Publications by authors named "Sayaka Shibata"
Background: Altered Fli1 expression is associated with various autoimmune diseases, yet its impact on B cells remains unexplored.
Objective: This study investigated the direct effects of Fli1 depletion on B cell populations, focusing on age-associated B cells (ABCs).
Methods: Splenocytes of Fli1 BcKO (Cd19-Cre; Fli1) and Cd19-Cre mice were analyzed flow cytometrically.
Structure guided modification of 2-chloro-5-(ethyl-phenyl-sulfamoyl)-N-[2-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide to afford selective inhibitors of Cryptosporidium parvum N-myristoyltransferase.
Dilep K Sigalapalli Sophia Groustra Michael K Fenwick Rachael Zigweid Matthew A Hulverson Sayaka Shibata
Bioorg Med Chem Lett
January 2025
Cryptosporidium parvum is a protozoan parasite that causes severe diarrheal illness in children and each year nearly 50,000 children under age 5 die due to the disease. Despite tremendous research efforts, there remains a lack of effective therapies and vaccines. Novel inhibitors against N-myristoyltransferase of C.
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- Biologics have improved outcomes for psoriasis patients, but some end up needing to switch therapies for various reasons.
- This study analyzed 13 years of data to identify factors that lead to patients switching biologics, focusing on clinical characteristics and lab results.
- Key findings showed that higher disease severity and the presence of arthritis increased the likelihood of switching, with systemic inflammation (measured by neutrophil to lymphocyte ratio) playing a significant role in treatment adherence.
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- Duplication of chromosome 15q11-13 is linked to autism spectrum disorder (ASD) and was studied in a mouse model known as 15q dup mice.
- The study involved behavioral tests for anxiety and social interactions, alongside MRI scans, to explore the connection between brain structure and behavior in these mice.
- Findings showed that 15q dup mice exhibited higher anxiety levels and varied social behaviors, with a correlation found between lower sociability and reduced gray matter in a specific brain region, highlighting the complexities of ASD's behavioral diversity.
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- - Psoriasis patients often need biologic treatments, particularly tumor necrosis factor (TNF) inhibitors, which can lead to the production of autoantibodies, but the link with antiphospholipid syndrome (APS) hasn't been thoroughly studied.
- - This study examined psoriasis patients on different biologics (TNF, IL-17, IL-23) to see how often they produced APS-related autoantibodies and how these correlated with their clinical condition and severity of the disease.
- - Results showed that TNF inhibitors were linked to higher rates of APS autoantibodies, especially in patients with more severe disease and arthritis, although no actual APS symptoms were reported, highlighting a complex relationship between autoimmunity
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- - Brentuximab vedotin (BV) is an effective treatment for refractory CD30+ mycosis fungoides and primary cutaneous anaplastic large-cell lymphoma, showing promising results in a study with Japanese patients.
- - The study involved two groups: one with CD30+ mycosis fungoides and pcALCL, and another with different CD30+ lymphoproliferative disorders, with treatment cycles continuing based on patient response.
- - The primary endpoint demonstrated a high objective response rate (69.2% for cohort 1 and 62.5% for cohort 2), with manageable side effects such as peripheral neuropathy and fever in some patients.
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- Atopic dermatitis (AD) is a skin condition associated with chronic changes influenced by inflammation and blood vessel formation (angiogenesis), but the role of factors that inhibit angiogenesis is not well understood.
- A study focused on vasohibin-1 (VASH1), an angiogenesis inhibitory factor, found higher levels of VASH1 in the serum and skin of AD patients compared to healthy individuals.
- The research indicated a correlation between increased serum VASH1 and the duration of the disease, as well as a relationship between VASH1 and another factor related to blood vessel growth, suggesting that these processes may contribute to the worsening inflammation seen in chronic AD.
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- * In experiments on glioblastoma mice, Q0/A significantly reduced tumor growth and improved survival rates, demonstrated by increased oxidative stress specifically in the tumor and increased blood flow to the tumor.
- * The treatment showed stronger anticancer effects compared to a previous method (menadione/ascorbate) and had no noticeable side effects, suggesting it could be a safe option for targeted glioblastoma therapy.
