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BACKGROUND: Many chronic disorders, including vascular diseases, metabolic syndrome, and neurological diseases, are known to share a common factor of excessive inflammation. It takes a lot of energy to heal damaged tissue, which is a complicated process. The outcome is often suboptimal, with some degree of fibrosis, depending on the tissue's ability to regenerate and the strength of the inflammatory response. We may get new insights into disease causation and therapeutic strategies by better understanding endogenous regulatory points within the inflammatory response.CONTENT: Despite of the benefit in raising an inflammatory response, it also have unfavourable effects. Unresolved inflammation can over accumulate collagenous connective tissue and induce fibrosis, promote tissue dysfunction, and finally organ failure. Currently, the resolution of inflammation was described in terms of contemporary molecules as a different mechanisms from anti-inflammatory, since in resolution, the pathogen and apoptotic cells crumbs will be cleared and the macrophages will set back the tissue homeostasis. An active transition in the mediators that predominate in exudates occurs in conjunction with the remission of inflammation. These groups of inborn pro-resolution named resolvins, maresins, and protectins work to reduce inflammation by triggering certain pathways that support homeostasis rather than by suppressing the immune system.SUMMARY: The resolution of inflammation, once believed to be a passive process, is now understood to entail active biochemical programs that allow inflamed tissues to regain equilibrium. In this review, we spotlight the resolution to inflammation as a strategy to prevent tissue fibrosis and hinder the organ damage.KEYWORDS: inflammation; resolution; fibrosis; wound healing; specialized pro-resolving mediators.

BACKGROUND: Immunotherapy, particularly the idea of immune checkpoint blockage is currently draw much attention in cancer treatment. It has been approved as an adjuvant, however, it cannot be a single cancer treatment.CONTENT: The discovery of the basic ligand-receptor interactions between immune and cancer cells inside the tumor microenvironment has led to the current interest in immunotherapy, specifically immune checkpoint inhibition. Different ligands produced by cancer cells interact with immune cells' surface receptors, activating inhibitory pathways, such programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1), that cause immune cells to become immunologically tolerant. On the other side, epigenetic modulators also play a critical role in enhancing the tumor microenvironment and regaining immunological recognition and immunogenicity. Some findings showed that such immune suppression can be reversed through various mechanisms involving antigens pathways, immune genetic, and epigenetic pathways. These findings have created a very encouraging foundation for research on the combination of epigenetic and immunotherapeutic drugs as cancer treatments.SUMMARY: The effectiveness of this suggested paradigm can only be demonstrated by clinical studies. Epigenetic treatment might replace immune checkpoint therapy as a powerful new cancer care technique that is generally well tolerated and should be proven with adequate clinical trials.KEYWORDS: epigenetics, immunotherapy, PTM, DNMT, HDAC, immune check point

BACKGROUND: Metastases are simply known as cancers spread to another part of the body, and often be responsible for the severity of cancer prognosis. Somehow, the complex mechanisms of metastases are not fully understood yet.CONTENT: The characteristic of cancer is akin to a never-healing wound. Cancer cells are plastic and dynamic as they build their niches and developed into metastases, even when they seem dormant. Therefore, cancer cells can survive the immune system. Recent research has shown the distinct biology of metastasis-initiating cell, which leads to tumor development in distant organs, immune surveillance evasion, and co-option of metastatic micro-environments. Effective cancer therapies must consider the regenerative states of metastatic malignancies and have careful observation of patient phenotypes.SUMMARY: This review aimed to provide an insight on genesis and characteristics of metastases, starting from its seeding and dormancy, until the advance phase. Thus, developing therapy for cancer metastases should not start as it grows, but even as earlier strategies since the primary tumor was detected.KEYWORDS: cancer metastasis, DTC, CTC, CSC, dormancy, pre-metastatic niche, plasticity

