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Biomolecules & Therapeutics Jul 2024Specific sensitivity of the skin to ultraviolet B (UVB) rays is one of the mechanisms responsible for widespread skin damage. This study tested whether...
Specific sensitivity of the skin to ultraviolet B (UVB) rays is one of the mechanisms responsible for widespread skin damage. This study tested whether 1,3,5-trihydroxybenzene (THB), a compound abundant in marine products, might inhibit UVB radiation-induced NADPH oxidase 4 (NOX4) in both human HaCaT keratinocytes and mouse dorsal skin and explore its cytoprotective mechanism. The mechanism of action was determined using western blotting, immunocytochemistry, NADP/NADPH assay, reactive oxygen species (ROS) detection, and cell viability assay. THB attenuated UVB-induced NOX4 expression both and , and suppressed UVB-induced ROS generation via NADP production, resulting in increased cell viability with decreased apoptosis. THB also reduced the expression of UVB-induced phosphorylated AMP-activated protein kinase (AMPK) and phosphorylated c-Jun N-terminal kinase (JNK). THB suppressed UVB-induced NOX4 expression and ROS generation by inhibiting AMPK and JNK signaling pathways, thereby inhibiting cellular damage. These results showed that THB could be developed as a UV protectant.
PubMed: 38914480
DOI: 10.4062/biomolther.2024.054 -
PLoS Biology Jun 2024In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of...
In the highly regulative embryo of the sea urchin Paracentrotus lividus, establishment of the dorsal-ventral (D/V) axis critically depends on the zygotic expression of the TGF-β nodal in the ventral ectoderm. nodal expression is first induced ubiquitously in the 32-cell embryo and becomes progressively restricted to the presumptive ventral ectoderm by the early blastula stage. This early spatial restriction of nodal expression is independent of Lefty, and instead relies on the activity of Panda, a maternally expressed TGF-β ligand related to Lefty and Inhibins, which is required maternally for D/V axis specification. However, the mechanism by which Panda restricts the early nodal expression has remained enigmatic and it is not known if Panda works like a BMP ligand by opposing Nodal and antagonizing Smad2/3 signaling, or if it works like Lefty by sequestering an essential component of the Nodal signaling pathway. In this study, we report that Panda functions as an antagonist of the TGF-β type II receptor ACVRII (Activin receptor type II), which is the only type II receptor for Nodal signaling in the sea urchin and is also a type II receptor for BMP ligands. Inhibiting translation of acvrII mRNA disrupted D/V patterning across all 3 germ layers and caused acvrII morphants to develop with a typical Nodal loss-of-function phenotype. In contrast, embryos overexpressing acvrII displayed strong ectopic Smad1/5/8 signaling at blastula stages and developed as dorsalized larvae, a phenotype very similar to that caused by over activation of BMP signaling. Remarkably, embryos co-injected with acvrII mRNA and panda mRNA did not show ectopic Smad1/5/8 signaling and developed with a largely normal dorsal-ventral polarity. Furthermore, using an axis induction assay, we found that Panda blocks the ability of ACVRII to orient the D/V axis when overexpressed locally. Using co-immunoprecipitation, we showed that Panda physically interacts with ACVRII, as well as with the Nodal co-receptor Cripto, and with TBR3 (Betaglycan), which is a non-signaling receptor for Inhibins in mammals. At the molecular level, we have traced back the antagonistic activity of Panda to the presence of a single proline residue, conserved with all the Lefty factors, in the ACVRII binding motif of Panda, instead of a serine as in most of TGF-β ligands. Conversion of this proline to a serine converted Panda from an antagonist that opposed Nodal signaling and promoted dorsalization to an agonist that promoted Nodal signaling and triggered ventralization when overexpressed. Finally, using phylogenomics, we analyzed the emergence of the agonist and antagonist form of Panda in the course of evolution. Our data are consistent with the idea that the presence of a serine at that position, like in most TGF-β, was the ancestral condition and that the initial function of Panda was possibly in promoting and not in antagonizing Nodal signaling. These results highlight the existence of key functional and structural elements conserved between Panda and Lefty, allow to draw an intriguing parallel between sea urchin Panda and mammalian Inhibin α and raise the unexpected possibility that the original function of Panda may have been in activation of the Nodal pathway rather than in its inhibition.
