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Several studies have shown the effects of that physical exercise can improve cognitive function.1

ABSTRACT. The immediate early gene exhibits activation markers in the nervous system consisting of ARC, EGR-1, and c-Fos and is related to synaptic plasticity, especially in the hippocampus. Immediate early gene expression is affected by physical exercise, which induces direct ARC, EGR-1, and c-Fos expression. Objective: To assess the impact of exercise, we conducted a literature study to determine the expression levels of immediate early genes (ARC, c-Fos, and EGR-1). Methods: The databases accessed for online literature included PubMed-Medline, Scopus, and ScienceDirect. The original English articles were selected using the following keywords in the title: (Exercise OR physical activity) AND (c-Fos) AND (Hippocampus), (Exercise OR physical activity) AND (ARC) AND (Hippocampus), (Exercise OR physical activity) AND (EGR-1 OR zif268) AND (Hippocampus). Results: Physical exercise can affect the expression of EGR-1, c-Fos, and ARC in the hippocampus, an important part of the brain involved in learning and memory. High-intensity physical exercise can increase c-Fos expression, indicating neural activation. Furthermore, the expression of the ARC gene also increases due to physical exercise. ARC is a gene that plays a role in synaptic plasticity and regulation of learning and memory, changes in synaptic structure and increased synaptic connections, while EGR-1 also plays a role in synaptic plasticity, a genetic change that affects learning and memory. Overall, exercise or regular physical exercise can increase the expression of ARC, c-Fos, and EGR-1 in the hippocampus. This reflects the changes in neuroplasticity and synaptic plasticity that occur in response to physical activity. These changes can improve cognitive function, learning, and memory. Conclusion: c-Fos, EGR-1, and ARC expression increases in hippocampal neurons after exercise, enhancing synaptic plasticity and neurogenesis associated with learning and memory.

Many adolescents have insufficient physical activity. Regular physical activity from young age can improve health and fitness. Getting regular exercise and eating healthy diet should be encouraged among kids and teenagers to prevent various diseases in adulthood and old age, such as osteoporosis and fractures. When exercising, a prescription is needed that is tailored to each individual abilities. The intensity of exercise will be different for each individual in accordance with their age, physiological function, genetics, economic status, and previous comorbid diseases. There is no standardised exercise prescription proven to increase bone mineral density in adolescents. Based on the above description, a study was conducted on the provision of different intensity exercise and its effect on bone morphology and density. In this study, male Wistar rats, aged 15–16 weeks (body weight ± 250-350 grams; n = 20), were split into 4 groups, namely control group, low intensity exercise group, moderate intensity exercise group, and high intensity exercise group. All groups were receiving intervention for 8 weeks. Then, the rats were sacrificed and the femoral bones were isolated. Femur weight and femur length was checked. Bone density was examined using X-Ray and calculated by statistical tests. Research was conducted in the Central Laboratory, Universitas Padjadjaran. There were significant differences of femur weight between high intensity exercise group and control and low intensity exercise groups (p 0.05). Moderate and high intensity exercises significantly increased femur length as opposed to control and low intensity exercise groups (p 0.05). Bone density was higher in moderate and high intensity exercise groups (p 0.05). Moderate to high intensity exercise can increase bone health, seen from significances of bone morphology analysis and a higher density compared to low intensity exercise.

Background: Cardioembolic stroke is a category of ischemic stroke that manifests more severe, is prone to recurrence, and is related to a higher mortality rate than the other categories of ischemic stroke. Anticoagulant therapy is recommended in cardioembolic stroke, both for primary and secondary prevention. Objective: The objective of this study is to understand the pattern of anticoagulant therapy in cardioembolic stroke patients admitted at Hasan Sadikin General Hospital Bandung. Methods: The methodology of this study uses retrospective descriptive cross-sectional and use data from medical records collected during January 2015 to December 2020 at Neurology Department of Hasan Sadikin General Hospital with total sampling method. The inclusion criteria were cardioembolic stroke patients that received anticoagulant therapy. Anticoagulant therapy was stratified into Warfarin and New Oral Anticoagulants (NOACs) which consist of dabigatran, rivaroxaban, and edoxaban. To assess stroke severity outcome between warfarin and NOACs we use the National Institutes of Health Stroke Scale (NIHSS) Score. Results: From the 162 cardioembolic stroke patients, the most common oral anticoagulant used was warfarin (90.12%), followed by dabigatran (4.94%), rivaroxaban (3.70%), and edoxaban (1.23%). Only 1 (0.62%) patient who experienced complications from anticoagulant therapy, the complication was non-major bleeding and occurred in warfarin users. Both warfarin and NOACs mainly had NIHSS on discharge in a moderate category with the mean of NIHSS 7.615 and 7.276 for warfarin and NOACs respectively. Conclusion: Warfarin is the most common oral anticoagulant used for cardioembolic stroke based on this study. Both warfarin and NOACs groups have similar stroke severity outcomes measured by NIHSS on discharge and NOACs have lower incidence of bleeding compared to warfarin group.

