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BACKGROUND: Age contributes to body composition alteration, rises a common disorder in elderly known as sarcopenic obesity (SO), which is characterized by the combination of obesity (excess fat mass) and sarcopenia (reduced skeletal muscle mass) clinical form and function. CONTENT: The primary cause of SO is insulin resistance. Glucose transporter 4 (GLUT4) dysfunction results in impaired fatty acids oxidation. Decreased muscle mass results in lower mitochondria number and volume. Both will increase oxidative stress. Together with altered myokines in SO, oxidative stress was promoted and lead to higher M1 macrophages and failure in autophagy. The pro-inflammatory condition and dysbiosis links SO to a variety of cardiometabolic conditions, including non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. The mortality, comorbidities, cardiometabolic diseases, and disability or impairment of SO is higher compare to obesity or sarcopenia alone. Some treatments have been developed for SO including adequate dietary intake, vitamin D and antioxidant supplementation, and exercises. SUMMARY: SO is more prevalent among the elderly and has a significant negative impact on their quality of life. Therefore, maintaining muscle mass and strength as well as preventing obesity should be the key goals of initiatives to support healthy aging. KEYWORDS: aging, body composition, obesity, sarcopenia, skeletal muscle, metabolic syndrome

Routine Dynamics has emerged as a potential action pattern within public organizations. In truth, there is a relationship between trust-based governance and collaborative innovation in developing Routine Dynamics in public organizations. This study aims to analyze the relationship between trust-based governance and collaborative innovation regarding the Routine Dynamics of public organizations in Central Sulawesi Province, Indonesia. The research uses quantitative analysis in the form of structural equation modelling on a research sample of 120 people. The study shows that trust-based governance and collaborative innovation have a significant relationship with Routine Dynamics in public organizations. The research also shows that there is a relationship between trust-based governance and collaborative innovation. Meanwhile, Routine Dynamics will better serve as a new perspective in public organizations to improve trust-based governance and collaborative innovation. Finally, the authors argue that the greater the level of achievement of trust-based governance and collaborative innovation, the easier it will be to develop the implementation of Routine Dynamics in public organizations.

Brazilian spinach is a highly nutritious leafy vegetable containing vitamins, minerals, and dietary fiber. This study assesses the impact of pruning intensities and non-nutrient ameliorants on Brazilian spinach growth in a floating cultivation system. The research follows a factorial randomized block design, with pruning intensity as the first factor and non-nutrient ameliorant as the second factor. Pruning intensity was categorized as light, moderate, and heavy, while the non-nutrient ameliorant included control, fine sand, rice-husk biochar, and fine sand + rice-husk biochar. The results show that moderate and heavy pruning effectively improved the response to NPK fertilization. Moderate pruning is proven to trigger the canopy area, especially starting 2 to 4 weeks after pruning. The Brazilian spinach canopy area demonstrated exponential growth and positively correlated with canopy diameter. The photosynthesis distribution in branch and shoot on moderate pruning was higher than heavy pruning, as indicated by dry weight. Moderate pruning produced a higher marketable yield than other pruning intensities. Regarding non-nutrient ameliorants, there are similarities in SPAD value, canopy area, index, dry weight, and yield. Therefore, moderate pruning is an effective practice to improve the growth and yield of Brazilian spinach, while the selected non-nutrient ameliorants have no impact.

BACKGROUND: Fibronectin type III domain-containing protein 5 (FNDC5), or also known as irisin, has been identified for two decades but almost completely disregarded for 10 years. It is present in skeletal muscle, heart, and brain, and in reaction to exercise can transform white adipose tissue into brown. Since then, irisin has gained a lot of attention for its potencies in treating metabolic disorders. In this review article, the potential future of irisin especially on metabolism and aging process will be discussed. CONTENT: Sedentary lifestyle is acknowledged as risk factor for type 2 diabetes mellitus, obesity, immune system issues, asthma, and neurological or heart illness. Irisin is secreted by muscle cells when exercising, produced after the proteolytic cleavage of FNDC5 protein. Irisin has positive impacts on maintaining physiological balance including reducing inflammation, keeping the bone homeostasis, as well as influencing metabolic processes and the neurological system function. Due to these many and advantageous characteristics, irisin could be a possible choice for preventing and managing disorders associated with modern society, and finding the agents to increase irisin can be beneficial. SUMMARY: Irisin offers a fresh potential basis for kinesitherapy and shows promise as a therapeutic target due to its various biological activities. Irisin pathway can be activated through dietary changes, the use of natural substances and drugs and can interact with this signalling pathway which involved peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and uncoupling protein mRNA 1 (UCP1) to resolve obesity and its metabolic comorbidities. KEYWORDS: irisin, FNDC5, exercise, inflammation, obesity, nervous system

Abstract The prediction of material properties from a given microstructure and its reverse engineering displays an essential ingredient for accelerated material design. However, a comprehensive methodology to uncover the processing-structure-property relationship is still lacking. Herein, we develop a methodology capable of understanding this relationship for differently processed porous materials. We utilize a multi-method machine learning approach incorporating tomographic image data acquisition, segmentation, microstructure feature extraction, feature importance analysis and synthetic microstructure reconstruction. Enhanced segmentation with an accuracy of about 95% based on an efficient annotation technique provides the basis for accurate microstructure quantification, prediction and understanding of the correlation of the extracted microstructure features and electrical conductivity. We show that a diffusion probabilistic model superior to a generative adversarial network model, provides synthetic microstructure images including physical information in agreement with real data, an essential step to predicting properties of unseen conditions.