BACKGROUND: Metabolism impairment in obese condition usually initially triggered by inflammation and insulin signaling impairment. The involvement of metabolites, including lipids, amino acids, and ketone bodies, in altering insulin sensitivity has been revealed after massive data sets were provided by the studies regarding metabolomics and lipidomics.CONTENT: Metabolites were now understood to serve more than just the metabolism products, but also as active signaling molecules including in insulin and immunological actions. Different lipid metabolites can serve as signaling molecules to induce insulin resistance of sensitivity through a similar pathway, and impact on the inflammation status. Branched Chain Amino Acids (BCAA) and many amino acids have been correlated with mitochondrial dysfunction and insulin impairment. Ketogenic diet, supplementation and microbiota transplantation become the current strategies to set a preferable metabolites composition to modulate insulin sensitivity.SUMMARY: Thousands of metabolites can now be measured using technical and bioinformatics developments. Different types of amino acids, fatty acids, and bile acids are being studied in relation to altered metabolic states, particularly obesity and type 2 diabetes mellitus. A thorough knowledge of the metabolic changes that contribute to insulin resistance might lead to the discovery of new targets for enhancing insulin sensitivity and preventing and treating many metabolic disorders.KEYWORDS: metabolites, insulin resistance, lipids, amino acids, ketone bodies

BACKGROUND: Obesity incidence has risen dramatically during the last 50 years, reaching epidemic proportions. Obesity's growing prevalence, as well as its numerous metabolic and cardiovascular problems, poses a danger to human health and lifespan across the world.CONTENT: Numerous studies have shown that obesity causes inflammation, and suggest that inflammation may have a causal role in the development of insulin resistance, defective insulin secretion, and energy homeostasis disturbance. Obesity-induced inflammation is different from other inflammatory models because it includes tonic activation of the innate immune system, which has a long-term influence on metabolic balance. Inflammation can cause tissue damage by causing maladaptive responses such as fibrosis and necrosis. Obesity-induced inflammation is unique since it affects a variety of organs, including the adipose tissue, pancreas, liver, skeletal muscle, heart, and brain. These characteristics of obesity-induced inflammation make it difficult to decipher the underlying processes and how they affect metabolic systems.SUMMARY: The disruption of energy homeostasis caused by a positive energy balance is most likely the first trigger of metabolic inflammation, and the initial adaptive response aim to relieve the anabolic pressure caused by obesity. However, over time, this adaptive reaction becomes maladaptive, and the persistence of inflammation shows that the initial response has failed. The inflammation affects so many organ systems during obesity, and to develop novel treatment methods, a greater knowledge of the process was needed.KEYWORDS: obesity, inflammation, diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular diseases, heart failure

BACKGROUND: Aging is an unavoidable part of life, defined by a gradual loss in tissue and organ function and an increasing chance of death. Current studies of aging connected the genetic and epigenetic changes to cause this process.CONTENT: When the aging-related epigenetic alterations is accumulated, it may result in irregulated gene expression, metabolic instability, stem cell senescence and exhaustion, and imbalance of tissue homeostasis, which all accelerate the aging process. Altered epigenetic gene regulatory mechanisms such as DNA methylation, histone modification and chromatin remodeling, and non-coding RNAs can induce aging process, thus manipulating these processes give a chance for the success of age-delaying interventions.SUMMARY: Given updated tools and technologies to investigate the epigenetic regulation affecting aging processes, new therapeutic strategies to delay this process can be developed to increase longevity and improve quality of life.KEYWORDS: aging, epigenetic, senescence, autophagy, mitochondria, metabolism, rejuvenation

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

BACKGROUND: Metabolomics is a developed technology that comprehensively analyzes the metabolites in biological specimens. It appears to be a prospective method in the practice of precision medicine.CONTENT: Metabolomic technologies currently surpass beyond the traditional clinical chemistry techniques. Metabolomic is capable to perform a precise analysis for hundreds to thousands of metabolites, therefore provide a detailed characterization of metabolic phenotypes and metabolic derangements that underlie disease, to represent an individual’s overall health status, furthermore to discover new precise therapeutic targets, and discovery of biomarkers, either for diagnosis or therapy monitoring purpose.SUMMARY: Adequate data processing and quantification methods are still needed to be developed to boost integrated -omics as a powerful clinical practice platform.KEYWORDS: metabolomic, precision medicine, phenotyping, biomarker, nutritional pattern