Introduction. Moringa leaves (Moringa oleifera), which are members of the Moringaceae family, are one of the herbal plants that are widely known in Indonesia. Phytochemical contents of moringa leaf, such as flavonoid, quercetin, and phenolic acid, are believed to have an effect on improvement of NAFLD. Therefore, moringa leaf is considered as one the herbal plants that can be used as supplementation in the form of adjuvant therapy to NAFLD. The study objective of our research is to review the effect of giving moringa leaf to the liver, especially the histopathologic features. This study will be conducted on literature review research design, more specifically in the form of a systematic review. Research Method. Five major electronic web databases, including PubMed, Cochrane Library, Google Scholar, Scopus, and ScienceDirect, were used in identifying literature from 2014 to 2023. Results. From a comprehensive analysis of 13 relevant literature sources, we elucidate the impact of Moringa oleifera leaf extract on liver histopathology, glucose, and lipid metabolism. Furthermore, we provide insights into its safety profile concerning human health. Conclusion. The phytochemical content of Moringa oleifera leaf extract had shown a significant benefit in plant medicinal sector. From the research that had been done, Moringa oleifera leaf extract contributes to give significant improvement on liver histopathological features, glucose, and lipid metabolism on animal sample model.

Sedentary lifestyle can cause the accumulation of energy reserves in the form of lipids in white adipose cells. Lifestyle modification by means of exercise is done to reduce fat reserves in white adipose tissue (WAT). This study aims to determine the effect of exercise in various intensities on the histological changes of white adipose cells. Research method exploratory with Federer formula to determine the number of samples carried out. Using 28 Wistar rats located at the Central Laboratory of Padjadjran University, Sumedang from May to June 2022. The data taken were the average diameter ± standard error (SEM) of the inguinal white adipose cells of the experimental rats. Data analysis using Microsoft Excel 2016 and SPSS v.28 software. Of the 28 samples studied, only 25 samples met the inclusion criteria. Group K is 0.15% (p = 0.024) greater than P2, and 0.25% (p 0.001) is greater than P3. The P1 group had a value of 0.17% (p = 0.025) greater than P3. Moderate and vigorous exercise can be used to reduce the size of white adipose cells. While low-intensity exercise is considered ineffective. Further research can be carried out to assess changes in white adipose cells based on exercise intensity from other sides besides their morphology.

We synthesised and biologically evaluated two new hybrid probes [131I]BPF-01 and [131I]BPF-02 which were built from three structural entities: benzothiazole-phenyl, fluorescein isothiocyanate (FITC), and iodine-131. These probes were designed for potential applications in assisting surgical procedures of solid cancers. The cytotoxicity study demonstrated that fluorescent probes BPF-01 (31.23 μg/mL) and BPF-02 (250 μg/mL) were relatively not toxic to normal immortalized human keratinocytes (HaCaT) cells, as indicated by the percentage of cell survival above 50 %. Furthermore, both probes displayed low to moderate anticancer activity against the breast cancer cells (MDA-MB-231) and prostate cancer cells (LNCaP and DU-145). The probe BPF-01 apparently showed an accumulation in the tumour tissues, as suggested by ex vivo fluorescence examinations. In addition, the cellular uptake study suggests that hybrid probe [131I]-BPF-01 was potentially accumulated in the MCF-7 cell line with the highest uptake of 16.11 ± 1.52 % after 2 h of incubation, approximately 50-fold higher than the accumulation of iodine-131 (control). The magnetic bead assay suggests that [131I]-BPF-02 and [131I]-BPF-02 showed a promising capability to interact with translocator protein 18 kDa (TSPO). Moreover, the computational data showed that the binding scores for ligands 7–8, BPF-01 and BPF-02, and [131I]-BPF-01 and [131I]-BPF-02 in the TSPO were considerably high. Accordingly, fluorescent probes BPF-01 and BPF-02, and hybrid probes [131I]BPF-01 and [131I]BPF-02 can be further developed for targeting cancer cells during intraoperative tumour surgery.

Background: One of the main problems of the Citarum River is the contamination of E. coli due to livestock activities, washing toilets, and industry. In addition, irrational use of antibiotics in the community and livestock can increase E. coli resistant strains to antibiotics. This study aimed to identify the presence of multidrug resistance (MDR) and extended-spectrum β-lactamase (ESBL) E. coli strains in Citarum river clusters, namely industrial, livestock, and residential clusters. Methods: This was a descriptive study. A sample of 100 mL surface water from each Citarum cluster. Culture, antibiotic sensitivity test, and PCR to identify blaCTX-M-15 gene carriers of ESBL E. coli were carried out in the sample. Results: There were 37 isolates of E. coli, with 24% of these isolates showing MDR properties, which can be found in industrial, livestock, and residential clusters at 13%, 8%, and 3% respectively. The most E. coli-resistant antibiotics found in these samples were ampicillin (45%), followed by tetracycline (37%), and azithromycin (29%). The PCR examination did not find the blaCTX-M-15 gene carrying ESBL properties in all three Citarum river clusters. Conclusion: The presence of E. coli isolates in each Citarum river cluster suggests the occurrence of river pollution due to animal, human or industrial waste. Therefore, it is necessary to make better government regulations regarding sanitation and education for the surrounding community regarding the importance of keeping the river clean.

Abstract Specific exercise intensities could improve lung vascular function by increasing nitric oxide (NO). The ACE2/MasR/eNOS axis is one of the pathways facilitating NO synthesis. This study examines the effect of different intensities of aerobic training on the ACE2/MasR/eNOS axis and histology of lung muscular arteries. Male Wistar rats were used in this study and randomized into control and exercise groups receiving low‐, moderate‐, and high‐intensity training. The training was conducted for 30 min daily, five times a week, for 8 weeks. We observed that different exercise intensities affect the ACE2/MasR/eNOS pathway differently. Compared to control, high‐intensity aerobic exercise significantly increased ACE2, Mas receptor (MasR), and eNOS mRNA expressions (p

Selenium (Se) deficiency is associated with certain abnormalities, such as Keshan disease, cancer, cardiovascular disease (CVD), viral infections, infertility, immune system abnormalities, metabolic diseases, neurological disorders, and growth retardation. Its antioxidant properties are integrated into various selenoenzymes, mainly glutathione peroxidase (GPx) and thioredoxin reductase (Trx). These selenoenzymes act as a protective mechanism to prevent oxidative stress-induced cellular injury, regulate DNA transcription, and cell proliferation. Decreased levels of antioxidants induce reactive oxygen species (ROS) accumulation resulting in loss of mitochondrial structure and function. The antioxidant properties of selenium could depress ROS and modulates autophagy by interfering initiation of autophagy and phagophore formation. Inhibition at the initiation stage not only involves mTOR and AMPK, an autophagy-related regulators, but also autophagy markers, including Beclin 1, Atg5, LC3, and p62; thus, phagophore and autophagosome are not formed. This review will discuss the role of selenium in modulating autophagy in various organs.

