Exercise induction at expression immediate early gene (c-Fos, ARC, EGR-1) in the hippocampus: a systematic review.

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.

O gene precoce imediato (GPI) exibe marcadores de ativação no sistema nervoso constituídos por ARC, EGR-1 e c-Fos e está relacionado à plasticidade sináptica, especialmente no hipocampo. A expressão do GPI é afetada pelo exercício físico, que induz a expressão direta de ARC, EGR-1 e c-Fos. Objetivo: Para avaliar o impacto do exercício físico, realizamos um estudo de literatura para determinar os níveis de expressão dos GPIs (ARC, c-Fos e EGR-1). Métodos: A base de dados utiliza literatura on-line, PubMed-Medline, Scopus e ScienceDirect. O artigo original em inglês usa as seguintes palavras-chave em seu título: (Exercise) AND (c-Fos) AND (Hippocampus), (Exercise) AND (ARC) AND (Hippocampus), (Exercise) AND (EGR-1) AND (Hippocampus). Resultados: O exercício físico pode afetar a expressão de EGR-1, c-fos e ARC no hipocampo, uma parte importante do cérebro envolvida na aprendizagem e na memória. O exercício físico aumenta a expressão do gene c-Fos; sua alta intensidade pode aumentar a expressão de c-Fos, indicando ativação neural. Além disso, a expressão do gene ARC aumentou devido ao exercício físico, onde ARC é um gene que desempenha um papel na plasticidade sináptica e na regulação da aprendizagem e da memória, nas mudanças na estrutura sináptica e no aumento das conexões sinápticas, enquanto o EGR-1 também desempenha um papel na plasticidade sináptica, uma mudança genética que afeta o aprendizado e a memória. De maneira geral, o exercício físico regular pode aumentar a expressão de ARC, c-fos e EGR-1 no hipocampo. Isso reflete as mudanças na neuroplasticidade e na plasticidade sináptica que ocorrem em resposta à atividade física. Essas mudanças podem melhorar a função cognitiva, o aprendizado e a memória. Conclusão: A expressão de c-Fos, EGR-1 e ARC aumenta após o exercício físico nos neurônios do hipocampo, para aumentar a plasticidade sináptica, a neurogênese associada ao aprendizado e à memória.

Effect of Low Protein Diet on Bone Structure of Young Wistar Mice.

<b>Background and Objective:</b> Malnutrition and stunting are major unresolved problems in Indonesia. Protein deficiency can cause stunted growth, as well as make physical and cognitive abilities cannot reach their maximum potential. During childhood the need for protein must be fulfilled so that the peak of bone formation during adolescence can be perfect. In malnourished children, a low protein diet will lead to thinning of the bone cortex. Due to the high rate of stunting and malnutrition in children due to protein deficiency, a study was conducted on the effects of feeding low protein diet on rat bones. <b>Materials and Methods:</b> Male Wistar rats (n = 10) at 6-8 weeks old (body weight around 250 g), control groups were fed a normal chow diet and low protein diet groups were given low protein chow diet (protein 5%) for 18 weeks, then the rats were sacrificed and the femoral bones were isolated. Body weight, femur weight, femur length were checked and bone density was examined using X-ray. <b>Results:</b> The body proportions of the low protein group rats were smaller and thinner than those of the control group. This difference is supported by the significant weight loss starting from the sixth week after low protein feeding. There are significant differences in body weight and femur weight between the control and low protein diet groups. Bone density decreases significantly in low protein diet group. Macroscopically, the femur length of the low protein group was shorter than the control group, however the femur length did not show significant differences statistically between the two groups. <b>Conclusion:</b> A low protein diet decreased the body weight of the rats, also causing impaired bone growth characterized by decreasing femur weight. The low protein diet also caused osteoporosis in the bones.

Research Trends in Molecular Biological Studies on Oral Squamous Cell Carcinoma: A Bibliometric Analysis.

