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Paclitaxel-induced downregulation of two-pore domain K+ channel 1.1 (K 2p 1.1) caused by increasing DNA methylation within its gene promoter in the dorsal root ganglion (DRG) contributes to neuropathic pain. Given that ten-eleven translocation methylcytosine dioxygenase 1 (TET1) promotes DNA demethylation and gene transcription, the present study investigated whether DRG overexpression of TET1 produces an antinociceptive effect on the paclitaxel-induced nociceptive hypersensitivity. TET1 was overexpressed in the DRG through unilateral microinjection of the herpes simplex virus expressing full-length Tet1 mRNA into the fourth and fifth lumbar DRGs of male rats. Behavioral tests were carried out to examine the effect of this overexpression on the paclitaxel-induced nociceptive hypersensitivity. Western blot analysis, chromatin immunoprecipitation assay and 5-hydroxymethylcytosine detection assay were performed to assess the levels of TET1/K 2p 1.1, 5-methylcytosine and 5-hydroxymethylcytosine, respectively. DRG overexpression of TET1 mitigated the paclitaxel-induced mechanical allodynia, heat hyperalgesia and cold hyperalgesia on the ipsilateral side during the development and maintenance periods. Locomotor function or basal (acute) responses to mechanical, heat or cold stimuli were not affected. Mechanistically, DRG overexpression of TET1 rescued the expression of K 2p 1.1 by blocking the paclitaxel-induced increase in the level of 5-methylcytosine and correspondingly reversing the paclitaxel-induced decreases in the amount of 5-hydroxymethylcytosine within the K 2p 1.1 promoter region in the microinjected DRGs of male rats. Our findings suggest that DRG overexpression of TET1 alleviated chemotherapy-induced neuropathic pain likely through rescuing DRG K 2p 1.1 expression. Our findings may provide a potential avenue for the management of this disorder. [ABSTRACT FROM AUTHOR]

Catalytic oxidation of lignocellulose to formic acid by vanadium-based catalysts is a promising method to obtain fine chemicals. Considerable progresses have been achieved on the conversion of polysaccharides components of lignocelluloses. However, the oxidation behavior and mechanism of lignin, which quite differs from the structures of polysaccharides, have not been studied in detail. This work presents an H 5 PV 2 Mo 10 O 40 -H 2 SO 4 catalytic oxidation of lignin to produce carboxylic acids (CAs, mainly including formic acid) using O 2. A total yield of CAs can be up to 41.9 wt%. The oxidation process includes the fast hydrolysis stage and the slow oxidation stage. A combined experimental and theoretical study is applied to further investigate the mechanism of the latter oxidation stage. The ring-opening reaction of hydrolysis products is the rate-controlling reaction in the CA formation pathway. Both phenol and o-quinone are active sites and indispensable intermediates, and the ring-opening reactions of them are faster than those of other aromatic structures. The vanadium catalyst helps the formation of o-quinone and reduces the activation energy of ring-opening reaction, thus accelerate the CA formation. The combined experimental and theoretical study could lead to an in-depth understanding of catalytic oxidation process and be helpful to make better utilization of biomass. [Display omitted] • An efficient method was proposed to convert lignin to valuable chemicals. • A yield of 41.9 wt% of carboxylic acids was obtained. • Catalytic oxidation process includes hydrolysis stage and oxidation stage. • Vanadium catalyst reduce the activation energy of the rate-controlling ring-opening reaction. [ABSTRACT FROM AUTHOR]