Objective(s): This study aims to explore the effect of mitoTEMPOL on histopathology, lipid droplet, and mitophagy gene expression of Wistar rat’s liver after injection of streptozotocin (STZ).Materials and Methods: Twenty male Wistar rats were divided into 4 groups: Control (n=5); 100 mg/kg BW/day mitoTEMPOL orally (n=5); 50 mg/kg BW STZ intraperitoneal injection (n=5); and mitoTEMPOL+STZ (n=5). STZ was given a single dose, while mitoTEMPOL was given for 5 weeks after 1 week of STZ injection. Histopathological appearance, lipid droplets, mitophagy, and autophagy gene expression were examined after the mitoTEMPOL treatment. Results: We found metabolic zone shifting that might be correlated with the liver activity of fatty acid oxidation in the STZ group, a decrease of lipid droplets in mitoTEMPOL and mitoTEMPOL + STZ compared with Control and STZ groups were found in this study. We also found significant changes in PINK1, Parkin, BNIP3, Mfn1, and LC3 gene expression, but no difference in Opa1, Fis1, Drp1, and p62 gene expression, suggesting a change of mitochondrial fusion rather than mitochondrial fission correlated with mitophagy.Conclusion: All this concluded that mitoTEMPOL could act as a modulator of mitophagy and metabolic function of the liver, thus amplifying its crucial role in preventing mitochondrial damage in the liver in the early onset of diabetes mellitus.

Highlight: • AKT or protein kinase B increase protein synthesis and control the degradation of proteins. • Satellite cells was provided remarkable ability to regenerate skeletal muscle. • Stimulation of protein synthesis is effective therapy to maintain muscle mass, prevent muscle wasting to reduce risk sarcopenia and improve quality of life in the elderly. Abstract: Muscles have an important role as a regulator of glucose and triglyceride metabolism. Some researches show the correlation between skeletal muscle mass and metabolic diseases, such as diabetes. Skeletal muscle mass decrease occurs due to chronic illness or physiological process of aging, thus increasing the risk of metabolic diseases as well as motion difficulty in the elderly. Skeletal muscle mass depends on balanced protein synthesis and degradation, controlled through a variety of signal transduction pathways including the AKT. AKT or protein kinase B increases protein synthesis through the mTOR and GSK3β and controls the degradation of proteins through FoxO transcription factors. Another factor that has an alleged role in the regulation of skeletal muscle is the satellite cells which provide remarkable ability to regenerate skeletal muscle. A comprehensive understanding of the biomolecular mechanism of muscle mass regulation is important to develop effective treatment or prevention of muscle atrophy in many cases, either caused by pathological conditions, such as chronic diseases, or the process of aging.

The high incidence of breast cancer cases in the world requires the use of applicative methods. The 7,12-dimethylbenz(a)anthracene (DMBA) induced breast cancer animal model is a widely used chemical-induced animal models for research on breast cancer. However, the molecular mechanism related to DMBA induction remains unclear. Good understanding on DMBA-induced animal models is crucial for studies related to future breast cancer treatments as animal models will provide a deeper understanding of anticancer medication, specifically those aimed for treating breast cancer. The aim of this study was to develop an DMBA-induced animal model for breast cancer. This study used female Wistar rats injected subcutaneously with DMBA as a carcinogen-induced agent (20 mg/kg) to induce tumor. Rat tumors were then evaluated and breast appearance was observed weekly, starting from day 28th after DMBA injection. Breast cancer tissue was then sampled and stored at -80°C until it was used for western blot and histological study. This study indicated that DMBA induced cancer in female Wistar rat’s breasts, and cytoplastic cells and lung metastatic was identified macroscopically and histopathologically. The metabolic sign was observed in the lung and breast sections. Interestingly, the DMBA induction in this study does not only induce organ cancers but also induces estrogen receptors and stimulates signaling of estrogen receptors α (ERα), ERβ, and Akt.

The incidence rate is directly proportional to the incidence of obesity or overweight and Type 2 diabetes mellitus. Garcinia is a plant that has been proven empirically, preclinically, and clinically to have activities for the avoidance and treatment of metabolic syndrome and on the pathogenesis and pathophysiology caused by the disease. The aim of this study is to create a discussion and summarize information regarding the activity or usefulness of the Garcinia plant. This review article was based on the published journals obtained from Google Scholar, Scopus, and PubMed databases using the keywords Garcinia obesity, Garcinia overweight, and Garcinia metabolic syndrome. Garcinia had many activities related to metabolic syndrome because it was able to reduce body fat mass, blood sugar level, body weight, total cholesterol, and triglyceride level. These activities were mediated by numerous apparatuses of feat together with a reserve of fatty acid synthase, α-amylase, α-glucosidase, and several other enzymes and pathways associated with the metabolic syndrome. Garcinia plant was able to be used as a candidate for a new herbal that had a good effect in treating metabolic syndrome in future.

