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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 -
Journal of Chemical Neuroanatomy Jun 2024The inferior colliculus (IC), a midbrain hub for integration of auditory information, receives dense cholinergic input that could modulate nearly all aspects of hearing....
The inferior colliculus (IC), a midbrain hub for integration of auditory information, receives dense cholinergic input that could modulate nearly all aspects of hearing. A key step in understanding cholinergic modulation is to identify the source(s) and termination patterns of cholinergic input. These issues have not been addressed for the IC in mice, an increasingly important model for study of hearing. We examined cholinergic inputs to the IC in adult male and female mice. We used retrograde tracing and immunochemistry to identify three sources of cholinergic innervation of the mouse IC: the pedunculopontine tegmental nucleus (PPT), the laterodorsal tegmental nucleus (LDT) and the lateral paragigantocellular nucleus (LPGi). We then used Cre-dependent labeling of cholinergic neurons in normal-hearing ChAT-Cre mice to selectively label the cholinergic projections to the IC from each of the cholinergic sources. Labeling of cholinergic projections from the PPT and LDT revealed cholinergic axons and boutons terminating throughout the IC, with the ipsilateral projection being denser. Electron microscopic examination showed that these cholinergic axons can form traditional synaptic junctions with IC neurons. In separate experiments, selective labeling of cholinergic projections from the LPGi revealed bilateral projections to the IC. The LPGi axons exhibited relatively equal densities on ipsilateral and contralateral sides, but on both sides the terminations were largely restricted to the non-lemniscal regions of the IC (i.e., the dorsal cortex, lateral cortex and intercollicular tegmentum). We conclude first that cholinergic axons can form traditional synapses in the IC. In addition, lemniscal and non-lemniscal regions of the IC receive different patterns of cholinergic innervation. The lemniscal IC (IC central nucleus) is innervated by cholinergic neurons in the PPT and the LDT whereas the non-lemniscal "shell" areas of the IC are innervated by the PPT and LDT and by cholinergic neurons in the LPGi. DATA AVAILABILITY: Data will be made available on request.
PubMed: 38914378
DOI: 10.1016/j.jchemneu.2024.102443 -
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 -
Ochsner Journal 2024Primary malignant melanoma rarely occurs in the oral cavity. The tongue is a particularly unusual primary site; lesions may be pigmented or amelanotic. Primary...
Primary malignant melanoma rarely occurs in the oral cavity. The tongue is a particularly unusual primary site; lesions may be pigmented or amelanotic. Primary malignant melanoma is frequently mistaken for squamous cell carcinoma. A 27-year-old male presented with a large, painless, ulceroproliferative mass on the dorsal surface of the tongue for 6 months. Squamous cell carcinoma was suspected, and the lesion was biopsied. Histopathology was compatible with primary amelanotic malignant melanoma. The patient had no cutaneous lesions consistent with malignant melanoma, and no definitive metastatic lesions were found. Ultrasound and computed tomography did not reveal any evidence of regional draining lymph node metastasis or suspicious lesions anywhere else in the body. The patient underwent composite resection of the tongue tumor and bilateral neck lymph node dissection, had an uneventful postoperative recovery, but was lost to follow-up. Primary oral amelanotic malignant melanoma is a highly aggressive, potentially fatal tumor and because of its rarity, presents a diagnostic challenge. The ideal treatment modality for primary malignant melanoma of the tongue is poorly defined, but surgery is regarded as the most effective course of therapy.
PubMed: 38912190
DOI: 10.31486/toj.23.0094 -
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 -
Plastic and Reconstructive Surgery.... Jun 2024The aim of this study was to compare the use of pedicled local (PFs) versus random pattern flaps (RpFs) in foot and ankle reconstruction in patients with chronic,...
BACKGROUND
The aim of this study was to compare the use of pedicled local (PFs) versus random pattern flaps (RpFs) in foot and ankle reconstruction in patients with chronic, nonhealing wounds.
METHODS
A single-center, retrospective review of 204 patients with 118 PFs and 86 RpFs was performed. The primary outcome included rates of limb salvage.