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- The study introduces a new approach to cancer treatment that targets cancerous mitochondria using "mitocans," specifically redox-cycling quinone/ascorbate (Q/A) pairs, which primarily harm cancer cells while sparing normal cells.
- Eleven different Q/A combinations were tested on both cultured cancer cells and mice with tumors, leading to a significant reduction in cancer cell growth and survival without major negative effects on healthy cells.
- The findings highlight that certain Q/A pairs, particularly benzoquinone/ascorbate, induce harmful oxidative stress in cancer cells while showing tolerable impacts on normal cells, attributed to changes in mitochondrial behavior and specific interactions within cancer cells.
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- Systemic inflammation is key to understanding psoriasis and was evaluated through various inflammatory markers in patients with psoriasis vulgaris and psoriatic arthritis.
- The study found that certain markers, like neutrophil and CRP levels, were linked to the severity of psoriasis and the likelihood of developing psoriatic arthritis.
- Higher levels of inflammatory markers before treatment were associated with lower rates of continuing conventional therapies but did not impact retention rates for biologic treatments.
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- A study was conducted to examine how radiation-induced hydrogen peroxide (HO) affects the biological response to X-rays and carbon-ion beams, using a selenium-deficient (SeD) mouse model that can't break down HO.
- The research found that SeD mice experienced higher lethality after exposure to radiation compared to normal mice, but there were no significant differences between the effects of X-rays and carbon-ion beams on SeD mice.
- Additionally, SeD mice did not show significant variations in brain redox status post-irradiation, indicating that while SeD affected the biological impact of radiation slightly, it did not dramatically change outcomes like leg contracture or brain oxidation levels.
Epigenetics has been well understood for its role in cell development; however, it is now known to regulate many processes involved in immune cell activation in a variety of cells. The skin maintains homeostasis crosstalk between immune and non-immune cells. Disruption of normal epigenetic regulation in these cells may alter the transcription of immune-regulatory factors and affect the immunological balance in the skin.
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- The study explores the role of Aquaporin-4 (AQP4), a protein in brain astrocytes, in the movement of water and its implications for brain function and diseases.
- Researchers administered deuterium-labeled water to both wild-type and AQP4 knockout mice, using advanced MRI techniques to monitor water dynamics in the brain after a surgical procedure.
- Findings indicate that the absence of AQP4 delays water movement in various brain regions, suggesting that AQP4 is crucial for maintaining normal water dynamics during brain activity and potentially during infarct conditions.
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- Bullous pemphigoid (BP) is an autoimmune disease that causes blister formation due to immune cell activation and autoantibodies, with a notable increase in extracellular DNA levels.
- The study identifies interleukin (IL)-26 as a key factor that binds to extracellular DNA from immune cells, which leads to the formation of IL-26DNA complexes in patients with BP.
- These complexes not only boost inflammatory cytokine production but also enhance protease activity, contributing to the damage of the dermal-epidermal junction, thus promoting blister formation in BP.
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- Recent studies highlight circulating cell-free DNA (cfDNA) as a promising biomarker for various cancers, showing elevated levels in patients that correlate with prognosis and disease activity.
- This research specifically focused on patients with cutaneous T-cell lymphoma (CTCL), finding significantly higher serum cfDNA levels compared to healthy individuals, which increased with the progression of the disease.
- The study suggests that cfDNA levels correlate with several clinical markers and indicate a worse prognosis, proposing it as a useful indicator for treatment decisions in CTCL.
The purpose of this study was to compare parameter estimates for the 2-compartment and diffusion kurtosis imaging models obtained from diffusion-weighted imaging (DWI) of aquaporin-4 (AQP4) expression-controlled cells, and to look for biomarkers that indicate differences in the cell membrane water permeability. DWI was performed on AQP4-expressing and non-expressing cells and the signal was analyzed with the 2-compartment and diffusion kurtosis imaging models. For the 2-compartment model, the diffusion coefficients (Df, Ds) and volume fractions (Ff, Fs, Ff = 1-Fs) of the fast and slow compartments were estimated.
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- Glioblastoma is a highly aggressive brain tumor with an imbalance in redox states, making its treatment challenging due to its unique oxidative nature.
