Association of serum and local GRP78 and CHOP expressions with disease progression in patients with non-traumatic osteonecrosis of femoral head

Journal of Orthopaedic Surgery and Research, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 29, 2025

The endoplasmic reticulum stress (ER stress) has been involved in various musculoskeletal disorders including non-traumatic osteonecrosis of femoral head (NT-ONFH). current study aimed to investigate the association glucose-regulated protein 78 (GRP78) as well CCAAT/enhancer-binding homologous (CHOP) expressions serum and (FH) tissues with NT-ONFH's severity. We enrolled NT-ONFH patients (n = 150) alongside healthy controls (HCs, n 150). Meanwhile, 49 neck fracture (FNF) were also enrolled. Serum CHOP GRP78 levels determined through enzyme linked immunosorbent assay (ELISA). Local detected by immunohistochemistry, western blot, real-time polymerase chain reaction (RT-PCR). Radiographic severity was assessed FICAT grading system. visual analogue scale (VAS) together Harris hip score (HHS) utilized determine symptomatic markedly increased than HCs. at stage 4 showed significant higher contrast those 3. Furthermore, 3 demonstrated 2. There a positive correlation observed between stages. A total 42 ONFH 3, 40 4, FNF received replacement (THR). mRNA elevated necrotic area compared non-necrotic FH statistical significance. expression within local significantly opposed Besides, ROC curve analysis indicated that may act indicators disease progression. GRP78, both site, VAS scores but an inverse relationship HHS. positively progression patients. Potential therapeutics targeting ER related serve method for alleviating NT-ONFH.

Язык: Английский

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Nitroxidative Stress, Cell—Signaling Pathways, and Manganese Porphyrins: Therapeutic Potential in Neuropathic Pain

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2050 - 2050

Опубликована: Фев. 26, 2025

Neuropathic pain, a debilitating condition arising from somatosensory system damage, significantly impacts quality of life, leading to anxiety, self-mutilation, and depression. Oxidative nitrosative stress, an imbalance between reactive oxygen nitrogen species (ROS/RNS) antioxidant defenses, plays crucial role in its pathophysiology. While are essential for physiological functions, excessive levels can cause cellular component neuronal dysfunction pain. This review highlights the complex interactions species, systems, cell signaling, neuropathic We discuss roles ROS/RNS detrimental effects oxidative stress. Furthermore, we explore potential manganese porphyrins, compounds with properties, as promising therapeutic agents mitigate stress alleviate pain by targeting key pathways involved Further research is needed fully understand their managing human non-human animals.

Язык: Английский

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Understanding the comorbidities among psychiatric disorders, chronic low-back pain, and spinal degenerative disease using observational and genetically informed analyses

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

ABSTRACT Psychiatric disorders and symptoms are associated with differences in pain perception sensitivity. These can have important implications treating spinal degenerative disease (SDD) chronic low-back (CLBP). Leveraging data from the UK Biobank (UKB) All of Us Research Program (AoU), we investigated effects linking psychiatric (alcohol use disorder, anxiety, attention deficit hyperactivity bipolar cannabis depression, opioid posttraumatic stress schizophrenia) to SDD CLBP. We applied multi-nominal regression models, polygenic risk scoring (PRS), one-sample Mendelian randomization (MR) triangulate underlying associations observed. also performed gene ontology drug-repurposing analyses dissect biology shared among mental illnesses, SDD, Comparing individuals affected only by (UKB N=37,745, AoU N=3,477), those CLBP N=15,496, N=23,325), both conditions N=11,463, N= 13,451) controls N=337,362, 117,162), observational genetically informed highlighted that strongest across three case groups were observed for alcohol disorder. Additionally, schizophrenia its PRS appeared an inverse relationship CLBP, their comorbidity. One-sample MR a potential direct effect internalizing on outcomes was particularly strong SDD. Our identified histone deacetylase inhibitors as targeting molecular pathways disorders, In conclusion, these findings support comorbidity is due contribution health outcomes. pleiotropic mechanisms together sociocultural factors play key role shaping SDD-CLBP patterns psychopathology spectrum.

Язык: Английский

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Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(4), С. 259 - 259

Опубликована: Апрель 8, 2025

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) are characterized progressive neuronal loss cognitive or motor decline, often underpinned pathological protein misfolding aggregation. Emerging evidence suggests potential mechanistic link between chronic NDs, with contributing neuroinflammatory states homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis aggregation serve bridge We systematically examine molecular pathways misfolding, proteostasis dysfunction shared neuroimmune mechanisms, highlighting prion-like propagation misfolded proteins, neuroinflammation, oxidative stress common denominators. further discuss from experimental models clinical studies linking accelerated pathology—including tau accumulation, amyloid dysregulation, microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting aggregation, enhancing chaperone function, modulating unfolded response (UPR), attenuating glial activation explored strategies mitigate possibly slow Understanding this intersection not only elucidates pain’s role decline but also interventions addressing inflammation could yield dual benefits management modification.

