Artemisia argyi volatile oil ameliorates allergic contact dermatitis via modulating TRPA1/CGRP signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Artemisia argyi Levl.et Vant. have a long history of being used to treat skin diseases such as pruritus and dermatitis in China, but the therapeutic effect on allergic contact dermatitis (ACD) is still unclear. AIM OF THE STUDY: To investigate the effect and molecular mechanisms of the volatile oil of A. argyi leaves (abbreviated as 'AO') in the treatment of ACD. MATERIALS AND METHODS: The main components in AO were analyzed using GC-MS. The effect of AO on channel currents in hTRPA1-transfected HEK293T cells was studied by whole-cell patch clamp. Subsequently, chloroquine-evoked acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch model was established to evaluate the antipruritic effect through counting scratching behavior, and the anti-inflammatory effects on ACD mice were measured using histological analysis. Meanwhile, the changes of CGRP, the infiltration of nerve fibers and the recruitment of dendritic cells, the expression of Il-23 and Il-17 mRNA in skin lesions, the phosphorylation of ERK and p38 in dorsal root ganglion (DRG), were evaluated by molecular biological methods. Then the inhibitory effect of AO on AITC- or SADBE-activated TRPA1 channels in primary DRG neurons of C57BL/6, Trpa1-/- or Trpv1-/- mice was elucidated by Ca2+ imaging and immunofluorescence. RESULTS: AO treatment inhibited the activation of TRPA1 in HEK293T cells and alleviated acute itch caused by chloroquine, but this effect was lacking in Trpa1-/- mice. Furthermore, administration of AO attenuated scratching behavior in SADBE-induced ACD mice. AO also inhibited the increase of nerve fibers and recruitment of dendritic cells, and down-regulated the expression of CGRP and the levels of Il-23 and Il-17 mRNA. Meanwhile, AO reduced the expression of p-p38 and p-ERK in the lesioned skin and DRG of SADBE-induced ACD mice. Additionally, AO blocked the activation of TRPA1 channels and decreased the levels of CGRP, p-p38, and p-ERK in DRG neurons. CONCLUSION: AO could inhibit TRPA1 channels in sensory neurons, thereby reducing the release of CGRP and exerting anti-pruritic and anti-inflammatory effect. These findings also provide a new strategy for exploring the role of A. argyi in treating ACD.

Diasporic Identity in Contemporary Sinophone Literature: The Role of Language and Cultural Elements.

Amidst the contemporary diasporic landscape in Sinophone literature, this research critically examines the nexus of language, culture, and identity. The study aims to analyze literary pieces composed in Sinophone languages across diverse diasporic communities and uncover the impact of language and cultural elements on the articulation and comprehension of diasporic identity. This paper used the following. comparative and typological research, an in-depth analysis of three Sinophonic texts, and contextual analysis. The subject of the study was three texts: The Joy Luck Club (Amy Tan), Balzac and the Little Chinese Seamstress (Dai Sijie), and The Woman Warrior (Maxine Hong Kingston). The results showed that In The Joy Luck Club, language and cultural facets unveil the characters' dual identity struggles due to living abroad, exemplified through code-switching's psychological tension. Balzac and the Little Chinese Seamstress utilizes language and cultural details to underscore the significance of preserving heritage within the diaspora, with literary allusions amplifying this endeavor. In The Woman Warrior, language and cultural elements reflect the heroine's inner conflict as she navigates her dual cultural allegiance. This scholarly revelation deepens comprehension of how these aspects influence identity formation in the diaspora. These findings broaden the understanding of Sinophone diasporic literature, spotlighting shared trends in identity portrayal through language and culture. The research has theoretical value for literary, cultural, and anthropological studies and practical significance, potentially informing educational initiatives on diasporic literature and cultural diversity. This study's outcomes hold relevance for students, researchers, and cultural scholars exploring the role of language and culture in diasporic identity expression.

Borneol exerts its antipruritic effects by inhibiting TRPA1 and activating TRPM8.