Dendritic cell (DC) vaccines, as immunotherapy agents, can gather up and transport cancer-related antigens to T lymphocytes, activating anti-tumor effector responses. After being activated by DC, cytotoxic T lymphocyte cells (CTL) will secrete the cytolytic granzyme B that can effectively induce rapid apoptosis of target cells. On the other hand, DC also secrete several cytokines and a large number of exosomes, which together operate as a whole antigen-presenting entity. The efficacy of the vaccine’s treatment may be affected by the sources used for DC vaccines. Umbilical cord blood (UCB) from healthy donors can be employed when autologous cancer patient’s peripheral blood (PB) cannot be used as a source for isolating DC due to genetic abnormalities. Comparing UCB to other sources, there is a painless method of collecting sources as opposed to PB, which necessitates a venipuncture or leukapheresis procedure to isolate the blood. Many studies related to the use of PB-DC have been carried out, but research on potential comparisons between PB-DC and UCB-DC is still very limited. In this review, the potential of PB- and UCB-derived DC and their secretomes for cancer will be discussed. Keywords: dendritic cells, vaccines, umbilical cord blood, peripheral blood

BACKGROUND: World Health Organization has reported four million people die every year due to obesity comorbidity, and the prevalence of obesity is keep increasing, especially after COVID-19. Obesity has been defined as a chronic disease involving adipose tissue dysfunction which leads to metabolic diseases and psychosocial consequences. The review article will highlight some recent researches regarding the new conceptual framework that integrates both metabolic drives, as well as to summarize the numerous discussions about the current understanding of hypothalamic control of food intake and energy homeostasis. CONTENT: Obesity apparently is not simply regulated only by food and exercise. Hypothalamus takes part in controlling energy intake and expenditure via appetite regulation. Hedonic control in cortical and subcortical brain areas process cognitive, reward, information, and executive function. Managing metabolic adaptation, browning the white adipose tissue, and preserving lean mass can be another strategy to safely manage obesity. SUMMARY: Obesity need to be managed in a multimodal strategy including neurophysiology and physiology approach, together with environment support. Thus, a weight regain can be prevented. Commitment from both scientific and regulation point of view can shed a light to eradicate obesity. KEYWORDS: adipocyte, appetite, nutrition, obesity, physical activity, reward, satiety

Brazilian spinach (Alternanthera sissoo) is a less prominent perennial leafy vegetable growing in the tropical ecosystem. Therefore, this research aimed to investigate the effects of different shading intensities and harvesting periods on the growth and yield of Brazilian spinach in a tropical lowland urban ecosystem. The investigation used a split-plot design, with different shading intensities (no-shading, 45%, 55%, and 80% shading) as the main plot and harvesting periods (every 2, 3, and 4 weeks) as the subplot. The results showed that Brazilian spinach growth was significantly enhanced under no-shading conditions compared to shading treatments. Furthermore, 80% shading negatively impacted plant growth during early stages, as evidenced by alterations in parameters including canopy area (26.47 cm2), diameter (7.98 cm), and index (0.52), as well as Soil Plant Analysis Development (SPAD) values. This led to reduced branch elongation, marketable yield (14.76 g), and non-marketable yield (4.68), along with a decreased dry weight of stems (0.25 g), branches (0.40 g), leaves (0.85 g), and roots (0.44 g). However, marketable leaves from unshaded plants had higher carbon content (34.64%) and lower nitrogen content (2.83%). More frequent harvesting every 2 weeks elevated marketable yield (67.22 g) but suppressed the growth of stems (1.05 g), branches (4.39 g), and roots (1.73 g). Based on these observations, the cultivation of Brazilian spinach in unshaded areas with a biweekly harvesting routine was recommended

