[Efficacy and Safety of Ixazomib Combined with Thalidomide and Dexamethasone in Treatment of Multiple Myeloma].

Objective: To investigate the efficacy and safety of ixazomib combined with thalidomide and dexamethasone in the treatment of multiple myeloma (MM).

Methods: The clinical data of 60 MM patients admitted to our center from January 2019 to June 2022 were analyzed retrospectively, including 43 newly diagnosed patients and 17 patients with recurrence and progression. All patients were treated with ixazomib combined with thalidomide and dexamethasone, and completed 2 to 7 treatment cycles.

Light-inducible T cell engagers trigger, tune, and shape the activation of primary T cells.

To mount appropriate responses, T cells integrate complex sequences of receptor stimuli perceived during transient interactions with antigen-presenting cells. Although it has been hypothesized that the dynamics of these interactions influence the outcome of T cell activation, methodological limitations have hindered its formal demonstration. Here, we have engineered the Light-inducible T cell engager (LiTE) system, a recombinant optogenetics-based molecular tool targeting the T cell receptor (TCR).

Effects of different irradiators on the establishment of osteoradionecrosis model of rat mandible.

Objectives: To compare the effects of different irradiators on the establishment of osteoradionecrosis of jaw model (ORNJ) to explore an ideal modeling method.

Methods: A total of 33 adult SD rats were included and randomly divided into three groups according to the radiation equipment, namely, the blank control (CN, 3 rats), group A (linear accelerator irradiation, 15 rats), and group B (small-animal irradiator irradiation, 15 rats). Groups A and B were irradiated with daily fractions of 7, 8, and 9 Gy for 5 days and further divided into three subgroups as follows: group A/B, 35 Gy; group A/B, 40 Gy; and group A/B, 45 Gy.

Rapid viscoelastic changes are a hallmark of early leukocyte activation.

To accomplish their critical task of removing infected cells and fighting pathogens, leukocytes activate by forming specialized interfaces with other cells. The physics of this key immunological process are poorly understood, but it is important to understand them because leukocytes have been shown to react to their mechanical environment. Using an innovative micropipette rheometer, we show in three different types of leukocytes that, when stimulated by microbeads mimicking target cells, leukocytes become up to 10 times stiffer and more viscous.

TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells.

T cell activation is initiated upon ligand engagement of the T cell receptor (TCR) and costimulatory receptors. The CD28 molecule acts as a major costimulatory receptor in promoting full activation of naive T cells. However, despite extensive studies, why naive T cell activation requires concurrent stimulation of both the TCR and costimulatory receptors remains poorly understood.

Phosphoinositides regulate the TCR/CD3 complex membrane dynamics and activation.

Phosphoinositides (PIs) play important roles in numerous membrane-based cellular activities. However, their involvement in the mechanism of T cell receptor (TCR) signal transduction across the plasma membrane (PM) is poorly defined. Here, we investigate their role, and in particular that of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in TCR PM dynamics and activity in a mouse T-cell hybridoma upon ectopic expression of a PM-localized inositol polyphosphate-5-phosphatase (Inp54p).

Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma.

Background: Accumulating evidence suggests long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of cancers. However, their functions in chromophobe renal cell carcinoma (chRCC) are not fully understood.

Methods: We analyzed the expression profiles of lncRNA, microRNA, and protein-coding RNA, along with the clinical information of 59 primary chRCC patients collected from The Cancer Genome Atlas database to identify lncRNA biomarkers for prognosis.

Glycosylation-Dependent IFN-γR Partitioning in Lipid and Actin Nanodomains Is Critical for JAK Activation.

Understanding how membrane nanoscale organization controls transmembrane receptors signaling activity remains a challenge. We studied interferon-γ receptor (IFN-γR) signaling in fibroblasts from homozygous patients with a T168N mutation in IFNGR2. By adding a neo-N-glycan on IFN-γR2 subunit, this mutation blocks IFN-γ activity by unknown mechanisms.

Imaging Spatiotemporal Activities of ZAP-70 in Live T Cells Using a FRET-Based Biosensor.

The zeta-chain-associated protein kinase 70 kDa (ZAP-70), a member of the spleen tyrosine kinase (Syk) family, plays an essential role in early T cell receptor (TCR) signaling. Defects in ZAP-70 lead to impaired thymocyte development and peripheral T cell activation. To better understand its activation dynamics and regulation, we visualized ZAP-70 activities in single live T cells with a Förster resonance energy transfer (FRET)-based biosensor, which was designed for probing kinase activities of the Syk family.

[Research Advances on Targeted Therapy for Acute Myeloid Leukemia--Review].

Although the traditional chemotherapy has achieved a certain effect for patients with acute myeloid leukemia (AML), but there are still limitations in terms of improving the rate of complete remission and overcome relapse after remission. The further study found that many cytogenetic molecular and epigenetic abnormalities occurred during the progression of AML, such as abnormal expression of cell surface molecules, mutation, gene aberrant methylation and so on. The drugs targeted at these changes can improve the prognosis for patients, and provide a new way for treating patients with AML.