ETHNOPHARMACOLOGICAL RELEVANCE: Borneol is a long-established traditional Chinese medicine that has been found to be effective in treating pain and itchy skin. However, whether borneol has a therapeutic effect on chronic itch and its related mechanisms remain unclear. AIM OF THE STUDY: To investigate the antipruritic effect of borneol and its molecular mechanism. MATERIALS AND METHODS: DrugBAN framework and molecular docking were applied to predict the targets of borneol, and the calcium imaging or patch-clamp recording analysis were used to detect the effects of borneol on TRPA1, TRPM8 or TRPV3 channels in HEK293T cells. In addition, various mouse models of acute itch and chronic itch were established to evaluate the antipruritic effects of borneol on C57BL/6J mice. Then, the borneol-induced pruritic relief was further investigated in Trpa1-/-, Trpm8-/-, or Trpa1-/-/Trpm8-/- mice. The effects of borneol on the activation of TRPM8 and the inhibition of TRPA1 were also measured in dorsal root ganglia neurons of wild-type (WT), Trpm8-/- and Trpv1-/- mice. Lastly, a randomized, double-blind study of adult patients was conducted to evaluate the clinical antipruritic effect of borneol. RESULTS: TRPA1, TRPV3 and TRPM8 are the potential targets of borneol according to the results of DrugBAN algorithm and molecular docking. Calcium imaging and patch-clamp recording analysis demonstrated that borneol activates TRPM8 channel-induced cell excitability and inhibits TRPA1 channel-mediated cell excitability in transfected HEK293T cells. Animal behavior analysis showed that borneol can significantly reduce acute and chronic itch behavior in C57BL/6J mice, but this effect was eliminated in Trpa1-/-, Trpm8-/- mice, or at least in Trpa1-/-/Trpm8-/- mice. Borneol elicits TRPM8 channel induced [Ca2+]i responses but inhibits AITC or SADBE-induced activation of TRPA1 channels in dorsal root ganglia neurons of WT and Trpv1-/- mice, respectively. Furthermore, the clinical results indicated that borneol could reduce itching symptoms in patients and its efficacy is similar to that of menthol. CONCLUSION: Borneol has therapeutic effects on multiple pruritus models in mice and patients with chronic itch, and the mechanism may be through inhibiting TRPA1 and activating TRPM8.

TRPA1 is involved in the inhibitory effect of Ke-teng-zi on allergic contact dermatitis via MAPK and JAK/STAT3 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Entada phaseoloides (Linn.) Merr. commonly named "Ke-teng-zi" is a traditional Chinese folk medicine and reported to treat dermatitis, spasm, and headache. However, the exact effect and the mechanism of Ke-teng-zi on the treatment of dermatitis is unclear. AIM OF THE STUDY: To elucidate the antipruritic effect and molecular mechanisms of Ke-teng-zi on the treatment of allergic contact dermatitis (ACD). MATERIALS AND METHODS: The main components of the n-butanol fraction of 70% ethanol extract from Ke-teng-zi (abbreviated as KB) were analyzed by HPLC. The chloroquine (CQ)-induced acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch in mice was established, and the TNF-α/IFN-γ stimulated Human keratinocytes (HaCaT) were used to evaluate the antipruritic and anti-inflammatory effects of KB. Behavioral tests, lesion scoring, and histology were also examined. The expression levels of molecules in MAPK and JAK/STAT3 pathways, the mRNA levels of chemokines and cytokines in both the skin of ACD mice and the HaCaT cells were detected by western blot and qPCR. Furthermore, whole-cell patch-clamp recordings in TRPA1-tranfected HEK293T cells were used to elucidate the effect of KB on TRPA1 channels. TRPA1 siRNA was used to evaluate the role of TRPA1 in the anti-inflammatory effect of KB in keratinocytes. RESULTS: The main compounds in KB could bind to the active sites of TRPA1 mainly through hydrogen bond and hydrophobic bond interactions. KB could inhibit the scratching behavior in CQ-induced acute itch, and the inhibitory effect of KB was blocked by TRPA1 inhibitor HC-030031. In addition, KB significantly decreased the scratching bouts of ACD mice, reduced the skin lesion scores, mast cells degranulation, and epidermal thickening, inhibited the production of inflammatory chemokines/cytokines and CGRP, and down-regulated the levels of p-ERK1/2, p-p38, and p-STAT3, compared to the ACD mice. Moreover, continuous application of KB induced the desensitization of TRPA1 channels. Also, KB inhibited the expression of p-ERK1/2, p-p38, and p-STAT3, and down-regulated the expression of inflammatory chemokines and cytokines in vitro, which were reversed by the TRPA1 siRNA. CONCLUSIONS: KB alleviated the pruritus and skin inflammation in ACD mice through TRPA1 channels desensitization and down-regulation of intracellular MAPK and JAK/STAT3 signaling pathways. Our results suggested that Ke-teng-zi is a potential drug for the treatment of inflammatory skin diseases such as ACD.