BACKGROUND: Stroke is one of many leading causes of death and disability worldwide. Despite decades of research, treatment for stroke recovery is still inadequate. Recently, mesenchymal stem cell (MSC) therapy is considered as one of the potential treatments for stroke due to their capabilities to repair or regenerate damaged tissues, as well as immunomodulators in inflammatory conditions. Many pre-clinical and clinical trials have shown MSC therapy feasibility, safety, and efficacy in treating stroke. However, evidence regarding the optimal treatment plan and factors that can improve stem cell functional outcomes in treating stroke needs to be further explored. Therefore, a systematic review was conducted. METHODS: Recent literatures from 2015-2022 regarding stem cell therapies, specifically MSC on ischemic stroke, were collected from two reliable databases: PubMed and PubMed Central. Collected literatures were properly applied to inclusion-exclusion criteria and appraised critically. Keyword strategies on databases were employed, including both medical subject headings (MeSH). RESULTS: Five literatures from 726 were identified and used for systematic review. All animal model in the literatures were prepared to have middle cerebral artery occlusion. All studies indicated that MSC therapy is a safe and reliable procedure despite the variety of transplantation routes. No report of toxicity, rejection reaction, nor infection on MSC treated groups. CONCLUSION: Stem cell sources, dosages, and delivery routes could be resourceful for future translational studies to ensure the safety and efficacy of MSC therapy for ischemic stroke. KEYWORDS: ischemic stroke, mesenchymal stem cells, regenerative medicine, immunomodulator

BACKGROUND: Dendritic cell (DC)-based cancer therapy is a promising adjuvant therapy for nasopharyngeal cancer (NPC) after chemoradiation. Owing to low immunity after chemoradiation, DC therapy activates immune responses. Moreover, DC-based cancer therapy can decrease tumor progression, prolong lifespan, and increase the quality of life of patients. Various studies regarding the use of DC therapy for NPC have been reported, however there are limited reviews on the implementation and foundation of DC immunotherapy to expand this technology. METHODS: A literature search was performed on EMBASE, ScienceDirect, PubMed (MEDLINE), and Cochrane Library, with the term dendritic cells therapy for nasopharyngeal cancer, dendritic cell immunotherapy in nasopharyngeal cancer patients, and DC therapy in NPC, as the search keywords. RESULTS: A total of 199 literatures were reviewed, and four clinical trials were identified as relevant for this review. DC vaccines can be processed with various maturation and activation processes. Selected literatures reported antigens used when incubating the DC are latent membrane protein (LMP) 1, LMP2, and Epstein–Barr virus nuclear antigen 1 (EBNA1). Although DC therapy was produced from different pathways, it has been reported that there are increases of cluster of differentiation (CD)8+ T cells, CD4+ T cells, and the progression free survival (PFS) rate in DC immunotherapy patients than the radiochemotherapy patients. CONCLUSION: It can be concluded that DC could be used as an adjuvant therapy alongside the standard therapy of NPC, which prolongs NPC patient survival. KEYWORDS: adjuvant cell therapy, nasopharyngeal cancer therapy, dendritic cells

Background. Obesity is expected to hinder efferocytosis due to ADAM17-mediated cleavage of the MER tyrosine kinase receptor, producing soluble MER (sMER) that disrupts MERTK binding to cell death markers. However, the intracellular efferocytosis pathway in central obesity remains elusive, particularly the role of low-grade chronic inflammation in its initiation and identification of binding signals that disrupt efferocytosis. Objective. We investigate the efferocytosis signaling pathway in men with central obesity and its relationship with inflammation, cell death, and related processes. Methods. A cross-sectional study was conducted, and clinical data and blood samples were collected from 56 men with central obesity (obese group) and 29 nonobese individuals (control group). Clinical evaluations and predefined biochemical screening tests were performed. The efferocytosis signaling pathway was investigated by measuring phosphatidylserine (PS), ADAM17, TNF-alpha (TNF-α), and sMER. Results. Metabolic syndrome was detected in more than half of the participants in the obese group according to the predefined tests. Mean levels of PS, TNF-α, and sMER were higher in the obese group but not significantly different from those of the control group. Further analysis based on waist circumference (WC) ranges in the obese group revealed a significant increase in PS and sMER levels between the control group and the obese group with WC greater than 120 cm. ADAM17 levels were significantly higher in the obese group than in the control group. PS was positively correlated with WC and ADAM17. ADAM17 was positively correlated with TNF-α and sMER, indicating impaired efferocytosis. Conclusions. Central obesity appeared to cause a disturbance in efferocytosis that began with cell damage and death, along with an enlargement of the WC and an ongoing inflammatory response. Efferocytosis was disrupted by proinflammatory cytokine regulators, which induced the production of sMER and interfered with the efferocytosis process.

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

Brazilian spinach is a leafy vegetable originating from the tropical region of South America. Despite the similarity in agroclimatic conditions, this nutrient-rich plant has not been widely cultivated in southeast Asia. Therefore, this research aimed to determine the most suitable growing technique (conventional, floating or bottom-wet culture systems) for Brazilian spinach grown in the wet tropical climate. Non-fertilizer ameliorants were applied to improve the physical characteristics of the growing substrate, making it more permeable. The addition of fine sand and/or rice husk biochar to the growing substrate did not increase the growth rate and the leaf yield of Brazilian spinach. The floating and bottom-wet culture systems performed better, when compared to the conventional system commonly practiced by farmers, particularly during the onset of the dry season. The harvest period lasted from 6 to 9 weeks after planting (WAP). The rate of leaf fresh weight to the total shoot weight gradually decreased during the harvest period, along with the percentage of marketable yield. Related to microclimate conditions, the floating and bottom-wet culture exhibited a higher substrate humidity, while the canopy temperature was not significantly affected by the air or substrate temperature. The substrate temperature measured at midday was significantly higher in the conventional system due to a decrease in the substrate water. In conclusion, Brazilian spinach is suitable for cultivation in wet tropical climate zones, with the application of floating or bottom-wet culture systems and harvest between 6 and 9 WAP emerging as the recommended approach.

