Lysophosphatidic acid receptor 1 (LPA1) antagonists as potential migrastatics for triple negative breast cancer
In this study, we report the synthesis and biological evaluation of fluorine-containing triazole derivatives as potent LPA1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compound 12f, the most potent and highly selective in this series with an IC50 value of 16.0 nM in the cAMP assay and 18.4 nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBC cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA1 as a migras...
Source: ChemMedChem - April 22, 2024 Category: Chemistry Authors: Wenjie Liu Amr Abdullah Kamel Mousa Austin M Hopkins Yin Fang Wu Kelsie L Thu Michael Campbell Simon J Lees Rithwik Ramachandran Jinqiang Hou Source Type: research
Lead exerts a depression of neurotransmitter release through a blockade of voltage dependent calcium channels in chromaffin cells
Toxicology. 2024 Apr 20:153809. doi: 10.1016/j.tox.2024.153809. Online ahead of print.ABSTRACTThe present work, using chromaffin cells of bovine adrenal medullae (BCCs), aims to describe what type of ionic current alterations induced by lead (Pb2+) underlies its effects reported on synaptic transmission. We observed that the acute application of Pb2+ lead to a drastic depression of neurotransmitters release in a concentration-dependent manner when the cells were stimulated with both K+ or acetylcholine, with an IC50 of 119,57 μM and of 5,19 μM, respectively. This effect was fully recovered after washout. Pb2+ also blocke...
Source: Toxicology - April 22, 2024 Category: Toxicology Authors: Victoria Jim énez Carretero Ninfa Liccardi Maria Arribas Tejedor Ricardo de Pascual Jorge Hern ández Campano Jes ús M Hernández-Guijo Source Type: research
Radiation-associated changes in saliva composition of head and neck cancer patients: A systematic review
Radiother Oncol. 2024 Apr 20:110279. doi: 10.1016/j.radonc.2024.110279. Online ahead of print.ABSTRACTXerostomia is a common radiation-associated toxicity in patients with head and neck cancer. Although several studies examined the decrease in saliva production due to radiotherapy (RT) and investigated the factors associated with this side effect, little is known about the change in radiation-associated saliva composition. This systematic review is the first to summarize existing data and give an overview of the change in pH/buffer capacity, electrolytes, proteins, enzymes, and mucins due to radiation to the salivary gland...
Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - April 22, 2024 Category: Radiology Authors: Michal Staruch Marlene M Speth Peter Neyer Oliver Riesterer Daniel M Aebersold Sonja Stieb Source Type: research
Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism
CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.PMID:38644730 | DOI:10.2174/0118715303260423231122111705 (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - April 22, 2024 Category: Endocrinology Authors: Fabio Vescini Giorgio Borretta Iacopo Chiodini Marco Boniardi Marina Carotti Elena Castellano Cristiana Cipriani Cristina Eller-Vainicher Sandro Giannini Maurizio Iacobone Antonio Stefano Salcuni Federica Saponaro Stefano Spiezia Annibale Versari Guido Za Source Type: research
Nardilysin in vascular smooth muscle cells controls blood pressure via the regulation of calcium dynamics
In this study, we aimed to clarify the role of NRDC in vascular smooth muscle cell (VSMC) by generating VSMC-specific Nrdc knockout (VSMC-KO) mice. Our findings reveal that VSMC-KO mice also exhibit hypotension. Aortas isolated from VSMC-KO mice exhibited a weakened contractile response to phenylephrine, accompanied by reduced phosphorylation of myosin light chain 2 and decreased rhoA expression. VSMC isolated from VSMC-KO aortas showed a reduced increase in intracellular Ca2+ concentration induced by α-stimulants. These findings suggest that NRDC in VSMC regulates vascular contraction and blood pressure by modulating Ca2...