Chemotherapy-induced phlebitis via the GBP5/NLRP3 inflammasome axis and the therapeutic effect of aescin.

BACKGROUND AND PURPOSE: Intravenous infusion of chemotherapy drugs can cause severe chemotherapy-induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear. EXPERIMENTAL APPROACH: RNA-sequencing analysis was used to identify potential disease targets in CIP. Guanylate binding protein-5 (GBP5) genetic deletion approaches also were used to investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in lipopolysaccharide (LPS) primed murine bone-marrow-derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and in mouse models of VIN-induced CIP in vivo. The anti-CIP effect of aescin was evaluated, both in vivo and in vivo. KEY RESULTS: Here, we show that the expression of GBP5 was upregulated in human peripheral blood mononuclear cells from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly alleviated VIN-induced CIP in the experimental mouse model. Mechanistically, GBP5 contributed to the inflammatory responses through activating NLRP3 inflammasome and driving the production of the inflammatory cytokine IL-1ß. Moreover, aescin, a mixture of triterpene saponins extracted from horse chestnut seed, can alleviate CIP by inhibiting the GBP5/NLRP3 axis. CONCLUSION AND IMPLICATIONS: These findings suggest that GBP5 is an important regulator of NLRP3 inflammasome in CIP mouse model. Our work further reveals that aescin may serve as a promising candidate in the clinical treatment of CIP.

Tibetan medicine Si-Wei-Qiang-Wei Powder ameliorates cholecystitis via inhibiting the production of pro-inflammatory cytokines and regulating the MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Wei-Qiang-Wei Powder (SWQ) is a formulated traditional Tibetan medicine preparation that has been used clinically to treat liver and gallbladder diseases for centuries. Previous work has confirmed its clinical effectiveness, however, the specific mechanism of SWQ is still unknown. AIM OF THE STUDY: This study aims to explore the anti-inflammatory effect of SWQ on cholecystitis and its possible mechanism. MATERIALS AND METHODS: The main chemical components of SWQ were analyzed by HPLC. The network pharmacology database was used to screen and construct the network of the main components and molecular targets of SWQ, and to predict the molecular pathways of its core targets. Cholecystitis guinea pig model and LPS stimulated cultured human gallbladder epithelial cells (HGBEC) were used, as in vivo and in vitro methods respectively, to study the anti-cholecystitis activity of SWQ. Specifically, gallbladder wall thickness, hematoxylin-eosin (H&E) staining, and liver function indexes were used to evaluate the anti-inflammatory activities of SWQ in cholecystitis; qRT-PCR and ELISA were used to detect the changes of the production of inflammatory cytokines; Western blot analysis was used to analyze the effects of SWQ on phosphorylation of P38, ERK1/2, JNK and AKT. RESULTS: SWQ decreased the indexes of ALT, AST, TBA, CHOL, DBIL in serum and TBIL, TC and Ca2+ in bile, and alleviated the wall thickness of gallbladder and hepatobiliary fibrosis in LCA-induced guinea pigs. In addition, SWQ attenuated the expression and production of TNF-α, IL-6, IL-1ß, COX-2 both in liver and gallbladder. Moreover, SWQ reversed the up-regulation of p-P38, p-ERK1/2, and p-JNK in animals with cholecystitis and LPS-induced HGBEC. Furthermore, mechanistic studies indicated that SWQ inhibited the activation of ERK1/2, thereby decreasing the expression of TNF-α, IL-6, IL-1ß and phosphorylation P38 and JNK. CONCLUSION: In summary, our research showed that SWQ relieves gallbladder inflammation by inhibiting the MAPK pathway.

How different nitrogen fertilizers affect arsenic mobility in paddy soil after straw incorporation?