Aim: This study aims to evaluate: the difference of soluble suppression of tumorigenicity 2 (sST2) level, a biomarker for cardiac remodeling and echocardiography parameters value prior to and 1 month after implantation; and the association between pacemaker parameters and pacemaker mode along with delta sST2 levels. Materials & methods: This prospective cohort study enrolled all symptomatic bradycardia patients aged >18 years with preserved ejection fraction who underwent permanent pacemaker (PPM) implantation. Results: A total of 49 patients were included in this study. The sST2 level (ng/ml) were significantly different between prior and 1 month following PPM implantation (23.4 ± 28.4 vs 39.9 ± 63.7; p = 0.001). Conclusion: The early cardiac remodeling has occurred within 1 month after PPM implantation as indicated by increasing delta sST2 level.

Selenium is a trace element that has antioxidant properties and is a component of selenoproteins. In certain circumstances, such as injury, selenium supplementation is required to regulate the inflammatory response. Contusion injury increases the inflammatory response to a muscle or tissue that begins with vasodilation, increases blood flow, increases vascular permeability, and leads to edema formation at the site of injury. Objectives: To determine the effect of selenium supplementation on changes in blood markers in rats treated with contusion injury. Methods: Experimental design, using experimental male rats (Rattus norwegius), eight weeks old, weighing 200-220 grams, divided into three groups, namely: The Control group, the contusion group, the contusion + Selenium group. Selenium supplementation was given orally on days 1-3 after injury at a dose of 0.0153 mg into 2% PGA. Examination of markers such as White Blood cells (WBC), lymphocytes, monocytes, and neutrophils was carried out on day three after treatment. Results: This study found that the administration of post-muscular selenium supplementation based on examination of blood markers such as WBC, Lymphocytes, Monocytes was higher in the contusion group and lower in the selenium group. Neutrophils were higher in the contusion and selenium groups. This was not significantly different from the control group. The result of blood marker examination tended to change, but it was not statistically significant. Conclusion: Selenium supplementation in post-contusive injury mice did not provide significant changes in blood markers such as WBC, lymphocytes, monocytes, and neutrophils. Keywords: antioxidant, blood marker, contusion, selenium

BackgroundRecent investigations suggest that premature ventricular complexes (PVCs) during an exercise test are associated with an elevated risk of mortality in asymptomatic individuals. However, given the small number of studies included, the association between these two entities in the asymptomatic population remains obscure. Our aim was to evaluate this matter.MethodsA comprehensive literature search was conducted utilizing several online databases up to April 2022. The study comprised cohort studies examining the relationship between exercise-induced premature ventricular complexes (EI-PVCs) and all-cause mortality (ACM) as well as cardiovascular mortality (CVM) in asymptomatic populations. To provide diagnostic values across the statistically significant parameters, we additionally calculated sensitivity, specificity, and area under the curve (AUC).ResultsA total of 13 studies consisting of 82,161 patients with a mean age of 49.3 years were included. EI-PVCs were linked to an increased risk of ACM (risk ratio (RR) = 1.30 (95% confidence interval (CI) = 1.18–1.42); p < 0.001; I2 = 59.6%, p-heterogeneity < 0.001) and CVM (RR = 1.67 (95% CI = 1.40–1.99); p < 0.001; I2 = 7.5%, p-heterogeneity = 0.373). Subgroup analysis based on the frequency of PVCs revealed that frequent PVCs were similarly related to a higher risk of ACM and CVM, but not infrequent PVCs. Moreover, diagnostic test accuracy meta-analysis showed that recovery phase EI-PVCs have a higher overall specificity than exercise phase EI-PVCs regarding our outcomes of interest.ConclusionEI-PVCs are correlated with a higher risk of ACM and CVM. When compared to the exercise phase, the specificity of PVCs generated during the recovery period in predicting interest outcomes is higher. As a result, we propose that the exercise ECG be utilized on a regular basis in middle-aged asymptomatic individuals to measure the frequency of PVCs and stratify the risk of mortality.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=328852], identifier [CRD42022328852].

This study aims to determine the appropriate training program and portion in order to improve the physical performance of athletes.This literature review inquiry was obtained from various PubMed and Google Scholar databases by entering keywords, namely: Sports, Yoga, Basic Physical Components, MDA and IL6. This inquiry reviewed 33 articles published in national and international online journals and have been accredited. The results literature review done on prior studies show basic physical components can be optimally improved through exercises based on the FITT formula, namely interval training, fartlek, weight training, circuit training, plyometrix, rope jump and PNF. In addition, showed that aerobic and anaerobic exercises decreased MDA levels. However, the control group experienced a very significant increase in MDA levels. High-intensity exercise was found able to trigger releasing inflammatory mediators such as TNF-ά and IL-6. Furthermore, some literature showed that long-term yoga practice can reduce MDA levels and IL-6 levels as it as it increases antioxidant levels and anti imflamatory levels. This literature review is expected to provide comprehensive explanation of good and measurable training programs for athletes, coaches and sports institutions. Thereby, athletes’ physical performance can be optimally improved and injuries can be avoided so that athletes get sports achievements.

