Hypoxia inhibition of camptothecin-induced apoptosis by Bax loss

Park, Kyoungsook,Woubit, Abdela,Fermin, Cesar,Reddy, Gopal,Habtemariam, Tsegaye,Chung, Jin,Park, Minseo,Seol, Dai-Wu,Kim, Moonil De Gruyter Open Sp. z o.o. 2012 BIOLOGIA -BRATISLAVA- Vol.67 No.3

<B>Abstract</B><P>Tumor cell hypoxia is linked to the resistance of human solid tumors to the various anti-cancer therapies: thus, its exploitation has been considered to be a potential target for cancer treatment. Previously, we demonstrated for the first time that hypoxia inhibits apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) through blocking translocation of Bax, a pro-apoptotic protein, from the cytosol to the mitochondria. Nevertheless, the molecular mechanism coupling hypoxia to resistance for drugs, especially for anti-cancer chemotherapeutics, still remains to be elucidated. Here, we demonstrate that hypoxia attenuates camptothecin (CPT)-induced apoptosis by decreasing the protein levels of Bax, thereby leading to resistance to the drug. DNA damage after exposure to CPT resulted in an increase of p53, and a concomitant up-regulation of p21, regardless of oxygen content. Under normoxic condition, CPT induced expression of p53 and its down-stream target molecule Bax as well, in the presence of increased p21. In contrast, when preexposed to hypoxia, Bax-inducing activity of CPT was completely lost and the Bax level was even decreased, although CPT increased both p53 and p21 as observed under normoxic condition. Our data indicate that hypoxia attenuates apoptosis via Bax. Our data also suggest that hypoxia regulates tumor cell apoptosis differentially, through regulating Bax translocation or through down-regulating Bax levels, depending on death-inducing signals as shown by TRAIL- or CPT-induced apoptosis.</P>

Flavonoids as Novel Therapeutic Agents Against Chikungunya Virus Capsid Protein: A Molecular Docking Approach

E. Vadivel,Gundeep Ekka,J. Fermin Angelo Selvin 대한화학회 2023 대한화학회지 Vol.67 No.4

Chikungunya fever has a high morbidity rate in humans and is caused by chikungunya virus. There are no treatments available until now for this particular viral disease. The present study was carried out by selecting 19 flavonoids, which are available naturally in fruits, vegetables, tea, red wine and medicinal plants. The molecular docking of selected 19 flavonoids was carried out against the Chikungunya virus capsid protein using the Autodock4.2 software. Binding affinity analysis based on the Intermolecular interactions such as Hydrogen bonding and hydrophobic interactions and drug-likeness properties for all the 19 flavonoids have been carried out and it is found that the top four molecules are Chrysin, Fisetin, Naringenin and Biochanin A as they fit to the chikungunya protein and have binding energy of -8.09, -8.01, -7.6, and 7.3 kcal/mol respectively. This result opens up the possibility of applying these compounds in the inhibition of chikungunya viral protein.

25-Hydroxyvitamin D level is sociated with mortality in patients with critical COVID-19: a prospective observational study in Mexico City

Israel Parra-Ortega,Diana Guadalupe Alcara-Ramirez,Alma Angelica Ronzon-Ronzon,Fermin Elias-Garcia,Jose Agustin Mata-Chapol,Alejandro Daniel Cervantes-Cot,Briceida Lopez-Martinez,Miguel Angel Villasis 한국영양학회 2021 Nutrition Research and Practice Vol.15 No.S

BACKGROUND/OBJECTIVES: Considering the high number of deaths from coronavirus disease 2019 (COVID-19) in Latin American countries, together with multiple factors that increase the prevalence of vitamin D deficiency, we aimed to determine 25-hydroxyvitamin D (25[OH]D) levels and its association with mortality in patients with critical COVID-19. SUBJECTS/METHODS: This was a prospective observational study including adult patients with critical COVID-19. Data, including clinical characteristics and 25(OH)D levels measured at the time of intensive care unit admission, were collected. All patients were followed until hospital discharge or in-hospital death. The patients were divided into those surviving and deceased patient groups, and univariate and multivariate logistic regression analyses were performed to determine independent predictors of in hospital mortality. RESULTS: The entire cohort comprised 94 patients with critical COVID-19 (males, 59.6%; median age, 61.5 years). The median 25(OH)D level was 12.7 ng/mL, and 15 (16%) and 79 (84%) patients had vitamin D insufficiency and vitamin D deficiency, respectively. The median serum 25(OH)D level was significantly lower in deceased patients compared with surviving (12.1 vs. 18.7 ng/mL, P < 0.001). Vitamin D deficiency was present in 100% of the deceased patients. Multivariate logistic regression analysis revealed that age, body mass index, other risk factors, and 25(OH)D level were independent predictors of mortality. CONCLUSIONS: Vitamin D deficiency was present in 84% of critical COVID-19 patients. Serum 25(OH)D was independently associated with mortality in critical patients with COVID-19.