Kemampuan literasi digital perangkat desa merupakan aspek yang paling utama dalam mendukung proses pelayanan kepada masyarakat. Aplikasi sistem informasi desa yang dikembangkan secara mandiri oleh Pemerintah Desa Mengen Kecamatan Tamanan dan Fakultas Teknik Universitas Nurul Jadid, hal ini karena perangkat desa belum memahami penggunaan Sistem Informasi Desa. Pelatihan penggunaan sistem informasi desa Berbasis Digital Kepada Perangkat Desa Mengen Kecamatan Tamanan dibutuhkan oleh perangkat desa untuk meningkatkan kemampuan literasi digital perangkat desa. Kegiatan pengabdian masyarakat ini bertujuan untuk meningkatkan kemampuan literasi digital perangkat Desa Mengen Kecamatan Tamanan yang merupakan desa binaan Fakultas Teknik Universitas Nurul Jadid. Metode yang digunakan adalah dengan metode pelatihan dan tutorial yang dilakukan dengan 6 tahapan, yaitu 1) Studi Pendahuluan, 2) Penyusunan Rencana, 3) Identifikasi, 4) Pelaksanaan, 5) Pendampingan dan 6) Evaluasi. Hasil dari pelatihan Pelatihan Penggunaan Sistem Informasi Desa Berbasis Digital Kepada Perangkat Desa Mengen Kecamatan Tamanan menghasilkan peningkatan keterampilan dan pengetahuan perangkat desa setelah mengikuti seluruh rangkaian materi yang diberikan

The role of nitrogen, phosphor and potassium distribution to all the plant tissue. so as to growth promoted the main crop high potential rice ratoon. The objective this research evaluated vegetative growth and productionof rice ratoon national varieties with nitrogen, phosphor, and potassium fertilizer. Using split plot design with three replicate. Varieties (G) main plot (G1: inpari 6, G2: inpari 10 and G3: inpari 29). Fertilizer (P)sub plot (P1= Urea 250 kg ha-1, TSP 100 kg ha-1 and KCl 50 kg ha-1. P2= Urea 300 kg ha-1, TSP 150 kg ha-1and KCl 100 kg ha-1. P3= Urea 300 kg ha-1, TSP 200 kg ha-1 and KCl 150 kg ha-1). The result show that inpari 29 significant in growth and production. The fertilizer treatment of Urea 300 kg ha-1, TSP 150 kg ha-1and KCl 100 kg ha-1 beter forvegetative growth and production. The combine of inpari 29 and 300 kg ha-1, TSP 150 kg ha-1 and KCl 100 kg ha-1 have high production.

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

Decision Support System (DSS) is a computer-based interactive application that combines data and mathematical models to assist the decision-making process in dealing with a problem.[1] At the Faculty of Engineering, Informatics Study Program, Nurul Jadid University, there are several stages in the process of preparing a thesis that students need to do, namely submission of thesis titles, submission of thesis proposals, proposal seminars, research and thesis guidance. After writing is considered ready and finished, students present the results of their thesis at the lecturer examines the thesis exam, but students whose thesis exam results pass with revisions, carry out the revision process in accordance with the examiner's input. The problem that is often experienced by students at the Faculty of Engineering Informatics Study Program is the process of submitting thesis titles, where students have difficulty determining the topic of thesis title. Then a Decision Support System for Thesis Title Topic Recommendations was created using the Naive Bayes Classifier Method at the Faculty of Engineering, Informatics Study Program, Nurul Jadid University, which aims to help facilitate lecturers and students in the management process of determining the recommendation criteria for thesis title topics, the process of managing thesis title recommendations and thesis title submissions, the method used is prototyping with the PHP programming language, MySQL database and the Naive Bayes Classifier method, for system design using Flowcharts, DFD, and ERD. Based on the results of the Naive Bayes Classifier method, it produces test results with very good Likert scale calculations with a high accuracy value of 96.6%.