- The study investigates a new treatment approach using a redox-active drug combination (menadione/ascorbate) to specifically target glioblastoma in both animal models and cell cultures, leading to reduced tumor growth and improved survival without harmful side effects.
- Results showed that the treatment increased oxidative stress and disrupted the cancer cells' functionality while selectively harming glioblastoma cells, as opposed to normal cells, highlighting the potential for targeted therapies in cancer treatment.
Article Synopsis
- - The study introduces a new drug combo, menadione/ascorbate (M/A), aimed at selectively targeting glioblastoma, comparing its effectiveness to the standard chemotherapy, temozolomide (TMZ).
- - Experiments on glioblastoma mice showed that M/A treatment slowed tumor growth and improved survival rates without the side effects common with TMZ, though M/A's tumor shrinkage was not as significant.
- - M/A was found to selectively harm glioblastoma cells by increasing mitochondrial superoxide production while leaving normal cells unharmed, suggesting a potential use alongside surgery and traditional treatments for better patient outcomes.
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- Drug delivery systems (DDS) aim to improve cancer treatment by targeting drugs to cancer cells while minimizing side effects, but current methods struggle with low transport efficiency due to stromal barriers.
- A novel approach using molecular blocks (MBs) is introduced, which enhances blood circulation and can penetrate stromal tissues, leading to self-assembly on cancer cell surfaces and subsequent cell death through membrane disruption.
- The study highlights deoxycholic acid (DCA) combined with a poly(ethylene glycol) structure (4-MB) as effective in targeting cancer cells while significantly suppressing tumor growth in in vivo models, suggesting a promising alternative to traditional DDS.
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- - Aquaporin-4 is a protein in brain cells that helps transport water, and reducing its function could help treat swelling in the brain after a stroke.
- - Researchers used mouse models to study the effects of aquaporin-4 suppression on water movement in the brain after a stroke, employing advanced imaging techniques for data analysis.
- - Results showed that knockout mice (without aquaporin-4) had higher water diffusion in normal areas but lower diffusion in injured brain regions compared to normal mice, indicating potential differences in how water is managed in brain injuries.
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- The study aimed to determine if MRS-measured levels of glutamate (Glu) and GABA effectively represent excitatory and inhibitory neural activities in living mice.
- Using a combination of MRS and calcium signaling imaging, researchers observed that during sensory stimulation, excitatory neuron activity increased while inhibitory activity remained stable initially, then significantly enhanced in the second session.
- In a mouse model of Dravet syndrome, findings revealed diminished inhibitory neuron activity and reduced GABA levels compared to normal mice, suggesting that MRS can accurately reflect the dynamic changes in neuronal activity and neurotransmitter levels in awake conditions.
The skin, which is constantly exposed to a wide variety of environmental insults, maintains its integrity by rapidly responding to external signals. In the epidermis, most genes are set in transcriptionally poised conditions to prepare for the prompt induction of stress responding genes. Local chromatin dynamics, supported by an interplay between epigenetic regulators and transcription factors, underlies transcriptional responses upon stress exposure.
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- Researchers developed two groups of new inhibitors for the enzyme methionyl-tRNA synthetase (MetRS) found in parasites, utilizing different chemical linkers in their design.
- Both groups of inhibitors were effective at low concentrations (EC < 10 nM) in stopping parasite growth, while showing minimal toxicity to human cells (CCs > 20,000 nM).
- Despite their effectiveness, the inhibitors had limited ability to cross the blood-brain barrier, indicating that further modifications are needed for treatment in advanced cases of human African trypanosomiasis.
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- - M/A (menadione/ascorbate) shows a unique capability to kill cancer cells while sparing normal cells, with its anticancer effects linked to mitochondrial dysfunction specifically in cancer cells.
- - The study revealed that M/A treatment in cancer cells led to significant mitochondrial superoxide production, reduced mitochondrial membrane potential, and lowered levels of ATP and other essential metabolites, showcasing a dose-dependent relationship.
- - Normal cells displayed only mild oxidative stress from M/A, indicating that this treatment is selectively harmful to cancer cells, suggesting a targeted therapeutic potential for anticancer strategies.