Epigenetic regulation is implicated in the neurogenesis of neuropathic pain. The repressor element 1 (RE1) silencing transcription factor (REST) corepressor (CoREST) proteins function as corepressors in the REST complex and/or LSD1 epigenetic complex. In the current study, we aimed to find the expression profile of CoREST1 in the dorsal root ganglion (DRG) and investigate whether it plays a role in neuropathic pain. The evoked pain behaviors in mice were examined by the von Frey test and thermal test in a spinal nerve ligation (SNL)-induced neuropathic pain mice model. CoREST1 siRNA or virus was administered by DRG microinjection or intrathecal injection. The CoREST1 expression in DRGs was examined by immunofluorescence, quantitative PCR, Western blotting, and co-immunoprecipitation. CoREST1 was non-selectively expressed in large, medium, and small DRG neurons, and it exclusively colocalized with LSD1. In neuropathic pain models, peripheral nerve injury induced the upregulation of CoREST1 and increased binding of CoREST1 with LSD1 in injured DRGs in male mice. Furthermore, CoREST1 siRNA prevented the development of SNL-induced pain hypersensitivity as well as led to the reduction of established pain hypersensitivity during the maintenance period in SNL mice. Conversely, the overexpression of CoREST1 in DRGs by in vivo transfection of virus-induced pain hypersensitivity in naive mice. Our study demonstrated that CoREST1, along with LSD1, was expressed in primary sensory neurons specifically in response to nerve injury, and promoted nociceptive pain hypersensitivity in mice. Thus, CoREST1 might serve as a potential target for treating neuropathic pain. In summary, CoREST1, along with LSD1, expressed in primary sensory neurons, was specifically in responses to nerve injury and further promotes the nociceptive pain hypersensitivity in mice. Knockdown of CoREST1 by siRNA could serve as a potential analgesic strategy for neuropathic pain. [Display omitted] • CoREST1 was expressed in the nuclei of DRG neurons, and it colocalized with LSD1. • Peripheral nerve injury increased CoREST1 expression and the binding of CoREST1 with LSD1 in injured DRGs in male mice. • Knockdown of CoREST1 in DRGs relieved SNL-induced neuropathic pain. [ABSTRACT FROM AUTHOR]

Modified Dingchuan Decoction (MDD) is a Chinese medicine formula containing 11 materials with cough suppression, asthma relief, and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of MDD on cough-variant asthma (CVA) and to investigate its mechanism of action. The chemical constituents of MDD were analyzed by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). A guinea pig CVA model was established using an intramuscular injection of ovalbumin (OVA), combined with an intraperitoneal injection of aluminum hydroxide [Al(OH) 3 ] and nebulized OVA. At the beginning of day 18, the low, medium, and high MDD groups were gavaged with 7.23 g/kg, 14.46 g/kg, and 28.92 g/kg of MDD, respectively, and the positive group was gavaged with 5 mg/kg of prednisone acetate combined with 1 mg/kg of montelukast sodium; the normal and model groups were given an equal volume of distilled water, once a day for 21 days. The cough was induced by 10−3 mol/L capsaicin solution 1 h after the last administration, and the number of coughs and the latency of coughs were evaluated. Hematoxylin and eosin staining (H&E) was used to observe pathological changes in the lungs and airways. The concentration of inflammatory factors in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunosorbent assay (ELISA). We analyzed the lung microbiota using 16 S ribosomal DNA (16 S rDNA) high-throughput sequencing. The 38 chemical components were found in MDD, and MDD reduced the number of coughs in guinea pigs with CVA, prolonged cough latency, improved pathological damage to the lungs and airways, regulated inflammatory factor levels in BALF, and modulated the lung microbiota. This study demonstrated that treating CVA with MDD may be related to inhibiting lung inflammation and regulating lung microbiota. [Display omitted] • Modified Dingchuan Decoction had a good therapeutic effect on cough-variant asthma. • Modified Dingchuan Decoction improves lung immune dysfunction. • Modified Dingchuan Decoction improves the disorder of lung microbiota. