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Aging is a dynamic and progressive process characterized by the gradual accumulation of cellular damage. The continuous functional decline in the intrinsic capacity of living organisms to precisely regulate homeostasis leads to an increased susceptibility and vulnerability to diseases. Among the factors contributing to these changes, body composition—comprised of fat mass and lean mass deposits—plays a crucial role in the trajectory of a disability. Particularly, visceral and intermuscular fat deposits increase with aging and are associated with adverse health outcomes, having been linked to the pathogenesis of sarcopenia. Adipose tissue is involved in the secretion of bioactive factors that can ultimately mediate inter-organ pathology, including skeletal muscle pathology, through the induction of a pro-inflammatory profile such as a SASP, cellular senescence, and immunosenescence, among other events. Extensive research has shown that natural compounds have the ability to modulate the mechanisms associated with cellular senescence, in addition to exhibiting anti-inflammatory, antioxidant, and immunomodulatory potential, making them interesting strategies for promoting healthy aging. In this review, we will discuss how factors such as cellular senescence and the presence of a pro-inflammatory phenotype can negatively impact body composition and lead to the development of age-related diseases, as well as how the use of polyphenols can be a functional measure for restoring balance, maintaining tissue quality and composition, and promoting health. [ABSTRACT FROM AUTHOR]

In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations. [ABSTRACT FROM AUTHOR]

Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota's substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine's anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine's influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites. [ABSTRACT FROM AUTHOR]

Ageing is a complex process characterized mainly by a decline in the function of cells, tissues, and organs, resulting in an increased risk of mortality. This process involves several changes, described as hallmarks of ageing, which include genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell depletion, and altered intracellular communication. The determining role that environmental factors such as diet and lifestyle play on health, life expectancy, and susceptibility to diseases, including cancer and neurodegenerative diseases, is wellestablished. In view of the growing interest in the beneficial effects of phytochemicals in the prevention of chronic diseases, several studies have been conducted, and they strongly suggest that the intake of dietary polyphenols may bring numerous benefits due to their antioxidant and anti-inflammatory properties, and their intake has been associated with impaired ageing in humans. Polyphenol intake has been shown to be effective in ameliorating several age-related phenotypes, including oxidative stress, inflammatory processes, impaired proteostasis, and cellular senescence, among other features, which contribute to an increased risk of ageing-associated diseases. This review aims to address, in a general way, the main findings described in the literature about the benefits of polyphenols in each of the hallmarks of ageing, as well as the main regulatory mechanisms responsible for the observed antiageing effects. [ABSTRACT FROM AUTHOR]

Wound healing is characterized by a systemic and complex process of cellular and molecular activities. Dipotassium Glycyrrhizinate (DPG), a side product derived from glycyrrhizic acid, has several biological effects, such as being antiallergic, antioxidant, antibacterial, antiviral, gastroprotective, antitumoral, and anti-inflammatory. This study aimed to evaluate the anti-inflammatory effect of topical DPG on the healing of cutaneous wounds by secondary intention in an in vivo experimental model. Twenty-four male Wistar rats were used in the experiment, and were randomly divided into six groups of four. Circular excisions were performed and topically treated for 14 days after wound induction. Macroscopic and histopathological analyses were performed. Gene expression was evaluated by real-time qPCR. Our results showed that treatment with DPG caused a decrease in the inflammatory exudate as well as an absence of active hyperemia. Increases in granulation tissue, tissue reepithelization, and total collagen were also observed. Furthermore, DPG treatment reduced the expression of pro-inflammatory cytokines (Tnf-α, Cox-2, Il-8, Irak-2, Nf-kB, and Il-1) while increasing the expression of Il-10, demonstrating anti-inflammatory effects across all three treatment periods. Based on our results, we conclude that DPG attenuates the inflammatory process by promoting skin wound healing through the modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. This involves modulation of the expression of pro- and anti-inflammatory cytokine expression; promotion of new granulation tissue; angiogenesis; and tissue re-epithelialization, all of which contribute to tissue remodeling. [ABSTRACT FROM AUTHOR]