In straw return fields, nitrogen-fertilizers are added to mitigate microbial competition for nitrogen with plants. However, in arsenic (As)-contaminated paddy fields, the specific effects of different nitrogen fertilizers on As mobility after straw incorporation and the interactions among iron(Fe)/carbon(C)/nitrogen(N)/As are not well understood. In the reported microcosm experiment we monitored As-mobility as a function of different dosages of KNO3, NH4Cl and rice straw incorporation. Addition of both KNO3 and NH4Cl significantly inhibited the As mobilization induced by straw incorporation. Following the KNO3 addition, the As concentration in porewater dropped by 51-66% after 2 days of the incubation by restraining Fe reduction and enhancing Fe oxidation. High-dose NH4Cl addition reduced As in porewater by 22-43% throughout the incubation by decreasing porewater pH. High-throughput sequencing results demonstrated that KNO3 addition enriches both the denitrifying and Fe-oxidizing bacteria, while diminishing Fe-reducing bacteria; NH4Cl addition has the opposite effect on Fe-reducing bacteria. Network analysis revealed that As and Fe concentrations in porewater were positively correlated with the abundance of denitrifying and Fe-reducing bacteria. This study broadens our insight into the As biogeochemistry associated with the N/C/Fe balance in soil, which are of great significance for agronomic management and mitigation the risk of As-contaminated paddy fields.

Analgesic and neuroprotective effects of Baimai Ointment on diabetic peripheral neuropathy.

ETHNOPHARMACOLOGY RELEVANCE: Baimai (BM) ointment, a traditional Tibetan medicine, has been widely used to treat "white vein" disease, paralysis, hemiplegia and claudication caused by trauma, because of its great effects on muscle stretching and collateral activation. As one of the most terrible complications in diabetes patients, diabetes peripheral neuropathy (DPN) is mainly manifested as abnormal pain or numbness in extremities. However, whether BM ointment is a potential drug for DPN treatment is unclear. AIMS OF THE STUDY: The aim of this study was to investigate the therapeutic effects of BM on DPN in a high-fat diet/low-dose of streptozotocin induced type 2 diabetes rat model and explore underlying mechanisms. METHODS: The chemical components of BM were determined by high performance liquid chromatography (HPLC), and the possible targets and related pathways candidates involved in the effects of BM on DPN were predicted using network pharmacology methods. Next, the effects of different doses (1.5, 3.0 and 6.0 g/kg) of BM on physiological changes, pain behaviors, motor nerve conduction velocity (MNCV) in DPN rats were assessed and compared with placebo- and mecobalamine (Meco)-treated DPN controls. Then, the effects of BM on the expression of pain associated genes as well as the phosphorylation of PI3K/AKT and MAPKs pathways in DRG of DPN rats were examined. RESULTS: Through HPLC analysis, curcumin was identified as one of the primary contents of BM. The information from network pharmacology indicated a series of target candidates for BM including IL6, IL10, TNF, CCL2, CXCL12, EGF, VEGFA, BDNF, TGFß1 and TNF, as well as PI3K-AKT and MAPK signaling pathways. Topical treatment of BM significantly improved the hypersensitivity of mechanical and thermal pain, MNCV and the morphological changes and demyelination of sciatic nerve fibers, without affecting the body weight, serum metabolism or blood glucose. The up-regulated levels of neuropeptides Cgrp, Sst, Sp and chemokines Ccl2 and Ccl3 along with the abnormal expression of p-P38, p-ERK and p-AKT in the DRG of DPN rats were alleviated by BM application. CONCLUSION: BM ointment has great activities in relieving pain hypersensitivity, neuroprotecting peripheral nerves damage caused by DPN, which may be related to the inhibition of related neuropeptide (Cgrp, Sst, Sp) and chemokine (Ccl2, Ccl3) expression and the regulation of PI3K/AKT and MAPKs signaling pathways in DRG.

Runoff Losses in Nitrogen and Phosphorus From Paddy and Maize Cropping Systems: A Field Study in Dongjiang Basin, South China.