Язык: Английский

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Kinsenoside attenuates ER stress and inhibits inflammatory responses through IL-10/STAT/SOCS3 pathway in chronic pain relief

Neuropharmacology, Год журнала: 2025, Номер unknown, С. 110463 - 110463

Опубликована: Апрель 1, 2025

Язык: Английский

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The analgesic effect of paeoniflorin: A focused review

Open Life Sciences, Год журнала: 2024, Номер 19(1)

Опубликована: Янв. 1, 2024

Pain has been a prominent medical concern since ancient times. Despite significant advances in the diagnosis and treatment of pain contemporary medicine, there is no therapeutic cure for chronic pain. Chinese herbaceous peony, traditional analgesic herb clinical use millennia, with widespread application substantial efficacy. Paeoniflorin (PF), main active ingredient antioxidant, anti-inflammatory, anticancer, analgesic, antispasmodic properties, among others. The effect PF, involving multiple critical targets regulatory pathways, hot spot current research. This article reviews literature related to PF past decade discusses molecular mechanism including protective effects nerve cells, inhibition inflammatory reactions, antioxidant effects, reduction excitability nociceptor, nociceptive excitatory neuroreceptor system, activation inhibitory system regulation other receptors involved sensitization. Thus, providing theoretical basis prevention Furthermore, prospect PF-based drug development presented propose new ideas therapy.

Язык: Английский

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Drug Binding to Partially Unfolded Serum Albumin: Insights into Nonsteroidal Anti-Inflammatory Drug Naproxen–BSA Interactions from Spectroscopic and MD Simulation Studies

The Journal of Physical Chemistry B, Год журнала: 2024, Номер unknown

Опубликована: Сен. 24, 2024

Understanding the binding details of a small-molecule drug to protein in its partially unfolded state is important for delivery as it provides insight into overall drug-binding ability protein, even when majority pockets are impaired. The interaction proteins with drugs remains poorly understood due lack structural information on their states. Here, we studied between serum albumin (bovine (BSA) model system), an abundant blood that effective carrier numerous known drugs, and nonsteroidal anti-inflammatory (NSAID) naproxen (NPS) using various spectroscopic computational methods. Molecular dynamics simulations starting from drug-unbound performed at physiological higher temperatures revealed novel hydrophobic sites BSA surface. We analyzed BSA-NPS presence absence cationic organized assembly CTAB two oligosaccharides (β-CD 2-HP-β-CD) different excitation wavelengths. solvation under NPS-bound conditions became ∼4.6% faster. Oligosaccharides were found increase solubility NPS by providing environment formation inclusion complexes through host-guest interactions. These findings provide comprehensive overview uncover mechanism BSA, revealing electrostatic interactions hydrogen bonds required bind these noncanonical sites. molecular-level understanding commonly used NSAIDs like will be useful designing pharmaceutically molecules efficient loading properties.

Язык: Английский

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Cluster Headache and Hypoxia: Breathing New Life into an Old Theory, with Novel Implications

Neurology International, Год журнала: 2024, Номер 16(6), С. 1691 - 1716

Опубликована: Дек. 4, 2024

Cluster headache is a severe, poorly understood disorder for which there are as yet virtually no rationally derived treatments. Here, Lee Kudrow’s 1983 theory, that cluster an overly zealous response to hypoxia, updated according current understandings of hypoxia detection, signaling, and sensitization. It shown the distinctive clinical characteristics (circadian timing attacks circannual patterning bouts, autonomic symptoms, agitation), risk factors (cigarette smoking; male gender), triggers (alcohol; nitroglycerin), genetic findings (GWAS studies), anatomical substrate (paraventricular nucleus hypothalamus, solitary tract nucleus/NTS, trigeminal caudalis), neurochemical features (elevated levels galectin-3, nitric oxide, tyramine, tryptamine), responsiveness treatments (verapamil, lithium, melatonin, prednisone, oxygen, histamine desensitization) can all be in terms hypoxic signaling. Novel treatment directions hypothesized, including repurposing pharmacological antagonists signaling molecules (HIF-2; P2X3) headache, breath training, physical exercise, high-dose thiamine, carnosine, flavonoid kaempferol. The limits knowledge described, program basic translational research proposed.

Язык: Английский

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