Nano-Based Theranostics Approach in the Management of Cancer: Review.

Cancer is a prevalent and potentially fatal disease worldwide. The proliferation of abnormal cells and uncontrolled cellular growth characterizes cancer. Cancerous tumors exhibit distinct microenvironments characterized by a deficient lymphatic drainage system and aberrant blood supply. Various medications and diagnostic systems exist for cancer treatment, but they all have inherent limitations and undesirable consequences. Consequently, the achievement of effective cancer detection and treatment remains challenging. Theranostics nanoparticles are becoming increasingly popular in nano drug delivery systems. These nanoparticles can diagnose and treat tumors, making them a promising approach in the field. They are designed to be small in size, allowing them to be effective in delivering drugs to targeted areas. Furthermore, these nanoparticles can fundamentally transform the identification and management of several ailments, including cardiovascular disorders and infectious diseases. Such nanoparticles possess dual capabilities, functioning as therapeutic agents and diagnostic tools. They can transport medicinal substances, such as medications, nucleic acids, or therapeutic proteins, and include substances that can be used for imaging, such as contrast agents or fluorescent dyes, to enable non-invasive diagnostics and monitoring of the effectiveness of the treatment. These techniques can be employed for diagnostic purposes to identify, locate, and determine the extent of disorders using imaging modalities such as magnetic resonance imaging, computed tomography, positron emission tomography, and fluorescence imaging. These nanoparticles can deliver therapeutic compounds to specific locations accurately during therapy. This leads to improved effectiveness of the treatment, decreased adverse effects, and better patient outcomes. They offer a potential nanomedicine approach by providing diagnostic and therapeutic capabilities for disease diagnosis and treatment. Theranostics nanoparticles have distinct characteristics and adaptability, which can transform the healthcare sector by facilitating personalized and precise medical treatments.

B and T lymphocyte attenuator regulates B cell receptor signaling by targeting Syk and BLNK.

B and T lymphocyte attenuator (BTLA) functions as a negative regulator of T cell activation and proliferation. Although the role of BTLA in regulating T cell responses has been characterized, a thorough investigation into the precise molecular mechanisms involved in BTLA-mediated lymphocyte attenuation and, more specifically, its role in regulating B cell activation has not been presented. In this study, we have begun to elucidate the biochemical mechanisms by which BTLA functions to inhibit B cell activation. We describe the cell surface expression of BTLA on various human B cell subsets and confirm its ability to attenuate B cell proliferation upon associating with its known ligand, herpesvirus entry mediator (HVEM). BTLA associates with the BCR and, upon binding to HVEM, recruits the tyrosine phosphatase Src homology 2 domain-containing phosphatase 1 and reduces activation of signaling molecules downstream of the BCR. This is exemplified by a quantifiable decrease in tyrosine phosphorylation of the protein tyrosine kinase Syk, as measured by absolute quantification mass spectrometry. Furthermore, effector molecules downstream of BCR signaling, including the B cell linker protein, phospholipase Cgamma2, and NF-kappaB, display decreased activation and nuclear translocation, respectively, after BTLA activation by HVEM. These results begin to provide insight into the mechanism by which BTLA negatively regulates B cell activation and indicates that BTLA is an inhibitory coreceptor of the BCR signaling pathway and attenuates B cell activation by targeting the downstream signaling molecules Syk and B cell linker protein.

My Life, My Way: A Quality Improvement Program to Increase Advance Care Planning in a Racially and Ethnically Diverse Patient Population.

BACKGROUND: A multilevel quality improvement program was implemented at an urban community hospital, serving a racially and ethnically pluralistic patient population, to increase participation in advance care planning (ACP). MEASURES: Number of eligible patients who completed an ACP form. INTERVENTION: Projects were implemented over the course of two years that targeted patients, health care providers, the organization, and the community. OUTCOMES: The intervention resulted in increased completion of four unique ACP forms. Completion of the Living Will increased by 60%, Health Care Proxy increased by 9%, Medical Orders for Life-Sustaining Treatment increased by 5%, and Do-Not-Resuscitate/Do-Not-Intubate orders increased by 3%. CONCLUSION: Multilevel interventions can increase ACP participation in a racially and ethnically pluralistic patient population.

Antibodies to CD1d enhance thymic expression of invariant NKT TCR and increase the presence of NOD thymic invariant NKT cells.

Natural Killer T (NKT) cells can effect both T cell development and peripheral immune responses through T(H)1/T(H)2 cytokines. Some humans with Type 1 Diabetes Mellitus (T1DM) have numerical and functional NKT deficiencies that contribute to disease severity. Correcting these deficiencies inhibits diabetes in the non-obese diabetic (NOD) T1DM model, which shares similar deficiencies. Here we show that antibodies to CD1d, when given during early thymic development, induce specific increases in surface TCR of developing NOD and C57BL/6 CD4(+)CD8(+) (DP) invariant NKT (iNKT) cells. However, the addition of anti-CD1d causes distinct strain-specific population changes in response to treatment. These changes include: (1) a dose-dependent increase in NOD iNKT(TCR)(+) cells and, conversely, (2) an inhibition of B6 iNKT(TCR)(+) cell production. The observed NOD iNKT expansions correlated with diabetes inhibition in an in vitro T1DM system, suggesting that intrathymic anti-CD1d treatment may correct NOD numerical iNKT deficiencies through developmental TCR enhancement.

A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator.

Immune cell cosignaling receptors are important modulators of immune cell function. For T cells, cosignaling receptors supply necessary secondary signals supporting activation or attenuation after engagement of antigen-presenting cells. The primary cosignaling receptors belong to either the Ig (CD28-like) or TNF receptor (TNFR) superfamilies. The CD28 family is comprised of coinhibitory and costimulatory receptors. The three coinhibitory receptors are cytotoxic T lymphocyte antigen 4, programmed death-1, and B and T lymphocyte attenuator (BTLA). Although cytotoxic T lymphocyte antigen 4 and programmed death-1 interact with B7-Ig family counter receptors, the ligand for BTLA is less clear. From a protein-protein interaction screen, we identified the TNFR family member herpesvirus entry mediator (HVEM) as a counter receptor for BTLA. Here we show that HVEM binds BTLA with high affinity and can form a ternary complex with its known ligands homologous to lymphotoxin, showing inducible expression, and competing with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT) or lymphotoxin alpha and BTLA. In addition, binding of HVEM to BTLA attenuates T cell activation, identifying HVEM/BTLA as a coinhibitory receptor pair. This study is a demonstration of a direct interaction between the primary T cell cosignaling receptors of the CD28 and TNFR families.