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The High Density Lipoprotein Cholesterol Hypothesis Revisited Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya
The Indonesian Biomedical Journal Vol 10, No 2 (2018)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v10i2.465

BACKGROUND: The strong inverse association of plasma levels of high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) found in human epidemiological studies led to the development of the ‘HDL-C hypothesis’, which posits that intervention to raise HDL-C will result in reduced risk of CHD. However, recent evidence has raised doubts about the hypotheses that elevating HDL-C is necessarily therapeutic. Genetic variations that associate with altered HDL-C do not strongly associate with altered cardiovascular disease risk.CONTENT: HDL-mediated cholesterol efflux from macrophage foam cells or measurements of the flux of cholesterol from macrophages to the liver and feces seem to correlate better with atherosclerotic burden than with HDL-C levels. Thus, it may be time to modify the HDL-C hypothesis to the ‘HDL flux hypothesis’, where intervention to promote cholesterol efflux and reverse cholesterol transport will reduce CHD risk, regardless of whether it affects plasma HDL-C levels. A deeper understanding of the complex biology of HDL metabolism and its relationship to reverse cholesterol transport and atherothrombotic events is urgently needed. This might lead to biomarkers of HDL flux and functionality that are more informative than simple measurements of HDL-C levels.SUMMARY: It is now clear from recent clinical trial and genetic studies that some approaches to raising HDL-C levels may have no effect on CHD. This suggests the need to evaluate HDL-C-raising therapies in different clinical populations, as well as therapies targeted toward HDL flux and function rather than simply HDL-C elevation. Perhaps moving from a focus on the HDL-C hypothesis to a focus on the HDL flux hypothesis will permit a biologically based reassessment of the optimal therapeutic approach to targeting HDL for reduction in cardiovascular risk.KEYWORDS: reverse cholesterol transport, cholesterol efflux capacity, HDL dysfunction, HDL particle size, HDL lipidomics, HDL proteomics

Mitochondria in Health and Disease Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya
The Indonesian Biomedical Journal Vol 11, No 1 (2019)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v11i1.779

BACKGROUND: Mitochondrial dysfunction known to be associated with most of human inherited disorders and diseases, including neurodegenerative disorders, cardiomyopathies, metabolic syndrome, muscle weakness, cancer, also obesity.CONTENT: Mitochondria charges for multiple anabolic and catabolic circuitries, as the main provider for adenosine triphosphate (ATP). Mitochondria also responsible for cellwide stress responses and control non-apoptotic cell death routines, such as autophagy and regulated necrosis. In other words, mitochondria play an extended role in regulating cellular functions, both vital and lethal, from physiological metabolism to stress responses and death to maintain adult tissue homeostasis. Furthermore, mitochondria are crucial for both embryonic and postembryonic development. Therefore, any defect or alteration in mitochondria signaling pathways will lead to a large number of diseases in human, including premature aging, neurodegenerative disorders, muscle weakness, cardiovascular disorders, and cancer.SUMMARY: Mitochondria perform a dynamic, integrated interconnected network, to maintain tissue homeostasis, beyond the cell boundaries and regulating cells and tissues communication. Certainly any mitochondrial dysfunction could direct to neurodegenerative diseases and metabolic disorders.KEYWORDS: mitochondria, UPR, mitochondrial quality control, proteostasis, mitohormesis, mitochondrial diseases

Nutritional Influences on Epigenetics, Aging and Disease Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya
The Indonesian Biomedical Journal Vol 11, No 1 (2019)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v11i1.780

BACKGROUND: Altered epigenetics is regarded to play quite a role in many chronic diseases including cancer, diabetes, obesity, dyslipidemia, hypertension and neurodegeneration, hence nutrition suggested to contribute in epigenetics and disease.CONTENT: Histone modifications, as a part of epigenetics mechanisms, depend on metabolites which acts as cofactors or substrates. Fluctuating levels of specific metabolites become the direct and rapid mechanisms to influence gene activity. Therefore, these metabolites may have a role as gatekeepers of chromatin, in chromatin landscape modulation as a response to key nutritional cues. Chemical modifications of histones and DNA have a critical role in epigenetic gene regulation including histone acetylation, and DNA methylation. Some enzymes add or remove such chemical modifications, and suggested to be sensitive to changes in intracellular metabolism, such as mutations in the metabolic enzymes succinate dehydrogenase (SDH), fumarate hydratase (FH) and isocitrate dehydrogenase (IDH) can result in cancer.SUMMARY: As a response to their nutrient environment, organisms tend to rapidly alter their gene expression. Many evidences showed an epigenetic regulation of chromatin is coupled to the changes on metabolites levels due to this kind of response. These metabolites will lead the recruitment of transcriptional regulatory complexes to DNA, thus clearly influencing the dynamic chromatin landscape.KEYWORDS: metabolites, enzymes, epigenetics, chromatin, nutrition

