Cardiovascular diseases are the leading cause of death worldwide, among which, ischemic heart disease is the most prevalent. Myocardial infarction results from occlusion of a coronary artery, which leads to an insufficient blood supply to the myocardium. As is well known, the massive loss of cardiomyocytes cannot be solved due the limited regenerative ability of the adult mammalian heart. In contrast, some lower vertebrate species can regenerate the heart after injury; their study has disclosed some of the involved cell types, molecular mechanisms and signaling pathways during the regenerative process. In this two-part review, we discuss the current state of the principal response in heart regeneration, where several involved processes are essential for full cardiac function in recovery.

Osteoarthritis (OA) is the most common arthritis affecting synovial joints such as knees and hips of millions of people globally. Usage-related joint pain and reduced function are the most common symptoms experienced by people with OA. To improve pain management, there is a need to identify validated biomarkers predicting therapeutic responses in targeted clinical trials. Our study aimed to identify the metabolic biomarkers for pain and pressure pain detection thresholds (PPTs) in participants with knee pain and symptomatic OA using metabolic phenotyping. Metabolite and cytokine measurements were done on serum samples using LC-MS/MS (liquid gas chromatography integrated magnetic resonance mass spectrometry) and Human Proinflammatory panel 1 kit respectively. Regression analysis was done in a test (n = 75) and replication study (n = 79) to investigate the metabolites associated with current knee pain scores and pressure pain detection thresholds (PPTs). Meta-analysis and correlation were done estimating precision of associated metabolites and identifying relationship between significant metabolites and cytokines respectively. Acyl ornithine, carnosine, cortisol, cortisone, cystine, DOPA, glycolithocholic acid sulphate (GLCAS), phenylethylamine (PEA) and succinic acid were found to be significantly (FDR <.1) associated with pain scores in meta-analysis of both studies. IL-10, IL-13, IL-1β, IL2, IL8 and TNF-α were also found to be associated with the significant metabolites. Significant associations of these metabolites and inflammatory markers with knee pain suggests that targeting relevant pathways of amino acid and cholesterol metabolism may modulate cytokines and these could be targeted as novel therapeutics development to improve knee pain and OA management. PERSPECTIVE: Foreseeing the global burden of knee pain in Osteoarthritis (OA) and adverse effects of current pharmacological therapies, this study is envisaged to investigate serum metabolites and molecular pathways involved in knee pain. The replicated metabolites in this study suggests targeting amino-acid pathways for better management of OA knee pain.

Introduction: Tobacco smoke is associated with oxidative and inflammatory pathways, increasing the risk of chronic-degenerative diseases. Our goal was to evaluate the effects of acute \"Pera\" and \"Moro\" orange juice consumption on inflammatory processes and oxidative stress in microRNA (miRNA) expression in plasma from healthy smokers. Methods: This was a randomized crossover study that included healthy smokers over 18 years old. Blood samples were collected before and 11 h after beverage ingestion. Participants were instructed to drink 400 mL of Pera orange juice (Citrus sinensis), Moro orange juice (Citrus sinensis L. Osbeck), or water. Each subject drank the beverages in a 3-way crossover study design. Inflammatory and oxidative stress biomarkers and circulating miRNA expression profiles were determined. The subjects maintained their usual tobacco exposure during the experiment. Results: We included 18 individuals (12 men and 6 women), with 37.0 ± 12.0 years old. All subjects received the 3 interventions. Increased expression of circulating miRNAs (miR-150-5p, miR-25-3p, and miR-451a) was verified after cigarette smoking, which were attenuated after intake of both types of orange juice. There was no difference regarding serum levels of TNF-α, IL-6, MMP-9, and C-reactive protein. Despite the increased activity of serum superoxide dismutase and glutathione peroxidase after \"Pera\" or \"Moro\" orange juice intake, respectively, no changes in lipid hydroperoxide levels were detected. Conclusion: Tobaccos smokers showed increased expression of miR-150-5p, miR-25-3p, and miR-451a was noted, and attenuated by orange juice intake. miRNAs were predicted to regulate 244 target genes with roles in oxidative stress, PI3K-Akt, and MAPK signaling, which are pathways frequently involved in smoking-related cardiovascular diseases and cancer.

UNASSIGNED: Ginseng, a traditional herbal medicine, has been used for thousands of years to treat various diseases including metabolic syndrome (MS). However, the underlying mechanism(s) of such beneficial actions of ginseng against MS is poorly understood. Emerging evidence indicates a close association of the host gut microbiota with MS. The present study was conducted to examine, whether the beneficial effects of Korean red ginseng (KRG) against MS could be influenced by gut microbial population and whether gut microbial profile could be considered a valuable biomarker for targeted treatment strategy for MS in compliance with the predictive, preventive, and personalized medicine (PPPM / 3PM).
UNASSIGNED: This clinical study was a randomized, double-blind, placebo-controlled trial evaluating the effects of KRG treatment for 8 weeks on patients with MS. The anthropometric parameters, vital signs, metabolic biomarkers, and gut microbial composition through 16S rRNA gene sequencing were assessed at the baseline and endpoint. The impact of KRG was also evaluated after categorizing the subjects into responders and non-responders, as well as enterotypes 1 and 2 based on their gut microbial profile at the baseline.
UNASSIGNED: Fifty out of 60 subjects who meet the MS criteria completed the trial without showing adverse reactions. The KRG treatment caused a significant decrease in systolic blood pressure (SBP). Microbial analysis revealed a decrease in Firmicutes, Proteobacteria, and an increase in Bacteroidetes in response to KRG. In patient stratification analysis, the responders showing marked improvement in the serum levels of lipid metabolic biomarkers TC and LDL due to the KRG treatment exhibited higher population of both the family Lachnospiraceae and order Clostridiales compared to the non-responders. The homeostasis model assessment-insulin resistance (HOMA-IR) and insulin level were decreased in enterotype 1 (Bacteroides-abundant group) and increased in enterotype 2 (prevotella-abundant group) following the KRG treatment.
UNASSIGNED: In this study, the effects of KRG on the glucose metabolism in MS patients were influenced by the relative abundances of gut microbial population and differed according to the individual enterotype. Therefore, the analysis of enterotype categories is considered to be helpful in predicting the effectiveness of KRG on glucose homeostasis of MS patients individually. This will further help to decide on the appropriate treatment strategy for MS, in compliance with the perspective of PPPM.