RESULTS
PFs were used more often in the hindfoot (44.1% versus 30.2%, = 0.045), lateral and medial surface (39.8% versus 18.6%, = 0.001), and wounds containing exposed bone and hardware (78.8% versus 62.8%, = 0.018). RpFs were used more for forefoot (19.8% versus 10.2%, = 0.053) and plantar defects (58.1% versus 30.3%, = 0.000). RpFs had a higher rate of immediate success (100% versus 95.8%, = 0.053), with no significant differences in rate of long-term limb salvage (77.1% versus 69.8%, = 0.237). PFs had higher rates of ischemia requiring intervention (11.0% versus 3.5%, = 0.048). RpFs had a higher rate of minor amputations (15.12% versus 6.8%, = 0.053) but similar rates of major amputation (15.1% versus 16.1%, = 0.848). There were no significant differences in rates of mortality or ambulatory status.
CONCLUSIONS
Both RpFs and PFs remain reliable options to reconstruct defects of the foot and ankle. Optimizing the use of each flap type should consider wound characteristics. RpFs are preferred for dorsal and plantar defects, whereas PFs are protective for minor infections and preferred for deeper wounds despite a higher rate of partial necrosis.
PubMed: 38911575
DOI: 10.1097/GOX.0000000000005921 -
Neurobiology of Language (Cambridge,... 2024Language processing relies on the communication between brain regions that is achieved through several white matter tracts, part of the dorsal, ventral, and medial...
Language processing relies on the communication between brain regions that is achieved through several white matter tracts, part of the dorsal, ventral, and medial pathways involved in language processing and control (Coggins et al., 2004; Friederici & Gierhan, 2013; Hickok & Poeppel, 2007; Luk et al., 2011). While changes in white matter tract morphology have been reported as a function of second language learning in bilinguals, little is known about changes that may be present in multilanguage users. Here we investigate white matter morphometry in a group of highly proficient multilinguals, (individuals with proficiency in four or more languages), compared to a group of monolinguals. White matter morphometry was quantified using a fixel-based analysis (Raffelt et al., 2015; Raffelt et al., 2017; Tournier et al., 2007). Higher fiber cross-section and lower fiber density values were observed for the multilinguals, in the dorsal pathways (superior longitudinal fasciculus and arcuate fasciculus) and the ventral pathway, including the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and the uncinate fasciculus. Segments of the corpus callosum, the fornix, and the cortico-spinal tract showed decreases in all three morphometry measures for multilinguals. The findings suggest differential efficiencies in neural communication between domain-specific language regions and domain-general cognitive processes underlying multilingual language use. We discuss the results in relation to the bilingual Anterior to Posterior and Subcortical Shift (BAPSS) hypothesis (Grundy et al., 2017) and the Dynamic Restructuring Model (Pliatsikas, 2020).
PubMed: 38911457
DOI: 10.1162/nol_a_00144 -
Journal of Orthopaedic Case Reports Jun 2024The aim of this study was to investigate whether surgery with a 10 mm approach for volar locking plate fixation provides equivalent early post-operative outcomes to...
INTRODUCTION
The aim of this study was to investigate whether surgery with a 10 mm approach for volar locking plate fixation provides equivalent early post-operative outcomes to conventional incision surgery for distal radius fractures.
MATERIALS AND METHODS
The subjects were divided into a conventional incision group (mean age: 59.1 years, 8 males and 23 females) and a 10 mm approach group (mean age: 59.9 years of age, 6 males and 20 females). The wrist range of motion; grip strength; visual analog scale (VAS); quick disabilities of the arm, shoulder, and hand (Q-DASH) score; and modified Mayo score were assessed at 3 months after surgery. In addition, radial inclination, ulnar variance, and volar tilt were evaluated on post-operative radiography.
RESULTS
There was no significant difference between the groups in the wrist range of motion, grip strength, VAS, Q-DASH score, modified Mayo wrist score, and three parameters of post-operative radiography. All patients in both groups had no complications during the perioperative period.
CONCLUSION
We found that a 10 mm approach obtained early post-operative outcomes and alignment comparable to conventional incision surgery for patients with dorsal displaced distal radius fractures.
PubMed: 38910991
DOI: 10.13107/jocr.2024.v14.i06.4546 -
Cureus May 2024Pilar cysts are common benign cysts of follicular origin that typically arise in areas of skin containing dense hair follicles such as the scalp. Here we describe a...
Pilar cysts are common benign cysts of follicular origin that typically arise in areas of skin containing dense hair follicles such as the scalp. Here we describe a unique case of a young woman who was found to have a pilar cyst on the dorsum of her hand, a rather atypical location given the relative lack of pilosebaceous units. This case illustrates the variability in pilar cyst presentation and the importance of considering a pilar cyst in the differential diagnosis of a patient presenting with a tumor of the dorsal hand.
PubMed: 38910694
DOI: 10.7759/cureus.60865