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Fulltext Risk factors for mortality among COVID-19 patients

Albitar O, Ballouze R, Ooi JP, Sheikh Ghadzi SM

Diabetes Res Clin Pract, 2020 Aug;166:108293.
PMID: 32623035 DOI: 10.1016/j.diabres.2020.108293

AIMS: COVID-19 is a current global pandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data.
METHODS: A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality.
RESULTS: Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients.
CONCLUSIONS: Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.
Intrapericardial Administration to Achieve Localized and Targeted Treatment for Cardiac Disease

Xu Y, Chen Y, Tan JJ, Ooi JP, Guo Z

J Cardiovasc Transl Res, 2024 Aug 20.
PMID: 39164600 DOI: 10.1007/s12265-024-10553-3

Intrapericardial administration has been proposed as an alternative delivery route of pharmacological agents via the bilaminar sac of pericardium surrounding the heart. To date, intrapericardial administration has entailed the localized administration of a broad spectrum of therapeutic agents. These agents include stem cells, extracellular matrix, growth factor, drugs, bioactive materials, and genetic materials, to the heart and coronary arteries. The route not only overcomes the limitations associated with traditional systemic administration methods, but also presents multiple intrinsic advantages over the other approaches, allowing greater therapeutic actions. Intrapericardial administration exhibits versatility in addressing certain cardiac conditions and ongoing research in this field certainly holds promise for further innovations and advancements to improve cardiac treatment. Thus, this review discusses the anatomy and physiology of the pericardium, the intrapericardial administration access routes, the recent application of intrapericardial delivery in the context of cardiac repair as well as the challenges associated with the approach.
Andrographolide and 14-deoxy-11, 12-didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells

Ooi JP, Kuroyanagi M, Sulaiman SF, Muhammad TS, Tan ML

Life Sci, 2011 Feb 28;88(9-10):447-54.
PMID: 21219911 DOI: 10.1016/j.lfs.2010.12.019

Cytochrome P450 (CYP) enzymes have been implicated in a large number of preventable drug-herb interactions. Andrographis paniculata Nees, a tropical herb widely used for various health conditions contains two major diterpenoids, andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide. These compounds were evaluated systematically for their effects on CYP1A2, CYP2D6 and CYP3A4 expressions in HepG2 cells.
Programmed cell death pathways and current antitumor targets

Tan ML, Ooi JP, Ismail N, Moad AI, Muhammad TS

Pharm Res, 2009 Jul;26(7):1547-60.
PMID: 19407932 DOI: 10.1007/s11095-009-9895-1

Apoptosis and autophagic cell deaths are programmed cell deaths and they play essential roles in cell survival, growth and development and tumorigenesis. The huge increase of publications in both apoptosis and autophagic signaling pathways has contributed to the wealth of knowledge in facilitating the understanding of cancer pathogenesis. Deciphering the molecular pathways and molecules involved in these pathways has helped scientists devise and develop targeted strategies against cancer. Various drugs targeting the apoptotic TRAIL, Bcl-2 and proteasome pathways are already in Phase II/III clinical trials. The first mTOR inhibitor, temsirolimus has already been approved by the FDA, USA for the treatment of advanced renal cell carcinoma and more mTOR inhibitors are expected to be in the market in a few years time. Strategizing against aberrant autophagy activities in various cancers by using either pro-autophagics or autophagy inhibitors are currently been investigated. This review aims to discuss the most recent antitumor strategies targeting the apoptosis and autophagy signaling pathways and the latest outcome of clinical trials of the above drugs.
Biocompatible magnesium-doped biphasic calcium phosphate for bone regeneration

Ballouze R, Marahat MH, Mohamad S, Saidin NA, Kasim SR, Ooi JP

J Biomed Mater Res B Appl Biomater, 2021 Oct;109(10):1426-1435.
PMID: 33484103 DOI: 10.1002/jbm.b.34802

Autologous bone grafting remains the gold standard for almost all bone void-filling orthopedic surgery. However, autologous bone grafting has several limitations, thus scientists are trying to identify an ideal synthetic material as an alternative bone graft substitute. Magnesium-doped biphasic calcium phosphate (Mg-BCP) has recently been in the spotlight and is considered to be a potential bone substitute. The Mg-BCP is a mixture of two bioceramics, that is, hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), doped with Mg2+ , and can be synthesized through chemical wet-precipitation, sol-gel, single diffusion gel, and solid state reactions. Regardless of the synthesis routes, it is found that the Mg2+ preferentially accommodates in β-TCP lattice instead of the HA lattice. The addition of Mg2+ to BCP leads to desirable physicochemical properties and is found to enhance the apatite-forming ability as compared to pristine BCP. In vitro results suggest that the Mg-BCP is bioactive and not toxic to cells. Implantation of Mg-BCP in in vivo models further affirmed its biocompatibility and efficacy as a bone substitute. However, like the other bioceramics, the optimum physicochemical properties of the Mg-BCP scaffold have yet to be determined. Further investigations are required regarding Mg-BCP applications in bone tissue engineering.
Intrapericardial Administration of Human Pericardial Fluid Cells Improves Cardiac Functions in Rats with Heart Failure

Xu Y, Zhang X, Fu Z, Dong Y, Yu Y, Liu Y, et al.

Stem Cells Dev, 2024 Nov;33(21-22):616-629.
PMID: 39155804 DOI: 10.1089/scd.2024.0072

Heart failure (HF) is still the main cause of mortality worldwide. This study investigated the characteristics of human pericardial fluid-derived cells (hPFCs) and their effects in treating doxorubicin (DOX)-induced HF rats through intrapericardial injection. hPFCs were isolated from patients who underwent heart transplantation (N = 5). These cells that primarily expressed SCA-1, NANOG, and mesenchymal markers, CD90, CD105, and CD73, were able to form adipocytes, osteoblasts, and cardiomyocytes in vitro. Passage 3 hPFCs (2.5 × 105 cells/heart) were injected into the pericardial cavity of the DOX-injured rat hearts, significantly improving cardiac functions after 4 weeks. The tracked and engrafted red fluorescent protein-tagged hPFCs coexpressed cardiac troponin T and connexin 43 after 4 weeks in the host myocardium. This observation was also coupled with a significant reduction in cardiac fibrosis following hPFC treatment (P < 0.0001 vs. untreated). The elevated inflammatory cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-α in the DOX-treated hearts were found to be significantly reduced (P < 0.001 vs. untreated), while the regional proangiogenic vascular endothelial growth factor A (VEGFA) level was increased in the hPFC-treated group after 4 weeks (P < 0.05 vs. untreated). hPFCs possess stem cell characteristics and can improve the cardiac functions of DOX-induced HF rats after 4 weeks through pericardial administration. The improvements were attributed to a significant reduction in cardiac fibrosis, inflammation, and elevated regional proangiogenesis factor VEGFA, with evidence of cellular engraftment and differentiation in the host myocardium.