Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68.

The molecular mechanisms of opium action with regard to coronary artery disease (CAD) have not yet been determined. The aim of this study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in CAD patients with and without opium addiction. This case-control study was conducted on three groups: (1) opium-addicted CAD patients (CAD + OA, n = 30); (2) CAD patients with no opium addiction (CAD, n = 30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n = 17). The protein and mRNA levels of CD9, CD36, and CD68 were evaluated by the flow cytometry and quantitative polymerase chain reaction (RT-qPCR) methods, respectively. The consumption of atorvastatin, aspirin, and glyceryl trinitrate was found be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD + OA group than in the CAD and Ctrl groups (p = 0.001 and p = 0.005, respectively). MDA levels significantly increased in CAD and CAD + OA patients in comparison with the Ctrl group (p = 0.010 and p = 0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Opium may affect coronary artery disease by inducing inflammation but not through the expression of CD9, CD36, and CD68.

The molecular mechanisms of opium with regard to coronary artery disease (CAD) have not yet been determined. The aim of the present study was to evaluate the effect of opium on the expression of scavenger receptors including CD36, CD68, and CD9 tetraspanin in monocytes and the plasma levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), malondialdehyde (MDA), and nitric oxide metabolites (NOx) in patients with CAD with and without opium addiction. This case-control study was conducted in three groups: (1) opium-addicted patients with CAD (CAD+OA, n=30); (2) patients with CAD with no opium addiction (CAD, n=30); and (3) individuals without CAD and opium addiction as the control group (Ctrl, n=17). Protein and messenger RNA (mRNA) levels of CD9, CD36, and CD68 were evaluated by flow cytometry and reverse transcription-quantitative PCR methods, respectively. Consumption of atorvastatin, aspirin, and glyceryl trinitrate was found to be higher in the CAD groups compared with the control group. The plasma level of TNF-α was significantly higher in the CAD+OA group than in the CAD and Ctrl groups (p=0.001 and p=0.005, respectively). MDA levels significantly increased in the CAD and CAD+OA groups in comparison with the Ctrl group (p=0.010 and p=0.002, respectively). No significant differences were found in CD9, CD36, CD68, IFN-γ, and NOx between the three groups. The findings demonstrated that opium did not have a significant effect on the expression of CD36, CD68, and CD9 at the gene and protein levels, but it might be involved in the development of CAD by inducing inflammation through other mechanisms.

Design, in silico and in vitro evaluation of curcumin analogues against Plasmodium falciparum.

The polyphenolic compound curcumin has been reported for its antimalarial properties in various scientific studies. Plasmodium falciparum ATP6, the parasite orthologue of mammalian sarcoplasmic Ca2+ ATPase (SERCA) has been identified as a key molecular target of both artemisinin and curcumin. The work was thereby undertaken to study the anti-malarial properties of two different series of curcumin analogues based on their docking interactions with PfATP6 and correlating the results with their anti-malarial activity. The compounds were designed retaining similar functional groups as that of the parent curcumin nucleus while incorporating changes in the carbon chain length, unsaturated groups and the number of ketone groups. The compounds (1E, 4E)-1,5-bis(4-methylphenyl)penta-1,4-dien-3-one (CD-9), (1E, 4E)-1,5-bis(4-methoxyphenyl)penta-1,4-dien-3-one (CD-8) and (E)-1,3-bis(4-hydroxylphenyl)prop-2-en-1-one (CD-1) showed IC50 values of 1.642 µM, 1.764 µM and 2.59 µM in 3D7 strain and 3.039 µM, 7.40 µM and 11.3 µM in RKL-2 strain respectively. Detailed structure-activity relationship studies of the compounds showed that CD-9 and CD-8 had a common hydrophobic interaction with the residue Leu268 of the PfATP6 protein and has been postulated through our study to be the reason for their antimalarial activity as seen after corroborating the results with the in vitro study. The study provided valuable insight about the ligand-protein interaction of the various functional groups of curcumin and its analogues against the PfATP6 protein and their importance in imparting antimalarial action.

Statins decrease lung inflammation in mice by upregulating tetraspanin CD9 in macrophages.

Tetraspanins organize protein complexes in tetraspanin-enriched membrane microdomains that are distinct from lipid rafts. Our previous studies suggested that reduction in the levels of tetraspanins CD9 and CD81 may be involved in the progression of inflammatory lung diseases, especially COPD. To search for agents that increase the levels of these tetraspanins, we screened 1,165 drugs in clinical use and found that statins upregulate CD9 and CD81 in RAW264.7 macrophages. The lipophilic statins, fluvastatin and simvastatin, reversed LPS-induced downregulation of CD9 and CD81, simultaneously preventing TNF-α and matrix metalloproteinase-9 production and spreading of RAW264.7 cells. These statins exerted anti-inflammatory effects in vitro in wild-type macrophages but not in CD9 knockout macrophages, and decreased lung inflammation in vivo in wild-type mice but not in CD9 knockout mice, suggesting that their effects are dependent on CD9. Mechanistically, the statins promoted reverse transfer of the LPS-signaling mediator CD14 from lipid rafts into CD9-enriched microdomains, thereby preventing LPS receptor formation. Finally, upregulation of CD9/CD81 by statins was related to blockade of GTPase geranylgeranylation in the mevalonate pathway. Our data underscore the importance of the negative regulator CD9 in lung inflammation, and suggest that statins exert anti-inflammatory effects by upregulating tetraspanin CD9 in macrophages.

B-cell depletion attenuates white and gray matter pathology in marmoset experimental autoimmune encephalomyelitis.

This study investigated the effect of CD20-positive B-cell depletion on central nervous system (CNS) white and gray matter pathology in experimental autoimmune encephalomyelitis in common marmosets, a relevant preclinical model of multiple sclerosis. Experimental autoimmune encephalomyelitis was induced in 14 marmosets by immunization with recombinant human myelin oligodendrocyte glycoprotein in complete Freund adjuvant. At 21 days after immunization, B-cell depletion was achieved by weekly intravenous injections of HuMab 7D8, a human-anti-human CD20 antibody that cross-reacts with marmoset CD20. In vivo magnetic resonance imaging showed widespread brain white matter demyelination in control marmosets that was absent in CD20 antibody-treated marmosets. High-contrast postmortem magnetic resonance imaging showed white matter lesions in 4of the 7 antibody-treated marmosets, but these were significantly smaller than those in controls. The same technique revealed gray matter lesions in 5 control marmosets, but none in antibody-treated marmosets. Histologic analysis confirmed that inflammation, demyelination, and axonal damage were substantially reduced in brain, spinal cord, and optic nerves of CD20 antibody-treated marmosets. In conclusion, CD20-postive B-cell depletion by HuMab 7D8 profoundly reduced the development of both white and gray matter lesions in the marmoset CNS. These data underline the central role of B cells in CNS inflammatory-demyelinating disease.