MicroRNA signature in hepatocellular carcinoma patients: identification of potential markers

MicroRNAs (miRNAs) play important roles in liver pathologies and they are potential biomarkers for diagnosis of liver diseases progression. Changes in miRNA sera expression can be used as non-invasive biomarkers for hepatocellular carcinoma (HCC). The aim of the study was to identify the miRNome profiling of HCC and its diagnostic value in distinguishing HCC from healthy individuals. Expression profiles of miRNAs in serum samples of 20 HCC patients and 10 healthy controls were detected. Whole miRNome profiling was done using next generation sequencing. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of the deregulated miRNAs for discriminating HCC cases from healthy controls. MiRNA 142 was highly expressed in HCC (P value?=?0.023) while miRNAs 191, 22, and 126 were higher in the controls (P value?=?0.005, 0.034, 0.010 respectively). We have identified 5 novel miRNAs and they were highly expressed in HCC than controls. Analysis of ROC curve demonstrated that these deregulated miRNAs can be used as a reliable biomarker for detection of HCC with high diagnostic accuracy (AUC?=?0.93). We have detected a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC. The study recommends further research to shed light on a possible role of the newly discovered novel miRNAs in HCC pathogenesis.

     

Basal ganglia hemorrhage in a case report following spinal surgery

Background

Intracranial hemorrhage is a rare but potentially severe complication of spinal surgery. Most reported post-operative ICH cases consist of cerebellar hemorrhage. There are fewer reported cases of supratentorial ICH following spinal surgery.

Case presentation

A 56-year-old woman underwent spinal surgery complicated by bilateral supratentorial intraparenchymal basal ganglia hemorrhage with both intraventricular extension and subarachnoid hemorrhage in both cerebral hemispheres.

Conclusion

The occurrence of neurological deterioration post-operatively following spinal surgery should alert physicians to the possibility of intracranial hemorrhage in order to facilitate rapid and optimal management. To our knowledge, this is the first case reporting basal ganglia hemorrhage following spinal surgery. Moreover, consideration should be given to the possibility of this complication prior to recommendation of elective spinal surgery.

     

Correlation between heat shock proteins,adiponectin, and T lymphocyte cytokine expression in type 2 diabetics

Type 2 diabetes mellitus (T2DM) features insulin resistance, hyperglycemia, dyslipidemia, overproduction of inflammatory cytokines, and systemic oxidative stress. Here, heat shock proteins Hsp70 and Hsp 90, adiponectin, and heme oxygenase-1 (HO-1, Hsp32) are profiled in peripheral blood mononuclear cells (PBMC) and serum from 25 T2DM patients and 25 healthy control subjects. Cells cultured with phorbol 12-myristate 13-acetate/ionomycin were evaluated by three-color flow cytometry for immunophenotypic biomarkers. Plasma HO-1, Hsp, and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA). Relative to healthy controls, T2DM patients exhibited significantly elevated plasma Hsp70, and representation of T helper immunophenotypes activated to express inflammatory cytokines, including CD4+ IFN-γ+, CD4+ TNF-α+, CD4+ IL-6+, CD4+ IL-1β+ T cells, significantly lower representation of CD4+ IL-10+ T cells, plasma adiponectin and cell-associated HO-1 expression—with no significant differences in plasma Hsp90 between T2DM and healthy controls. Plasma HO-1 and adiponectin in T2DM patients inversely correlated with TNF-α and showed inverse correlation between serum LDL and plasma HO-1. Moreover, TNF-α and Hsp90 in T2DM patients correlated positively with fasting blood glucose (FBG). These results demonstrate correlation between potentially pathogenic T cells, HO-1, and adiponectin, additionally revealing a T helper (Th)1-related character of T2DM immunopathogenesis, suggesting potential for novel T cell-related management strategies for T2DM and related co-morbidities.     

PCA based population generation for genetic network optimization

A gene regulatory network (GRN) represents a set of genes and its regulatory interactions. The inference of the regulatory interactions between genes is usually carried out using an appropriate mathematical model and the available gene expression profile. Among the various models proposed for GRN inference, our recently proposed Michaelis–Menten based ODE model provides a good trade-off between the computational complexity and biological relevance. This model, like other known GRN models, also uses an evolutionary algorithm for parameter estimation. Considering various issues associated with such population based stochastic optimization approaches (e.g. diversity, premature convergence due to local optima, accuracy, etc.), it becomes important to seed the initial population with good individuals which are closer to the optimal solution. In this paper, we exploit the inherent strength of principal component analysis (PCA) in a novel manner to initialize the population for GRN optimization. The benefit of the proposed method is validated by reconstructing in silico and in vivo networks of various sizes. For the same level of accuracy, the approach with PCA based initialization shows improved convergence speed.     

Enzymatic properties of lipase and characteristics production byLactobacillus delbrueckii subsp.bulgaricus

Some properties of an extracellular lipase produced byLactobacillus delbrueckii subsp.bulgaricus were studied. Maximum enzyme activity was found against olive and butter oil as enzyme substrates. Addition of 9% acacia gum, 0.1% Na-deoxycholate and 0.01 M CaCl₂ to the enzyme reaction mixture increased-lipase activity from 5.3 to 14.5 (FFA/mg protein/minute) at pH 6.0 and at 40° C. Maximum lipase production was reached in the presence of glucose as a sole source of carbon, wheat bran as nitrogen source, olive oil as a sole lipid source and butyric acid as fatty acid supporting the growth medium. An initial pH value of the culture medium of 6.0 and a temperature of 35° C gave the highest lipolytic activity.     

