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Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer.

CX3CL1 and its unique receptor, CX3CR1, are leukocyte migration factors and are involved in the pathogenesis and progression of many inflammatory diseases and malignancies. The CX3CL1-CX3CR1 axis induces a variety of responses, including cell proliferation, migration, invasion, and apoptosis resistance. CX3CL1 is a transmembrane protein, and proteolysis generates a soluble form. The membrane and soluble forms of CX3CL1 exhibit different functions, but both bind to the chemokine receptor CX3CR1. The CX3CL1-CX3CR1 axis is a chemokine system that has attracted attention not only as a therapeutic

Skin Telocytes Could Fundament the Cellular Mechanisms of Wound Healing in Platelet-Rich Plasma Administration.

For more than 40 years, autologous platelet concentrates have been used in clinical medicine. Since the first formula used, namely platelet-rich plasma (PRP), other platelet concentrates have been experimented with, including platelet-rich fibrin and concentrated growth factor. Platelet concentrates have three standard characteristics: they act as scaffolds, they serve as a source of growth factors and cytokines, and they contain live cells. PRP has become extensively used in regenerative medicine for the successful treatment of a variety of clinical (non-)dermatological conditions like alopec

VEXAS Syndrome in a Patient with Myeloproliferative Neoplasia.

VEXAS syndrome stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The syndrome is a combined hematological and rheumatological condition caused by a somatic mutation in the UBA1. There is an association between VEXAS and hematological conditions such as myelodysplastic syndrome (MDS), monoclonal gammopathies of uncertain conditions (MGUS), multiple myeloma (MM), and monoclonal B-cell lymphoproliferative conditions. There are not many descriptions of patients having VEXAS in combination with myeloproliferative neoplasm (MPN). With this article, we want to present a ca

Effects of Obesity and Calorie Restriction on Cancer Development.

The risk of malignant tumor development is increasing in the world. Obesity is an established risk factor for various malignancies. There are many metabolic alterations associated with obesity which promote cancerogenesis. Excessive body weight leads to increased levels of estrogens, chronic inflammation and hypoxia, which can play an important role in the development of malignancies. It is proved that calorie restriction can improve the state of patients with various diseases. Decreased calorie uptake influences lipid, carbohydrate and protein metabolism, hormone levels and cell processes. Ma

DLBCL 1L-What to Expect beyond R-CHOP?

The R-CHOP immunochemotherapy protocol has been the first-line (1L) standard of care (SOC) for diffuse large B-cell lymphoma (DLBCL) patients for decades and is curative in approximately two-thirds of patients. Numerous randomized phase III trials, most of them in an "R-CHOP ± X" design, failed to further improve outcomes. This was mainly due to increased toxicity, the large proportion of patients not in need of more than R-CHOP, and the extensive molecular heterogeneity of the disease, raising the bar for "one-size-fits-all" concepts. Recently, an R-CHP regimen extended by the anti-CD79b anti

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… Likewise, an insufficient decline in circulating tumor DNA at an interim time point is indicative of poor long-term outcome [ 165 , 166 , 167 ]. …

Application of NMR-based metabolomics and machine learning for non-invasive disease screening in dogs.

BackgroundBlood-based metabolomics is increasingly recognised as a powerful tool for disease detection in human medicine. However, its application in veterinary science remains limited.ObjectiveTo evaluate the ability of an NMR-based metabolomics platform combined with machine learning to screen dogs for cancer, cardiovascular disease (CVD), and overall health status.AnimalsClient-owned dogs were recruited from two sites. Of 156 animals enrolled, 139 remained after exclusions and were used for training and cross-validation of classification models.MethodsBlood samples were obtained from clinic

Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.

Therapeutic resistance remains a major obstacle to durable cancer control, with functional reprogramming of the DNA damage response (DDR) network playing a central role. The poly(ADP-ribose) polymerase (PARP) family, particularly PARP1 and PARP2, is crucial for maintaining genomic integrity. By exploiting synthetic lethality, PARP inhibitors (PARPi) selectively target tumors with homologous recombination deficiency (HRD) and are integral to precision therapy in ovarian, breast, and prostate cancers. However, over 40% of patients with BRCA1/2 alterations develop resistance, and patient eligibil

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op

Challenges and breakthroughs: current landscape and future prospects of CAR-T cell therapy clinical trials for solid tumors.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated significant efficacy in the treatment of hematological malignancies; however, its application in the solid tumor setting remains challenging. Given that solid tumors account for the vast majority of clinically diagnosed cancers, there is an urgent and significant clinical need to develop effective CAR-T therapy. This review focuses on the latest clinical trials of CAR-T therapy in major solid tumors, including glioma, colorectal, pancreatic, prostate, and lung cancers. It systematically evaluates the results of studies targeting

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… A key limitation was the omission of planned correlative analyses, including circulating tumor DNA sequencing, circulating tumor cell gene expression profiling, and CAR immunogenicity assessment, which compromised the study’s translational value. … Use circulating tumor DNA to monitor tumor burden and clonal evolution, combine multiparametric imaging to assess tumor metabolism and immune infiltration, and apply artificial intelligence to integrate multi-omics data to perform dynamic assessment and prediction, and to guide individualized treatment …

BCMA/CD19 CAR T cell therapy for refractory myasthenia gravis: Proteomic signatures and single-cell transcriptomics of disease flares.