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (ApoE) is an apolipoprotein involved in lipid metabolism and is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). The aim of this study is to explore the role of ApoE in the pathological development of neuropathic pain. First, we examined the location of ApoE in the dorsal root ganglion (DRG) and spinal cord in male mice using immunohistochemistry, and found that ApoE was predominantly expressed in DRG satellite glial cells (SGCs) and macrophages and spinal cord astrocytes. Using a spinal nerve ligation (SNL)-induced neuropathic pain mouse model, we found that nerve injury caused an increase in ApoE expression in the injured DRGs, but not in the spinal cord after SNL surgery. Furthermore, we observed reduced SNL-induced pain hypersensitivity in ApoE knockout mice compared to wild-type mice. Moreover, an antisense oligonucleotide (ASO) targeting the Apoe gene sequence, which was microinjected into the DRG or administered intrathecally, not only reduced ApoE expression in DRG but also attenuated SNL-induced pain hypersensitivity. Finally, we found that a tyrosine kinase receptor AXL, which was previously demonstrated to contribute to neuropathic pain, may mediate ApoE function under neuropathic pain condition. In conclusion, our data suggest that ApoE in DRG promote pain hypersensitivity via the DRG membrane receptor AXL in neurons under neuropathic pain conditions. This study revealed a novel mechanism between lipid homeostasis and neuropathic pain. [Display omitted] • ApoE is expressed in DRG SGCs and macrophages and spinal astrocytes. • Peripheral nerve injury induces the upregulation of ApoE in the injured DRGs. • ApoE knockout or ApoE ASO attenuates SNL-induced pain hypersensitivity. • AXL mediates the function of ApoE under neuropathic pain condition. [ABSTRACT FROM AUTHOR]

Qisheng Wan formula (QWF) was first described in the book Sheng Ji Zong Lu in 1117. The book states that QWF can cure forgetfulness, improve the mind, and make people smart. Hence, QWF has been widely used to treat patients with forgetfulness or dementia. QWF, a classic Chinese formulation, comprises seven herbal drugs: the sclerotium of Poria cocos (Schw.) Wolf, bark of Cinnamomum cassia Presl, root of Polygala tenuifolia Willd., root and rhizome of Panax ginseng C. A. Mey., root of Asparagus cochinchinensis (Lour.) Merr., root and rhizome of Acorus tatarinowii Schott, and root bark of Lycium chinense Mill. This study aimed to utilize modern pharmacological methods to evaluate the therapeutic effects and explore the underlying mechanism of QWF action on rats with Alzheimer's disease (AD). The chemical profile of QWF was characterized using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The AD rat model was established via a bilateral intraventricular injection of amyloid-β (1–42) (Aβ 1–42). The rats were subsequently treated daily with QWF for 4 weeks. The Morris water maze test was performed to evaluate the cognition processes in the rats, whereas histological changes in the hippocampus were observed using hematoxylin and eosin staining. The expression levels of Aβ 1–42 , nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in the hippocampus and colon were assessed. Moreover, the diversity and composition of the intestinal microbiota were analyzed using 16S rDNA gene sequencing. One hundred and fourteen compounds were characterized in QWF. QWF significantly ameliorated the cognition processes and histopathological damages due to AD in rats by decreasing the deposition of Aβ 1-42 and downregulating the expression of NF-κB, TNF-α, and IL-6. QWF also modulated changes in the diversity and composition of intestinal microbiota to suppress the relative abundance of inflammation-associated microbiota. This study showed that QWF can suppress proinflammatory factors and modulate the intestinal microbiota in AD rats. [Display omitted] [ABSTRACT FROM AUTHOR]

Escin is a natural mixture of triterpene saponins extracted from the seeds of Aesculus wilsonii Rehd. And has been reported to possess the therapeutic effects against neuropathic pain (NP). However, the underlying mechanisms remain unclear. The present study aimed to investigate the therapeutic effects and explore the underlying mechanisms of escin on rats of NP induced by chronic constriction injury (CCI) of sciatic nerve. Rats were treated with escin (7, 14, and 28 mg/kg, i. g.) daily from the third day after the surgery (day 0) for consecutive 14 days. Regular behavior and thermal threshold were measured on days 0, 3, 5, 