Source: Cell Research - April 22, 2024 Category: Cytology Authors: Mend Amar Batbaatar Takeshi Kinoshita Shinya Ikeda Kiyoto Nishi Hirotaka Iwasaki Narangerel Ganbaatar Mikiko Ohno Eiichiro Nishi Source Type: research
Acutely shaky hand
Clinical introduction A 57-year-old man presented acutely with involuntary movements of his left hand. He had hypertension, chronic kidney disease and chronic obstructive pulmonary disease. These movements were best described as sudden, recurrent and arrhythmic loss of tone and power of the left wrist and fingers (video 1). They were most prominent when extending the left wrist, but were absent when the arms were at rest and were not elsewhere. There were no additional neurological deficits. Serum urea, ammonia, sodium, potassium, calcium, magnesium, phosphate and glucose levels were normal. His haematological profile, inf...
Source: Emergency Medicine Journal - April 22, 2024 Category: Emergency Medicine Authors: Tan, Y.-J., Teo, C. H., Chan, C. Tags: EMJ Image Challenge Source Type: research
Simultaneous TIRF imaging of subplasmalemmal Ca < sup > 2+ < /sup > dynamics and granule fusions in insulin-secreting INS-1 cells reveals coexistent synchronized and asynchronous release
Cell Calcium. 2024 Apr 8;120:102883. doi: 10.1016/j.ceca.2024.102883. Online ahead of print.ABSTRACTThe basal and glucose-induced insulin secretion from pancreatic beta cells is a tightly regulated process that is triggered in a Ca2+-dependent fashion and further positively modulated by substances that raise intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) or by certain antidiabetic drugs. In a previous study, we have temporally resolved the subplasmalemmal [Ca2+]i dynamics in beta cells that are characterized by trains of sharply delimited spikes, reaching peak values up to 5 µM. Applying total interna...
Source: Cell Calcium - April 21, 2024 Category: Cytology Authors: Charlotte Suckert Carolin Zosel Michael Schaefer Source Type: research
Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia Procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis
This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). FTIR analysis affirmed polymer compatibility, while Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic in...
Source: Chemical and Pharmaceutical Bulletin - April 21, 2024 Category: Drugs & Pharmacology Authors: Sudipta Mukherjee Jasmina Khanam Source Type: research
Simultaneous TIRF imaging of subplasmalemmal Ca < sup > 2+ < /sup > dynamics and granule fusions in insulin-secreting INS-1 cells reveals coexistent synchronized and asynchronous release
Cell Calcium. 2024 Apr 8;120:102883. doi: 10.1016/j.ceca.2024.102883. Online ahead of print.ABSTRACTThe basal and glucose-induced insulin secretion from pancreatic beta cells is a tightly regulated process that is triggered in a Ca2+-dependent fashion and further positively modulated by substances that raise intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) or by certain antidiabetic drugs. In a previous study, we have temporally resolved the subplasmalemmal [Ca2+]i dynamics in beta cells that are characterized by trains of sharply delimited spikes, reaching peak values up to 5 µM. Applying total interna...
Source: Cell Calcium - April 21, 2024 Category: Cytology Authors: Charlotte Suckert Carolin Zosel Michael Schaefer Source Type: research
Poly (vinyl alcohol)/sodium alginate/carboxymethyl chitosan multifunctional hydrogel loading HKUST-1 nanoenzymes for diabetic wound healing
In this study, a copper-based MOF (TAX@HKUST-1) highly loaded with taxifolin (TAX) with a drug loading of 41.94 ± 2.60 % was prepared. In addition, it has excellent catalase activity, and by constructing an oxygen-releasing hydrogel (PTH) system with calcium peroxide (CaO2), it can be used as a nano-enzyme to promote the generation of oxygen from hydrogen peroxide (H2O2) to provide sufficient oxygen to the wound, and at the same time, solve the problem of the oxidative stress damage caused by excess H2O2 to the cells during the oxygen-releasing process. On the other hand, TAX and HKUST-1 in PTH synergistically promoted an...
Source: International Journal of Biological Macromolecules - April 21, 2024 Category: Biochemistry Authors: Guodong Chai Ning Wang Meiling Xu Lina Ma Xinglong Liu Qiteng Ding Shuai Zhang Anning Li Guofeng Xia Yingchun Zhao Wencong Liu Dadong Liang Chuanbo Ding Source Type: research
Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia Procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis
This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). FTIR analysis affirmed polymer compatibility, while Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic in...
