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IBRO Neuroscience Reports Dec 2024First-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve...
First-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve sufficient analgesia with these drugs. Opioids are considered third-line analgesics in NP due to potential severe and unpredictable adverse effects in long-term use. Also, opioid tolerance and NP may have shared mechanisms, raising further concerns about opioid use in NP. We set out to further elucidate possible shared and separate mechanisms after chronic morphine treatment and oxaliplatin-induced and diabetic polyneuropathies, and to identify potential diagnostic markers and therapeutic targets. We analysed thermal nociceptive behaviour, the transcriptome of dorsal root ganglia (DRG) and the metabolome of cerebrospinal fluid (CSF) in these three conditions, in rats. Several genes were differentially expressed, most following oxaliplatin and least after chronic morphine treatment, compared with saline-treated rats. A few genes were differentially expressed in the DRGs in all three models (e.g. and ). Some, e.g. were differentially expressed in both diabetic and oxaliplatin models. Other differentially expressed genes were associated with nociception, inflammation, and glial cells. The CSF metabolome was most significantly affected in the diabetic rats. Interestingly, we saw changes in nicotinamide metabolism, which has been associated with opioid addiction and withdrawal, in the CSF of morphine-tolerant rats. Our results offer new hypotheses for the pathophysiology and treatment of NP and opioid tolerance. In particular, the role of nicotinamide metabolism in opioid addiction deserves further study.
PubMed: 38933596
DOI: 10.1016/j.ibneur.2024.05.006 -
Ecology and Evolution Jun 2024A new species of the extant staphylinid genus Moore & Legner, sp. nov., is reported from mid-Cretaceous Kachin amber of northern Myanmar. is distinguishable from...
A new species of the extant staphylinid genus Moore & Legner, sp. nov., is reported from mid-Cretaceous Kachin amber of northern Myanmar. is distinguishable from extant members of by the smoother dorsal surface of head, pronotum and elytra, less prominent median projection of clypeus, unnotched mesal edge of mandibles, semiglabrous antennomere 6, and longer tarsomere 1. The pollen-containing coprolite attached to the beetle and the crystals within the beetle body provide valuable information about the biology and taphonomy of the fossil.
PubMed: 38932960
DOI: 10.1002/ece3.11487 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic...
Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP's anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1β, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP.
PubMed: 38931456
DOI: 10.3390/ph17060789 -
Nutrients Jun 2024The skin, serving as the body's primary defense against external elements, plays a crucial role in protecting the body from infections and injuries, as well as...
The skin, serving as the body's primary defense against external elements, plays a crucial role in protecting the body from infections and injuries, as well as maintaining overall homeostasis. Skin aging, a common manifestation of the aging process, involves the gradual deterioration of its normal structure and repair mechanisms. Addressing the issue of skin aging is increasingly imperative. Multiple pieces of evidence indicate the potential anti-aging effects of exogenous nucleotides (NTs) through their ability to inhibit oxidative stress and inflammation. This study aims to investigate whether exogenous NTs can slow down skin aging and elucidate the underlying mechanisms. To achieve this objective, senescence-accelerated mouse prone-8 (SAMP8) mice were utilized and randomly allocated into Aging, NTs-low, NTs-middle, and NTs-high groups, while senescence-accelerated mouse resistant 1 (SAMR1) mice were employed as the control group. After 9 months of NT intervention, dorsal skin samples were collected to analyze the pathology and assess the presence and expression of substances related to the aging process. The findings indicated that a high-dose NT treatment led to a significant increase in the thickness of the epithelium and dermal layers, as well as Hyp content ( < 0.05). Additionally, it was observed that low-dose NT intervention resulted in improved aging, as evidenced by a significant decrease in p16 expression ( < 0.05). Importantly, the administration of high doses of NTs could improve, in some ways, mitochondrial function, which is known to reduce oxidative stress and promote ATP and NAD production significantly. These observed effects may be linked to NT-induced autophagy, as evidenced by the decreased expression of p62 and increased expression of LC3BI/II in the intervention groups. Furthermore, NTs were found to upregulate pAMPK and PGC-1α expression while inhibiting the phosphorylation of p38MAPK, JNK, and ERK, suggesting that autophagy may be regulated through the AMPK and MAPK pathways. Therefore, the potential induction of autophagy by NTs may offer benefits in addressing skin aging through the activation of the AMPK pathway and the inhibition of the MAPK pathway.
Topics: Animals; Skin Aging; Autophagy; Mice; AMP-Activated Protein Kinases; Nucleotides; Oxidative Stress; Skin; Male; MAP Kinase Signaling System; Signal Transduction; Mitogen-Activated Protein Kinases
PubMed: 38931262
DOI: 10.3390/nu16121907 -
Journal of Clinical Medicine Jun 2024: Defects of the ascending ramus of the mandible, including the condylar head and neck or the whole temporomandibular joint (TMJ), are difficult to reconstruct....
