Novel lithocholic acid-diindolylmethane hybrids as potent sialyltransferase inhibitors targeting triple-negative breast cancer: a molecular hybridization approach.

Molecular hybridization, an emerging strategy for the discovery of new anticancer therapeutics, shows promise as a powerful tool for the development of new sialyltransferase (ST) inhibitors for cancer treatment. This concept inspired the design of novel ST inhibitors through the hybridization of lithocholic acid and diindolylmethane, leading to the discovery of LCA-DIM hybrids as potential chemical entities targeting STs. Preliminary screening revealed the significance of the DIM moiety and incorporation of Asp linker on enhancing the inhibitory activity and selectivity of the hybrids towards ST6GAL1, inhibiting up to 100% of ST6GAL1 activity at 25 μM with no ST3GAL1 inhibition even at 500 μM.

Scalable Biofabrication of Functional 3D Scaffolds via Synergy of Autopilot Single-Jet Electrospun 3D PCL Fiber Scaffolds and Cell-Laden Hydrogels.

3D bioprinting enables cell-laden hydrogel construct fabrication in a layer-by-layer fashion but faces scalability challenges due to the mechanical weakness of hydrogels. Matrix reinforcement compromises cellular activity, creating a scalability-functionality trade-off that remains unresolved as sophisticated strategies including sequential and embedded printing fail to effectively overcome these limitations. This study presents an alternative approach by integrating autopilot single-jet electrospun (AJ-3D ES) 3D PCL fiber scaffolds with hydrogels, achieving anatomical precision, mechanical robustness, and enhanced cell function.

Polystyrene Nanoplastics Exacerbate HFD-induced MASLD by Reducing Cathepsin Activity and Triggering Large Vacuole Formation via Impaired Lysosomal Acidification.

Environmental nanoplastics (NPs) have harmful effects on health. This study investigated the effects of polystyrene (PS) NPs on steatosis and fatty liver disease. PS-NP oral administration, in conjunction with a high-fat diet (HFD), synergistically exacerbated the symptoms of steatosis in mice, leading to increased alanine transaminase, aspartate aminotransferase, and cholesterol levels; no effects were observed with PS-NPs on a normal chow diet.

Optimizing ST6GAL1 inhibition and selectivity using lithocholic acid-amino acid conjugates for antimetastatic and antiangiogenic agent development.

A series of LCA-aromatic amino acid conjugates were synthesized and tested for their inhibitory effects on N-glycan specific ST6GAL1 and O-glycan specific ST3GAL1. The LCA-amino acid conjugates with phenyl and indole moieties showed enhanced inhibitory activity and selectivity towards the N-glycan-specific ST6GAL1, with the indole-containing compound 4e exhibiting the highest activity (IC = 20.0 ± 0.

Establishing an Electrophysiological Recording Platform for Epidural Spinal Cord Stimulation in Neuropathic Pain Rats.

Purpose: Spinal cord stimulation (SCS) is pivotal in treating chronic intractable pain. To elucidate the mechanism of action among conventional and current novel types of SCSs, a stable and reliable electrophysiology model in the consensus animals to mimic human SCS treatment is essential. We have recently developed a new in vivo implantable pulsed-ultrahigh-frequency (pUHF) SCS platform for conducting behavioral and electrophysiological studies in rats.

Effect of Advillin Knockout on Diabetic Neuropathy Induced by Multiple Low Doses of Streptozotocin.

Advillin is an actin-binding protein involved in regulating the organization of actin filaments and the dynamics of axonal growth cones. In mice, advillin is exclusively expressed in somatosensory neurons, ubiquitously expressed in all neuron subtypes during neonatal ages and particularly enriched in isolectin B4-positive (IB4 + ) non-peptidergic neurons in adulthood. We previously showed that advillin plays a key role in axon regeneration of somatosensory neurons during peripheral neuropathy.

Deficiency of thioredoxin-interacting protein results in age-related thrombocytopenia due to megakaryocyte oxidative stress.

Background: Platelets are generated from megakaryocytes (MKs), mainly located in the bone marrow (BM). Megakaryopoiesis can be affected by genetic disorders, metabolic diseases, and aging. The molecular mechanisms underlying platelet count regulation have not been fully elucidated.

Novel Pulsed Ultrahigh-frequency Spinal Cord Stimulation Inhibits Mechanical Hypersensitivity and Brain Neuronal Activity in Rats after Nerve Injury.

Background: Spinal cord stimulation (SCS) is an important pain treatment modality. This study hypothesized that a novel pulsed ultrahigh-frequency spinal cord stimulation (pUHF-SCS) could safely and effectively inhibit spared nerve injury-induced neuropathic pain in rats.

Methods: Epidural pUHF-SCS (± 3V, 2-Hz pulses comprising 500-kHz biphasic sinewaves) was implanted at the thoracic vertebrae (T9 to T11).

Role of proprioceptors in chronic musculoskeletal pain.

Proprioceptors are non-nociceptive low-threshold mechanoreceptors. However, recent studies have shown that proprioceptors are acid-sensitive and express a variety of proton-sensing ion channels and receptors. Accordingly, although proprioceptors are commonly known as mechanosensing neurons that monitor muscle contraction status and body position, they may have a role in the development of pain associated with tissue acidosis.