PubMed: 38913712
DOI: 10.1371/journal.pbio.3002701 -
JCI Insight May 2024Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel...
Peripheral nerve injury-induced neuronal hyperactivity in the dorsal root ganglion (DRG) participates in neuropathic pain. The calcium-activated potassium channel subfamily N member 1 (KCNN1) mediates action potential afterhyperpolarization (AHP) and gates neuronal excitability. However, the specific contribution of DRG KCNN1 to neuropathic pain is not yet clear. We report that chronic constriction injury (CCI) of the unilateral sciatic nerve or unilateral ligation of the fourth lumbar nerve produced the downregulation of Kcnn1 mRNA and KCNN1 protein in the injured DRG. This downregulation was partially attributed to a decrease in DRG estrogen-related receptor gamma (ESRRG), a transcription factor, which led to reduced binding to the Kcnn1 promoter. Rescuing this downregulation prevented CCI-induced decreases in total potassium voltage currents and AHP currents, reduced excitability in the injured DRG neurons, and alleviated CCI-induced development and maintenance of nociceptive hypersensitivities, without affecting locomotor function and acute pain. Mimicking the CCI-induced DRG KCNN1 downregulation resulted in augmented responses to mechanical, heat, and cold stimuli in naive mice. Our findings indicate that ESRRG-controlled downregulation of DRG KCNN1 is likely essential for the development and maintenance of neuropathic pain. Thus, KCNN1 may serve as a potential target for managing this disorder.
Topics: Animals; Neuralgia; Ganglia, Spinal; Mice; Down-Regulation; Sensory Receptor Cells; Male; Peripheral Nerve Injuries; Mice, Inbred C57BL; Sciatic Nerve; Disease Models, Animal; Intermediate-Conductance Calcium-Activated Potassium Channels; Action Potentials
PubMed: 38912580
DOI: 10.1172/jci.insight.180085 -
Revista Brasileira de Ortopedia Jun 2024Wrist and hand arthroscopy, despite being an old tool, has gained popularity and advanced in assisting in the treatment of various injuries and conditions in the region...
Wrist and hand arthroscopy, despite being an old tool, has gained popularity and advanced in assisting in the treatment of various injuries and conditions in the region in recent years. Dorsal, volar, ulnar, and radial accessory portals are used to reach all points of the carpal and hand joints. The minimal tissue damage, lesser injury to the capsule and its mechanoreceptors, the assessment of injuries associated with the reason for surgery, and aesthetically more favorable scars have attracted many doctors and their patients. As a result, there has been an increase in publications and diversifications of arthroscopic techniques. The aim of this update article is to present the advances and the evidence available in the literature to assist readers in their decision on which technique to use in the treatment of wrist and hand conditions.
PubMed: 38911879
DOI: 10.1055/s-0044-1779336 -
Journal of Pain Research 2024Minimally invasive sacroiliac (SI) joint fusion has become the mainstay treatment for chronic refractory sacroiliac joint dysfunction. Multiple procedures are now...
INTRODUCTION
Minimally invasive sacroiliac (SI) joint fusion has become the mainstay treatment for chronic refractory sacroiliac joint dysfunction. Multiple procedures are now available including transfixing procedures with implants placed in the lateral or posterolateral transiliac trajectories, and intra-articular procedures with devices and/or allograft placed via a dorsal approach. To date, the published literature on the lateral approach has been primarily by surgeons. This retrospective chart review aims to evaluate the safety and preliminary effectiveness when the procedure is performed by physicians trained in interventional pain management.
METHODS
Retrospective analysis of patients who underwent lateral SI joint fusion using a lateral transiliac approach between December 2022 and September 2023 by a single physician. Data on demographics, perioperative details, complications, and postoperative outcomes were collected and analyzed. The study was reviewed by WCG IRB and received an exemption authorization.
RESULTS
Medical charts were reviewed for the first 49 consecutive cases performed. Mean (SD, range) age was 64 (11, 34-83), BMI was 32.5 (8.4), 59% were female, 35% were smokers, and 82% were on opioids at baseline. Mean (SD) operative time was 40 (11) minutes and all procedures were performed at an ambulatory surgery center under monitored anesthesia care. No device- or procedure-related complications occurred. Mean follow up was 175 days; Mean (SD) baseline reported pain was 9 (1.5) on a 0-10 numerical rating scale. At follow up, 88% of the patients reported ≥50% pain relief. Six patients who reported 0% relief suffer from multiple pain generators and are on long term opioids.