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

Product development activities must be well managed; this will increase company productivity by optimizing the success factor strategy, which will inevitably lead to success. Furthermore, Some evidence suggests that product development that considers culture could lead to greater success in Indonesia, even on a global scale. This paper aims to build a mathematical model of successful product development by considering Hofstede culture and deciding the culture’s contribution to product success and at the same time to do Indonesian culture mapping. The first step of this research was started by deciding the relationship of culture to product success and by clustering the culture based on 805 Indonesian respondents. The next step was deciding success factor variable and building the mathematical model of product development by using 304 data of automotive products, netbooks, smartphones, souvenirs, and services. Furthermore, the research used methods to manage culture such as Hofstede dimension counting, Principal Component Analysis and Agglomerative Hierarchical Cluster. In the step on building mathematical model of successful product, experiment designed and Kano were used. The result of the Indonesian cultural cluster dimension showed that Indonesian culture could be divided into four clusters, including cluster 1 (C1), Cluster 2 (C2), cluster 3 (C3), and cluster 4 (C4), which are presented in Table 2. The Indonesian culture is divided into two dimensions such as intrinsic characteristics and environmental and future characteristics. While the result of the Kano mathematical model showed that price, product performance, services and marketing were put into a one-dimensional category. The model which considered culture was able to increase determination value (R2) and it was included in a one-dimensional category, so explicitly it was the most desired by the customers and was able to increase customer’s satisfaction indeed. That model was expected to be a quidance on product development in increasing its product market share.

BACKGROUND: Statins have been used for around three decades as the primary way to lower cholesterol and reduce the risk of atherosclerosis, but in some groups, statin resistance is common, and the danger of atherosclerosis is still high. CONTENT: Atherosclerosis was once believed to be caused by cholesterol and thrombotic material passively accumulating in the walls of arteries. However, current knowledge shows that the immune cells and inflammatory processes are essential in the formation, progression, and consequences of atherosclerotic lesions, characterized by a persistent inflammatory response, including thrombotic complications. Study of genetic, creating risk score for atherosclerosis, add more information to create more new therapies targeting low density lipoprotein cholesterol (LDL-C) receptor, and shows prospect. SUMMARY: Over time, atherosclerosis theories and treatment strategies have changed. While statins were widely used, they have now been supplanted by alternative options like the proprotein convertase subtilisin/kexin type 9 (PSCK9) inhibitor that manage atherosclerosis more effectively and comprehensive. KEYWORDS: atherosclerosis, cholesterol, inflammation, immune system, metabolism

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: Aging tissues lose their homeostatic and regenerative capacities, which has been linked to the degeneration of the stem cells such as the tissue-specific stem cells, the stem cell niches, and systemic cues that regulate stem cell activity. CONTENT: The maintenance of tissue homeostatic and regeneration dependent on its tissue-specific stem cells, that —long-lived cells with the ability to self-renew and differentiate into mature cells. Understanding the molecular mechanisms that governs stem cell survival, self-renewal, quiescence, proliferation, and commitment to specific differentiated cell lineages is critical for identifying the drivers and effectors of age-associated stem cell failure. Such understanding will be critical for the development of therapeutic approaches that can decrease, and possibly reverse and repair the age-related degenerative process in aging tissues. SUMMARY: The exact mechanisms and reasons of aging process were not fully elucidated until now. Stem cells is one of the keys for maintaining tissues heath and understanding how stem cell decline with age will give us opportunities to find strategy in increasing somatic stem cells regenerative capacity and delay the aging process. KEYWORDS: adult stem cell, aging, epigenetic, metabolism, quiescence, senescence

Alternanthera sissoo is currently propagated using stem or terminal cuttings, since it does not produce fertile seeds. This research aimed to identify the most effective propagation planting material among rooted stump, stem cutting and terminal cutting, as well as their response to the application of NPK fertilizer. The results showed a better performance for stem cutting than for rooted stump or apical cutting. The canopy area was positively related to the longest diameter (R2 = 0.92) and the average of two-way cross-sectional diameter (R2 = 0.89). The number of branches, branch fresh weight, leaf fresh and dry weights did not vary among the planting materials; however, the total number of leaves, branch and root dry weights were higher for stem cutting. Stem cutting is also available in a larger quantity than the other two planting materials when collected from each mother plant. Therefore, it is recommended for optimizing leaf yield in A. sissoo. The species positively responded to NPK fertilization, as shown by the increase of the SPAD value for 6 to 12 days after the initial application. Therefore, for maximizing yield, it should be regularly fertilized with NPK every 3 weeks, coinciding with the time that the SPAD index falls back to pre-NPK application levels.

BACKGROUND: Mitochondria became a driving force in evolution due to their ability to manufacture adenosine triphosphate (ATP) through respiration. The functioning of mitochondria within eukaryotic cells has evolved dramatically as a result of evolution. Recent research has revealed mitochondria form plasticity to keep the cell's needs and function. CONTENT: Mitochondria have long been regarded as the cell's "powerhouse," providing energy for cell metabolism through oxidative phosphorylation (OXPHOS). A lot of physiological processes were known to be mediated by mitochondria including immunity and autophagy, cell death mechanism, and stem cell reprogramming. Mitochondria can change their shape to form a tubular network that is controlled by fission and fusion processes. Mitochondrial dynamics is the equilibrium between these two opposing processes that regulates mitochondrial number, size, and positioning within the cytoplasm. SUMMARY: All of these discoveries opened up new research avenues and revealed new targets for targeted medication development. Calorie restriction, and the mimetic agents were developed to increase mitochondria biogenesis to improve human lifespan. KEYWORDS: mitochondria, metabolism, homeostasis, stress response, aging, epigenetic

