TRPM8 modulation alters uptake of Transferrin-mediated Fe, mitochondrial Fe and intracellular Ca-levels in microglia.

Microglia play an important role in the immunity of the central nervous system, crucial in maintaining homeostasis. However, under diseased conditions, this cell accumulates Fe, triggering inflammatory and neurotoxic effects that contribute to neurodegenerative disorders such as Alzheimer's and Parkinson's. Hence, the study of dysregulated microglial activation and overload of Fe is crucial in the context of neurodegenerative conditions.

In vitro study for bone tissue regeneration using composite of bioglass and gelatin nanofiber scaffolds.

Current bio-medical situation necessitates the development of natural and/or synthetic biomaterials that can enhance biomineralization both in-vitro and in-vivo. Towards that aim, we synthesized nanofibrous scaffolds of 81S(81SiO₂-12CaO-2P₂O₅-1Na₂O-4MgO) and 85S(85SiO₂-10CaO-5P₂O₅ mol%) bio-glass of varying concentrations with gelatin using electrospinning. XRD and FTIR confirm scaffold formation, while SEM-EDS analysis reveals fibrous structure with homogenous distribution of nBG inside the fibre.

Amino acids critical for lipid/s-interaction at the lipid-water-interface of TRPV5/TRPV6 remain different during vertebrate radiation: Relevance in cancer, bone disorders and other pathophysiologies.

TRPV5 and TRPV6 are members of the TRP superfamily of ion channels and are present in almost all vertebrates as linked-genes with high homology and functional similarities. Abnormalities in the regulation or function of these two channels cause multiple pathological conditions, making these highly relevant for several diseases and pharmacological applications. In this context, how these two channels differ from each other is largely unknown.

Transient receptor potential vanilloid 2 (TRPV2) channels modulate the nigrostriatal dopaminergic activity in rats.

Thermosensitive TRPV1-4-channels have emerged as novel regulators of neuronal function and behaviour. In midbrain, while TRPV1/TRPV3 regulates ventral tegmental area dopamine (DA) (VTA) neurons, TRPV1/TRPV3/TRPV4 play a role in the modulation of substantia nigra DA (SN) neurons. Although TRPV2 is widely expressed in the brain, its significance in the regulation of VTA/SN neurons is unclear.

A Remarkable ParaCEST Activity Shown by a Co(II) Complex of Bis-Dipicolinamideacetamide With One Inner Sphere Water Molecule.

Reaction of the BDPAA (N,N-dimethyl pyridine-based tri(carboxamide)) with iron tetrafluoroborate, cobalt chloride and nickel triflate separately in methanol/acetonitrile affords the complex, [Fe(BDPAA)(HO)](BF), [Co(BDPAA)(HO)]Cl and [Ni(BDPAA)(HO)](CFSO), respectively. The solid-state structural analysis of cobalt and nickel complexes of bis-dipicolinamideacetamide (BDPAA) ligand and the solution state paraCEST studies of all three complexes are presented. Among these complexes, only Co(II)-BDPAA complex exhibits remarkable paraCEST activity due to exchangeable carboxamide NH protons, whereas the corresponding Fe complex shows very little CEST effect and Ni complex did not show CEST activity at all.

Conserved and Unique Mitochondrial Target Sequence of TRPV4 Can Independently Regulate Mitochondrial Functions.

Though mitochondria have their own genome and protein synthesis machineries, the majority of the mitochondrial proteins are actually encoded by the nuclear genome. Most of these mitochondrial proteins are imported into specific compartments of the mitochondria due to their mitochondrial target sequence (MTS). Unlike the nuclear target sequence, the MTS of most of the mitochondrial localized proteins remain poorly understood, mainly due to their variability, heterogeneity, unconventional modes of action, mitochondrial potential-dependent transport, and other complexities.

TRPV4 modulation affects mitochondrial parameters in adipocytes and its inhibition upregulates lipid accumulation.