7, 10 and 14. Investigations into mechanisms involved measurement of inflammatory factors and biochemical factors in dorsal root ganglion (DRG). Inflammatory pain responses and nerve injuries were induced by the CCI model. Tonic pain model and acute inflammatory model induced by formalin or carrageenan were established to evaluated the pharmacological effects of escin on acute inflammatory pain. Corresponding behaviors were monitored and relevant gene expression such as c-fos, mu opioid receptor (MOR) and KCNK1 were detected by qRT-PCR. Investigate the neuroprotective effects of escin on PC12 cell injury induced by lipopolysaccharide (LPS). Cell morphology was observed under inverted microscope and neuroprotective effect of escin on cell activity was assessed by MTT assay. Escin could widen thermal threshold, downregulate the concentration of inflammatory factors like tumor necrosis factor (TNF)-α and interleukin (IL)-1β, suppress the gene expression of toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), decrease the level of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) remarkably. In addition, escin significantly lowered the duration of licking, numbers of flinches and increase in paw edema, showing great therapeutic effects on inflammatory pain responses. Moreover, the activity of injured PC12 cells was significantly improved after escin administrated. Escin exerted the ameliorative effects on NP induced by CCI which may be related to downregulating the release of pro-inflammatory cytokines, suppressing TLR-4/NF-κB signal pathway, thereafter decreasing the level of GFAP and NGF. Image 1 • Escin could downregulate the concentration of inflammatory factors like tumor necrosis factor-α and interleukin-1β. • Escin could suppress toll-like receptor 4/nuclear factor κB signal pathway, decrease the level of glial fibrillary acidic protein and nerve growth factor. • Escin exerted a good therapeutic effect on acute inflammation pain induced by formalin and carrageenan. • Escin had a neuroprotective effect on PC12 cells. [ABSTRACT FROM AUTHOR]

• The ethanol extract of Usnea diffracta shows a positive antiatherogenic effect. • The ethanol extract of Usnea diffracta promotes lipid metabolism. • The ethanol extract of Usnea diffracta reduces the plaque area in atherosclerotic model rats. • The mechanism may be related to the inhibition of TLR5/NF-κB signaling pathway. Usnea diff ;racta Vain. (U. diffracta) belonging to the Usnea genus, is widely used as a folk medicine for the treatment of ulcer, abdominal pain, diarrhea, malaria and so on. However, the antiatherogenic effect of U. diffracta has not yet been reported. This study aims to investigate the antiatherogenic effects of the ethanol extract of U. diffracta and its mechanism. A high fat diet and VD3 were used to establish the atherosclerotic rat model, with 0.004 g/kg/d of simvastatin as a positive control, fed with 0.7, 1.4, and 2.8 g/kg/d of Usnea ethanol extract for 21 days. The blood, liver, and aorta samples from each rat were collected after the last administration. Pharmacodynamic effects were evaluated. The inflammation related factors, the gene expressions of Toll-like receptor 5 (TLR5), myeloid differentiating factor 88 (MyD88), and nuclear factor-κB (NF-κB) were detected. Compared with the model group, simvastatin and ethanol extract of U. diffracta can significantly reduce the serum levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), Ca2+, AST, ALT, the liver contents of total cholesterol (TC), TG, AI and liver index, as well as significantly increase the contents of high-density lipoprotein cholesterol (HDL-C) both in serum and liver (p < 0.01 or p < 0.05). The serum level of ox-LDL can be significantly reduced by simvastatin, low and medium U. diffracta ethanol extract doses (p < 0.01). In addition, simvastatin and low dosage of U. diffracta ethanol extract can significantly reduce the liver content of LDL-C (p < 0.01). U. diffracta ethanol extract shows a positive antiatherogenic effect. Furthermore, the mechanism may be related to promoting the expression of serum IL-10 and inhibition of TLR5/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]