Search

In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies. While the mechanism of action of ICIs seems promising, the lack of a robust response limits their widespread use. Although the expression levels of programmed death ligand 1 (PD-L1) on tumor cells are used to predict ICI response, identifying new biomarkers, particularly those associated with the tumor microenvironment (TME), is crucial to address this unmet need. Recently, inflammatory cytokines such as interleukin-1 beta (IL-1β) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1β inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations. Recent advancements in our understanding of the intricate relationship between inflammation and oncogenesis, particularly involving the IL-1β/PD-1/PD-L1 pathway, have shed light on their application in lung cancer development and clinical outcomes of patients. Targeting these pathways in cancers like NSCLC holds immense potential to revolutionize cancer treatment, particularly for patients lacking targetable genetic mutations. However, despite these promising prospects, there remain certain aspects of this pathway that require further investigation, particularly regarding treatment resistance. Therefore, the objective of this review is to delve into the role of IL-1β in NSCLC, its participation in inflammatory pathways, and its intricate crosstalk with the PD-1/PD-L1 pathway. Additionally, we aim to explore the potential of IL-1β as a therapeutic target for NSCLC treatment.

Abrupt changes in gait speed can interfere with the symmetry of the overall gait apparatus and result in unstable joint movement patterns. Because unstable joint movements may cause slips, trips, and falls, it is necessary to quantitatively characterize the changes in joint movement patterns in response to sudden speed changes. The purpose of this study is to examine how abrupt changes in gait speed affect gait dynamics. Twenty-two healthy young subjects walked for four minutes, including a warm-up period, under three different speed conditions. Utilizing nonlinear dynamics tools, including the maximum Lyapunov exponent, Sample Entropy, and Detrended Fluctuation Analysis, we quantitatively assessed gait dynamics for the different speed conditions. Our findings highlight how different speed change patterns impact joint instability, notably within the knee joint during gait (p < 0.05). Furthermore, introducing a resting phase during random speed changes exhibited the potential to restore gait symmetry and control movement patterns. This research offers valuable insights into human gait stability dynamics, especially concerning sudden speed changes. Understanding how controlled speed variations affect gait and joint instability informs fall prevention and rehabilitation strategies, emphasizing speed management to improve gait symmetry and reduce joint instability. [ABSTRACT FROM AUTHOR]

The transcription factor NR4A3 (also known as NOR-1) is a member of the Nr4a family of nuclear receptors and is expressed in myeloid and lymphoid cells. Here, we have shown that Nr4a3 is essential for the migration of [CD103.sup.+] dendritic cells (DCs) to lymph nodes (LNs). Nr4a3-deficient mice had very few [CD103.sup.+] migratory DCs (mDCs) present in LNs, and mixed- chimera studies revealed that this migratory defect was cell intrinsic. We further found that [CD103.sup.+] DCs from Nr4a3- deficient mice displayed a marked loss of surface expression of the chemokine CCR7. This defect in CCR7 expression was confined to [CD103.sup.+] DCs, as CCR7 expression on T lymphocytes was unaffected. Moreover, CCR7 was not induced on [CD103.sup.+] DCs from Nr4a3-deficient mice in response to either administration of the TLR7 agonist R848 or infection with Citrobacter rodentium in vivo. The transcription factor FOXO1 has been shown to regulate CCR7 expression. We found that FOXO1 protein was reduced in Nr4a3-deficient DCs through an AKT-dependent mechanism. Further, we found a requirement for NR4A3 in the maintenance of homeostatic mitochondrial function in [CD103.sup.+] DCs, although this is likely independent of the NR4A3/FOXO1/CCR7 axis in the regulation of DC migration. Thus, NR4A3 plays an important role in the regulation of [CD103.sup.+] mDCs by regulating CCR7-dependent cell migration., Introduction The intestine has a mucosal surface that directly interacts with large quantities of food antigens and microorganisms daily. As a consequence, the gut is the accessible entry site for [...]