Background: Since the discovery of PCR and ELISA, in vitro research in the realm of molecular biology pertaining to oral squamous cell carcinoma (OSCC) has witnessed significant expansion. Objective: to provide a comprehensive overview of molecular biology research on OSCC through visual mapping techniques. Methods: We conducted an analysis of publications within the "oral squamous cell carcinoma" category from Scopus' core collection. On 20 January 2023, we screened these publications using an advanced search employing the keywords "oral squamous cell cancer" and "cell line." Data analysis was performed using Microsoft Excel 2010 and VOSviewer, facilitating the examination of author contributions, journal productivity, institutional affiliations, and contributions by nations. VOSviewer was further utilized for co-occurrence and reference analysis of keywords. Results: A total of 781 papers spanning from 1992 to 2023 were collected. Notably, Japan, China, and the United States emerged as significant contributors in this field. The Osaka University Graduate School of Dentistry (Japan) ranked first with 21 publications. Chae J-I of Chonbuk National University (South Korea) emerged as the most prolific author, with 14 publications. The International Journal of Oncology and the Journal of Oral Pathology and Medicine were identified as the two most prolific journals. The central themes that emerged were epidermal growth factor receptor, invasion, epithelial-mesenchymal transition, angiogenesis, apoptosis, and metastasis. Conclusion: The rate of publications focused on the molecular biology of OSCC has seen a remarkable increase. Research priorities have shifted from topics such as "radiation, RANKL, cyclin D1, RNA interference, and matrix metalloproteinase" to encompass areas such as "chemoresistance due to cisplatin, other therapeutic agents (metformin and monoclonal antibody), autophagy, inflammation, microRNA, cancer-associated fibroblasts, and STAT3 (with roles in cell migration and tumorigenesis)." These seven significant future research areas hold promise in identifying reliable biological markers for oral cancer detection and treatment, thereby improving clinical outcomes.

New hybrid radio-fluorescent probes [131I]-BPF-01 and [131I]-BPF-02 for visualisation of cancer cells: Synthesis and preliminary in vitro and ex vivo evaluations.

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.

Understanding the Roles of Selenium on Thyroid Hormone-Induced Thermogenesis in Adipose Tissue.

Brown adipose tissue (BAT) and white adipose tissue (WAT) are known to regulate lipid metabolism. A lower amount of BAT compared to WAT, along with adipose tissue dysfunction, can result in obesity. Studies have shown that selenium supplementation protects against adipocyte dysfunction, decreases WAT triglycerides, and increases BAT triiodothyronine (T3). In this review, we discuss the relationship between selenium and lipid metabolism regulation through selenoprotein deiodinases and the role of deiodinases and thyroid hormones in the induction of adipose tissue thermogenesis. Upon 22 studies included in our review, we found that studies investigating the relationship between selenium and deiodinases demonstrated that selenium supplementation affects the iodothyronine deiodinase 2 (DIO2) protein and the expression of its associated gene, DIO2, proportionally. However, its effect on DIO1 is inconsistent while its effect on DIO3 activity is not detected. Studies have shown that the activity of deiodinases especially DIO2 protein and DIO2 gene expression is increased along with other browning markers upon white adipose tissue browning induction. Studies showed that thermogenesis is stimulated by the thyroid hormone T3 as its activity is correlated to the expression of other thermogenesis markers. A proposed mechanism of thermogenesis induction in selenium supplementation is by autophagy control. However, more studies are needed to establish the role of T3 and autophagy in adipose tissue thermogenesis, especially, since some studies have shown that thermogenesis can function even when T3 activity is lacking and studies related to autophagy in adipose tissue thermogenesis have contradictory results.

Exercise intensities modulate ACE2/MasR/eNOS pathway in male Wistar rat's lung.

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 < 0.01). Moderate-intensity exercise significantly increased MasR and eNOS mRNA expressions compared to the control (p < 0.05), and this intensity also increased ACE2 mRNA but not significantly. Low-intensity exercise increased ACE2, MasR, and eNOS mRNA expressions but not significantly. Low-, moderate-, or high-intensity exercises reduced the medial wall thickness of the lung muscular arteries but not significantly. In conclusion, high-intensity exercise may induce NO synthesis in the lung by increasing mRNA expression of ACE2, MasR, and eNOS without decreasing the medial wall thickness of the muscular artery. Thus, high-intensity exercise may be the optimal intensity to improve NO synthesis and vascular function in the lung.