IntroductionRisk stratification in Brugada Syndrome (BrS) patients is still challenging due to the heterogeneity of clinical presentation; thus, some additional risk markers are needed. Several studies investigating the association between RVOT conduction delay sign on electrocardiography (ECG) and major arrhythmic events (MAE) in BrS patients showed inconclusive results. This meta-analysis aims to evaluate the association between RVOT conduction delay signs presented by aVR sign and large S wave in lead I, and MAE in BrS patients.MethodsThe literature search was performed using several online databases from the inception to March 16th, 2022. We included studies consisting of two main components, including ECG markers of RVOT conduction delay (aVR sign and large S wave in lead I) and MAE related to BrS (syncope/VT/VF/SCD/aborted SCD/appropriate ICD shocks)ResultsMeta-analysis of eleven cohort studies with a total of 2,575 participants showed RVOT conduction delay sign was significantly associated with MAE in BrS patients [RR = 1.87 (1.35, 2.58); p < 0.001; I2= 52%, Pheterogeneity = 0.02]. Subgroup analysis showed that aVR sign [RR = 2.00 (1.42, 2.83); p < 0.001; I2= 0%, Pheterogeneity = 0.40] and large S wave in lead I [RR = 1.74 (1.11, 2.71); p = 0.01; I2= 60%, Pheterogeneity = 0.01] were significantly associated with MAE. Summary receiver operating characteristics analysis revealed the aVR sign [AUC: 0.77 (0.73–0.80)] and large S wave in lead I [AUC: 0.69 (0.65–0.73)] were a good predictor of MAE in BrS patients.ConclusionRVOT conduction delay sign, presented by aVR sign and large S wave in the lead I, is significantly associated with an increased risk of MAE in BrS patients. Hence, we propose that these parameters may be useful as an additional risk stratification tool to predict MAE in BrS patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022321090.

The prevention of liver disease could be conducted through preventive strategies, such as antioxidants and exercise. Moringa leaf extract has substances that could act as antioxidant, while exercise is also known protecting the liver from disease by changing hepatic metabolism and autophagy. This study aimed to investigate the effect of moringa leaf extract and moderate intensity exercise on histopathological appearance and autophagy gene expression of wistar rat liver. The method used in this study was animal experiment using 24 male wistar rats divided into 4 groups, including control group, moringa group, exercise group, and moringa + exercise group. Moringa leaf extract was given in low dose (5.7 mg/kgW) per oral, 5 times a week, for 4 weeks. Meanwhile, the 20 m/minute treadmill exercise was given for 30 minutes per day, 5 times a week, for 4 weeks. Results showed a significant change on histopathological scoring in exercise group (p=0.011) compared to control group. Increased autophagy gene expression was found in moringa + exercise group compared to control group (LC3 0.90 fold; p62 0.87 fold). In summary, this study presented that moderate intensity exercise induced changes on histopathological appearance of wistar rat liver that might be associated with physiological inflammation. Moringa, with its antioxidant properties, combined with increased autophagy might improve histopathological changes in moringa + exercise group.

BACKGROUND: Nutmeg (Myristica fragrans H.), one of native plants of Maluku Indonesia, has long been used as traditional medicines especially to treat tumors, externally to treat skin infections. M. fragrans also has important biological activities as anticancer. However, antimelanoma activity of M. fragrans remains unknown. The aim of this study is to compare M. fragrans extracts as anticancer on melanoma B16-F10 cells by inducing apoptosis. METHODS: M. fragrans seed was extracted with ethanol then fractionated with n-hexane, ethyl acetate, and n-butanol. B16-F10 melanoma cells were cultured and treated with various doses and tested using resazurin reduction assay. Apoptosis signalling via caspase-3 was measured by using western blot. RESULTS: The extract and fractions of M. fragrans reduced viability of cells with IC50 value for ethanol extract 21.83 µg/mL, ethyl acetate fraction 21.66 µg/mL, n-hexane fraction 47.53 µg/mL, and n-butanol fraction >1,000 µg/mL. The active fraction of ethyl acetate induced apoptosis via caspase-3 proteins similar with cisplatin as positive control in B16-F10 cells at 10 hours treatment. CONCLUSION: Taken together, M. fragrans ethyl acetate fraction has the highest IC50 than n-hexane and n-butanol fractions that significantly inhibited B16-F10 cell proliferation by inducing apoptosis via caspase-3. It provides the insight that it has the most potential activity as a chemopreventive agent for addressing melanoma skin cancer. KEYWORDS: M. fragrans, apoptosis, fraction, melanoma

BACKGROUND: Recently, coffee is widely used for preventing photoaging because of its antioxidant capacity. Among two kinds of coffee, robusta coffee has higher content of antioxidant such as chlorogenic acid (CGA) and caffeine. Researchs about robusta coffee bean effect on photoaging due to UVB radiation is still limited. Therefore, the aim of this study was to examine the effect of robusta extract cream (RE cream) on preventing wrinkle in mice induced by ultraviolet-B (UVB) radiation. METHODS: RE cream was made by mixing RE coffee with moisturizing cream in different concentration (10%, 20%, and 40%). Twenty-five male of Mus musculus Balb/c strain mice aged 4 weeks were divided into five groups; control group, UVB group, UVB + 10% RE group, UVB + 20% RE group, and UVB + 40% RE group. The UVB groups were given UVB radiation three times a week with an exposure duration of 100 seconds per time for ten weeks. At the end of the treatment, skin samples were excised and statined histologically, also were analyzed for their protein expression. Evaluation of wrinkles was carried out using the Bissete method before and after treatment. To evaluate the thickness of the epidermis, HE staining was performed, while masson Trichome staining was performed to determine the collagen content. RESULTS: RE cream-treated groups showed lower wrinkle score compared to the control group. Furthermore, in UVB + 10% RE group, the RE cream application reduce wrinkle formation. In UVB + 10% RE group and UVB + 20% RE group, the RE cream application increased epidermal thickness and collagen content (p=0.00). While collagenase, matrix metalloproteinase-1 (MMP-1) expression was lower in UVB + 20% RE group compared to the UVB group (p

