected in the diseased tissues. AP2α binding and regulation was confirmed experimentally in human carcinoma cells for novel target genes involved in tumor progression and resistance to chemotherapeutics, providing a molecular interpretation of AP2α role in cancer chemoresistance. Overall, we conclude that this approach provides quantitative and accurate assays of the specificity and activity of tumor suppressor and oncogenic proteins in clinical samples, interfacing genomic and proteomic assays

Essential control of the function of the striatopallidal neuron by pre-coupled complexes of adenosine A2A-dopamine D2 receptor heterotetramers and adenylyl cyclase

The central adenosine system and adenosine receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by the strategic co-localization of different adenosine and dopamine receptor subtypes in the two populations of striatal efferent neurons, striatonigral and striatopallidal, that give rise to the direct and indirect striatal efferent pathways, respectively. With optogenetic techniques it has been possible to dissect a differential role of the direct and indirect pathways in mediating 'Go' responses upon exposure to reward-related stimuli and 'NoGo' responses upon exposure to non-rewarded or aversive-related stimuli, respectively, which depends on their different connecting output structures and their differential expression of dopamine and adenosine receptor subtypes. The striatopallidal neuron selectively expresses dopamine D2 receptors (D2R) and adenosine A2A receptors (A2AR), and numerous experiments using multiple genetic and pharmacological in vitro, in situ and in vivo approaches, demonstrate they can form A2AR-D2R heteromers. It was initially assumed that different pharmacological interactions between dopamine and adenosine receptor ligands indicated the existence of different subpopulations of A2AR and D2R in the striatopallidal neuron. However, as elaborated in the present essay, most evidence now indicates that all interactions can be explained with a predominant population of striatal A2AR-D2R heteromers forming complexes with adenylyl cyclase subtype 5 (AC5). The A2AR-D2R heteromer has a tetrameric structure, with two homodimers, which allows not only multiple allosteric interactions between different orthosteric ligands, agonists, and antagonists, but also the canonical Gs-Gi antagonistic interaction at the level of AC5. We present a model of the function of the A2AR-D2R heterotetramer-AC5 complex, which acts as an integrative device of adenosine and dopamine signals that determine the excitability and gene expression of the striatopallidal neurons. The model can explain most behavioral effects of A2AR and D2R ligands, including the psychostimulant effects of caffeine. The model is also discussed in the context of different functional striatal compartments, mainly the dorsal and the ventral striatum. The current accumulated knowledge of the biochemical properties of the A2AR-D2R heterotetramer-AC5 complex offers new therapeutic possibilities for Parkinson's disease, schizophrenia, SUD and other neuropsychiatric disorders with dysfunction of dorsal or ventral striatopallidal neurons

Intra-cluster knowledge exchange and frequency of product innovation in a digital cluster.

We investigate how intra-cluster knowledge exchange affects the frequency of product innovation. Based on self-administered survey data of digital SMEs from Bournemouth and Poole regions of England, this study shows that digital firms that sustain both temporary and prolonged relationships with outbound employees have a higher probability of introducing frequent product innovation. Moreover, while cognitive proximity and the use of external knowledge providers increase the probability of frequent product innovation, geographical proximity reduces it. Our findings suggest that managers of young digital firms with limited resources in peripheral regions should ‘act near’ before reaching out

Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells

Hepatocellular carcinoma (HCC) usually arises from hepatic fibrosis caused by chronic inflammation. In chronic liver damage, hepatic stellate cells undergo progressive activation to myofibroblasts (MFB), which are important extracellular-matrix-producing mesenchymal cells. Concomitantly, perturbation of transforming growth factor (TGF)-β signaling by pro-inflammatory cytokines in the epithelial cells of the liver (hepatocytes) promotes both fibrogenesis and carcinogenesis (fibro-carcinogenesis). Insights into fibro-carcinogenic effects on chronically damaged hepatocytes have come from recent detailed analyses of the TGF-β signaling process. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create phosphoisoforms phosphorylated at the COOH-terminal, linker, or both (L/C) regions. After acute liver injury, TGF-β-mediated pSmad3C signaling terminates hepatocytic proliferation induced by the pro-inflammatory cytokine-mediated mitogenic pSmad3L pathway; TGF-β and pro-inflammatory cytokines synergistically enhance collagen synthesis by activated hepatic stellate cells via pSmad2L/C and pSmad3L/C pathways. During chronic liver disease progression, pre-neoplastic hepatocytes persistently affected by TGF-β together with pro-inflammatory cytokines come to exhibit the same carcinogenic (mitogenic) pSmad3L and fibrogenic pSmad2L/C signaling as do MFB, thereby accelerating liver fibrosis while increasing risk of HCC. This review of Smad phosphoisoform-mediated signals examines similarities and differences between epithelial and mesenchymal cells in acute and chronic liver injuries and considers Smad linker phosphorylation as a potential target for the chemoprevention of fibro-carcinogenesis