In this review, the author highlights the role of IL4 in mitigating all the \"hallmarks\" of cancer growth and resistance to current immunotherapy, providing a framework for its role in GBM as well as guideline for future treatment regimens. This review is organized around six strategies by which IL4 contributes to the immune resistance seen in GBM: (i) apoptosis evasion, (ii) self-sufficiency in growth signals, (iii) insensitivity to anti-growth signals, (iv) invasion and metastasis, (v) limitless replicative potential, (vi) sustained angiogenesis.

Aging is currently viewed as a result of multiple biological processes that manifest themselves independently, reinforce each other and in their totality lead to the aged phenotype. Genetic and pharmaceutical approaches targeting specific underlying causes of aging have been used to extend the lifespan and healthspan of model organisms ranging from yeast to mammals. However, most interventions display only a modest benefit. This outcome is to be expected if we consider that even if one aging process is successfully treated, other aging pathways may remain intact. Hence solving the problem of aging may require targeting not one but many of its underlying causes at once. Here we review the challenges and successes of combination therapies aimed at increasing the lifespan of mammals and propose novel directions for their development. We conclude that both additive and synergistic effects on mammalian lifespan can be achieved by combining interventions that target the same or different hallmarks of aging. However, the number of studies in which multiple hallmarks were targeted simultaneously is surprisingly limited. We argue that this approach is as promising as it is understudied.

Oral squamous cell carcinoma (OSCC) is considered the most common type of head and neck squamous cell carcinoma (HNSCC) as it holds 90 % of HNSCC cases that arise from multiple locations in the oral cavity. The last three decades witnessed little progress in the diagnosis and treatment of OSCC the aggressive tumor. However, in-depth knowledge about OSCC\'s pathogenesis, staging & grading, hallmarks, and causative factors is a prime requirement in advanced diagnosis and treatment for OSCC patients. Therefore present review was intended to comprehend the OSCCs\' prevalence, staging & grading, molecular pathogenesis including premalignant stages, various hallmarks, etiology, diagnostic methods, treatment (including FDA-approved drugs with the mechanism of action and side effects), and theranostic agents. The current review updates that for a better understanding of OSCC progress tumor-promoting inflammation, sustained proliferative signaling, and growth-suppressive signals/apoptosis capacity evasion are the three most important hallmarks to be considered. This review suggests that among all the etiology factors the consumption of tobacco is the major contributor to the high incidence rate of OSCC. In OSCC diagnosis biopsy is considered the gold standard, however, toluidine blue staining is the easiest and non-invasive method with high accuracy. Although there are various therapeutic agents available for cancer treatment, however, a few only are approved by the FDA specifically for OSCC treatment. The present review recommends that among all available OSCC treatments, the antibody-based CAR-NK is a promising therapeutic approach for future cancer treatment. Presently review also suggests that theranostics have boosted the advancement of cancer diagnosis and treatment, however, additional work is required to refine the role of theranostics in combination with different modalities in cancer treatment.

The advent of novel 2D and 3D models for human development, including trophoblast stem cells and blastoids, has expanded opportunities for investigating early developmental events, gradually illuminating the enigmatic realm of human development. While these innovations have ushered in new prospects, it has become essential to establish well-defined benchmarks for the cell sources of these models. We aimed to propose a comprehensive characterization of pluripotent and trophoblastic stem cell models by employing a combination of transcriptomic, proteomic, epigenetic, and metabolic approaches. Our findings reveal that extended pluripotent stem cells share many characteristics with primed pluripotent stem cells, with the exception of metabolic activity. Furthermore, our research demonstrates that DNA hypomethylation and high metabolic activity define trophoblast stem cells. These results underscore the necessity of considering multiple hallmarks of pluripotency rather than relying on a single criterion. Multiplying hallmarks alleviate stage-matching bias.

Ageism is a type of discrimination characterized by negative social representations of old age and aging, with prejudices and stereotypes that cause rejection and marginalization of older adults, generally considering them as fragile and unproductive. For this reason, it is recognized as one of the main enemies of healthy aging, especially when it arises from the scientific and professional fields. In this sense, the proposals promoted by some researchers regarding the World Health Organization (WHO) classifying aging as a disease goes against the healthy aging approach. In this sense, we consider that there is no theoretical or scientific support to classify aging as a disease, so we must advocate before the WHO so that aging is eliminated within its disease classification codes. In this framework, this review proposes the concept of \"hallmarks of ageism\" defined as the characteristics, representations and attitudes of rejection and discrimination towards aging, old age and older people, at the political and institutional, scientific or professional, technological and digital, social, family and personal levels, which are presented in an articulated and structured manner. For this reason, it is essential to comprehensively identify and analyze the \"hallmarks of ageism\", in order to propose programs that include strategies and public policies that promote \"anti-ageism\" as a counterproposal to the \"hallmarks of aging\", whose biological changes related to aging are intended to be comparable to chronic non-communicable diseases.