Abstract Background Browning of white adipose tissue (WAT) is a promising approach to obesity treatment. During browning, WAT transforms into beige adipose tissue through stimulation of the peroxisome proliferator activated receptor γ (PPARγ). Nutmeg, one of the Indonesian herbs, reportedly has dual roles as a PPARα/γ partial agonist. Even though nutmeg has been traditionally used in body weight reduction, there is limited information regarding the potential role of nutmeg in browning of WAT. Objectives In this study, we explored the effect of nutmeg seed extract (NuSE) as a potential inductor of WAT browning. Methods Twelve male Wistar rats, 5–6 weeks old, were divided into control and nutmeg groups. The rats in nutmeg group were given NuSE for 12 weeks by oral gavage. After 12 weeks, the rat's inguinal WAT and brown adipose tissue (BAT) were collected, weighed and stored at − 80°C until use. Results We observed that even though NuSE did not reduce the final body weight, it significantly reduced body weight gain. NuSE also increased protein levels of peroxisome proliferator activated receptor γ coactivator 1α (PGC‐1α) and uncoupling protein 3 (UCP3) significantly and tended to increase UCP2 and UCP1 levels. Furthermore, NuSE induced macroscopic and microscopic morphological changes of inguinal WAT, marked by significantly increased adipocyte numbers and decreased adipocyte size. Conclusions Even though NuSE did not increase UCP1 significantly, it potentially alters inguinal WAT characteristics and leads to browning through PGC‐1α and UCP3 induction. However, UCP3’s specific mechanism in WAT browning remains unclear. Our findings could contribute to obesity treatment in the future.

Exercise could delay the degeneration process by increasing Klotho, which is an endogen antioxidant. Klotho protects against oxidative damages, regulates hippocampal synaptic plasticity, and enhances GluN2B expression. This study aimed to analyze the effect of 14-day and 8-week moderate-intensity exercise on Klotho and GluN2B mRNA expressions in rat hippocampus. This study was an animal experimental study using Wistar rats that was performed from June to September 2019 at the Central Laboratory, Universitas Padjadjaran, Indonesia. Rats were divided into 4 groups: control (14-day control and 8-week control) and exercise group (14-day exercise and 8-week exercise). The exercise groups ran at a moderate intensity (20m/min) for 30min/day, 5x/week. Hippocampus was then subjected to klotho and GluN2B gene expression analysis. The exercise groups showed a higher Klotho expression, both in 14 days (0.844±0.124 vs. 1.057±0.013) and 8 weeks (0.897±0.072 vs. 1.380±0.168) although statistically insignificant (p=0.24). No difference in GluN2B gene expression was observed between control and exercise groups on 14 days (1±0.09 vs. 1.22±0.09) and 8 weeks (1.24±0.03 vs. 1.38±0.05; p=0.11). In conclusion, 14-day and 8-week moderate-intensity exercise did not alter Klotho and GluN2B expressions in rat hippocampus.

BACKGROUND: Ethionamide usage as one of the drug regimens still becomes a challenge due to high numbers of patients developing hypothyroid. Ethionamide had been associated with the inhibition of thyroid hormone (TH) synthesis and interestingly, ethionamide (C8H10N2S)-induced hypothyroidism is supported by its similar structure with thioamides, propythiouracil (C7H8N2S). However, hypothyroidism is not solely caused by its production, it could be caused by signaling alteration. Therefore, knowing that important TH action is determined via genomic pathway, alteration of this receptor could bring serious clinical problem. Unfortunately, there is limited study about the regulation of ethionamide and its connection on TH genomic signaling especially thyroid hormone receptor (TR) gene expression in soleus, gastrocnemius and cardiac muscle. METHODS: Thirty-eight rats were divided into control, ethionamide and propylthiouracyl groups. After 12-week treatment, rat were sacrificed, then gastrocnemius, soleus and cardiac muscles were dissected out, snap freezed using liquid nitrogen, and stored in -80oC until use. RNA was extracted and run for reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In soleus muscle, ethionamide stimulated TR mRNA expressions and deiodinase compared to control group. In contrast, TRα1 gene expression was not affected by ethionamide administration. In gastrocnemius muscle, only TRβ1 gene and Dio2 gene expressions that were significantly increased compared to control group. In cardiac muscle, ethionamide significantly stimulated all the thyroid hormone receptor isoform and iodothyronine deiodinase gene expression compared to the control group. CONCLUSION: Long ethionamide treatment upregulates TR gene expressions and deiodinase in soleus and cardiac muscle, there is different expression pattern of soleus, gastrocnemius and cardiac muscle after ethionamide stimulation. KEYWORDS: ethionamide, hypothyroid, TRα1, TRα2, TRβ1, TRβ2

Exercise-induced hearth muscle adaptation is important for physiological process after exercise. This adaptation will ensure basal mitochondrial homeostasis and as a part of the mitochondria quality control. This process is reflected by equal level of biogenesis stimulation and as well as the selective degradation of old and undesirable mitochondria through fusion or fission cycle and Mitophagy. There is limited information about genetic regulation stimulated by training in cardiomyocytes. We believe there is a specific myokines or protein release in the serum and initiate cardiac muscle adaptation process. In the present study, twelve male wistar rats were appointed to two group: sedentary control and aerobic-intensity (AE, 15m/minute). Rats were trained for running with specific protocol as follows: 30 minutes/day with a 5 times/week interval for 8 weeks. On the last day, serum form control and exercise groups were taken via retro-orbital sinus. Then, 3.105 H9C2 cells (Rat cardiomyocytes cell line) were cultured and incubated by this serum for 24 hours. After treatment, cell were extracted using trisure for RNA purification and continue with reverse transcriptase PCR. Our data showed that expression of the Pgc-1α, Mfn1, Mfn2, Opa1, Drp1, Pink, and Parkin genes were altered and modulated. Specifically, Mfn1, Mfn2, and Opa1 gene expression levels significantly increased. Interestingly, we did not find significant modulation for Pgc-1α, Drp1, Pink, and Parkin. Taken together, serum of exercise rats might be contained with myokines or specific protein which was released during training and it altered mitochondrial genes expression in cardiomyocytes culture cell. We believe that myokines release in the serum had a contribution in cardiacmyocyte adaptation.