CONCLUSION
Results of this single center experience support the safety of lateral SI joint fusion using a threaded implant when performed by interventional pain management physicians. However, further prospective studies with larger sample sizes and longer follow-ups are warranted to validate these findings.
PubMed: 38910592
DOI: 10.2147/JPR.S462072 -
NeuroImage Jun 2024Contextual information may shape motor resonance and support intention understanding during observation of incomplete, ambiguous actions. It is unclear, however, whether...
Contextual information may shape motor resonance and support intention understanding during observation of incomplete, ambiguous actions. It is unclear, however, whether this effect is contingent upon kinematics ambiguity or contextual information is continuously integrated with kinematics to predict the overarching action intention. Moreover, a differentiation between the motor mapping of the intention suggested by context or kinematics has not been clearly demonstrated. In a first action execution phase, 29 participants were asked to perform reaching-to-grasp movements towards big or small food objects with the intention to eat or to move; electromyography from the First Dorsal Interosseous (FDI) and Abductor Digiti Minimi (ADM) was recorded. Depending on object size, the intentions to eat or to move were differently implemented by a whole-hand or a precision grip kinematics, thus qualifying an action-muscle dissociation. Then, in a following action prediction task, the same participants were asked to observe an actor performing the same actions and to predict his/her intention while motor resonance was assessed for the same muscles. Of note, videos were interrupted at early or late action phases, and actions were embedded in contexts pointing toward an eating or a moving intention, congruently or incongruently with kinematics. We found greater involvement of the FDI or ADM in the execution of precision or whole-hand grips, respectively. Crucially, this pattern of activation was mirrored during observation of the same actions in congruent contexts, but it was cancelled out or reversed in the incongruent ones, either when videos were interrupted at either early or long phases of action deployment. Our results extend previous evidence by showing that contextual information shapes motor resonance not only under conditions of perceptual uncertainty but also when more informative kinematics is available.
PubMed: 38909762
DOI: 10.1016/j.neuroimage.2024.120702 -
Scientific Reports Jun 2024Glucagon-like peptide-1 receptor (GLP-1R) agonists are now commonly used to treat type 2 diabetes and obesity. GLP-1R signaling in the spinal cord has been suggested to...
Glucagon-like peptide-1 receptor (GLP-1R) agonists are now commonly used to treat type 2 diabetes and obesity. GLP-1R signaling in the spinal cord has been suggested to account for the mild tachycardia caused by GLP-1R agonists, and may also be involved in the therapeutic effects of these drugs. However, the neuroanatomy of the GLP-1/GLP-1R system in the spinal cord is still poorly understood. Here we applied in situ hybridization and immunohistochemistry to characterize this system, and its relation to cholinergic neurons. GLP-1R transcript and protein were expressed in neuronal cell bodies across the gray matter, in matching distribution patterns. GLP-1R-immunolabeling was also robust in dendrites and axons, especially in laminae II-III in the dorsal horn. Cerebrospinal fluid-contacting neurons expressed GLP-1R protein at exceedingly high levels. Only small subpopulations of cholinergic neurons expressed GLP-1R, including a subset of sympathetic preganglionic neurons at the rostral tip of the intermediolateral nucleus. GLP-1 axons innervated all regions where GLP-1R neurons were distributed, except laminae II-III. Scattered preproglucagon (Gcg) mRNA-expressing neurons were identified in the cervical and lumbar enlargements. The results will facilitate further studies on how GLP-1 regulates the sympathetic system and other autonomic and somatic functions via the spinal cord.
Topics: Animals; Glucagon-Like Peptide-1 Receptor; Male; Spinal Cord; Mice; Glucagon-Like Peptide 1; Cholinergic Neurons; Proglucagon; Mice, Inbred C57BL; Axons
PubMed: 38909126
DOI: 10.1038/s41598-024-65442-1 -
Nature Communications Jun 2024Metacognitive evaluations of confidence provide an estimate of decision accuracy that could guide learning in the absence of explicit feedback. We examine how humans...