Surface runoff is one of the predominant routes for agricultural nitrogen (N) and phosphorus (P) losses, yet their characteristics and corresponding control measures are not fully understood. In 2019 and 2020, field-scale plot experiments were performed at Dongjiang Basin in South China to investigate the characteristics of N and P runoff losses from paddy and maize cropping systems. The results showed that N and P losses from maize fields via surface runoff (27.85 and 1.24 kg ha-1 year-1) were significantly higher than those from paddy fields (15.37 and 0.8 kg ha-1 year-1). The main forms of N losses were nitrate ( NO 3 - -N) and ammonium ( NH 4 + -N) in paddy and maize fields, respectively, whereas particulate P form predominated in surface runoff losses from both the paddy and maize fields. Considerable proportions of agricultural N and P (71-83% of the total runoff loss) were lost during basal fertilization and first topdressing application. Moreover, frequent rainfall events following fertilizer application triggered N and P losses from the monitored fields. About 26.22 and 37.48% of N fertilizer was recovered from grains and straw of paddy and maize, respectively, whereas only 12.35 and 19.51% of P fertilizer were recovered during the crop harvesting stage. Surface runoff was one of the dominant liquid pathways in N loss, whereas most of P loss (introduced from fertilizers without crops utilization) was fixed in the soil. Principal component analysis (PCA) proved that the primary sources of N and P losses were fertilizers rather than N and P in the soil. The current results suggest controlled management relating to fertilization, irrigation, and tillage strategies are effective measures for reducing N and P losses, thereby controlling agricultural non-point source pollution. It is hoped that this study will provide comprehensive field-based inputs on characteristics of N and P runoff losses and formulate appropriate control strategies to protect aquatic environments from eutrophication.

Highly effective removal of bisphenol A by greigite/persulfate in spiked soil: Heterogeneous soil/water system balance and degradation.

The degradation of bisphenol A (BPA) in spiked soil was studied to investigate persulfate (PS) activation by the environment-friendly heterogeneous material greigite for removing organic pollutants from soil. The effects of the PS and greigite doses were investigated, and the BPA degradation rate in the lateritic red soil was lower than that in kaolin. Notably, 500 mg/kg of BPA could be effectively removed by the flower-like greigite (FLG)/PS system in 30 min. The difference in BPA degradation in kaolin and the lateritic red soil was negligible, thus indicating that the contents of components such as total organic matters in the lateritic red soil did not affect the BPA degradation rate of the FLG/PS system considerably. Furthermore, the distribution processes of BPA in the soil and liquid phase were also investigated in detail. The results showed that the water contents were a key factor in the distribution and degradation of BPA. The transfer of BPA from kaolin to the liquid phase was simpler than that from the lateritic red soil to the liquid phase. BPA might be transferred to the liquid phase first and then degraded by the FLG/PS system in that phase. Regarding BPA degradation in the lateritic red soil, BPA was degraded in the soil and liquid phases at the same time. This study proposed a pathway for BPA degradation in soil slurries by heterogeneous material/PS systems for first time, providing a deeper understanding of the degradation mechanism of organic pollutants in soil and new methods for soil remediation.

Genistein suppresses allergic contact dermatitis through regulating the MAP2K2/ERK pathway.

Genistein is one of the main components of soybeans and has been reported to be a potential candidate for the treatment of obesity, cancer, osteoporosis and cardiovascular diseases. Recently, genistein has been shown to have therapeutic effects on some chronic skin diseases, but its underlying mechanisms remain unclear. In this study, we evaluated the role of genistein in alleviating squaric acid dibutylester (SADBE)-induced allergic contact dermatitis (ACD) in mice, and elucidated the potential molecular mechanisms in human keratinocyte (HaCaT) cell line. The impacts of genistein on the production of pro-inflammatory chemokines and cytokines including CXCL9, TSLP, TNF-α, IL-1ß and IL-6 in the skin and serum of ACD mice were assessed, as well as the phosphorylation of components in the MAPK and JAK-STAT3 signaling pathways in the skin and dorsal root ganglions (DRGs). The results showed that genistein exerted protective effects on skin damage and inflammatory cell infiltration. Moreover, genistein significantly inhibited the increased expressions of pro-inflammatory factors in skin and peripheral blood, and down-regulated the levels of p-ERK, p-p38 and p-STAT3 in skin and DRGs. Furthermore, genistein inhibited the phosphorylation of ERK and STAT3 to downregulate the expression of cytokines and chemokines, and feedback downregulate phospho-p38 in TNF-α/IFN-γ-induced HaCaT cells. The genistein-mediated inhibitory effect on the MAPK pathway can be reversed by siMAP2K2 but not by siMAP2K4. Altogether, our findings demonstrated that genistein exhibits strong antipruritic and anti-inflammatory effects in ACD mice by inhibiting the production of pro-inflammatory cytokines and intracellular MAP2K2/ERK cell signaling, which makes genistein a potentially valuable candidate for the treatment of skin conditions and systemic syndromes in the setting of contact dermatitis.