Combination of cysteine- and oligomerization domain-mediated protein immobilization on a surface plasmon resonance (SPR) gold chip surface

Park, Kyoungsook,Lee, Jeong Min,Jung, Yongwon,Habtemariam, Tsegaye,Salah, Abdela Woubit,Fermin, Cesar D.,Kim, Moonil Royal Society of Chemistry 2011 The Analyst Vol.136 No.12

<P>Here we report an effective method for protein immobilization on a surface plasmon resonance (SPR) gold chip, describing the combination of cysteine- and oligomerization domain-mediated immobilization of enhanced green fluorescent protein (EGFP) as a model protein for the purpose of orientation-controlled surface density packing. In order to facilitate the oligomerization of EGFP, the dimeric and trimeric constructs derived from GCN4- leucine zipper domain were chosen for multimeric EGFP assembly. For orientation-controlled immobilization of the protein, EGFP modified with cysteine residues showing excellent orientation on a gold chip was used as a starting protein, as previously reported in our earlier study (<I>Anal. Chem.</I>, 2007, <B>79</B>, 2680–2687). Constructs of EGFP with oligomerization domains were genetically engineered, and corresponding fusion proteins were purified, applied to a gold chip, and then analyzed under SPR. The immobilized EGFP density on a gold chip increased according to the states of protein oligomerization, as dimeric and trimeric EGFPs displayed better adsorption capability than monomeric and dimeric forms, respectively. Fluorescence measurement corroborated the SPR results. Taken together, our findings indicated that the combination of cysteine- and oligomerization domain-mediated immobilization of protein could be used in SPR biosensor applications, allowing for an excellent orientation and high surface density simultaneously.</P> <P>Graphic Abstract</P><P>Here we report an effective method for protein immobilization on a SPR gold chip, describing the combination of cysteine- and oligomerization domain-mediated immobilization of EGFP as a model protein for the purpose of orientation-controlled surface density packing. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0an00966k'> </P>

Concentrations of Cyclosporin A and Metabolites in the Gingival Tissues of Transplant Patients

Camargo, Paulo M.,Wolinsky, Lawrence E.,McBride, James H.,Barrie Kenney, E.,Carranza, Fermin A.,Klokkevold, Perry R.,Robert Ettinger,Jennifer Marik Korean Academy of Oral Biology and the UCLA Dental 1999 International Journal of Oral Biology Vol.24 No.4

Cyclosporin A (CyA) is a potent immunosuppressive drug used to avert rejection following human organ transplant surgery and as therapy for various atuoimmune diseases. One complication associated with CyA therapy is gingival enlargement observed post transplantation. The purpose of this study was to determine if concentrations of CyA and its metabolites in the gingival tissues of patients presenting with gingival enlargement (responders) were higher than those in patients without enlargement (nonresponders). Ten organ transplant recipients (9 kidney, 1 liver) woh were receiving CyA for at least 6 months were classified clinically as responders and nonresponders. Site selection for biopsy was based on the degree of gingival enlargement and all biopsy sites presented minimal plaque and gingival inflammation. One biopsy was taken from each of the nonresponders and two were taken from the responders (one enlarged and one nonenlarged area). CyA concentrations in the biopsies were determined by HPLC and CyA plus metabolites was determined by Abbott TDx. Mean results demonstrated that enlarged and nonenlarged sites in responders presented with similar concentrations of CyA and CyA plus metabolites No statistically significantdifferences were found between the concentration of cya or cya plus metabolites in nonenlarged sites of responders when compared to nonenlarged sites of nonresponders, although nonresponders demonstrated higher values. Finally, enlarged sites in responders showed lower but not statistically significant concentrations of CyA or CyA plus metabolites than nonenlarged sites in nonresponders. This study demonstrates that the concentration of CyA and CyA plus metabolites in the gingival tissues of individuals taking the drug is not the single determinant factor in the development of gingival enargement.

PAS1-modified optical SIS sensor for highly sensitive and specific detection of toluene

Dung, Tran Thi,Lee, Ui Jin,Kim, Myung Hee,Kim, Kyoon Eon,Cho, Hyun Mo,Fermin, Cesar D.,Kim, Dong Hyung,Kim, Moonil Elsevier 2019 Biosensors & bioelectronics Vol.141 No.-

<P><B>Abstract</B></P> <P>We report on a novel solution immersed silicon (SIS) sensor modified with bio-receptor to detect toluene. To perform this approach, bio-receptor PAS1 which specifically interacts with toluene was chosen as a capture agent for SIS ellipsometric sensing. We constructed wild PAS1 and mutant PAS1 (F46A and F79Y) which are toluene binding-defective. Especially, we utilized an easily accessible capturing approach based on silica binding peptide (SBP) for direct immobilization of PAS1 on the SiO<SUB>2</SUB> surfaces. After the immobilization of SBP-tagged PAS1 to the sensing layers, PAS1-based SIS sensor was evaluated for its ability to recognize toluene. As a result, a significant up-shift in Psi (Ψ) was clearly observed with a low limit of detection (LOD) of 0.1 μM, when treated with toluene on wild PAS1-surface, but not on mutant PAS1-sensing layers, indicating the selective interactions between PAS1 and toluene molecule. The PAS1-SIS sensor showed no changes in Psi (Ψ), if any, negligible, when exposed to benzene, phenol, xylene and 4-nitrophenol as negative controls, thereby demonstrating the specificity of interaction between PAS1 and toluene. Taken together, our results strongly indicate that PAS1-modified ellipsometry sensor can provide a high fidelity system for the accurate and selective detection of toluene.</P> <P><B>Highlights</B></P> <P> <UL> <LI> SIS sensor modified with bio-receptor (PAS1) was developed for highly sensitive and specific detection of toluene. </LI> <LI> PAS1 receptor was tagged with silica binding peptide (SBP) to immobilize directly on the biosensing layers. </LI> <LI> The biosensing performance of SIS coupled with PAS1 represented a low detection limit of 0.1 μM to toluene. </LI> <LI> The PAS1-based SIS sensor showed an analytical specificity to toluene without cross-reactions by other toxic molecules. </LI> </UL> </P>