BACKGROUND: Millions of cells in multicellular organisms regenerate every day to replace aged and died cells. Effective cell clearance (efferocytosis) is critical for tissue homeostasis, as the human body recycles its cellular components. We summarize what is known about the mechanisms of efferocytosis and how it impacts the physiology of the organism, effects on inflammation and the adaptive immune response, as well as the consequences of defects in this critical homeostatic mechanism in this review. CONTENT: Cell death is the process by which the human body replaces aged or damaged cells with new ones. It can be triggered by genetically encoded machinery or regulated cell death, or by specific pharmacologic or genetic interventions, resulting in accidental cell death. Dying cells release signals that entice phagocytes to engulf them in a process known as efferocytosis. Efferocytosis is a multistep process involving the release of “find me” and “eat me” signals and destruction of death cells by phagocytes. Different types of cell death including apoptosis and necroptosis can express pro- or anti-inflammatory signals via macrophage activity modulation. SUMMARY: Failed or ineffective efferocytosis can result in disruption of tissue homeostasis, which can contribute to the development of chronic inflammatory diseases such as atherosclerosis, obesity, diabetes, and heart failure. Therefore, any therapeutic strategy that enhances efferocytosis will have a beneficial effect on the treatment of these metabolic disorders. KEYWORDS: apoptosis, necroptosis, phagocytosis, efferocytosis, macrophage.

Compared to the normal tissues, cancer cells tend to have higher proliferation rate and often lost their ability to undergo apoptosis. In addition, cancer cells can separate themselves from their original tissue thus causing metastasis in other part of body. While undergoing program cell death, disordered cellular programming can happen. The main causes of this cellular programming anomaly are epigenetic and genetic alterations, which have been known as two separate mechanisms in carcinogenetic. A recent outcome of whole exome sequencing of thousands of human cancers has been the unexpected discovery of many inactivating mutations in genes that control the epigenome. These mutations have the potential to disturb the DNA methylation patterns, histone modifications, and nucleosome positioning, hence, the causing gene expression alternation. Genetic alteration of the epigenome therefore contributes to cancer just as epigenetic process can cause point mutations and disable DNA repair functions. Epigenetic mechanisms changes could cause genetic mutations, and genetic mutations in epigenetic regulators could cause epigenome changes. Knowing that epigenome play a major role in the hierarchy of gene control mechanisms suggests that mutations might have impact on multiple pathways related to cancer phenotype. This pinpoint the fact that recently, the way the genes are organized and controlled are suggested to be a relevant factor for human carcinogenesis. Keywords: cancer genetic, cancer epigenetic, oncogens, tumor suppressor genes, driver mutation, passenger mutation

Purpose: Rapid worldwide growth in megaprojects has attracted academic interest. In practice, complexity is one of the main causes for the failure of megaprojects. This study proposes a system of project manager leadership to overcome problems of complexity in achieving success with a megaproject. Design/methodology/approach: This study uses configuration analysis, fuzzy-set qualitative comparative analysis (fsQCA), to investigate the combination of complexity and leadership competencies that promote megaproject success. This study analyzes three megaproject manager leadership competencies—technical, emotional–social and adaptive—with three megaproject complexities—structural, social and emergent—to determine the combinations and levels required to ensure a megaproject’s short- and long-term success. Seven Indonesian infrastructure megaprojects were involved in this explorative study. Findings: This study has identified four combinations between complexity and leadership competencies and three necessary conditions that can lead to a successful megaproject. This study also reports that insufficient project manager leadership competence in the technical, emotional-social, and adaptive aspects can lead to lower megaproject performance. Research limitations/implications: By using fsQCA, this study is sufficient to understand the combination of complexity and leadership competencies in the megaproject performance. However, configuration comparative analysis using small samples is unable to explain results that are more rigorous when compared with the statistical approach. Having higher cases and additional analytical approaches that can lead to a more robust quantitative analysis method is strongly needed to address these limitations. Practical implications: For practitioners, this study proposes effective leadership competency combinations for managing various complexities of the megaproject. Originality/value: This study provides an insight into the competencies of megaproject management leadership. This study contributes to the literature by providing fresh perspectives on megaproject management, especially in terms of complexity and leadership. This is an important research area for the development of megaproject management theory as it fills theoretical gaps in megaproject management in terms of the leadership aspect.