Metacognitive evaluations of confidence provide an estimate of decision accuracy that could guide learning in the absence of explicit feedback. We examine how humans might learn from this implicit feedback in direct comparison with that of explicit feedback, using simultaneous EEG-fMRI. Participants performed a motion direction discrimination task where stimulus difficulty was increased to maintain performance, with intermixed explicit- and no-feedback trials. We isolate single-trial estimates of post-decision confidence using EEG decoding, and find these neural signatures re-emerge at the time of feedback together with separable signatures of explicit feedback. We identified these signatures of implicit versus explicit feedback along a dorsal-ventral gradient in the striatum, a finding uniquely enabled by an EEG-fMRI fusion. These two signals appear to integrate into an aggregate representation in the external globus pallidus, which could broadcast updates to improve cortical decision processing via the thalamus and insular cortex, irrespective of the source of feedback.
Topics: Humans; Decision Making; Male; Magnetic Resonance Imaging; Female; Adult; Basal Ganglia; Young Adult; Learning; Electroencephalography; Brain Mapping
PubMed: 38909014
DOI: 10.1038/s41467-024-49538-w -
Systematic Parasitology Jun 2024Eight species of Pandarus Leach, 1816 collected from hosts caught off South Africa are reported. These species include P. bicolor Leach, 1816, P. niger Kirtisinghe, 1950...
Eight species of Pandarus Leach, 1816 collected from hosts caught off South Africa are reported. These species include P. bicolor Leach, 1816, P. niger Kirtisinghe, 1950 and P. carcharhini Ho, 1963 belonging to the "bicolor" group and P. cranchii Leach, 1819, P. satyrus Dana, 1849, P. smithii Rathbun, 1886 and P. sinuatus Say, 1818 belonging to the "cranchii" group. Notes on previous and new distinguishing features are provided with illustrations, specifically the relative lengths of the dorsal plates and caudal rami as well as the structure of the distomedial spine on the second segment of leg 1 exopod. Additionally, illustrated re-descriptions are provided for P. satyrus and P. sinuatus. Furthermore, a new species Pandarus echinifer n. sp., also belonging to the "cranchii" group, collected from the snaggletooth shark Hemipristis elongata (Klunzinger) is described. This species is most similar to P. sinuatus but can be distinguished from it by the heavily spinulated distomedial spine on the last segment of the first leg exopod. Molecular analysis of the cytochrome oxidase I partial gene is used to calculate sequence divergences amongst different individuals and species. According to the results (as well as based on morphological characters) P. rhincodonicus Norman, Newbound & Knott, 2000 is a synonym of P. cranchii. New hosts and geographic localities from South Africa (and Ningaloo Park, Western Australia) are reported.
Topics: Animals; South Africa; Species Specificity; Elasmobranchii; Copepoda; Phylogeny; Electron Transport Complex IV; Male; Female
PubMed: 38907944
DOI: 10.1007/s11230-024-10167-y -
Scientific Reports Jun 2024Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to...
Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to emulate the visual experience of movement during head fixation, but a low inertia floating real-world environment (mobile homecage, MHC) has the potential to engage more sensory modalities and provide a richer experimental environment for complex behavioral tasks. However, it is not known whether mice react to this adapted environment in a similar manner to real environments, or whether the MHC can be used to implement validated, maze-based behavioral tasks. Here, we show that hippocampal place cell representations are intact in the MHC and that the system allows relatively long (20 min) whole-cell patch clamp recordings from dorsal CA1 pyramidal neurons, revealing sub-threshold membrane potential dynamics. Furthermore, mice learn the location of a liquid reward within an adapted T-maze guided by 2-dimensional spatial navigation cues and relearn the location when spatial contingencies are reversed. Bilateral infusions of scopolamine show that this learning is hippocampus-dependent and requires intact cholinergic signalling. Therefore, we characterize the MHC system as an experimental tool to study sub-threshold membrane potential dynamics that underpin complex navigation behaviors.
Topics: Animals; Mice; Spatial Navigation; Maze Learning; Male; Hippocampus; Pyramidal Cells; Mice, Inbred C57BL; Membrane Potentials; CA1 Region, Hippocampal; Virtual Reality; Scopolamine; Patch-Clamp Techniques
PubMed: 38906952
DOI: 10.1038/s41598-024-64807-w