Metabolic Reprogramming and Molecular Rewiring in Cancer: Therapeutic Opportunities Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya
The Indonesian Biomedical Journal Vol 13, No 2 (2021)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v13i2.1598

BACKGROUND: A lot of contemporary cancer research has concentrated on genetic influence. However, cancer also involves biochemical changes, such as metabolic adaptation to support the aberrant cell proliferation.CONTENT: The fast cell proliferation in cancer cells enforce a metabolic re-arrangement to promote their long-term survival. The increased glucose uptake and fermentation of glucose to lactate are common features of this altered metabolism known as “the Warburg effect”. These metabolic pathways regulation enable cancer cells to produce adenosine triphosphate (ATP) in an efficient way. Epigenetic and metabolic changes also both affect molecular rewiring in cancer cells and promote cancer development and progression.SUMMARY: Metabolic rewiring and epigenetic remodeling establishing a direct link between metabolism and nuclear transcription to promote the survival of tumor cells. A further understanding of how metabolic remodeling can result in epigenetic changes in tumors, affecting cancer cell differentiation, proliferation, and/or apoptosis, will lead to a new strategy for cancer therapy.KEYWORDS: cancer metabolism, epigenetics, metabolic reprogramming, molecular rewiring

Measurement of Motor Evoked Potential in Acute Ischemic Stroke: Based on Latency, Amplitude, Central Motoric Conduction Time and Resting Motor Threshold Tugas Ratmono; Andi Wijaya; Cahyono Kaelan; Andi Asadul Islam; Ferry Sandra
The Indonesian Biomedical Journal Vol 8, No 3 (2016)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v8i3.208

BACKGROUND: After stroke, there are dynamic changes of motor evoked potential (MEP), including latency, amplitude, central motoric conduction time (CMCT) and resting motor threshold (RMT) in cerebral. However, latency, CMCT, amplitude and RMT have not been clearly shown in acute ischemic stroke patients with motoric function impairment based on Modified Motoric Research Council Scale (MRCs).METHODS: Patients with motoric function impairment after acute ischemic stroke were recruited, scored based on MRCs and grouped. Latency, amplitude, CMCT and RMT (% intensity) was measured using transcranial magnetic stimulation (TMS). Latency, amplitude, CMCT and RMT of subjects based on affected hemisphere (AH) and unaffected hemisphere (UH); stroke onset; and motoric severity; were analyzed and compared statistically.RESULTS: Thirty-seven subjects with complete assessments were selected. Results of MEP size measurement between AH and UH showed that latency, amplitude, CMCT and RMT of AH and UH were significantly different (p<0.05). In accordance to AH and UH results, latency, amplitude, CMCT and RMT of mild, moderate and severe groups based on motoric severity, showed that latency and CMCT were prolonged, RMT was increased, while amplitude was decreased along with severity increment. The amplitude and RMT among the groups were significantly different with p=0.034 and p=0.029, respectively.CONCLUSION: MEP size measurement including latency, amplitude, CMCT and RMT have significant different in AH and UH. In addition, amplitude and RMT were significantly different in MRCs groups, therefore the MEP size measurement could be suggested as prognostic tool.KEYWORDS: MEP, latency, amplitude, CMCT, RMT

The Immunobiology of Cancer: An Update Review Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya
The Indonesian Biomedical Journal Vol 9, No 2 (2017)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v9i2.342

BACKGROUND: The introduction of mechanism based targeted therapies to treat human cancers has been pledge as one of the results of three decades of remarkable progress of research into the mechanisms of cancer pathogenesis. We ponder how the description of hallmark principles is start to inform therapeutic development currently and may increasingly do so in the future.CONTENT: There are 10 biological capabilities involved as the hallmarks of cancer, during the multistep of human tumors development. These hallmarks simplify the complexities of neoplastic disease into a structured rational principles, includes sustaining proliferative signaling, eluding growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genome instability, inflammation, reprogramming energy metabolism and evading immune destruction.SUMMARY: The 10 hallmarks of cancer, in other words, the tumor’s distinctive and complementary capabilities that enable its growth and metastatic dissemination, continue to provide a solid foundation for understanding the biology of cancer. The acknowledgment of the widespread applicability of these concepts will increasingly influence the development of new manners to treat human cancer.KEYWORDS: hallmark of cancer, cancer genome, inflammation, cancer immunology, metastasis

Hormesis in Health and Disease: Molecular Mechanisms Anna Meiliana; Andi Wijaya
The Indonesian Biomedical Journal Vol 12, No 4 (2020)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v12i4.1315