Dysregulation of non-coding RNAs in gastric cancer.

Gastric cancer (GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients.

APE1 promotes antioxidant capacity by regulating Nrf-2 function through a redox-dependent mechanism.

APE1 is a multifunctional protein that has recently been implicated in protecting cells from oxidative stress. In the current study, we confirmed that APE1׳s effect on cellular antioxidant capacity is related to its redox activity through the use of an APE1 functional mutant, and we investigated the mechanism through which this multifunctional protein affects the function of the transcription factor Nrf-2 in regulating oxidative stress-induced genes. Using a pair of mutants for both the redox activity and the acetylation-regulated activity of APE1, in vitro assays showed that the redox activity of APE1 is crucial for its nuclear association with Nrf-2 and subsequent activation of Nrf-2׳s transcription of several downstream genes during oxidative challenge.

Barcoding T cell calcium response diversity with methods for automated and accurate analysis of cell signals (MAAACS).

We introduce a series of experimental procedures enabling sensitive calcium monitoring in T cell populations by confocal video-microscopy. Tracking and post-acquisition analysis was performed using Methods for Automated and Accurate Analysis of Cell Signals (MAAACS), a fully customized program that associates a high throughput tracking algorithm, an intuitive reconnection routine and a statistical platform to provide, at a glance, the calcium barcode of a population of individual T-cells. Combined with a sensitive calcium probe, this method allowed us to unravel the heterogeneity in shape and intensity of the calcium response in T cell populations and especially in naive T cells, which display intracellular calcium oscillations upon stimulation by antigen presenting cells.

Probing the plasma membrane organization in living cells by spot variation fluorescence correlation spectroscopy.

While intrinsic Brownian agitation within a lipid bilayer does homogenize the molecular distribution, the extremely diverse composition of the plasma membrane, in contrast, favors the development of inhomogeneity due to the propensity of such a system to minimize its total free energy. Precisely, deciphering such inhomogeneous organization with appropriate spatiotemporal resolution remains, however, a challenge. In accordance with its ability to accurately measure diffusion parameters, fluorescence correlation spectroscopy (FCS) has been developed in association with innovative experimental strategies to monitor modes of molecular lateral confinement within the plasma membrane of living cells.

Membrane dynamics shape TCR-generated signaling.

Despite intensive investigation, the mechanisms of T cell receptor (TCR)-mediated signal generation remain poorly understood. Here we review various dynamic processes at the cell membrane that might critically control this signaling. Firstly, we summarize recent reports providing new information on the sensitivity of TCR/ligand interaction to the membrane environment and particularly to applied forces.

A FRET-Based Biosensor for Imaging SYK Activities in Living Cells.

Spleen tyrosine kinase (SYK) is crucial to cellular functions mediated by immunoreceptors and integrins. We have developed and characterized a new genetically-encoded Förster resonance energy transfer (FRET)-based biosensor for studying the dynamics of SYK activities in living cells at a subcellular level. It contains an N-terminal ECFP, SH2 domain, a peptide derived from a SYK substrate VAV2, and a C-terminal YPet.

Heroin affects purine nucleotides metabolism in rat brain.

Objective: To explore the effects of heroin on purine nucleotides metabolism in rat brain.

Methods: Biochemical changes in association with heroin administration were compared between heroin-administered rats and non-heroin rats. HPLC method was used to detect the absolute content of purine nucleotides in brain tissues.

Probing orientational behavior of MHC class I protein and lipid probes in cell membranes by fluorescence polarization-resolved imaging.

Steady-state polarization-resolved fluorescence imaging is used to analyze the molecular orientational order behavior of rigidly labeled major histocompatibility complex class I (MHC I) proteins and lipid probes in cell membranes of living cells. These fluorescent probes report the orientational properties of proteins and their surrounding lipid environment. We present a statistical study of the molecular orientational order, modeled as the width of the angular distribution of the molecules, for the proteins in the cell endomembrane and plasma membrane, as well as for the lipid probes in the plasma membrane.

Detecting nanodomains in living cell membrane by fluorescence correlation spectroscopy.

Cell membranes actively participate in numerous cellular functions. Inasmuch as bioactivities of cell membranes are known to depend crucially on their lateral organization, much effort has been focused on deciphering this organization on different length scales. Within this context, the concept of lipid rafts has been intensively discussed over recent years.

Siah1 proteins enhance radiosensitivity of human breast cancer cells.

Background: Siah proteins play an important role in cancer progression. We evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant with the RING finger deleted (Siah1DeltaR) on radiosensitization of human breast cancer cells.

Methods: The status of Siah1 and Siah1L was analysed in five breast cancer cell lines.

Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling.

Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR)-induced immunological synapse (IS) formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of alpha beta T cells, together with defects in cell activation and cytokine production following TCR triggering.