Simple Summary: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. A promising approach to overcome the low life expectancy of patients with MCL is drug repurposing, a strategy focused on finding novel therapeutic weapons in approved drugs. Statins are well-tolerated, inexpensive, and widely prescribed as cholesterol-lowering agents that have also shown anti-cancer activity. The present study aimed to elucidate the effect of simvastatin on MCL cells. Our preclinical data demonstrate for the first time that simvastatin treatment impairs MCL proliferation and triggers a caspase-independent, ROS-mediated death of MCL cultures. Furthermore, we show that simvastatin significantly inhibits MCL migration and invasion ability, thereby impairing the growth of MCL tumors, suggesting that the use of statins might be considered for repurpose as a precise MCL therapy. Background: Mantle cell lymphoma (MCL) is a rare and aggressive subtype of B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. Statins are well-tolerated, inexpensive, and widely prescribed as cholesterol-lowering agents to treat hyperlipidemia and to prevent cardiovascular diseases through the blockage of the mevalonate metabolic pathway. These drugs have also shown promising anti-cancer activity through pleiotropic effects including the induction of lymphoma cell death. However, their potential use as anti-MCL agents has not been evaluated so far. Aim: The present study aimed to investigate the activity of simvastatin on MCL cells. Methods: We evaluated the cytotoxicity of simvastatin in MCL cell lines by CellTiter-Glo and lactate dehydrogenase (LDH) release assays. Cell proliferation and mitotic index were assessed by direct cell recounting and histone H3-pSer10 immunostaining. Apoptosis induction and reactive oxygen species (ROS) generation were evaluated by flow cytometry. Cell migration and invasion properties were determined by transwell assay. The antitumoral effect of simvastatin in vivo was evaluated in a chick embryo chorioallantoic membrane (CAM) MCL xenograft model. Results: We show that treatment with simvastatin induced a 2 to 6-fold LDH release, inhibited more than 50% of cell proliferation, and enhanced the caspase-independent ROS-mediated death of MCL cells. The effective impairment of MCL cell survival was accompanied by the inhibition of AKT and mTOR phosphorylation. Moreover, simvastatin strongly decreased MCL cell migration and invasion ability, leading to a 55% tumor growth inhibition and a consistent diminution of bone marrow and spleen metastasis in vivo. Conclusion: Altogether, these data provide the first preclinical insight into the effect of simvastatin against MCL cells, suggesting that this agent might be considered for repurpose as a precise MCL therapy. [ABSTRACT FROM AUTHOR]

Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), are a significant source of morbidity and mortality worldwide. Epidemiological data have shown that IBD patients are at an increased risk for the development of CRC. IBD-associated cancer develops against a background of chronic inflammation and oxidative stress, and their products contribute to cancer development and progression. Therefore, the discovery of novel drugs for the treatment of intestinal diseases is urgently needed. Licorice (Glycyrrhiza glabra) has been largely used for thousands of years in traditional Chinese medicine. Licorice and its derived compounds possess antiallergic, antibacterial, antiviral, anti-inflammatory, and antitumor effects. These pharmacological properties aid in the treatment of inflammatory diseases. In this review, we discuss the pharmacological potential of bioactive compounds derived from Licorice and addresses their anti-inflammatory and antioxidant properties. We also discuss how the mechanisms of action in these compounds can influence their effectiveness and lead to therapeutic effects on intestinal disorders. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of guarana on mitochondrial biogenesis in a high-fat diet (HFD)-fed mice. C57BL6J mice were divided in two groups: high-fat diet HFD and high-fat diet + guarana (HFD-GUA). Both groups received HFD and water ad libitum and the HFD-GUA group also received a daily gavage of guarana (1 g/kg weight). Body weight and food intake was measured weekly. Glycemic, triglyceride, and cholesterol levels were determined. VO2 and energy expenditure (EE) were determined by indirect calorimetry. Gene expression was evaluated by real-time PCR and protein content by western blotting. The HFD-GUA group presented lower body weight, subcutaneous, retroperitoneal, visceral, and epididyimal adipose tissue depots, and glycemic and triglyceride levels, with no change in food intake and cholesterol levels. Furthermore, the HFD-GUA group presented an increase in VO2 and basal energy expenditure (EE), as well as Pgc1α, Creb1, Ampka1, Nrf1, Nrf2, and Sirt1 expression in the muscle and brown adipose tissue. In addition, the HFD-GUA group presented an increase in mtDNA (mitochondrial deoxyribonucleic acid) content in the muscle when compared to the HFD group. Thus, our data showed that guarana leads to an increase in energetic metabolism and stimulates mitochondrial biogenesis, contributing to control of weight gain, even when associated with high-fat diet. [ABSTRACT FROM AUTHOR]