BACKGROUND: Hormesis was initially defined as a phenomenon where a small dose of harmful agent exposure to living organisms gives beneficial effects. The dose and time of this ‘tress’ exposure has become the object of investigation across the broad range of biomedical studies.CONTENT: Hormesis characterized by the biphasic dose-effect or time-effect relationship for any substance. Some hormetic mechanisms performed biological plasticity, involve oxidative damage which instead induce antioxidant enzyme production in various cells. Early-life stress can increase resilience in later life and lack of stress can lead to vulnerability. Many stressors like dietary factors and natural environmental toxins can be occupied for healthy growth or homeostasis, which exemplifies how illness is the doorway to health.SUMMARY: Hormesis reconcile many paradoxical phenomena exert opposite effects of the same substance, either a xenobiotic or an endogenous substance, a hormone or a metabolite, a genetic manipulation or an epigenetic alteration, an experimental intervention or a natural event. Human bodies are highly adaptive. A resilient body would be resulted after the ‘training’. In this review, we will elucidate the hormesis’ definition, mechanisms and pathways, and also how hormesis impacts in human health and lifespan.KEYWORDS: biphasic, cell signaling, dose response, hormesis, preconditioning

Intervertebral Disc Degeneration and Low Back Pain: Molecular Mechanisms and Stem Cell Therapy Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya
The Indonesian Biomedical Journal Vol 10, No 1 (2018)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v10i1.426

BACKGROUND: Low back pain (LBP) mostly caused by disc degeneration, reflects to a tremendous of health care system and economy. More knowledge about these underlying pathologies will improve the opportunities that may represent critical therapeutic targets.CONTENT: Basic research is advancing the understanding of the pathogenesis and management of LBP at the molecular and genetic levels. Cytokines such as matrix metalloproteinases, phospholipase A2, nitric oxide, and tumor necrosis factor-α are thought to contribute to the development of LBP. Mesenchymal stem cells (MSCs) transplant to cartilage-like cells and secrete extracellular matrix and encourage nucleus pulposus (NP) cell activity inhibiting NP cell apoptosis, together with some chemical mediators such as cytokines and growth factors become a safe and effective new strategy for intervertebral disc degeneration (IDD) treatment and regeneration.SUMMARY: IDD occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians to help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.KEYWORDS: low back pain, intervertebral disc, degeneration, nucleus pulposus, annulus fibrosus, extracellular matrix, genetic, stem cells

Nutrigenetics, Nutrigenomics and Precision Nutrition Anna Meiliana; Andi Wijaya
The Indonesian Biomedical Journal Vol 12, No 3 (2020)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v12i3.1158

BACKGROUND: Since our conception to death, we were permanently exposed to nutrition. Indeed, food intake is the key of the environmental factor that modulates our gene. Nutrigenomics focus on how common dietary chemicals altering an individual’s genetic makeup including genome, proteome, and metabolome. While nutrigenetics refer to how the genetic variation gives different responses to nutrients.CONTENT: Nutrigenomics applied the high-throughput genomic-related tools to find out the influence of nutrients on the genes’ expression. While nutrigenetics (nutritional genetics) focus on the heterogenous response of gene variants to nutrients and dietary factors. Application nutrigenomics and nutrigenetics, integrated with system biology result in a precision nutrition as a relevant precise personal dietary change recommendation, thus will increase the motivation and sustain to whom the intervention is being delivered.SUMMARY: Individual diet recommendation is not simple. Many factors and tools should be involved adequately. The application of integrated -omics approaches, together with nutrigenomic and nutrigenetics for novel biomarker discovering and precision nutrition tailoring were expected to develop a healthier lifestyle and behavior.KEYWORDS: nutrigenetics, nutrigenomics, precision nutrition, metabolomics, system biology

Red Meats and Processed Meat as the Carcinogenic Foods and Phytochemical-chemoprevention Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya
The Indonesian Biomedical Journal Vol 11, No 3 (2019)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v11i3.965

BACKGROUND: Along with its increased prevalence, in the past decade, cancer had joined the list of chronic debilitating diseases. Nutrition become substantial aspects, due to its time-dependent effect to modulate inflammation thus trigger carcinogenic effects by altering the immune check point. Thus, nutrition contributes to the progression and therapeutic response of cancer, both in human or animal models.CONTENT: Meat is well favored food with appreciable appealing. Due to its high nutritional values it plays a central role in human development. Meat or meat derivate are important sources of proteins, minerals and vitamins. Their nutritional importance is worth compare to their economic impact but recent publication of WHO has set the social alarm about the relationship between red and/or processed meat consumption and cancer. On the other side, some natural or biologic agents may inhibit or reverse tumor growth. Some phytochemical agents including curcumin, resveratrol, lycopene, folates and tea polyphenols clinically proved to tune the signaling pathways regulating cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents.SUMMARY: Recent studies on chemopreventive agents involves a wide range of molecules, natural (plants, fruits and vegetables) or synthetic will provide better insights for cancer early pathogenesis, important end-point biomarker, and finally potential for reducing the burden of cancer.KEYWORDS: blocking agents, suppressing agents, red meat, processed meat, chemoprevention, phytochemicals

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