Effect of Moringa oleifera Leaf Powder on Hematological Profile of Male Wistar Rats.

Background: Indonesia is a country with high biodiversity of more than 20,000 plant species, and 35% of them are identified as having health benefits. Moringa oleifera is one plant that almost all of its parts have been used as nutritional supplements and traditional medicines. Moringa leaves contain nutrients, antioxidants, and bioactive substances that have anti-inflammatory, wound healing, and anti-anemia properties. Purpose: This study aimed to investigate the hematological effect of Moringa leaf powder in male Wistar rats under normal conditions. Methods: Twenty-four male Wistar rats strain (Rattus norvegicus) 9-10 weeks old and 250-275 grams were divided into four groups (n=6), normal as a control group and three other groups were given Moringa leaf powder at doses 200, 400, and 800 mg/kgBW during 12 weeks. Blood samples at week 12 were administered to determine blood count. Results: The results of this study showed differences between the various doses of Moringa leaf powder for each hematological profile. These differences were more significant for MCH parameters that indicated a decrease in the D800 group compared with the control group. Conclusion: In conclusion, this study revealed that the consumption of Moringa leaf powder for 12 weeks did not have a significant change in the hematological profile, except for the MCH value that revealed a modification.

Exercise-Induced Autophagy Ameliorates Motor Symptoms Progressivity in Parkinson's Disease Through Alpha-Synuclein Degradation: A Review.

This study reviews the molecular mechanism of exercise-induced autophagy/mitophagy and its possible mechanism in delaying motor symptoms progressivity in Parkinson's disease (PD). Relevant articles obtained from PubMed and EBSCOhost were reviewed. After analyzing the articles, it was found that autophagy can be induced by exercise and can possibly be activated through the AMPK-ULK1 pathway. Mitophagy can also be induced by exercise and can possibly be activated through PINK1/Parkin pathway and AMPK-dependent pathway. Moreover, exercise-induced autophagy can decrease the accumulation of toxic α-synuclein aggregates in PD and therefore can delay motor symptoms progressivity.

The soluble suppression of tumorigenicity 2 as a biomarker of early cardiac remodeling in bradycardia patients receiving permanent pacemaker therapy.

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.

It is widely known that pacing induced cardiomyopathy, which results from the utilization of a permanent pacemaker (PPM) within a long-term duration, will increase the risk of mortality and morbidity. Hence, early detection of the cardiac remodeling process is warranted in order to prevent this course. In this study, the soluble suppression of tumorigenicity 2 level (ng/ml), known as an indicator of cardiac remodeling, was significantly higher in 1 month following PPM implantation compared with the baseline (23.4 ± 28.4 vs 39.9 ± 63.7; p = 0.001). Thus, it denotes that early cardiac remodeling might occur earlier than expected, within 1 month following PPM implantation.

Synthesis and Biological Evaluation of New Fluorescent Probe BPN-01: A Model Molecule for Fluorescence Image-guided Surgery.

Fluorescence image-guided surgery (FIGS) can serve as a tool to achieve successful resection of tumour tissues during surgery, serving as a surgical navigator for surgeons. FIGS relies on the use of fluorescent molecules that can specifically interact with cancer cells. In this work, we developed a new model of fluorescent probe based on benzothiazole-phenylamide moiety featuring the visible fluorophore nitrobenzoxadiazole (NBD), namely BPN-01. This compound was designed and synthesised for potential applications in the tissue biopsy examination and ex-vivo imaging during FIGS of solid cancers. The probe BPN-01 exhibited favourable spectroscopic properties, particularly in nonpolar and alkaline solvents. Moreover, in vitro fluorescence imaging revealed that the probe appeared to recognise and be internalised in the prostate (DU-145) and melanoma (B16-F10) cancer cells, but not in the normal cells (myoblast C2C12). The cytotoxicity studies revealed that probe BPN-01 was not toxic to the B16 cells, suggesting excellent biocompatibility. Furthermore, the computational analysis showed that the calculated binding affinity of the probe to both translocator protein 18 kDa (TSPO) and human epidermal growth factor receptor 2 (HER2) was considerably high. Hence, probe BPN-01 displays promising properties and may be valuable for visualising cancer cells in vitro. Furthermore, ligand 5 can potentially be labelled with NIR fluorophore and radionuclide, and serves as a dual imaging agent for in vivo applications.

