efficacy-fu-s-subcutaneous-needling-on-sciatic-nerve-pain-behavioral

Efficacy of Fu's Subcutaneous Needling on Sciatic Nerve Pain: Behavioral and Electrophysiological Changes in a Chronic Constriction Injury Rat Model

Fu&#39;s subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the ...

Chang Bing Show Chwan Memorial Hospital

Tajen University

In traditional Chinese medicine, the skin reflects the health of body organs. A skin whitening agent, named seven whitening creams (also called Chi-Bai-San), has been used since ancient times in China. Chi-Bai-San reduces melanin and helps to reduce wrinkles.

Attenuation of in vitro and in vivo melanin synthesis using a Chinese herbal medicine through the inhibition of tyrosinase activity.

Hot compress modalities are used to ameliorate pain despite prevalent confusion about which modality should be used and when. Most recommendations for hot compresses are based on empirical experience, with limited evidence to support its efficacy. To obtain insight into the nerve transmission mechanism of hot compresses and to identify the nerve injury marker proteins specifically associated with sciatic nerve pain, we established a rat model of chronic constriction injury (CCI) and performed mechanical allodynia, electrophysiology, and histopathological analysis. All CCI rats exhibited geometric representation of the affected hind paw, which indicated a hyper-impact on both mechanical gait and asymmetry of gait on day 28. The CCI model after 28 days of surgery significantly reduced compound muscle action potential (CMAP) amplitude, but also significantly reduced latency. Administration of hot compress for 3 weeks (heated at 40-42°C, cycle of 40 min, and rest for 20 min, three cycles each time, three times per week) significantly increased the paw withdrawal thresholds in response to stimulation by Von Frey fibers and reversed the CCI-induced reduced sciatic functional index (SFI) scores. Hot compress treatment in the CCI model improved CMAP amplitude and latency. The S100 protein expression level in the CCI+Hot compression group was 1.5-fold higher than in the CCI group; it dramatically reduced inflammation, such as tumor necrosis factor alpha and CD68 expression in nerve injury sites. Synaptophysin (Syn) expression in the CCI+Hot compression group was less than threefold in the CCI group at both nerve injury sites and brain (somatosensory cortex and hippocampus). This finding indicates that local nerve damage and inflammation cause significant alterations in the sensorimotor strip, and hot compress treatment could significantly ameliorate sciatic nerve pain by attenuating Syn and inflammatory factors from local pathological nerves to the brain. This study determines the potential efficacy and safety of hot compress, and may have important implications for its widespread use in sciatic nerve pain treatment.

Ameliorative Potential of Hot Compress on Sciatic Nerve Pain in Chronic Constriction Injury-Induced Rat Model.

Diabetic retinopathy (DR) is a pathophysiologic vasculopathic process with obscure mechanisms and limited effective therapeutic strategies. Aryl hydrocarbon receptor (AhR) is an important regulator of xenobiotic metabolism and an environmental sensor. The aim of the present study was to investigate the role of AhR in the development of DR and elucidate the molecular mechanism of its downregulation. DR was evaluated in diabetes-induced retinal injury in wild type and AhR knockout (AhR-/-) mice. Retinal expression of AhR was determined in human donor and mice eyes by immunofluorescence since AhR activity was examined in diabetes. AhR knockout (AhRKO) mice were used to induce diabetes with streptozotocin, high-fat diet, or genetic double knockout with diabetes spontaneous mutation (Leprdb) (DKO; AhR-/-×Leprdb/db) for investigating structural, functional, and metabolic abnormalities in vascular and epithelial retina. Structural molecular docking simulation was used to survey the pharmacologic AhR agonists targeting phosphorylated AhR (Tyr245). Compared to diabetic control mice, diabetic AhRKO mice had aggravated alterations in retinal vasculature that amplified hallmark features of DR like vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration, and neovascularization. AhR agonists effectively inhibited inflammasome formation and promoted AhR activity in human retinal microvascular endothelial cells and pigment epithelial cells. AhR activity and protein expression was downregulated, resulting in a decrease in DNA promoter binding site of pigment epithelium-derived factor (PEDF) by gene regulation in transcriptional cascade. This was reversed by AhR agonists. Our study identified a novel of DR model that target the protective AhR/PEDF axis can potentially maintain retinal vascular homeostasis, providing opportunities to delay the development of DR.

Aryl hydrocarbon receptor deficiency augments dysregulated microangiogenesis and diabetic retinopathy.