The addition of degradable chelating agents enhances maize phytoremediation efficiency in Cd-contaminated soils.

Chelating agent-induced phytoremediation is a viable approach to completely remove heavy metals from soil. However, little attention has been paid to the interaction mechanisms between the concentration of the chelating agent and the application time on the physiological and biochemical properties of soil and plants. In this study, five chelating agents, namely ethylenediamine tetraacetic acid (EDTA), diethylenetriacetic acid (NTA), tetrasodium N, N-diacetate (GLDA), aspartate dibutyric acid ether (AES), and iminodisuccinic acid (IDSA), were used to support phytoremediation with maize and to explore the removal effect of Cd in soil. The results showed that chelating agent concentrations of 9 mmol kg-1 significantly reduced the biomass of maize. Treatment with AES at a dose of 6 mmol kg-1 significantly increased aboveground biomass, reaching a maximum of 0.92 g pot-1 in all treatments. At an AES concentration of 6 mmol kg-1, the highest shoot and root Cd levels of 7.79 and 9.86 mg kg-1, respectively, were observed, which were 3.05 and 1.60 times higher than those of the control. Total Cd extraction followed the order AES (6 mmol kg-1) > GLDA > NTA > EDTA > IDSA (3 mmol kg-1). Chelating agent treatment significantly increased the activity of antioxidant enzymes and promoted plant growth. The self-degradation of AES significantly reduced soil pH, increased soil Cd activity, and promoted Cd uptake and transportation in maize.

Paeonol Ameliorates Chronic Itch and Spinal Astrocytic Activation via CXCR3 in an Experimental Dry Skin Model in Mice.

Paeonol is a bioactive phenol presents mainly in Paeonia suffruticosa Andr. (Paeoniaceae), Paeonia lactiflora Pall., and Dioscorea japonica Thunb. (Dioscoreaceae), harboring various pharmacological activities including anti-inflammatory, antioxidant, immune regulatory activity and reverse chemoresistance. Recent reports revealed paeonol exhibited good effects on chronic dermatitis, such as atopic dermatitis (AD) and psoriasis. However, whether paeonol is effective for dry skin disease and its mechanism of action still remain unclear. In this study, we analysed the effects of paeonol on a mouse model of dry skin treated with acetone-ether-water (AEW), which showed impressive activities in reducing scratching behavior and skin inflammation. To elucidate the underlying molecular targets for the anti-pruritic ability of paeonol, we screened the expression of possible chemokine pathways in the spinal cord. The expression of CXCR3 was significantly alleviated by paeonol, which increased greatly in the spinal neurons of AEW mice. In addition, treatment of paeonol significantly inhibited AEW-induced expression of astrocyte activity-dependent genes including Tlr4, Lcn2 and Hspb1 et al. The inhibitory effects of paeonol on scratching behavior and astrocytic activation in the spinal cord induced by AEW were abolished when CXCR3 was antagonized or genetically ablated. Taken together, our results indicated that paeonol can ameliorate AEW-induced inflammatory response and itching behavior, and reduce the expression of spinal astrocyte activity-dependent genes induced by AEW, which are driven by CXCR3.

GRPR/Extracellular Signal-Regulated Kinase and NPRA/Extracellular Signal-Regulated Kinase Signaling Pathways Play a Critical Role in Spinal Transmission of Chronic Itch.

Intractable or recurrent chronic itch greatly reduces the patients' QOL and impairs their daily activities. In this study, we investigated whether there are certain key signaling molecules downstream of the recently identified peptides mediating itch in the spinal cord. RNA sequencing analysis of mouse spinal cord in chronic itch models induced by squaric acid dibutylester and imiquimod showed that extracellular signal-regulated kinase (ERK) 1/2 cascade is the most significantly upregulated gene cluster in both models. In four different mouse models of chronic itch, sustained ERK phosphorylation was detected mainly in spinal neurons, and MAPK/ERK kinase inhibitors significantly inhibited chronic itch in these models. Phosphorylated ERK was observed in the interneurons expressing the receptors of different neuropeptides for itch, including gastrin-releasing peptide receptor, natriuretic peptide receptor A, neuromedin B receptor, and sst2A. Blocking gastrin-releasing peptide receptor and natriuretic peptide receptor A by genetic approaches or toxins in mice significantly attenuated or ablated spinal phosphorylated ERK. When human embryonic kidney 293T cells transfected with these receptors were exposed to their respective agonists, ERK was the most significantly activated intracellular signaling molecule. Together, our work showed that phosphorylated ERK is a unique marker for itch signal transmission in the spinal cord and an attractive target for the treatment of chronic itch.

