Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146

CD146, also known as melanoma cell adhesion molecule or MCAM, is a key cell adhesion protein in vascular endothelial cell activity and angiogenesis. CD146 promotes tumor progression of many cancers including melanoma and prostate. Strikingly, its expression is frequently lost in breast carcinoma cells, and it may act as a suppressor of breast cancer progression. While upstream mechanisms regulating CD146 are well documented, our understanding of the downstream molecular events underlying its mode of action remains to be elucidated. This review aims to focus on the progress in understanding the signaling mechanisms and the functional relevance of CD146, a multifaceted molecule, in cancer with particular emphasis on its role in inhibiting breast cancer progression.     

Electrocatalytic oxidation of rice starch using mixed oxidant generated via titanium/rhodium thermally activated modified electrode: Part (I)

Oxidation of rice starch was achieved via electro-generated mixed oxidant due to the electrolysis of saline solution using the titanium/rhodium thermally activated modified electrode. The factors affecting the oxidation criteria such as the pH value of the reaction medium, current density, duration, temperature of oxidation, and the supporting electrolyte concentration were studied. The resultant oxidized starch was evaluated via determining the carbonyl and carboxyl contents as well as the apparent viscosity at different rates of shears. Results obtained indicate that, the optimum operating conditions for the electrocatalytic oxidation of rice starch “suitable sizing materials for cellulosic based textile warps” by the titanium/rhodium thermally activated modified electrode are, current density 7.5 mA/cm², pH 3, solution temperature 25 °C, time of electrolysis 60 min. and 7.5 g/l of sodium chloride as supporting electrolyte.     

Biodiesel production via transesterification of palm olein using waste mud crab (Scylla serrata) shell as a heterogeneous catalyst

A recent rise in crab aquaculture activities has intensified the generation of waste shells. In the present study, the waste shells were utilized as a source of calcium oxide to transesterify palm olein into methyl esters (biodiesel). Characterization results revealed that the main component of the shell is calcium carbonate which transformed into calcium oxide when activated above 700 °C for 2 h. Parametric studies have been investigated and optimal conditions were found to be methanol/oil mass ratio, 0.5:1; catalyst amount, 5 wt.%; reaction temperature, 65 °C; and a stirring rate of 500 rpm. The waste catalyst performs equally well as laboratory CaO, thus creating another low-cost catalyst source for producing biodiesel. Reusability results confirmed that the prepared catalyst is able to be reemployed up to 11 times. Statistical analysis has been performed using a Central Composite Design to evaluate the contribution and performance of the parameters on biodiesel purity.     

Synthesis of potent antitumor and antiviral benzofuran derivatives

A new series of potent antitumor and antiviral benzofuran derivatives was synthesized by the reaction of the furochromone-6-carboxaldehydes 1 and 2 with different heterocyclic amines to yield the benzofuran-5-carbonyl derivatives 4–11. The synthesized compounds 1, 3–11 were tested against twelve different human cancer cell lines and all of the compounds were more potent than the comparative standards. The HIV inhibitory activity of the tested compounds 1, 3–11 showed that they have higher potency than Atevirdine. Moreover, compound 6 was significantly potent with wider therapeutic index. The HIV-1 RT inhibitory activity showed that compounds 10, 11, 3 and 4 were notably potent but with lower therapeutic index than Atevirdine. The HCV NS3-4A protease inhibitor activity of the tested compounds revealed that they have weaker potency and less therapeutic index than VX-950, although compounds 1, 4, 9 and 6, respectively exhibited significant activity.     

Glycerol: An unexpected major metabolite of energy metabolism by the human malaria parasite

Background

Malaria is the third most prevalent cause of infectious disease in the world. Resistance of the parasite to classical drugs makes the discovery of new and effective drugs more urgent. The oxidized derivative of hydroxy- cis terpenone (OHCT) is a synthetic molecule that is not toxic to cultured human liver cells at concentrations as high as 60 μM and inhibits activity of cytochrome P450s that metabolize many drugs.

Methods

OHCT activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum, and a P. falciparum clone that is partially resistant to artemisinin was assayed in vitro.

Results

OHCT at nanomolar concentrations was effective against all intraerythrocytic stages of P. falciparum and exhibited activity in vitro against both chloroquine-sensitive and -resistant strains of P. falciparum as well as a P. falciparum clone that is partially resistant to artemisinin. Moreover, OHCT exhibited potent activity against gametocytes, the form that is transmitted by mosquitoes and essential for the spread of malaria.

Conclusion

OHCT displays strong growth inhibitory activity against all stages of P. falciparum and no evidence of toxicity to human cells in culture. It is easily synthesized and has the potential for inhibiting metabolism of drugs used in combination therapies.     

Genotypic detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis strains by DNA sequencing: a randomized trial

Background

Tuberculosis is a growing international health concern. It is the biggest killer among the infectious diseases in the world today. Early detection of drug resistance allows starting of an appropriate treatment. Resistance to drugs is due to particular genomic mutations in specific genes of Mycobacterium tuberculosis(MTB). The aim of this study was to identify the presence of Isoniazid (INH) and Rifampicin(RIF) drug resistance in new and previously treated tuberculosis (TB) cases using DNA sequencing.

Methods

This study was carried out on 153 tuberculous patients with positive Bactec 460 culture for acid fast bacilli.

