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Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities.

Discovered as inflammatory cytokines, MIF and DDT exhibit widespread expression and have emerged as critical mediators in the response to infection, inflammation, and more recently, in cancer. In this comprehensive review, we provide details on their structures, binding partners, regulatory mechanisms, and roles in cancer. We also elaborate on their significant impact in driving tumorigenesis across various cancer types, supported by extensive in vitro, in vivo, bioinformatic, and clinical studies. To date, only a limited number of clinical trials have explored MIF as a therapeutic target in c

Stepping forward: T-cell redirecting bispecific antibodies in cancer therapy.

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens, thereby engaging with CD3 on the T cell receptor. This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells. These antibodies have emerged as one of the most promising avenues within tumor immunotherapy. However, despite success in treating hematological malignancies, significant advancements in solid tumors have yet to be explored. In this review, we aim to address the critical challenges associated with T

Tumour Immunotherapy and Applications of Immunological Products: A Review of Literature.

Malignant tumors, characterized by uncontrolled cell proliferation, are a leading global health challenge, responsible for over 9.7 million deaths in 2022, with new cases expected to rise to 35 million annually by 2050. Immunotherapy is preferred to other cancer therapies, offering precise targeting of malignant cells while simultaneously strengthening the immune system's complex responses. Advances in this novel field of science have been closely linked to a deeper knowledge of tumor biology, particularly the intricate interplay between tumor cells, the immune system, and the tumor microenvir

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy.

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening co

Epigenetic Therapies for Acute Myeloid Leukemia and Their Immune-Related Effects.

Over the past decades, our molecular understanding of acute myeloid leukemia (AML) pathogenesis dramatically increased, thanks also to the advent of next-generation sequencing (NGS) technologies. Many of these findings, however, have not yet translated into new prognostic markers or rationales for treatments. We now know that AML is a highly heterogeneous disease characterized by a very low mutational burden. Interestingly, the few mutations identified mainly reside in epigenetic regulators, which shape and define leukemic cell identity. In the light of these discoveries and given the increasi

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… De novo epigenetic programs inhibit PD-1 blockade-mediated T cell rejuvenation. Cell 170:142-157.e19. 10.1016/j.cell.2017.06.007 Gibaja V., Shen F., Harari J., Korn J., Ruddy D., Saenz-Vash V., et al. (2016). …

Does Regular Exercise Counter T Cell Immunosenescence Reducing the Risk of Developing Cancer and Promoting Successful Treatment of Malignancies?

Moderate intensity aerobic exercise training or regular physical activity is beneficial for immune function. For example, some evidence shows that individuals with an active lifestyle exhibit stronger immune responses to vaccination compared to those who are inactive. Encouragingly, poor vaccine responses, which are characteristic of an ageing immune system, can be improved by single or repeated bouts of exercise. In addition, exercise-induced lymphocytosis, and the subsequent lymphocytopenia, is thought to facilitate immune surveillance, whereby lymphocytes search tissues for antigens derived

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, a

Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma-A Review.

Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The c

Tumor Vaccines: Unleashing the Power of the Immune System to Fight Cancer.

This comprehensive review delves into the rapidly evolving arena of cancer vaccines. Initially, we examine the intricate constitution of the tumor microenvironment (TME), a dynamic factor that significantly influences tumor heterogeneity. Current research trends focusing on harnessing the TME for effective tumor vaccine treatments are also discussed. We then provide a detailed overview of the current state of research concerning tumor immunity and the mechanisms of tumor vaccines, describing the complex immunological processes involved. Furthermore, we conduct an exhaustive analysis of the con

Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies.

The increasing cancer incidence has certified oncological management as one of the most critical challenges for the coming decades. New anticancer strategies are still needed, despite the significant advances brought to the forefront in the last decades. The most recent, promising therapeutic approaches have benefitted from the application of human perinatal derivatives (PnD), biological mediators with proven benefits in several fields beyond oncology. To elucidate preclinical results and clinic outcomes achieved in the oncological field, we present a narrative review of the studies resorting

Epigenetic Regulation of Autophagy in Bone Metabolism.

The skeletal system is crucial for supporting bodily functions, protecting vital organs, facilitating hematopoiesis, and storing essential minerals. Skeletal homeostasis, which includes aspects such as bone density, structural integrity, and regenerative processes, is essential for normal skeletal function. Autophagy, an intricate intracellular mechanism for degrading and recycling cellular components, plays a multifaceted role in bone metabolism. It involves sequestering cellular waste, damaged proteins, and organelles within autophagosomes, which are then degraded and recycled. Autophagy's i

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… During the degradation phase, sizable cellular molecules are disintegrated into amino acids, lipids, nucleotides, and energy, facilitating both the cell's metabolic necessities and the rejuvenation of specific organelles. 135 Currently, there are more than 40 ATG genes known to regulate autophagy. 136 …

Delayed gastric emptying in critical illness: is enhanced enterogastric inhibition with cholecystokinin and peptide YY involved?