Involvement of ASIC3 and Substance P in Therapeutic Ultrasound-Mediated Analgesia in Mouse Models of Fibromyalgia.

Therapeutic ultrasound (tUS) is widely used in chronic muscle pain control. However, its analgesic molecular mechanism is still not known. Our objective is to reveal the mechanism of the tUS-induced analgesia in mouse models of fibromyalgia.

Proliferative ability of circulating tumor cells is a prognostic factor in Early-Stage lung adenocarcinoma.

Introduction: Circulating tumor cells (CTCs) and their proliferative ability in lung adenocarcinoma (LUAD) were not well-investigated. We developed a protocol combining an efficient viable CTC isolation and in-vitro cultivation for the CTC enumeration and proliferation to evaluate their clinical significance.

Method: The peripheral blood of 124 treatment-naïve LUAD patients were processed by a CTC isolation microfluidics, DS platform, followed by in-vitro cultivation.

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells.

Multiomic characterization and drug testing establish circulating tumor cells as an tool for personalized medicine.

Matching the treatment to an individual patient's tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells.

Generation of An Induced Pluripotent Stem Cell Line from Human Liver Fibroblasts from A Patient with Combined Hepatocellular-Cholangiocarcinoma.

Objective: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare type of primary liver cancer with characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The pathogenesis of cHCCCC is poorly understood due to a shortage of suitable in vitro models. Due to scarce availability of human liver tissue, induced pluripotent stem cells (iPSCs) are a useful alternative source to produce renewable liver cells.

Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro.

Background: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants.

Hyperglycosylated spike of SARS-CoV-2 gamma variant induces breast cancer metastasis.

SARS-CoV-2 exploits the host cellular machinery for virus replication leading to the acute syndrome of coronavirus disease 2019 (COVID-19). Growing evidence suggests SARS-CoV-2 also exacerbates many chronic diseases, including cancers. As mutations on the spike protein (S) emerged as dominant variants that reduce vaccine efficacy, little is known about the relation between SARS-CoV-2 virus variants and cancers.

Generation of human induced pluripotent stem cell line, KRIBBi003-A, from urinary cells of a patient with glycogen storage disease type IXa.

Glycogen storage disease type IXa (GSD IXa) is a rare genetic disorder characterized by phosphorylase kinase (PhK) deficiency, which leads to excessive glycogen accumulation in the liver. Urinary cells (UCs) were isolated from a GSD IXa patient and reprogrammed into induced pluripotent stem cells (iPSCs) using Sendai virus. The established iPSC line, KRIBBi003-A, exhibited pluripotency marker expression and a normal karyotype.

A role for substance P and acid-sensing ion channel 1a in prolotherapy with dextrose-mediated analgesia in a mouse model of chronic muscle pain.

Prolotherapy is widely used in pain control and tissue repair in pain medicine. The classical mode is injection with hypertonic dextrose in muscle or perimysium. However, the analgesic mechanism is still not known.

Early Detection and Dynamic Changes of Circulating Tumor Cells in Transgenic NeuN Transgenic (NTTg) Mice with Spontaneous Breast Tumor Development.

Background: This study used NeuN transgenic (NTTg) mice with spontaneous breast tumor development to evaluate the dynamic changes of circulating tumor cells (CTCs) prior to and during tumor development.

Methods: In this longitudinal, clinically uninterrupted study, we collected 75 μL of peripheral blood at the age of 8, 12, 16, and 20 weeks in the first group of five mice, and at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability in the second group of four mice. Diluted blood samples were run through a modified mouse-CMx chip to isolate the CTCs.

Cellular Chaperone Function of Intrinsically Disordered Dehydrin ERD14.

Disordered plant chaperones play key roles in helping plants survive in harsh conditions, and they are indispensable for seeds to remain viable. Aside from well-known and thoroughly characterized globular chaperone proteins, there are a number of intrinsically disordered proteins (IDPs) that can also serve as highly effective protecting agents in the cells. One of the largest groups of disordered chaperones is the group of dehydrins, proteins that are expressed at high levels under different abiotic stress conditions, such as drought, high temperature, or osmotic stress.

Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2016-2020).

: Hypoxia-inducible factor (HIF) is a master regulator of oxygen homeostasis. The increased expression of genes targeted by HIF is associated with many human diseases, including ischemic cardiovascular disease, stroke, chronic lung disease, and cancer.: This patent survey summarizes the information about patented HIF inhibitors over the last 5 years.

Effect of Microbial Short-Chain Fatty Acids on CYP3A4-Mediated Metabolic Activation of Human Pluripotent Stem Cell-Derived Liver Organoids.

The early and accurate prediction of the hepatotoxicity of new drug targets during nonclinical drug development is important to avoid postmarketing drug withdrawals and late-stage failures. We previously established long-term expandable and functional human-induced pluripotent stem cell (iPSC)-derived liver organoids as an alternative source for primary human hepatocytes. However, PSC-derived organoids are known to present immature fetal characteristics.