MitoTEMPOL modulates mitophagy and histopathology of Wistar rat liver after streptozotocin injection.

Objectives: 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.

Effects of Vitamin D on Satellite Cells: A Systematic Review of In Vivo Studies.

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.

Revisiting exercise-induced premature ventricular complexes as a prognostic factor for mortality in asymptomatic patients: A systematic review and meta-analysis.

Background: Recent 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. Methods: A 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). Results: A 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; I 2 = 59.6%, p-heterogeneity < 0.001) and CVM (RR = 1.67 (95% CI = 1.40-1.99); p < 0.001; I 2 = 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. Conclusion: EI-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].

Calcitriol potentially alters HeLa cell viability via inhibition of autophagy.

Objective: This study was conducted to evaluate the effect of Calcitriol on cellular death in HeLa cells via autophagy and turn over due to mitochondria homeostasis. Methods: HeLa cell lines were grown in 24-well plates and treated with Calcitriol at varying doses (0.013 µM-0.325 µM) for varying time periods (2, 6, 12, and 18 h). Cell proteins were extracted with scrapers and lysed using RIPA buffer. Western blots were performed for proteins involved with autophagy (Lc3, p62), signaling (mTOR, PI3K, HIF1α), mitochondria (PGC1α, COX4, and Tom 20), and apoptosis (Caspase 3, Caspase 9, and PARP). Protein carbonyl levels were determined by measuring the indirect ROS level. An inhibition study using L-mimosine was performed to analyze the significance of HIF1α. Results: Calcitriol treatment induced cytotoxicity in a dose- and time-dependent manner and caused growth arrest in HeLa cells. The PI3K-AKT-mTOR pathway was activated, leading to inhibition of autophagy and alterations in mitochondria biogenesis homeostasis. Treatment with Calcitriol produced protein carbonyl levels similar to those in the cisplatin-treated and control groups. Increased ROS levels may cause toxicity and induce cell death specifically in cancer cells but not in normal cells. The inhibition of HIF1α partially rescued the HeLa cells from the toxic effects of Calcitriol treatment. Conclusion: We suggest that Calcitriol may shut down mitochondrial homeostasis in HeLa cells by inducing the PI3K-AKT-mTOR pathway and inhibiting autophagy, which leads to cell death.

MitoTEMPOL Inhibits ROS-Induced Retinal Vascularization Pattern by Modulating Autophagy and Apoptosis in Rat-Injected Streptozotocin Model.

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.

Electrocardiographic Markers Indicating Right Ventricular Outflow Tract Conduction Delay as a Predictor of Major Arrhythmic Events in Patients With Brugada Syndrome: A Systematic Review and Meta-Analysis.

Introduction: Risk 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. Methods: The 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). Results: Meta-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; I 2= 52%, P heterogeneity = 0.02]. Subgroup analysis showed that aVR sign [RR = 2.00 (1.42, 2.83); p < 0.001; I 2= 0%, P heterogeneity = 0.40] and large S wave in lead I [RR = 1.74 (1.11, 2.71); p = 0.01; I 2= 60%, P heterogeneity = 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. Conclusion: RVOT 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 Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022321090.

Calcitriol Inhibits Proliferation and Potentially Induces Apoptosis in B16-F10 Cells.