: Defects of the ascending ramus of the mandible, including the condylar head and neck or the whole temporomandibular joint (TMJ), are difficult to reconstruct. Reconstruction is mainly based on the use of alloplastic joint prosthesis, costochondral grafting, distraction osteogenesis of the dorsal part of the mandibular ramus, or osseous microvascular flaps of various origin. With the objective of developing a method that overcomes the restrictions of these methods, we recently introduced a sequential chimeric flap consisting of a lateral femoral condyle flap (LFC) and deep circumflex iliac artery flap (DCIA) for reconstruction of up to half of the mandible and the condylar head and neck. : The chimeric flap was used in four patients with the following diagnoses: therapy-refractory osteomyelitis, extended recurrent odontogenic keratozyst, Goldenhar syndrome, and adenocarcinoma of the parotid gland. After a diagnostic workup, LFC and DCIA flaps were harvested in all patients and used in a sequential chimeric design for the reconstruction of the mandibular body and condylar head and neck. : Follow-up from at least 24 months up to 70 month after surgery showed a successful reconstruction in all four patients. The LFC provided a cartilaginous joint surface, allowing for a satisfactory masticatory function with a stable occlusion and unrestricted mouth opening and preserved or regained lateral and medial excursions in all patients. The DCIA allowed for a bony reconstruction anatomically resembling a non-atrophied mandibular body. No flap-related complications were observed. : The sequential chimeric LFC and DCIA flap is an appropriate method for reconstructing up to half of the mandible and the condylar head and neck. It is suitable in cases where alloplastic joint replacement cannot be used or where other methods have failed. Due to the necessity of harvesting two flaps, the burden of care is increased, and a careful indication is required. The technique is reserved for maxillofacial surgeons who have already gained significant experience in the field of microsurgery.
PubMed: 38930140
DOI: 10.3390/jcm13123613 -
Journal of Clinical Medicine Jun 2024Floating-Harbor syndrome (FHS) is an extremely rare genetic disorder connected with a distinctive facial appearance, various skeletal malformations, delayed bone age,...
Floating-Harbor syndrome (FHS) is an extremely rare genetic disorder connected with a distinctive facial appearance, various skeletal malformations, delayed bone age, and expressive language delays. It is caused by heterozygous mutations in the Snf2-related CREBBP activator protein (SRCAP) gene. The aim of this paper is to describe the case of a 14-year-old male with FHS, referring to a review of the literature, and to collect all reported symptoms. In addition, the orthodontic treatment of the patient is described. For this, the electronic databases PubMed and Scopus were searched using the keyword "Floating-Harbor syndrome". Similar to previous cases in the literature, the patient presented with short stature; a triangular face with a large bulbous nose; deep-set eyes and narrow eyelid gaps; a wide mouth with a thin vermilion border of the upper lip; and dorsally rotated, small ears. They also presented some less-described symptoms, such as macrodontia and micrognathia. Moreover, mild mental retardation, microcephaly, and delayed psychomotor development were found. On the basis of an extraoral, intraoral examination, X-rays, and CBCT, he was diagnosed with overbite, canine class I and angle class III, on both sides. To the best of our knowledge, orthodontic treatment of this disease has not been assessed in detail so far, so this is the first case.
PubMed: 38929963
DOI: 10.3390/jcm13123435 -
Life (Basel, Switzerland) Jun 2024Traditional anatomy-based penile venous surgery is deemed inadequate. Based on revolutionary insights into penile vasculature, penile venous stripping (PVS) shows...
INTRODUCTION
Traditional anatomy-based penile venous surgery is deemed inadequate. Based on revolutionary insights into penile vasculature, penile venous stripping (PVS) shows promise in treating adolescent erectile dysfunction (AED). We aimed to report on this novel approach.
METHODS
We conducted a retrospective analysis of 223 individuals under 30 diagnosed with veno-occlusive dysfunction (VOD) between 2009 and 2023. Among them, 83 were diagnosed with AED and divided into the PVS ( = 37) and no-surgery (NS, = 46) groups. All participants had been dissatisfied with conventional therapeutic options. Dual pharmaco-cavernosography was the primary diagnostic modality. PVS involved stripping the deep dorsal vein and two cavernosal veins after securing each emissary's vein with a 6-0 nylon suture. Erection restoration was accessed using the abridged five-item version of the International Index of Erectile Function (IIEF-5) score system and the erection hardness scale (EHS). Statistical analysis was performed using IBM SPSS 21.0.
RESULTS
There were significant differences (both < 0.001) between the preoperative and postoperative IIEF-5 scores in the PVS and NS groups (9.8 ± 3.0 vs. 20.4 ± 2.2; 9.9 ± 2.5 vs. 9.5 ± 2.1), as well as in the EHS scores (1.7 ± 0.7 vs. 3.5 ± 0.6 and 1.8 ± 0.5 vs. 1.3 ± 0.4). The satisfaction rate was 87.9% (29/33) in the PVS group and 16.7% (17/41) in the NS group.