Source: Chemical and Pharmaceutical Bulletin - April 21, 2024 Category: Drugs & Pharmacology Authors: Sudipta Mukherjee Jasmina Khanam Source Type: research
A case of insulinoma misidentified as schizophrenia due to its manifestation in neuropsychiatric symptoms
AbstractInsulinomas can present with neuroglycopenic symptoms suggesting neuropsychiatric disorders, delaying diagnosis and treatment. We recently treated a 65-year-old woman with insulinoma who was misdiagnosed at her nearby psychiatric clinic as having schizophrenia because of personality changes and memory impairment; she was treated with brexpiprazole, which was discontinued due to persistence of the symptoms. Despite her relatively low casual plasma glucose (70 mg/dL), the physician at the psychiatric clinic did not investigate the possibility of hypoglycemia, partly because her HbA1c level (5.2%) was within normal ...
Source: Diabetology International - April 21, 2024 Category: Endocrinology Source Type: research
Exploring Micronutrient Dynamics in COVID-19 Severity and Mortality: Unraveling the Roles of Vitamin D, Calcium, Phosphorus, Magnesium and ALP
This study explores the impact of Vitamin D, calcium, phosphorus, magnesium, and alkaline phosphatase (ALP) on COVID-19 severity and mortality. The study involves 200 participants (100 COVID-19 patients, 100 controls), we meticulously analyzed micronutrient dynamics. Calcium, phosphorus, magnesium and ALP was measured spectrophotometrically. Vitamin D was measured using Chemiluminescent method. The study reveals that diminished levels of calcium, phosphorus, magnesium, and with elevated ALP, are significantly associated with COVID-19 cases. Whereas the Vitamin D levels in severe group was increased when compared to mild ca...
Source: Indian Journal of Clinical Biochemistry - April 21, 2024 Category: Biochemistry Source Type: research
Piezo1 stretch-activated channel activity differs between murine bone marrow-derived and cardiac tissue-resident macrophages
This study explores the activity of mechanosensitive ion channels (MSC) in murine MΦBM and compares it to MSC activity in MΦ enzymatically isolated from cardiac tissue (tissue-resident MΦ; MΦTR). We show that MΦBM and MΦTR have stretch-induced currents, indicating the presence of functional MSC in their plasma membrane. The current profiles in MΦBM and in MΦTR show characteristics of cation non-selective MSC such as Piezo1 or transient receptor potential channels. While Piezo1 ion channel activity is detectable in the plasma membrane of MΦBM using the patch-clamp technique, or by measuring cytosolic calcium concen...
Source: The Journal of Physiology - April 20, 2024 Category: Physiology Authors: Ana Simon-Chica Alexander Klesen Ramona Emig Andy Chan Joachim Greiner Dominic Gr ün Achim Lother Ingo Hilgendorf Eva A Rog-Zielinska Ursula Ravens Peter Kohl Franziska Schneider-Warme R émi Peyronnet Source Type: research
The anoctamins: Structure and function
Cell Calcium. 2024 Apr 15;120:102885. doi: 10.1016/j.ceca.2024.102885. Online ahead of print.ABSTRACTWhen activated by increase in intracellular Ca2+, anoctamins (TMEM16 proteins) operate as phospholipid scramblases and as ion channels. Anoctamin 1 (ANO1) is the Ca2+-activated epithelial anion-selective channel that is coexpressed together with the abundant scramblase ANO6 and additional intracellular anoctamins. In salivary and pancreatic glands, ANO1 is tightly packed in the apical membrane and secretes Cl-. Epithelia of airways and gut use cystic fibrosis transmembrane conductance regulator (CFTR) as an apical Cl- exit ...
Source: Cell Calcium - April 20, 2024 Category: Cytology Authors: Rainer Schreiber Jiraporn Ousingsawat Karl Kunzelmann Source Type: research