The rapidly increasing aging prevalence, complexity, and heterogeneity pose the scientific and medical communities in front of challenges. These are delivered by gaps between basic and translational research, as well as between clinical practice guidelines to improve survival and absence of evidence on personalized strategies to improve functions, wellbeing and quality of life. The triumphs of aging science sheding more and more light on mechanisms of aging as well as those of medical and technological progress to prolong life expectancy are clear. Currently, and in the next two to three decades, all efforts must be put in a closer interdisciplinary dialogue between biogerontologists and geriatricians to enable real-life measures of aging phenotypes to be used to uncover the physiological - and therefore translational - relevance of newly discovered aging clocks, biomarkers, and hallmarks.

In this narrative review, we sought to provide a comprehensive overview of the mechanisms underlying cutaneous senescence, framed by the twelve traditional hallmarks of aging. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, impaired macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. We also examined how topical interventions targeting these hallmarks can be integrated with conventional aesthetic medicine techniques to enhance skin rejuvenation. The potential of combining targeted topical therapies against the aging hallmarks with minimally invasive procedures represents a significant advancement in aesthetic medicine, offering personalized and effective strategies to combat skin aging. The reviewed evidence paves the way for future advancements and underscores the transformative potential of integrating scientifically validated interventions targeted against aging hallmarks into traditional aesthetic practices.

Ras homolog enriched in brain (Rheb1 and Rheb2), small GTPases, play a crucial role in regulating neuronal activity and have gained attention for their implications in cancer development, particularly in breast cancer. This study delves into the intricate connection between the multifaceted functions of Rheb1 in neurons and cancer, with a specific focus on the mTOR pathway. It aims to elucidate Rheb1\'s involvement in pivotal cellular processes such as proliferation, apoptosis resistance, migration, invasion, metastasis, and inflammatory responses while acknowledging that Rheb2 has not been extensively studied. Despite the recognized associations, a comprehensive understanding of the intricate interplay between Rheb1 and Rheb2 and their roles in both nerve and cancer remains elusive. This review consolidates current knowledge regarding the impact of Rheb1 on cancer hallmarks and explores the potential of Rheb1 as a therapeutic target in cancer treatment. It emphasizes the necessity for a deeper comprehension of the molecular mechanisms underlying Rheb1-mediated oncogenic processes, underscoring the existing gaps in our understanding. Additionally, the review highlights the exploration of Rheb1 inhibitors as a promising avenue for cancer therapy. By shedding light on the complicated roles between Rheb1/Rheb2 and cancer, this study provides valuable insights to the scientific community. These insights are instrumental in guiding the identification of novel targets and advancing the development of effective therapeutic strategies for treating cancer.

Pericytes (PCs) are located surrounding the walls of small blood vessels, particularly capillaries and microvessels. In addition to their functions in maintaining vascular integrity, participating in angiogenesis, and regulating blood flow, PCs also serve as a reservoir for multi-potent stem/progenitor cells in white, brown, beige, and bone marrow adipose tissues. Due to the complex nature of this cell population, the identification and characterization of PCs has been challenging. A comprehensive understanding of the heterogeneity of PCs may enhance their potential as therapeutic targets for metabolic syndromes or bone-related diseases. This mini-review summarizes multiple PC markers commonly employed in lineage-tracing studies, with an emphasis on their contribution to adipogenesis and functions in different adipose depots under diverse metabolic conditions.

In the early 1990\'s a group of unrelated genes were identified from the sites of recurring translocations in B-cell lymphomas. Despite sharing the nomenclature \'Bcl\', and an association with blood-borne cancer, these genes have unrelated functions. Of these genes, BCL2 is best known as a key cancer target involved in the regulation of caspases and other cell viability mechanisms. BCL3 on the other hand was originally identified as a non-canonical regulator of NF-kB transcription factor pathways - a signaling mechanism associated with important cell outcomes including many of the hallmarks of cancer. Most of the early investigations into BCL3 function have since focused on its role in NF-kB mediated cell proliferation, inflammation/immunity and cancer. However, recent evidence is coming to light that this protein directly interacts with and modulates a number of other signaling pathways including DNA damage repair, WNT/β-catenin, AKT, TGFβ/SMAD3 and STAT3 - all of which have key roles in cancer development, metastatic progression and treatment of solid tumours. Here we review the direct evidence demonstrating BCL3\'s central role in a transcriptional network of signaling pathways that modulate cancer biology and treatment response in a range of solid tumour types and propose common mechanisms of action of BCL3 which may be exploited in the future to target its oncogenic effects for patient benefit.