Enhanced lipid-droplet formation by adipocytes is a complex process and relevant for obesity. Using knock-out animals, involvement of TRPV4, a thermosensitive ion channel in the obesity has been proposed. However, exact role/s of TRPV4 in adipogenesis and obesity remain unclear and contradictory.

Cytocompatible Hyperbranched Polyesters Capable of Altering the Ca Signaling in Neuronal Cells In Vitro.

Synthetic hyperbranched polyesters with potential therapeutic properties were synthesized using the bifunctional polyethylene glycol or PEG with different molecular weights, ca., 4000, 6000, and 20,000 g/mol, and the trifunctional -aconitic acid or TAA. During polycondensation, a fixed amount of PEG was allowed to react with varying amounts of TAA (1:1 and 1:3) to control the branching extents.

Tubulin interaction at tubulin-binding sequence 1 (TBS1) is required for proper surface expression and TRPV1 channel activity.

TRPV1, a polymodal and nonselective cation channel has unique gating mechanisms which is regulated by supramolecular complexes at the plasma membrane formed with membrane proteins, lipids and kinase pathways. Crosstalk between microtubule cytoskeleton with TRPV1 at various level has been established. Previously we demonstrated that the positively-charged residues present at specific tubulin-binding stretch sequences (i.

Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.

TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues.

Taxol-treatment alters endogenous TRPV1 expression and mitochondrial membrane potential in mesenchymal stem cells: Relevant in chemotherapy-induced pathophysiology.

Microtubule-based chemotherapeutics, primarily Taxane-derived agents are still used as the major live-saving agents, yet have several side effects including serious loss of immune cells, bone density etc. which lowers the quality of life. This imposes the need to understand the effects of these agents on Mesenchymal Stem Cells (MSCs) in details.

Sperm-Specific CatSper is Not Conserved in All Vertebrates and May Not be the Only Progesterone-Responsive Ion Channel Present in Sperm.

Progesterone (P4) acts as a key conserved signalling molecule in vertebrate reproduction. P4 is especially important for mature sperm physiology and subsequent reproductive success. "CatSpermasome", a multi-unit molecular complex, has been suggested to be the main if not the only P4-responsive atypical Ca-ion channel present in mature sperm.

TRPM8 affects relative "cooling and heating" of subcellular organelles in microglia in a context-dependent manner.

Thermoregulation and thermal homeostasis at the cellular and subcellular organelle level are poorly understood events. In this work, we used BV2, a microglial cell line, and a series of thermo-sensitive subcellular organelle-specific probes to analyze the relative changes in the spatio-temporal temperatures of different subcellular organelles, both qualitatively and quantitatively. These methodologies allowed us to understand the thermal relationship of different subcellular organelles also.

Evaluation of Osteogenic Potential of a Polysaccharide-Based Hydrogel Coating on Titanium.

Introduction: Reducing the healing period after surgical placement of dental implants can facilitate the loading of dental prostheses.

Aim: The aim is to compare the osteogenic potential of unmodified titanium disks with titanium disks that were surface-modified or hydrogel-coated.

Materials And Methodology: One hundred eight titanium disks (Ø6 × 2-mm) were divided into three groups: (1) unmodified titanium as control (Ti-C); (2) sandblasted and acid-etched (Ti-SLA), and (3) coated with tamarind kernel polysaccharide hydrogel grafted with acrylic acid (Ti-TKP-AA).

Upregulation, Functional Association, and Correlated Expressions of TRPV1 and TRPA1 During Telmisartan-Driven Immunosuppression of T Cells.

TRPV1 and TRPA1, are known to be functionally expressed in T cells, where these two channels differentially regulate effector immune responses. Telmisartan (TM), an anti-hypertension drug, has been recently repurposed to suppress various inflammatory responses. However, the possible involvement of TRP channels during TM-driven suppression of T cells responses has not been explored yet.

TRPV4 Activator-Containing CMT-Hy Hydrogel Enhances Bone Tissue Regeneration by Enhancing Mitochondrial Health.