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: 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

BACKGROUND: Hypothalamus is the master regulator of body’s systemic homeostasis including energy balance, body temperature, sleep, blood pressure, and circadian rhythms. This review article will highlight the shifting of the old paradigm of obesityinflammation-metabolic syndrome, which was focused on visceral organs and systemic inflammation, into a new model involving microinflammation in the master regulator of endocrine system, i.e., hypothalamus. CONTENT: Since the early stage of over-nutritional conditions and aging process, microinflammation in hypothalamus has started to emerge, due to the activation of several proinflammatory signaling pathways, especially the nuclear factor kappa B (NF-kB) and c-Jun N-terminal kinase (JNK)-mediated nuclear transcriptional programs. Together with intracellular organelle stress signals, these pathways develop a chronic microinflammatory environment in the hypothalamus leading to obesity and metabolic disorders. SUMMARY: Hypothalamic inflammation has been noted not only as an important driver of impaired energy balance, but also contribute in altered neurocircuit functions and promote obesity-associated metabolic impairment. KEYWORDS: hypothalamus, inflammation, metabolism, obesity, metabolic syndrome

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

Background: The calcium in the artery was thought to be the result of the imbalance or dysregulation of the promoter and inhibitor cytokines influenced by various subclinical and clinical conditions. This study aimed to investigate the interaction between central obesity, as an early subclinical condition, also known as a chronic low grade inflammation condition and coronary artery calcium (CAC) in non-diabetic population including the underlying pathomechanisms of a CAC in the early stage of atherosclerosis. Materials and Methods: This was a cross-sectional pathway analysis study enrolling 60 central obesity non-diabetic men that underwent coronary calcium score scan, anthropometrics and biomarker assays. Results: There was a positive correlation between increasing free leptin index/adiponectin (FLI/A) ratio and CAC (r=0.297; p

BACKGROUND: Obesity has been decades become a highly interest study, accompanied by the realization that adipose tissue (AT) plays a major role in the regulation of metabolic function. CONTENT: In past few years, adipocytes classification, development, and differentiation has been significant changes. The white adipose tissue (WAT) can transform to a phenotype like brown adipose (BAT) type and function. Exercise and cold induction were the most common factor for fat browning; however batokines such as fibroblast growth factor (FGF)-21, interleukin (IL)-6, Slit homolog 2 protein (SLIT2)-C, and Meteorin-like protein (METRNL) perform a beneficial browning action by increasing peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α protein levels, a key factor to stimulate mitochondrial biogenesis and uncoupling Protein 1 (UCP1) transcription, thus change the WAT phenotype into beige. SUMMARY: AT recently known as a complex organ, not only bearing a storage function but as well as the master regulator of energy balance and nutritional homeostasis; brown and beige fat express constitutively high levels of thermogenic genes and raise our expectation on new strategies for fighting obesity and metabolic disorders. KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, inflammation, IR, metabolic disease

Shallow water table (SWT) is an acute problem in cultivating vegetables at riparian wetland during transitional period from dry to rainy season. SWT limits volume of aerobic rhizosphere and reduces oxygen availability. Meanwhile, 5-aminolevulinic acid (ALA) has been known for its effectiveness in offsetting negative effects of abiotic stresses. The aim of this study was to evaluate effectiveness of ALA application at pre- or during continuous 20-day SWT exposure in snap bean. SWT exposures were set at depth of 5 cm (SWT-5), 10 cm (SWT-10) and 15 cm (SWT-15) below substrate surface. ALA was applied at 4 days before SWT initiation (14 DAP), mid of SWT exposure period (28 DAP), or at end of SWT exposure (38 DAP). Results of this study indicated that SWT exposure affected growth of shoots and roots, leaf water status, proline content, and SPAD value in snap bean plant. Shallowest water table (SWT-5) caused the most severe effects. Effectiveness of ALA application was depended on time difference between ALA application and onset of SWT exposure. ALA application did not significantly improve recovery of snap bean plants after SWT exposure was terminated.

Soil drought occurrence during dry season has been the main constraint, besides prolonged flooding during rainy season, in increasing cropping intensity and rice productivity in tropical riparian wetland. Use of drought tolerant rice genotype might be a suitable option for overcoming such problem. This study focused on the effects of gradual soil drying during early vegetative growth stage on morphological and physiological traits of five Oryza glaberrima genotypes, namely RAM12, RAM14, RAM59, RAM97 and RAM101, and two Oryza sativa subsp japonica genotypes, i.e. Koshihikari and Minamihatamochi. The plants were subjected to 6 d of gradual soil drying condition from 15 days after transplanting (DAT) to 20 DAT, and were allowed to recover until 22 DAT. Gradual soil drying reduced plant growth as indicated by dry mass accumulation. Drought reduced stomatal conductance and increased leaf rolling score of all the genotypes. All the genotypes showed comparable response on stomatal conductance, but O. glaberrima genotypes performed higher in leaf rolling recovery. Meanwhile, O. sativa genotypes decreased total leaf area and specific leaf area, but increased specific leaf weight in order to avoid further damages due to drought stress. Drought tolerance mechanisms in RAM101, RAM12, RAM59 and RAM14 were associated with leaf morpho-physiological responses, root traits and dry biomass accumulation. Keywords: Drought tolerance, Leaf rolling, Root trait, Stomatal conductance, Dry matter accumulation

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: 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