BACKGROUND: Cancer stem cells (CSCs) eradication might serve as a robust approach for cancer eradication. MCF-7 as breast cancer continuous cell line is known to contain breast CSCs (BCSCs) for its capability to maintain its original tumor population. CSCs enriched culture is a fundamental tool for CSCs targeted therapy development. Effective and unsophisticated CSCs dedifferentiation protocol for producing CSCs enriched culture is needed.METHODS: MCF-7 cells were cultured initially in Dulbecco's Modified Eagle Medium (DMEM) low glucose medium then changed to DMEM:F12. Serum starvation was performed during each medium refreshment gradually with fetal bovine serum (FBS) concentration of 10%, 5%, 2.5% until reaching 1% FBS concentration. Stable MCF-7 culture was then adapted to serum free culture system, containing DMEM:F12, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and B27 supplement as dedifferentiation protocol for 18 days. Cluster of differentiation (CD)44 and CD24 double staining immunocytochemistry was performed to evaluate cell stemness.RESULTS: The population of cells expressing BCSCs markers (CD44+/CD24low) in non-adherent single cells subpopulation was significantly increased after the dedifferentiation procedure (70.39%) compared to control groups (0.71%) (p

BACKGROUND: Carbohydrate antigens 15-3 (CA 15-3) is a conventional tumor marker in breast cancer, with low sensitivity and specificity. MicroRNA (miRNA)-21 showed its stability in circulation and could serve as powerful biomarker. The aim of this study was to evaluate miRNA-21 as breast cancer biomarker compared to CA 15-3 in Indonesian population.METHODS: Circulating plasma miRNA-21 expression was measured using qRT-PCR in 49 patients at various stages of breast cancer and 16 healthy controls. The relative expression value of miRNA-21 was calculated using 2-ΔΔCt. Meanwhile, CA 15-3 was quantified using electrochemiluminescence immunoassay (ECLIA) methods. The results of miRNA-21 and CA 15-3 plasma circulating expression were compared with controls at each stage and between stages of breast cancer.RESULTS: CA 15-3 median level in breast cancer group was 1.60 times higher compared to control group (p=0.019), 21.00 m/mL and 13.05 m/mL, respectively. Median miRNA-21 expression in breast cancer group was elevated 4.92 folds compared to control group (p=0.001), 4.43 and 0.90, respectively. There was no significant difference of CA 15-3 level between controls and all stages of breast cancer group. CA 15-3 cut-off value was 15.05 m/mL (p=0.016) with 59.2% sensitivity and 62.5% specificity. Meanwhile, there was a significant difference of miRNA-21 expression between controls and most stages of breast cancer group. Circulating miRNA-21 expression cut-off value was 2.07 (p=0.000) with 91.8% sensitivity and 87.5% specificity.CONCLUSION: Circulating miRNA-21 expression and CA 15-3 levels were significantly increased in breast cancer group compared to control group. The miRNA-21 expression increased consistently with breast cancer stage progression. miRNA-21 could serve as superior biomarker compared to CA 15-3.KEYWORDS: biomarker, breast cancer, circulating plasma, liquid biopsy, miRNA-21

BACKGROUND: Irisin is secreted by our muscle during physical exercise, which has been recently studied to be linked with lipid metabolism. The aim of this study was to investigate the role of irisin that interact with the oxidized-low density lipoprotein (ox-LDL) and high density lipoprotein cholesterol (HDL-C) levels that are affected by moderate intensity exercise in obese men aged ≥50 years.METHODS: This was a cross-sectional study with 70 obese men whose age ≥50 years old as participants. Participants were classified into two groups of men with and without physical exercised, based on American College of Sports Medicine (ACSM). Irisin and ox-LDL plasma levels were analyzed using enzyme-linked immunosorbent assay (ELISA), meanwhile the HDL-C serum level was analyzed using homogenous enzymatic methods.RESULTS: The result showed an association between the duration of physical exercise per week and irisin level (R=0.584, p0.05).CONCLUSION: Moderate-intensity physical exercise may decrease cardiovascular risk and improve the quality of life among obese subjects aged ≥50 years old, which was indicated by the decrease of ox-LDL and the increase of irisin level. In addition, it can be concluded that the higher the irisin level showed the lower levels of ox-LDL and higher level of HDL-C.KEYWORDS: obesity, elderly, irisin, ox-LDL, HDL-C, physical exercise

BACKGROUND: Giant transformations are going on currently in health care, and the greatest force behind this phenomenon is data.CONTENT: Big data has arrived into medicine field, lead to potential enhancement in accountability, quality, efficiency, and innovation. Most updated, artificial intelligence (AI) and machine-learning (ML) techniques rapidly developed, bring forth the big data analysis into more useful applications, from resource allocation to complex disease diagnosis. To realize this, a very large set of health-care data is needed for algorithms training and evaluation, including patients’ treatment data, patients respond to treatment, and personal patient information, such as genetic data, family history, health behavior, and vital signs.SUMMARY: Precision Health involving preventive, predictive, personalized and precise. The arrival of AI and ML will enhance and facilitates the improvement of this relationship through better accuracy, productivity, and workflow, thus develop a health system that will go beyond just curing disease, but further into wellness that preventing disease before it strikes, thus the patient–doctor bond is expected to be reformed and not be eroded.KEYWORDS: artificial intelligence, machine learning, deep learning, electronic health records, big data