A myokine is one of the proteins that are produced and released by myocytes in response to muscular contractions when doing physical exercise. One protein that is thought to function as myokine is FGF23.The purpose of this study was to determine the effect of acute physical exercise with moderate intensity on the expression of FGF23 gene in Wistar rat heart. This was an animal experimental study using 24 male Wistar rats that were divided into 4 groups:treatment groups that performed 30 minute acutephysical exercise with moderate intensity (20 m/min) for 3 days, 6 days, and 15 days and a control group without physical exercise. The study was conducted in the Animal Laboratory and Central Laboratory of Universitas Padjadjaran during the period of February to July 2019. Data observed were the FGF23 gene expressions in Wistar rats heart. Data were analyzed using Kruskal-Wallis and Mann-Whitney tests. The results from the Kruskal-Wallis test showed that acute physical exercise with moderate intensity did not increase the FGF23 gene expression in Wistar rat heart (p>0.05), and the average of relative ratios of FGF23/GAPDH gene expression were as follows: control (0.970±0,03), 3 days (0.992±0.03), 6 days (1.014±0.05), and 15 days (1.056±0.02). GAPDH was used in this study as a housekeeping gene since its expression is very constant. This study proves that FGF23 is more likely to take a role in the cardiac remodeling process, especially those associated with cardiac hypertrophy after chronic exercise with no effect observed after acute physical exercise with moderate intensity in Wistar rat heart.

Hypertension is a condition of persistently high blood pressure. It is currently a big health issue as its prevalence is high in Indonesia and its complications are numerous and deadly. Salt intake is one of the modifiable factors of hypertension. According to a study by Indonesian Ministry of Health, salt consumption in Indonesia is almost two times greater than the recommended salt diet from WHO. Sodium reabsorption in kidney plays a role in regulating blood pressure. Epithelial sodium channel (ENaC) is one of the structures that function in sodium reabsorption in kidney tubules. This study was conducted at the Central Laboratory and Animal Laboratory of the Faculty of Medicine Universitas Padjadjaran from June to Desember 2018. The aim of this study was to analyze the effect of high sodium diet on the expression of ENaC gene in kidney tubules of rats. Twelve Rattus norvegicus wistar rats were divided into two groups of control and treatment. Treatment group was given daily 2 mL NaCl solution treatment using gavage for 8 weeks. The expression of ENaC α, β, and γ was obtained by running tissue samples from kidney cortex and medulla in polymerase chain reaction and electrophoresis. The result showed that there was an insignificant decrease in ENaC α, β, and γ gene expressions in both kidney cortex and medulla of the treatment group when compared to control groupThis study concludes that ENaC gene expression is not significantly affected by high sodium diet.

The non-classical role of vitamin D has been investigated in recent decades. One of which is related to its role in skeletal muscle. Satellite cells are skeletal muscle stem cells that play a pivotal role in skeletal muscle growth and regeneration. This systematic review aims to investigate the effect of vitamin D on satellite cells. A systematic search was performed in Scopus, MEDLINE, and Google Scholar. In vivo studies assessing the effect of vitamin D on satellite cells, published in English in the last ten years were included. Thirteen in vivo studies were analyzed in this review. Vitamin D increases the proliferation of satellite cells in the early life period. In acute muscle injury, vitamin D deficiency reduces satellite cells differentiation. However, administering high doses of vitamin D impairs skeletal muscle regeneration. Vitamin D may maintain satellite cell quiescence and prevent spontaneous differentiation in aging. Supplementation of vitamin D ameliorates decreased satellite cells’ function in chronic disease. Overall, evidence suggests that vitamin D affects satellite cells’ function in maintaining skeletal muscle homeostasis. Further research is needed to determine the most appropriate dose of vitamin D supplementation in a specific condition for the optimum satellite cells’ function.

Background: Prolonged pacing of the right ventricle (RV) is associated with left ventricular (LV) systolic dysfunction. Several studies have shown that the RV pacing location, pacing burden (percentage), and paced QRS duration may affect LV systolic function. Subclinical LV dysfunction may occur early after implantation of a permanent pacemaker (PPM). Therefore, this study aims to detect early subclinical LV systolic dysfunction measured by global longitudinal strain (GLS) using speckle tracking echocardiography (STE) at one month after PPM implantation. Methods: A single-center, prospective cohort study was conducted, and all patients indicated for PPM implantation with preserved LV systolic function were included. Data of RV pacing location (RV apical vs right ventricular outflow tract (RVOT), pacing burden (percentage) (≤40% vs >40%), and paced QRS duration (≤150 ms and >150 ms) were obtained. The change of GLS was also measured before and one month after PPM implantation (delta GLS). Results: 37 patients were enrolled in this study, which demonstrated significant difference between GLS before (-20.30 SD 3.38) and after (-16.93 SD 3.47) PPM implantation (p=150ms ((1.70 (0.30–8.30) vs 3.45 (0.0–10.5)), p=0.266). Meanwhile, there was a significant difference of delta GLS between patients with pacing burden ≤40% vs >40% (Mean 1.92 SD 1.37 vs 3.98 SD 3.04), p=0.007). Further analysis found that pacing burden only affected the delta GLS in group with apical RV pacing (≤40% (1.58 SD 0.59) vs > 40% (4.67 SD 3.47), p = 0.008) and did not affect the delta GLS in group with RVOT pacing (≤40% (2.32 SD 1.98) vs > 40% (3.29 SD 2.48), p = 0.446). Conclusion: The pacing parameter, particularly pacing burden > 40% may induce the subclinical LV systolic dysfunction after one month of pacemaker implantation as shown by decline of GLS, especially when the RV pacing location was placed on apical.