BACKGROUND: Mesenchymal stem (stromal) cells (MSCs) have a multipotent character, able to differentiate into several cell types, thus MSC serve as a cell reservoir for regenerative medicine. MSC therapeutic potency more associated to their immunosuppressive and anti-inflammatory properties rather than the multipotency, by its mechanism to secrete soluble factors with paracrine actions. CONTENT: MSC paracrine function was known to mediated partly by extracellular vesicles (EVs), which were released predominantly from the endosomal compartment contained in MSC secretome. EV contain a cargo bring micro RNA (miRNA), messenger RNA (mRNA), and proteins from their cells of origin, propose EV as a novel alternative to whole cell therapies, regarding the benefit of EV in safety and easier storage compared to the parent cells. SUMMARY: The discovery of EVs including exosomes in MSC secretome as key of stem cells beneficial function lead to the future hope of using cell-free regenerative therapies. KEYWORDS: MSC, secretome, conditioned media, extracellular vesicle, exosome

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

This research is expected to know whether there is significant different score of vocabulary test before and after treatment has been given. This research is a quasi-experimental design where the population is Tenth Grade of SMA Muhammadiyah 2 Cipondoh Tangerang. The researcher took sample from X.4 class as control class and X.5 class as experiment class. The sample is 40 students for each class. In collecting the data, the researcher used interview, pretest and posttest of vocabulary and applied peer drilling as a technique in teaching learning process. Furthermore the researcher calculated the data by using t test. In addition the hypothesis test result at the degree of significance 0.05 indicates that in control group H₀ is rejected and H₁ is accepted because t count > t table (4.70 > 1.684) where there is a little significant difference of student’s vocabulary test whereas in experiment class, H₀ is rejected and H₁ is accepted with t count > t table (18.08 > 1.684). It means that there is more significant difference of student’s vocabulary test. In other words, Peer Drilling can improve student’s vocabulary mastery in the classroom.

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

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

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

Productivity and cropping intensity on non-tidal wetland in South Sumatra are considerably low and has been underutilized up to now. The majority of farmers in this ecosystem are smallholders with limited adoption capacity on introduced technologies and modern agricultural practices. The objectives of this research were (1) to comprehensively capture multidimensional constrains that restrained local farmers in increasing their agricultural productivity; and (2) to identify, assess, and develop substantially-relevant, financially-affordable, and socially-acceptable agricultural technologies and practices for smallholder farmers to increase productivity. This research was organized in three main activities: qualitative research employing Grounded Theory procedure, quantitative questionnaire-guided survey, and a series of laboratory and field experiments. The research results indicated that the main constraints in increasing productivity and cropping intensity on the non-tidal wetland in South Sumatra include (1) unpredictable flooding occurrence and low soil nutrients content (agronomic constraint), (2) low financial and technology adoption capacity of local farmers (economic constraint), and (3) public policy has not significantly escalated farmer’s motivation to increase food production (social and institutional constraint). This research suggests that multidimensional (technical, financial, ecological, and socio-cultural) approaches should be integrated in collective efforts for sustainably intensifying food production on the non-tidal wetland.

BACKGROUND: Current understanding in molecular character of natural killer (NK) cell, its function and mechanisms, send people the ideas to develop a NK cell-based immunotherapeutic strategies against human cancer. CONTENT: Before being regards as a cell-based cellular therapy, NK cell have to be clinical proven. Early studies with NK cells infusions for acute myeloid leukemia and lung cancer showed a promising result. NK cells need simplified methods for enriching and expanding, in addition to its transfection with chimeric antigen receptors (CARs). NK-92 arise as an assuring effector cells to augment monoclonal and bispecific antibody therapy. Thus, NK cells show a potential opportunity for cell engineering, outstep the era of T cells. SUMMARY: It is believed that NK cells bring a bright hope for future cancer immunotherapies, either alone or in combination as a harmonious therapy. KEYWORDS: NK cells, NK-92 cells, immunotherapy, CAR

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: Current cancer drugs and treatments are aiming at eradicating tumor cells, but often are more toxic then effective, killing also the normal cells and not selectively the tumor cells. There is good personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity, which called adoptive cell therapy (ACT). A review of the unique biology of T cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities. CONTENT: Chimeric antigen receptors (CAR) are recombinant receptors which provide both antigen-binding and T cell-activating functions. Many kind of CARs has been reported for the past few years, targeting an array of cell surface tumor antigens. Their biologic functions have extremely changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. The combination of CARs with costimulatory ligands, chimeric costimulatory receptors, or cytokines can be done to further enhance T cell potency, specificity and safety. CARs reflects a new class of drugs with exciting potential for cancer immunotherapy. SUMMARY: CAR-T cells have been arising as a new modality for cancer immunotherapy because of their potent efficacy against terminal cancers. They are known to exert higher efficacy than monoclonal antibodies and antibodydrug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors. KEYWORDS: chimeric antigen receptor, CAR-T cells, adoptive cell therapy, ACT, T cell receptor, TCR, cancer, immunotherapy