Results

Of the 153 patients, 105 (68.6%) were new cases and 48 (31.4%) were previously treated cases. Drug susceptibility testing on Bactec revealed 50 resistant cases for one or more of the first line antituberculous. Genotypic analysis was done only for rifampicin resistant specimens (23 cases) and INH resistant specimens (26 cases) to detect mutations responsible for drug resistance by PCR amplification of rpoB gene for rifampicin resistant cases and KatG gene for isoniazid resistant cases. Finally, DNA sequencing was done for detection of mutation within rpoB and KatG genes. Genotypic analysis of RIF resistant cases revealed that 20/23 cases (86.9%) of RIF resistance were having rpoB gene mutation versus 3 cases (13.1%) having no mutation with a high statistical significant difference between them (P < 0.001). Direct sequencing of Kat G gene revealed point mutation in 24/26 (92.3%) and the remaining 2/26 (7.7%) had wild type KatG i.e. no evidence of mutation with a high statistical significant difference between them (P < 0.001).

Conclusion

We can conclude that rifampicin resistance could be used as a useful surrogate marker for estimation of multidrug resistance. In addition, Genotypic method was superior to that of the traditional phenotypic method which is time-consuming taking several weeks or longer.     

Tissue allograft coding and traceability in USM Tissue Bank,Malaysia

In Malaysia, tissue banking activities began in Universiti Sains Malaysia (USM) Tissue Bank in early 1990s. Since then a few other bone banks have been set up in other government hospitals and institutions. However, these banks are not governed by the national authority. In addition there is no requirement set by the national regulatory authority on coding and traceability for donated human tissues for transplantation. Hence, USM Tissue Bank has taken the initiatives to adopt a system that enables the traceability of tissues between the donor, the processed tissue and the recipient based on other international standards for tissue banks. The traceability trail has been effective and the bank is certified compliance to the international standard ISO 9001:2008.     

Curcumin ameliorates diclofenac sodium‐induced nephrotoxicity in male albino rats

Exposure to drugs often results in toxicity in the kidney which represents the major control system maintaining homeostasis of the body and thus is especially susceptible to xenobiotics. Nephrotoxicity is a life‐threatening side‐effect of nonsteroidal anti‐inflammatory drugs (NSAIDs). Diclofenac is one of the most frequently prescribed NSAIDs and have been reported to cause multiple organs damage. Curcumin (CUR) exhibits nephroprotective properties. Therefore, rats were divided into four groups; rats of groups 3 and 4 received diclofenac (100 mg/kg, i.m.), whereas rats of groups 2 and 4 received CUR (100 mg/kg, p.o.) for 3 days. Diclofenac revealed a significant increase in urea and creatinine levels and malondialdehyde concentration and marked reduction in catalase activity and reduced glutathione concentration. Histopathologically, diclofenac produced fatty changes and eosinophilic casts were detected in the renal tubules, those were attenuated by administration of CUR prior diclofenac.     

The antidepressant-like effect of Ocimum basilicum in an animal model of depression

We investigated the efficacy of Ocimum basilicum (OB) essential oils for treating depression related behavioral, biochemical and histopathological changes caused by exposure to chronic unpredictable mild stress (CUMS) in mice and to explore the mechanism underlying the pathology. Male albino mice were divided into four groups: controls; CUMS; CUMS plus fluoxetine, the antidepressant administered for pharmacological validation of OB; and CUMS plus OB. Behavioral tests included the forced swim test (FST), elevated plus-maze (EPM) and the open ?eld test (OFT); these tests were performed at the end of the experiment. We assessed serum corticosterone level, protein, gene and immunoexpression of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) as well as immunoexpression of glial fibrillary acidic protein (GFAP), Ki67, caspase-3 in the hippocampus. CUMS caused depression in the mice as evidenced by prolonged immobility in the FST, prolonged time spent in the open arms during the EPM test and reduction of open field activity in the OFT. OB ameliorated the CUMS induced depressive status. OB significantly reduced the corticosterone level and up-regulated protein and gene expressions of BDNF and GR. OB reduced CUMS induced hippocampal neuron atrophy and apoptosis, and increased the number of the astrocytes and new nerve cells. OB significantly increased GFAP-positive cells as well as BDNF and GR immunoexpression in the hippocampus.     

Environmental relationships of aquatic vegetation in the fresh water ecosystem of the Nile Delta,Egypt

In generalized four sectors, 350 stands (water channels) in 50 selected and geo‐referenced sites with eighteen environmental factors were surveyed. The total number of recorded species varied from a sector to another: 21 in the northern, nineteen in the middle, seventeen in the western and sixteen in the eastern. New populations of Cyperus papyrus were explored. Vallisneria spiralis, Elodea canadensis and Najas armata were among seven extinct species that were not recorded few decades ago. The floristic composition alteration may be because of the addition of organic matter of plant and animal origin and the discharge of industrial and sewage effluents. Classification and ordination analyses (DCA) resulted in the segregation of seventeen vegetation groups (communities), three of them were repeatedly recorded; namely Phragmites australis‐Eichhornia crassipes, Phragmites australis‐Myriophyllum spicatum and Potamogeton pectinatus‐Myriophyllum spicatum. Phragmites australis‐Cyperus papyrus group was a new community spreading in the eastern sector of the Delta. Electric conductivity, Fe, Hg and chemical oxygen demand (COD) showed high significant variation (P < 0.001) among the vegetation groups. Other significant variables were Cl, Ca, NO₃, pH and SO₄ (P < 0.047). Redundancy analysis (RDA) was chosen as the appropriate ordination method to perform direct gradient analysis. Trace elements Cu, Fe, Hg and Pb participated in the floristic and chemical composition of each sector.