CONCLUSIONS
AED can be effectively treated using physiological methods, although larger patient cohorts are needed for validation.
PubMed: 38929745
DOI: 10.3390/life14060762 -
Medicina (Kaunas, Lithuania) Jun 2024: This study aimed to investigate the relationship between neuropathic pain and CREB-binding protein (CBP) and methyl-CpG-binding protein 2 (MeCP2) expression levels in...
: This study aimed to investigate the relationship between neuropathic pain and CREB-binding protein (CBP) and methyl-CpG-binding protein 2 (MeCP2) expression levels in a rat model with spared nerve injury (SNI). : Rat (male Sprague-Dawley white rats) models with surgical SNI (n = 6) were prepared, and naive rats (n = 5) were used as controls. The expression levels of CBP and MeCP2 in the spinal cord and dorsal root ganglion (DRG) were compared through immunohistochemistry at 7 and 14 days after surgery. The relationship between neuropathic pain and CBP/MeCP2 was also analyzed through intrathecal siRNA administration. : SNI induced a significant increase in the number of CBPs in L4 compared with contralateral DRG as well as with naive rats. The number of MeCP2 cells in the dorsal horn on the ipsilateral side decreased significantly compared with the contralateral dorsal horn and the control group. SNI induced a significant decrease in the number of MeCP2 neurons in the L4 ipsilateral DRG compared with the contralateral DRG and naive rats. The intrathecal injection of CBP siRNA significantly inhibited mechanical allodynia induced by SNI compared with non-targeting siRNA treatment. MeCP2 siRNA injection showed no significant effect on mechanical allodynia. : The results suggest that CBP and MeCP2 may play an important role in the generation of neuropathic pain following peripheral nerve injury.
Topics: Animals; Rats, Sprague-Dawley; Methyl-CpG-Binding Protein 2; Neuralgia; Male; Rats; Disease Models, Animal; CREB-Binding Protein; Ganglia, Spinal; RNA, Small Interfering; Peripheral Nerve Injuries; Spinal Cord; Immunohistochemistry
PubMed: 38929606
DOI: 10.3390/medicina60060989 -
Animals : An Open Access Journal From... Jun 2024The skin of bony fish is the first physical barrier and is responsible for maintaining the integrity of the fish. Lesions make the skin vulnerable to potential infection...
The skin of bony fish is the first physical barrier and is responsible for maintaining the integrity of the fish. Lesions make the skin vulnerable to potential infection by pathogens present in the aquatic environment. In this way, wound repair has barely been studied in gilthead sea bream. Thus, this study investigated the modulation of peripheral neuro-endocrine and tissue repair markers at the transcriptional level in the skin of teleost fish subjected to mechanical damage above or below the lateral line (dorsal and ventral lesions, respectively). Samples were evaluated using RT-qPCR at 2-, 4-, and 20-days post-injury. Fish with a ventral lesion presented a trend of progressive increase in the expressions of (), (), (), (), (), (), and (less pronounced) (). By contrast, fish with a dorsal lesion registered no significant increase or biological trend for the genes evaluated at the different sampling times. Collectively, the results show a rapid and more robust response of neuro-endocrine and tissue repair markers in the injuries below than above the lateral line, which could be attributable to their proximity to vital organs.
PubMed: 38929434
DOI: 10.3390/ani14121815 -
Animals : An Open Access Journal From... Jun 2024This study evaluates the change in an MRI of the proximal metacarpal region in a group of sport horses that returned to work. This retrospective analysis evaluated 18...
BACKGROUND
This study evaluates the change in an MRI of the proximal metacarpal region in a group of sport horses that returned to work. This retrospective analysis evaluated 18 limbs represented by 17 horses.
RESULTS
The hyperintense signal within the dorsal collagenous part of the proximal suspensory ligament (PSL) on T1W/T2*W GRE sequences decreased or stayed the same in the majority of cases. The hyperintense STIR signal within the dorsal collagenous part of the PSL resolved in the majority of the patients, and the third metacarpal bone (McIII) hyperintense STIR signal resolved in all patients. The dorsal margin irregularity of the PSL stayed the same, and McIII sclerosis and resorption of the palmar margin of McIII stayed the same in the majority of cases. McIII hyperintense STIR signal resolution carries a broad time range, with a mean of 94 days and a range of 47-202 days.
CONCLUSIONS
Complete normalization of the dorsal collagenous part of the PSL does not appear necessary for a return to soundness, but a resolution of the McIII hyperintense STIR signal is expected for horses returning to soundness. A rescan period of 120 days for the proximal metacarpal region is suggested. In addition, there was no significant change in the size of the PSL between the initial and final MRI.
PubMed: 38929351
DOI: 10.3390/ani14121731