Simple Summary: Dysregulated B-cell receptor (BCR) signaling is considered a potent contributor to tumor survival in different subtypes of B-cell non-Hodgkin lymphomas (B-NHLs). In the last decade, BCR-targeted therapies have emerged as promising alternative treatment options to standard chemoimmunotherapy. Despite the initial excitement and strong biological rationale, BCR-targeting drugs often fail to produce durable responses. This review will discuss the current understanding of the role of BCR signaling in B-NHLs. In addition, the mechanisms of action of BCR-targeted therapies, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, will also be discussed. The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte's life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B-cell non-Hodgkin lymphomas (B-NHLs). In the last decade, the emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma such as diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients. [ABSTRACT FROM AUTHOR]

Excess caloric intake and body fat accumulation lead to obesity, a complex chronic disease that represents a significant public health problem due to the health-related risk factors. There is growing evidence showing that maternal obesity can program the offspring, which influences neonatal phenotype and predispose offspring to metabolic disorders such as obesity. This increased risk may also be epigenetically transmitted across generations. Thus, there is an imperative need to find effective reprogramming approaches in order to resume normal fetal development. Polyphenols are bioactive compounds found in vegetables and fruits that exert its anti-obesity effect through its powerful anti-oxidant and anti-inflammatory activities. Polyphenol supplementation has been proven to counteract the prejudicial effects of maternal obesity programming on progeny. Indeed, some polyphenols can cross the placenta and protect the fetal predisposition against obesity. The present review summarizes the effects of dietary polyphenols on obesity-induced maternal reprogramming as an offspring anti-obesity approach. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-based treatment strategies, which include immune checkpoint inhibition, have recently become a new frontier for the treatment of B-cell-derived lymphoma. Whereas checkpoint inhibition has given oncologists and patients hope in specific lymphoma subtypes like Hodgkin lymphoma, other entities do not benefit from such promising agents. Understanding the factors that determine the efficacy and safety of checkpoint inhibition in different lymphoma subtypes can lead to improved therapeutic strategies, including combinations with various chemotherapies, biologics and/or different immunologic agents with manageable safety profiles. For years, immunotherapy has been considered a viable and attractive treatment option for patients with cancer. Among the immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionised the treatment of several subtypes of tumours. These approaches, aimed at restoring an effective antitumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because, in these diseases, the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and build a projection of how the field may evolve in the near future. In particular, we will analyse the current strategies being evaluated both preclinically and clinically, with the aim of fostering the use of immune-checkpoint inhibitors in lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies. [ABSTRACT FROM AUTHOR]

Although the classification of breast carcinomas into molecular or immunohistochemical subtypes has contributed to a better categorization of women into different therapeutic regimens, breast cancer nevertheless still progresses or recurs in a remarkable number of patients. Identifying women who would benefit from chemotherapy could potentially increase treatment effectiveness, which has important implications for long-term survival. Metabolomic analyses of fluids and tissues from cancer patients improve our knowledge of the reprogramming of metabolic pathways involved in resistance to chemotherapy. This review evaluates how recent metabolomic approaches have contributed to understanding the relationship between breast cancer and the acquisition of resistance. We focus on the advantages and challenges of cancer treatment and the use of new strategies in clinical care, which helps us comprehend drug resistance and predict responses to treatment., Competing Interests: The authors declare no conflict of interest.