Aerobic physical activity is known to induce skeletal muscle adaptation. Some genes, including MyoD, are known to have a major role in the process of muscle adaptation. Several studies has stated that the expression of MyoD increases during the aerobic activity process; however, the studies were carried out in a single bout. Studies on the effects of acute phase exercise (

Diabetic retinopathy leads to retinal malfunction, blindness, and reduced quality of life in adult diabetes patients. The involvement of reactive oxygen species (ROS) regulation stimulated by high blood glucose levels opens the opportunity for ROS modulator agents such as MitoTEMPOL. This study aims to explore the effect of MitoTEMPOL on ROS balance that may be correlated with retinal vascularization pattern, autophagy, and apoptosis in a streptozotocin-induced rat model. Four groups of male Wistar rats (i.e., control, TEMPOL (100 mg/kg body weight [BW]), diabetic (streptozotocin, 50 mg/kg BW single dose), and diabetic + TEMPOL; n = 5 for each group) were used in the study. MitoTEMPOL was given for 5 weeks, followed by funduscopy, and gene and protein expression were explored from the rat’s retina. Streptozotocin injection decreased bodyweight and increased food and water intake, as well as fasting blood glucose. The results showed that MitoTEMPOL reduced retinal vascularization pattern and decreased superoxide dismutase gene expression and protein carbonyl, caspase 3, and caspase 9 protein levels. A modulation of autophagy in diabetes that was reversed in the diabetic + TEMPOL group was found. In conclusion, MitoTEMPOL modulation on autophagy and apoptosis contributes to its role as a potent antioxidant to prevent diabetic retinopathy by inhibiting ROS-induced retinal vascularization patterns.

Fitness becomes an important benchmark for public health in every age group. Activities with poor adverse fitness are at risk of injury. Good fitness is gained from a balance in everyday physical activity with conditions that are free of metabolic syndrome. This study investigated the relationship of physical activity, energy balance, and metabolic syndrome to the fitness of 166 professors of Universitas Padjadjaran who underwent a 1-month fitness checkup at BAPELKES Bandung in the period of 2017. Based on the regression analysis, the results showed a significant relationship between physical activity, energy balance, and metabolic syndrome on the physical fitness of the elderly group (F = 25.9290> F table = 2.427) with normal data distribution (Kolmogorov-Smirnov test). The results also showed a moderate relationship (R = 0.569 and R2 = 0.324). It also partially showed significant influence between physical activity and fitness (t = 8.541> t table = 1.975), significant influence between energy balance and physical fitness (t = 2.248> t table = 1.975), and no significant partial influence between metabolic syndrome and physical fitness of the elderly group (t = -0.029 Ftable=2,427) dengan distribusi data normal (tes Kolmogorov-Smirnov). Hasil juga menunjukkan hubungan yang moderat (R= 0,569 dan R2= 0,324). Secara parsial juga menunjukkan pengaruh yang signfikan aktivitas fisik dengan kebugaran (t= 8.541> t tabel= 1.975), pengaruh signifikan keseimbangan energi dengan kebugaran fisik (t= 2,248> t tabel= 1,975), dan tidak ada pengaruh signifikan secara parsial terhadap sindrom metabolik dengan kebugaran fisik kelompok usia lanjut (t= -0,029 < t tabel= 1,975). Berdasar atas hasil penelitian dapat disimpulkan hubungan = aktivitas fisik, keseimbangan energi, dan sindrom metabolik dengan kebugaran fisik guru besar Universitas Padjadjaran. Kata kunci: Kebugaran, keseimbangan energi, sindrom metabolik

Using single-stranded adeno-associated virus serotype 9 (ssAAV9) vectors containing the neuron-specific synapsin-I promoter, we examined whether different administration routes (direct cerebellar cortical (DC), intrathecal (IT) and intravenous (IV) injections) could elicit specific transduction profiles in the CNS. The DC injection route robustly and exclusively transduced the whole cerebellum, whereas the IT injection route primarily transduced the cerebellar lobules 9 and 10 close to the injection site and the spinal cord. An IV injection in neonatal mice weakly and homogenously transduced broad CNS areas. In the cerebellar cortex, the DC and IT injection routes transduced all neuron types, whereas the IV injection route primarily transduced Purkinje cells. To verify the usefulness of this method, we generated a mouse model of spinocerebellar ataxia type 1 (SCA1). Mice that received a DC injection of the ssAAV9 vector expressing mutant ATXN1, a protein responsible for SCA1, showed the intranuclear aggregation of mutant ATXN1 in Purkinje cells, significant atrophy of the Purkinje cell dendrites and progressive motor deficits, which are characteristics of SCA1. Thus, ssAAV9-mediated transduction areas, levels, and cell types change depending on the route of injection. Moreover, this approach can be used for the generation of different mouse models of CNS/neurodegenerative diseases.