Treating different types of bone defects is difficult, complicated, time-consuming, and expensive. Here, we demonstrate that transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechanosensitive, thermogated, and nonselective cation channel, is endogenously present in the mesenchymal stem cells (MSCs). TRPV4 regulates both cytosolic Ca levels and mitochondrial health.

Modulation of calcium-influx by carboxymethyl tamarind‑gold nanoparticles promotes biomineralization for tissue regeneration.

Gold nanoparticles (AuNPs) have been reported to modulate bone tissue regeneration and are being extensively utilized in biomedical implementations attributable to their low cytotoxicity, biocompatibility and simplicity of functionalization. Lately, biologically synthesized nanoparticles have acquired popularity because of their environmentally acceptable alternatives for diverse applications. Here we report the green synthesis of AuNPs by taking the biopolymer Carboxymethyl Tamarind (CMT) as a unique reducing as well as a stabilizing agent.

Robust Optical Detection of Ga by a Rhodamine- and Coumarin-Based Proficient Probe: Theoretical Investigations and Biological Applications.

The present investigation highlights a rhodamine-B- and coumarin-based efficient probe that selectively detects Ga over other metal ions. The active pocket of the ligand for trapping the metal ions and the binding stoichiometry of its Ga complex were discovered by single-crystal X-ray diffraction (SC-XRD) analysis. This binding stoichiometry was further confirmed in the solution state by mass spectrometry and Job's plot.

Modulation of TRPM8 alters the phagocytic activity of microglia and induces changes in sub-cellular organelle functions.

In this work, we investigated the presence and function of TRPM8, a non-selective and cold-sensitive Ca-permeable ion channel in the primary microglia cell as well as in microglia cell line BV2. We demonstrate that primary microglia as well as BV2 express TRPM8 endogenously. Both pharmacological activation or inhibition of TRPM8 causes enhanced uptake of bacterial particles at early time points of infection.

Menthol causes mitochondrial Ca-influx, affects structure-function relationship and cools mitochondria.

Menthol is a small bioactive compound able to cause several physiological changes and has multiple molecular targets. Therefore, cellular response against menthol is complex, and still poorly understood. In this work, we used a human osteosarcoma cell line (Saos-2) and analysed the effect of menthol, especially in terms of cellular, subcellular and molecular aspects.

Easily synthesizable molecular probe for the nanomolar level detection of Cd in near aqueous media: Theoretical investigations and live cell imaging.

The present investigation highlights a quinoline-based small molecule probe (DEQ) for the detection of Cd among other metal ions in near-aqueous media. The probe DEQ and its Cd complex (DEQ-Cd) have been synthesized and characterized by all possible spectroscopic methods. The weakly emissive DEQ showed its strong emission in the presence of Cd, which is attributed to the photoinduced electron transfer (PET) along with the chelation-enhanced fluorescence (CHEF) mechanism.

TRPA1 activation and Hsp90 inhibition synergistically downregulate macrophage activation and inflammatory responses in vitro.

Background: Transient receptor potential ankyrin 1 (TRPA1) channels are known to be actively involved in various pathophysiological conditions, including neuronal inflammation, neuropathic pain, and various immunological responses. Heat shock protein 90 (Hsp90), a cytoplasmic molecular chaperone, is well-reported for various cellular and physiological processes. Hsp90 inhibition by various molecules has garnered importance for its therapeutic significance in the downregulation of inflammation and are proposed as anti-cancer drugs.

Progesterone interacts with the mutational hot-spot of TRPV4 and acts as a ligand relevant for fast Ca-signalling.

Steroids are also known to induce immediate physiological and cellular response which occurs within minutes to seconds, or even faster. Such non-genomic actions of steroids are rapid and are proposed to be mediated by different ion channels. Transient receptor potential vanilloid sub-type 4 (TRPV4), is a non-specific polymodal ion channel which is involved in several physiological and cellular processes.