BACKGROUND Melanoma is one of the most aggressive types of cancer and it has shown a remarkable surge in incidence during the last 50 years. Melanoma has been projected to be continuously rising in the future. Therapy for advanced-type melanoma is still a challenge due to the low response rate and poor 10-year survival. Interestingly, several epidemiological and preclinical studies had reported that vitamin D deficiency was associated with disease progression in several cancer types. In vivo and in vitro studies revealed anti-proliferative, anti-angiogenic, apoptosis, and differentiation induction effects of calcitriol in various cancers. However, information on the effects of calcitriol (1,25(OH)2D3) on melanoma is still limited, and its mechanism remains unclear. MATERIAL AND METHODS In the present study, by utilizing B16-F10 cells, which is a melanoma cell line, we explored the anti-proliferative effect of calcitriol using cell viability assay, near-infrared imaging, expression of apoptosis-related genes using real-time polymerase chain reactions (PCR), and the expression of apoptosis proteins levels using western blot. In addition, we also assessed calcitriol uptake by B16-F10 cells using high-performance liquid chromatography (HPLC). RESULTS We found that calcitriol inhibits melanoma cell proliferation with an IC50 of 93.88 ppm (0.24 µM), as shown by cell viability assay. Additionally, we showed that B16-F10 cells are capable of calcitriol uptake, with a peak uptake time at 60 min after administration. Calcitriol was also able to induce apoptosis-related proteins such as caspase-3, caspase 8, and caspase-9. These effects of calcitriol reflect its potential utility as a potent adjuvant therapy for melanoma. CONCLUSIONS Calcitriol inhibits cell proliferation and induces apoptosis in B16-F10 cells.

Importance of gut microbiome regulation for the prevention and recovery process after SARS-CoV-2 respiratory viral infection (Review).

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported to affect organs other than the lungs, including the liver, brain, kidneys and intestine, and gastrointestinal symptoms, such as nausea, vomiting, diarrhea and abdominal discomfort, have also been reported. Thus, SARS-CoV-2 could potentially directly or indirectly regulate the gut microbiome profile and its homeostasis. The abundance of Coprobacillus, Clostridium ramosum and Clostridium are associated with the severity of COVID-19, and Firmicutes, Bacteriodetes, Proteobacteria and Actinobacteria are also related to COVID-19 infection. The four phyla are correlated with the severity of COVID-19 infection in patients. The modulation of factors that control the physiological growth of the gut microbiome will determine the proportionate ratio of microbiome types (profile). Taken together, gut microbiome profile alterations in COVID-19 patients may have a cross effect with the modulation of cytokine levels in COVID-19 infection. With these findings, several factors that regulate gut microbiome homeostasis may support the degree of the clinical symptoms and hasten the recovery process after COVID-19 infection.

Type, Intensity, and Duration of Exercise as Regulator of Gut Microbiome Profile.

ABSTRACT: Gut microbiome profile is related to individual health. In metabolic syndrome, there is a change in the gut microbiome profile, indicated by an increase in the ratio of Firmicutes to Bacteroidetes. Many studies have been conducted to determine the effect of exercise on modifying the gut microbiome profile. The effectiveness of exercise is influenced by its type, intensity, and duration. Aerobic training decreases splanchnic blood flow and shortens intestinal transit time. High-intensity exercise improves mitochondrial function and increases the essential bacteria in lactate metabolism and urease production. Meanwhile, exercise duration affects the hypothalamic-pituitary-adrenal axis. All of these mechanisms are related to each other in producing the effect of exercise on the gut microbiome profile.

Selenium Supplementation Alters IL-1ß and IL-6 Protein Levels in Contusion Model Rats.

<b>Background and Objective:</b> Contusion in skeletal muscles were common in athletes.Contusions usually occur when the tissue is exposed to a rapid and strong compressive force, for example, a direct blow, which usually results in the formation of a hematoma within the muscle. Contusion injuries impair the physiological function of the muscle. Supplementation is needed to shorten the healing process. Alternative therapy is antioxidant supplementation. Therefore, we conducted a study on the administration of the antioxidant selenium in contusion rats. <b>Materials and Methods:</b> The subject of this study were male Wistar rats. Rats were divided into 3 groups, namely control group, contusion group and selenium group. Each group consisted of 5 rats. Selenium dose was 0.0513 mg kg¹ b.wt., dissolved into 2% PGA given once a day, for 3 consecutive days. After treatment periods, CK-MM level, IL-1ß and IL-6 level were examined. <b>Results:</b> Protein expression of IL-1ß and IL-6 were significantly lower in the selenium treatment group compared to the contusion group. These results were confirmed by improved step gait in the selenium group. But there was no significant decrease in serum CK-MM levels expression in the selenium treatment group when compared to the contusion group. <b>Conclusion:</b> Selenium supplementation improved gait function after contusion by suppressing IL-1ß and IL-6 expression. However, selenium administration did not alter CK-MM levels.