Triterpene saponins from Guo-gang-long attenuate collagen-induced arthritis via regulating A20 and inhibiting MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The stems of Entada phaseoloides (L.) Merr commonly named "Guo-gang-long", is a traditional Chinese folk medicine that has been used clinically in China for the treatment of arthritis. Our previous study described that triterpene saponins isolated from "Guo-gang-long" could inhibit the inflammatory response. However, the potential mechanism of "Guo-gang-long" on treatment of arthritis, and whether the triterpene saponins responsible for its anti-arthritic effect are unclear. AIM: To investigate the function and mechanisms of the triterpene saponins from E. phaseoloides (ES) in collagen-induced arthritis (CIA) rats. MATERIALS AND METHODS: The chemical components of ES were analyzed by HPLC. Anti-arthritic activity of ES was investigated in CIA rats, which was established by immunization with bovine type II collagen. Three doses of ES (25, 50 and 100 mg/kg) were administrated using oral gavage to CIA rats daily for 3 weeks. The anti-arthritic activity of ES was evaluated by clinical arthritis scoring, paw swelling and mechanical sensitivity, as well as histological changes in CIA rats. The impacts of ES on the regulation of the ubiquintin-editing enzyme A20 and MAPK signaling pathway, and production of pro-inflammatory cytokines in CIA rats were examined by Western blot, quantitative real-time PCR, ELISA, and immunohistochemical staining, respectively. RESULTS: ES treatment relieved the paw swelling, hyperalgesia and joint destruction, and prevented the progression of arthritis in CIA rats. Meanwhile, ES suppressed the excessive mRNA levels and protein expression of TNF-α and IL-17 in synovial tissues and hind paw joints, and reduced the production of IL-1ß, TNF-α and IL-17 in serum. Furthermore, ES up-regulated A20 and suppressed the phosphorylation of p38 and ERK1/2 in hind paw joints, as well as inhibiting the activation of spinal p38 in CIA rats. CONCLUSION: ES could relieve rheumatic symptoms and prevent the development of rheumatoid arthritis. The effects of ES may be mediated by reducing proinflammatory cytokine levels, up-regulating A20 expression, reducing p38 and ERK1/2 activation in periphery, and inhibiting of phospho-p38 in spinal cord.

Spatial distribution of soil bulk density and its relationship with slope and vegetation allocation model in rehabilitation of dumping site in loess open-pit mine area.

Studies of soil bulk density (BD) spatial variations of land reclaimed after mining have become a focus of land reclamation and ecological restoration research. However, there have been few studies on the relationship among the reconstructed BD, terrain conditions, and vegetation growth. We examined the southern dumping site of the Pingshuo Antaibao open-pit coal mine located in a loess area in China. Field sampling data, digital elevation models (DEMs), and high-definition images were obtained, and indoor testing, geostatistics, and inverse distance weighting (IDW) were applied. This paper aims to analyze the spatial distribution law of the reconstructed BD and focus on its relationship with slope and vegetation allocation models. We demonstrated that (1) BD increased with soil depth and varied moderately within each layer. (2) The BD variation amplitude of the top 0-20-cm soil layer in both the east-west and south-north directions was small and more similar in the east-west direction than in the south-north direction, which was affected by herbaceous root systems. In the next four layers from 20 to 60 cm, the variation in BD in the east-west direction was far larger than that in the south-north direction, which was affected by vegetation classification. (3) On the whole, BD decreased with increasing slope, but when the slope was between 0° and 21°, BD exhibited a specific change law. (4) From the perspective of vegetation classification, the orders of magnitude of BD in the 0-20-cm and 20-60-cm layers differed. Overall, BD in areas vegetated with Korshinsk Peashrub was the lowest, and BD was moderate in areas with mixed vegetation, while BD was the highest in areas without vegetation or only vegetated with Black Locust. The mixed grass-bush-tree or bush-tree mode attained the best effect in regulating BD. These results can improve the basic principles of land reclamation in mining areas and provide a basis for further optimizing land reclamation technology in practice.