Myasthenia gravis (MG) is an autoimmune disorder characterized by B cell dysfunction. Here, we designed B cell maturation antigen (BCMA)/CD19 chimeric antigen receptor T cell (CAR T cell) therapy for six refractory MGs, demonstrating favorable safety with grade 1 cytokine release syndrome observed. CAR T cell expansion induced profound B cell depletion, a sustained reduction in acetylcholine receptor (AChR) antibody titers, and symptom improvement. Five patients achieved drug-free remission with minimal manifestations by month 6, persisting through the 12-month follow-up despite B cell reconst

Cardiac Monitoring for Patients Undergoing Treatment With MEK Inhibitor Monotherapy.

PURPOSE OF REVIEW: Aberrant activation of the RAS-RAF-MEK-ERK signaling pathway contributes to numerous malignancies, congenital syndromes, and cardiovascular disorders, establishing MEK inhibitors (MEKi) as crucial therapeutic agents. MEKi demonstrate substantial clinical benefit as monotherapy (e.g., NF1-associated tumors) or combination therapy (e.g., melanoma, glioma, congenital RASopathies). Cardiovascular adverse events, primarily asymptomatic reductions in left ventricular ejection fraction (LVEF), have prompted intensive echocardiographic monitoring. RECENT FINDINGS: Emerging evidence

Диабет мелитус в множестве миэломы и связанных с ним расстройства плазменных клеток: обзор риска, прогноза и результатов.

Существует четкая связь между типом 2 сахарный диабет и общий риск заболевания раком. Однако исследования, посвященные оценке типа 2 Риск ДМ и множественной миэломы (ММ) ограничен, и связь менее ясна. Понимание воздействия давнишнего типа 2 Важнейшее значение имеет DM о системах органов и симптоматологии у пациентов с последующим диагнозом MM, а также потенциальные перекликающиеся токсичные вещества, связанные с лечением MM. В настоящем обзоре резюмируется роль вида 2 ДМ о рисках и результатах ММ и изучает различные механизмы, лежащие в основе этих ассоциаций. Более глубокое понимание этой асс

Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.

The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this rev

Targeting the RANKL/RANK/OPG Axis for Cancer Therapy.

RANKL and RANK are expressed in different cell types and tissues throughout the body. They were originally described for their essential roles in bone remodeling and the immune system but have subsequently been shown to provide essential signals from regulating mammary gland homeostasis during pregnancy to modulating tumorigenesis. The success of RANKL/RANK research serves as a paragon for translational research from the laboratory to the bedside. The case in point has been the development of Denosumab, a RANKL-blocking monoclonal antibody which has already helped millions of patients sufferin

NK cell based immunotherapy against oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck cancers, presents significant challenges due to its aggressive feature and limited therapeutic efficacy of conventional treatments. In response to these challenges, Natural Killer (NK) cells, a vital component of the innate immune system, are being explored for their therapeutic potential in OSCC due to their inherent ability to target and eliminate cancer cells without prior sensitization. This review uniquely focuses on the evolving role of NK cells specifically in OSCC, incorporating recent advancements in CAR-NK cell eng

The Battlefield of Chemotherapy in Pediatric Cancers.

The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses

A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.

Molecular glue degraders (MGDs) constitute a class of innovative therapeutic agents within the field of targeted protein degradation (TPD). In contrast to proteolysis-targeting chimeras (PROTACs), MGDs induce protein degradation by stabilizing the interaction between an E3 ubiquitin ligase and a target protein. They typically exhibit favorable drug-like characteristics, including lower molecular weight and enhanced bioavailability. Although their discovery was historically serendipitous, recent advances in high-throughput screening, bioinformatics, and artificial intelligence are enabling more

The versatile emodin: A natural easily acquired anthraquinone possesses promising anticancer properties against a variety of cancers.

Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

Targeting tumor immunosuppressive microenvironment for pancreatic cancer immunotherapy: Current research and future perspective.

Pancreatic cancer is one of the most malignant tumors with increased incidence rate. The effect of surgery combined with chemoradiotherapy on survival of patients is unsatisfactory. New treatment strategy such as immunotherapy need to be investigated. The accumulation of desmoplastic stroma, infiltration of immunosuppressive cells including myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs), as well as tumor associated cytokine such as TGF-β, IL-10, IL-35, CCL5 and CXCL12 construct an immunosuppres