The prognosis of systemic lupus erythematosus (SLE) is unpredictable. This study aimed to examine the regulatory mechanism of the AHR/TET2/NT5E pathway during SLE progression. The AHR, TET2 and NT5E expression levels were examined in T regulatory cells (Tregs) of patients with SLE. The correlation of AHR, TET2 or NT5E expression levels with the immunosuppressive functions of Tregs was analysed. In patients with SLE, the number of CD4 IL2RA FOXP3 T cell subset was positively correlated with the SLE disease activity index value and negatively correlated with the AHR and TET2 expression levels in CD4 IL2RA FOXP3 Tregs. Transcriptional profiles of 79 patients with SLE obtained from the Gene Expression Omnibus database (GSE61635 dataset) revealed a significant positive correlation between the mRNA expression levels of AHR and TET2. In silico analysis predicted that the TET2 promoter comprises an AHR-binding site. Kynurenine (KYN) promoted the binding of AHR to the TET2 promoter in Tregs of patients with SLE and Jurkat T cell lines. Furthermore, NT5E expression was significantly downregulated in Tregs of patients with SLE, which can be attributed to the dysregulation of NT5E promoter methylation status induced by downregulated TET2 activity. Furthermore, the Treg immunosuppressive activity, which is mediated through the TET2 and A2AR-adenosine pathways, in the KYN-treated group was approximately two-fold higher than that in the control group. The AHR/TET2/NT5E axis mediates the Treg immunosuppressive activity. These findings provide novel insights for the development of therapeutic approaches for SLE and related autoimmune diseases.

AHR/TET2/NT5E axis downregulation is associated with the risk of systemic lupus erythematosus and its progression.

Age-related macular degeneration is the leading cause of visual deficiency in older adults worldwide. Melatonin (MT) can potentially reduce retinal deterioration. However, the mechanism by which MT mediates regulatory T cells (Tregs) in the retina is not yet fully understood.

Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration.

Hepatocellular carcinoma (HCC) is recognized as the fifth most common cancer and the third most common cause of death in Asian population. Studies reported that HCC is relatively insensitive to radiotherapy (RT); thus, considering how to sensitize HCC to RT is worth to be elucidated. Epidermal growth factor receptor (EGFR)-mediated signalling transduction plays the important role in regulating treatment efficacy of HCC. An active compound, 18beta-glycyrrhetinic acid (18β-GA), has been reported to own anti-tumour effect. However, whether 18β-GA possess RT sensitization ability in HCC remains unclear. Here, we used RNA data from TCGA-LIHC (Liver hepatocellular carcinoma) to identify the role between EGFR/ERK/nuclear factor kappa B (NF-κB) signalling and RT by radiosensitivity index (RSI) analysis. We suggested that patients with activated NF-κB signalling may show resistance to RT treatment, whereas combining 18β-GA may reinforce RT efficacy in a Hep3B-bearing animal model. 18β-GA combined with RT showed superior tumour inhibition capacity as compared to monotherapy and even reached similar efficacy as erlotinib combined with RT. Treatment promotion of RT by 18β-GA in HCC is not only through diminishing RT-induced EGFR/ERK/NF-κB signalling but also promoting RT-induced apoptosis pathways. 18β-GA may act as radiosensitizer through inactivating EGFR-mediated HCC progression and inducing caspase-dependent apoptosis signalling.

Inactivation of EGFR/ERK/NF-κB signalling associates with radiosensitizing effect of 18β-glycyrrhetinic acid on progression of hepatocellular carcinoma.

Article	Year
Attenuation of in vitro and in vivo melanin synthesis using a Chinese herbal medicine through the inhibition of tyrosinase activity. Phytomedicine : international journal of phytotherapy and phytopharmacology\| PubMed ID: 34923233	2022
Ameliorative Potential of Hot Compress on Sciatic Nerve Pain in Chronic Constriction Injury-Induced Rat Model. Frontiers in synaptic neuroscience\| PubMed ID: 35685245	2022
Aryl hydrocarbon receptor deficiency augments dysregulated microangiogenesis and diabetic retinopathy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 36152407	2022
AHR/TET2/NT5E axis downregulation is associated with the risk of systemic lupus erythematosus and its progression. Immunology\| PubMed ID: 36314527	2023
Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 36905808	2023
Inactivation of EGFR/ERK/NF-κB signalling associates with radiosensitizing effect of 18β-glycyrrhetinic acid on progression of hepatocellular carcinoma. Journal of cellular and molecular medicine\| PubMed ID: 37177859	2023

De-Wei Lai

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