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… There is no currently available storage or rejuvenation solution that optimizes these cellular constituents. The majority of blood transfusions are in the form of PRBCs, the component indicated for normovolemic patients or those for whom intravascular volume constraints are necessary. …

Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.

Adoptive T-cell transfer therapy (ACT) has significantly propelled the advancement of tumor immunotherapy. Among various strategies targeting solid tumors, the T-cell receptor (TCR)-engineered T-cell (TCR-T cell) therapy has emerged as a highly promising approach, exhibiting an expanded therapeutic window across diverse patient populations and superior tumoricidal activity in certain solid malignancies compared with chimeric antigen receptor T cell (CAR-T) and tumor-infiltrating T cells/lymphocyte (TIL) therapies. However, its clinical efficacy remains constrained. In this paper, we introduce

Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.

ABSTRACT: Oncofertility has emerged as a critical interdisciplinary field addressing the reproductive challenges faced by cancer patients, particularly those undergoing chemotherapy. While chemotherapeutic agents remain indispensable in cancer therapy, their gonadotoxic effects frequently result in diminished ovarian reserve, impaired spermatogenesis, and long-term infertility. Exosomes - small extracellular vesicles enriched with nucleic acids, proteins, and lipids - are increasingly recognized as key mediators of intercellular communication in both pathological and regenerative contexts. Rec

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… Investigation has explored the regenerative potential of autologous platelet-derived exosomes for ovarian rejuvenation in women with diminished ovarian reserve. …

Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.

Osteocytes, once viewed mainly as passive bone-embedded cells, are now recognized as active regulators of the metastatic bone niche. Emerging evidence indicates that these cells integrate mechanical, inflammatory, and tumor-derived cues to influence metastatic seeding, dormancy, reactivation, and lesion progression in bone. This review synthesizes current understanding of osteocyte contributions to skeletal metastasis. We discuss core signaling axes, including osteocyte-derived RANKL/OPG balance, Wnt antagonists (sclerostin/DKK1), mechanotransduction pathways (Piezo1 signaling and connexin-43

Advanced biomaterial-based approaches for medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect linked to anti-resorptive and anti-angiogenic therapies, with an incidence of 4.34 % (6.22 % in oncology patients and 0.59 % in osteoporosis patients) based on a pooled analysis of 92 observational studies (2015-2020), characterized by persistent bone exposure and poor healing. Conventional treatment modalities often yield suboptimal outcomes, with recurrence and procedural morbidity. In recent years, biomaterial-based strategies have emerged as promising alternatives by targeting MRONJ's complex pathophysiolo

Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

PurposeThe International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis.MethodsEvidence for the re

An overview of multiple myeloma: A monoclonal plasma cell malignancy's diagnosis, management, and treatment modalities.

Multiple Myeloma (MM) is a plasma cell cancer with high mortality and morbidity rates. Its incidence rate has increased by 143% since 1975. Adipokines, cytokines, chemokines, and genetic variations influence the development and progression of MM. Chromosomal translocations cause mutations associated with MM. The pathogenesis of MM is complicated by novel issues like miRNAs, RANKL, Wnt/DKK1, Wnt, and OPG. Conventional diagnosis methods include bone marrow biopsy, sPEP or uPEP, sIFE and uIFE, and sFLC assay, along with advanced techniques such as FISH, SNPA, and gene expression technologies. A n

Polyphenols as Antitumor Agents Targeting Key Players in Cancer-Driving Signaling Pathways.

Polyphenols constitute an important group of natural products that are traditionally associated with a wide range of bioactivities. These are usually found in low concentrations in natural products and are now available in nutraceuticals or dietary supplements. A group of polyphenols that include apigenin, quercetin, curcumin, resveratrol, EGCG, and kaempferol have been shown to regulate signaling pathways that are central for cancer development, progression, and metastasis. Here, we describe novel mechanistic insights on the effect of this group of polyphenols on key elements of the signaling

Терапевтические и диагностические проблемы передневременного слабоумия.

В поисках терапевтических модификаторов фронтовременное слабоумие (ФТР) традиционно омрачалось другими заболеваниями, такими, как болезнь Альцгеймера (AD). Будучи клиническим и патологическим по своему характеру заболеванием, ПТО было вызвано рядом недавних открытий, таких, как новые генетические варианты семейных и спорадических форм заболеваний и выявление белка, связывающего ДНК с ДНК. 43 kDa (kDa)TDP-43) в качестве определяющего компонента включения более чем в половине случаев. В сочетании с постоянно расширяющимися знаниями о функции и дисфункции белка тау-а, который патологически агреги

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… Rejuvenation Res. 13 , 509 – 517 10.1089/rej.2010.1017 20645878 Borroni B. Bonvicini C. Alberici A. Buratti E. Agosti C. Archetti S. ( 2009a ). Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease . Hum. …