Antimicrobial activities of some novel thiazoles

2-(4-Phenylthiazol-2(3H)-ylidene)-malononitrile was synthesized by treating 1-phenyl-2-thiocyanatoethanone with malononitrile. Reaction of 2-(4-phenylthiazol-2(3H)-ylidene)-malononitrile with hydrazine hydrate afforded 4-(4-phenylthiazol-2-yl)-1H-pyrazole-3,5-diamine, reaction with benzylidenemalononitrile yielded 2-(5-benzylidene-4-phenyl-5H-thiazol-2-ylidene)-malononitrile, and coupling with benzenediazonium chloride gave 2-(4-phenyl-5-phenylazo-3H-thiazol-2-ylidene)-malononitrile. Diaminopyrazole reacted with enaminonitrile to yield the 3-(4-phenylthiazol-2-yl)pyrazolo[1,5-a]pyrimidine-2,7-diamine. All synthesized compounds showed significant antimicrobial activities with MIC range of 5–750 µg/mL. The results demonstrated a correlation of the hydrophobicity of the compounds with their antimicrobial activity. The most potent antimicrobial compound was 2-(4-phenylthiazol-2(3H)-ylidene)-malononitrile.     

Semisynthetic latrunculin B analogs: Studies of actin docking support a proposed mechanism for latrunculin bioactivity

Latrunculins are unique macrolides containing a thiazolidinone moiety. Latrunculins A, B and T and 16-epi-latrunculin B were isolated from the Red Sea sponge Negombata magnifica. N-Alkylated, O-methylated analogs of latrunculin B were synthesized and biological evaluation was performed for antifungal and antiprotozoal activity. The natural latrunculins showed significant bioactivity, while the semisynthetic analogs did not. Docking studies of these analogs into the X-ray crystal structure of G-actin showed that, in comparison with latrunculins A and B, N-alkylated latrunculins did not dock satisfactorily. This suggests that the analogs do not fit well into the active site of G-actin due to steric clashes and provides an explanation for the absence of bioactivity.     

Sarcophine-diol,a Chemopreventive Agent of Skin Cancer,Inhibits Cell Growth and Induces Apoptosis through Extrinsic Pathway in Human Epidermoid Carcinoma A431 Cells

Sarcophine-diol (SD), a structural modifications of sarcophine, has shown chemopreventive effects on 7,12-dimethylbenz(a)anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor developments in mice. Tumorigenesis is associated with uncontrolled cell growth and loss of apoptosis. In the present study, the effects of SD on cell growth and apoptosis in human epidermoid carcinoma A431 cells were determined to assess whether SD could inhibit cell growth and/or induce apoptosis, thus elucidating possible mechanism of action. MTT assay was used for cell viability; bromodeoxyuridine incorporation assay was used for cell proliferation; fluorescence-activated cell sorting analysis of annexin V/propidium iodide staining and TUNEL assay were used for determining apoptotic cells; Western blot analysis was used for determining the expression of caspase-3 and colorimetric caspase activity assays were used for determination of caspase-3, -8, and -9 activity. The results showed that SD treatment at concentration of 200 to 600 µM resulted in a concentration-dependent decrease in cell viability and cell proliferation in A431 cells, which largely inhibited cell growth. Sarcophine-diol treatment induced a strong apoptosis and significantly (P < .05) increased DNA fragmentation in A431 cells. Furthermore, SD treatment significantly (P < .05) increased the activity and expression of caspase-3 through activation of upstream caspase-8 in A431 cells rather than the activation of caspase 9. Sarcophine-diol treatment is relatively much less cytotoxic in monkey kidney normal CV-1 cells. These results suggest that SD decreases cell growth and induces apoptosis through caspase-dependent extrinsic pathway in A431 cells, and this may contribute to its overall chemopreventive effects in mouse skin cancer models.     

Identification of Newly Isolated Talaromyces pinophilus and Statistical Optimization of β-Glucosidase Production Under Solid-State Fermentation

Fungi able to degrade agriculture wastes were isolated from different soil samples, rice straw, and compost; these isolates were screened for their ability to produce β-glucosidase. The most active fungal isolate was identified as Talaromyces pinophilus strain EMOO 13-3. The Plackett–Burman design is used for identifying the significant variables that influence β-glucosidase production under solid-state fermentation. Fifteen variables were examined for their significances on the production of β-glucosidase in 20 experimental runs. Among the variables screened, moisture content, Tween 80, and (NH₄)₂SO₄ had significant effects on β-glucosidase production with confidence levels above 90% (p < 0.1). The optimal levels of these variables were further optimized using Box–Behnken statical design. As a result, the maximal β-glucosidase activity is 3648.519 U g^?1, which is achieved at the following fermentation conditions: substrate amount 0.5 (g/250 mL flask), NaNO₃ 0.5 (%), KH₂PO₄ 0.3 (%), KCl 0.02 (%), MgSO₄ · 7H₂O 0.01 (%), CaCl₂ 0.01 (%), yeast extract 0.07 (%), FeSO₄ · 7H₂O 0.0002 (%), Tween 80 0.02 (%), (NH₄)₂SO₄ 0.3 (%), pH 6.5, temperature 25°C, moisture content 1 (mL/g dry substrate), inoculum size 0.5 (mL/g dry substrate), and incubation period 5 days.