BACKGROUND: The mechanism of aging goes along with age, one of which is characterized by cellular senescent, which occurs mostly in adipose tissue. Adipose tissue is the site of accumulation of large cell senescent, in the regulation of obesity and aging. Proteins p53 is marker for cell senescent, which are also known to induce inflammation. This study was aimed to determine the relationship between circulating protein p53 and high sensitivity C-reactive protein (hsCRP) in central obese men with inflammaging.METHODS: The study design is an observational study with cross-sectional approach. The subjects were 75 central obese men (waist circumference/WC > 90 cm), aged ≥ 45 years old. Subjects were divided into 2 age groups, those are middle age group: 45-59 years old (50.7%) and elderly group: ≥ 60 years old (49.3%). Examination of circulating p53 was done using enzyme-linked immunosorbent assay (ELISA) method, and the hsCRP examination was done by chemiluminescent method.RESULTS: It was found that there was a correlation between circulating p53 and hsCRP in elderly (r=-0.414; p

BACKGROUND: The association between caffeine with blood pressure (BP) still remains controversial. Caffeine is mainly metabolized by cytochrome-P450 (CYP)1A2 enzyme. Polymorphism of CYP1A2 is known to cause interindividual variation on enzymatic activity, thus affects caffeine metabolism and its effect on cardiovascular (CV) system.METHODS: We conducted a cross-sectional study and recruited 121 Indonesian subjects aged 25-60 years with varying coffee-drinking habits. DNA was extracted from peripheral blood and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique. Blood pressures were measured in the morning prior to the daily activity. Caffeine concentration in blood plasma was measured using high-performance liquid chromatography (HPLC). The differences between variables were analyzed using MannWhitney analysis and the correlations among variables were determined using multivariate logistic regression analysis.RESULTS: This study showed that the frequencies of single nucleotide polymorphisms (SNPs) among Indonesian were 31.8%, 18.2%, 25.2% and 24.8% respectively for CYP1A2*1A, CYP1A2*1B, CYP1A2*1C and CYP1A2*1F alleles. The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. There were no significant differences in term of BP levels among CYP1A2 genotypes and coffee drinking habit groups.CONCLUSIONS: The frequencies of CYP1A2 SNPs in Indonesian are different with frequencies in other populations. Since the association were not statistically significant, CYP1A2 polymorphisms as the predictor of elevated blood pressuare should be investigated further.KEYWORDS: coffee, caffeine, blood pressure, single nucleotide polymorphism, CYP1A2

BACKGROUND: Atherosclerosis is a leading cause of vascular disease worldwide. During the past several decades, landmark discoveries in the field of vascular biology have evolved our understanding of the biology of blood vessels and the pathobiology of local and systemic vascular disease states and have led to novel disease-modifying therapies for patients. This review is made to understand the molecular mechanism of atherosclerosis for these future therapies.CONTENT: Advances in molecular biology and -omics technologies have facilitated in vitro and in vivo studies which revealed that blood vessels regulate their own redox milieu, metabolism, mechanical environment, and phenotype, in part, through complex interactions between cellular components of the blood vessel wall and circulating factors. Dysregulation of these carefully orchestrated homeostatic interactions has also been implicated as the mechanism by which risk factors for cardiopulmonary vascular disease lead to vascular dysfunction, structural remodeling and, ultimately, adverse clinical events.SUMMARY: Atherosclerosis is a heterogeneous disease, despite a common initiating event of apoB-lipoproteins. Despite of acute thrombotic complications, an adequate resolution response is mounted, where efferocytosis prevents plaque necrosis and a reparative scarring response (the fibrous cap) prevents plaque disruption. However, a small percentage of developing atherosclerotic lesions cannot maintain an adequate resolution response, which leading to the formation of clinically dangerous plaques that can trigger acute lumenal thrombosis and tissue ischemiaand infarction.KEYWORDS: atherosclerosis, oxidative stress, inflammation, efferocytosis, foam cells, thrombosis