Thymol activates TRPM8-mediated Ca2+ influx for its antipruritic effects and alleviates inflammatory response in Imiquimod-induced mice.

Psoriasis is a highly prevalent chronic dermatitis, characterized by widespread skin inflammation and spontaneous itch. Given the adverse reactions and drug dependence of current treatment, new drugs for psoriasis therapy are urgently needed. This study aims to explore the anti-psoriatic effects of thymol in imiquimod (IMQ) induced mice, and elucidate the potential mechanisms for its therapeutic activities. Thymol reduced the scratching behavior in IMQ mice, and activated Ca2+ response in cervical DRG neurons via TRPM8 channel. Also, thymol alleviated psoriasis-like skin lesions, and attenuated the enhanced infiltration of dermal neutrophils, dendritic cells (DCs) and Th17 cells. In addition, it reversed the upregulated expression of pro-inflammatory cytokines in the skin (TNF-α, IL-22, IL-23, IL-17A, IL-17F, IL-17C, IL-6, IL-1ß and IFN-γ) and serum (TNF-α, IL-6, IL-1ß, IL-17A and IFN-γ). Our results indicated that thymol can effectively ameliorate pruritus and the symptoms of psoriasis-like inflammation induced by IMQ, which makes it a promising drug for the treatment of psoriasis.

Oxymatrine ameliorates imiquimod-induced psoriasis pruritus and inflammation through inhibiting heat shock protein 90 and heat shock protein 60 expression in keratinocytes.

In this work, we aimed to investigate whether oxymatrine exerts its anti-pruritic and anti-inflammatory efficacy in the imiquimod-induced psoriasis mice and the related mechanism. We established the psoriasis model by applying the imiquimod ointment topically and oxymatrine was injected intraperitoneally as the treatment. The behavior and skin morphology results indicated that oxymatrine inhibits imiquimod-induced pruritus alleviating keratinization of skin and inflammatory infiltration. Moreover, we examined the expression of various indicators and found heat shock protein (HSP) 90 and 60 upregulated in model group, which were reversed in oxymatrine treated groups. Molecular docking and the studies in vivo confirmed that HSP90 and HSP60 participate in the inhibitory effect of oxymatrine on the phenotypes of psoriasis mice. Mechanically, immunofluorescence staining demonstrated that oxymatrine-induced downregulation of HSP90 and HSP60 was mainly in keratinocytes. In vitro results showed that oxymatrine decreases the expression of HSP90 and HSP60 upregulated by TNF-α and IFN-γ in HaCaTs cells and the siRNA mediated HSP90 and HSP60 silencing reverses inflammation inhibited by oxymatrine. Taken together, these results indicate that oxymatrine relieves psoriasis pruritic and inflammation by inhibiting the expression of HSP90 and HSP60 in keratinocytes through MAPK signaling pathway.

The reclaimed coal mine ecosystem diverges from the surrounding ecosystem and reaches a new self-sustaining state after 20-23 years of succession in the Loess Plateau area, China.

Whether or not the completely destroyed ecosystem would follow a succession trajectory towards the surrounding forest ecosystem after restoration remains debatable. Here, a comprehensive dataset of thirty-five ecosystem functions were measured on five reclaimed opencast coal mine forest plots (two Robinia pseudoacacia - Pinus tabuliformis mixed forests with different technosol conditions: RPT and RPM; one R. pseudoacacia - Ulmus pumila - Ailanthus altissima mixed forest: RUA; one Picea meyeri - Picea wilsonii - Hippophae rhamnoides mixed forest: PPH; one R. pseudoacacia monoculture forest: RM) and one natural forest plot (Populus simonii monoculture forest: PM) in Pingshuo opencast coal mine, Shanxi Province, China. These functions were employed to examine the reclamation effects among plots in terms of four management scenarios (i.e., biomass productivity, carbon sequestration, general biodiversity conservation and nutrient accumulation) and to determine the affinities between reclaimed ecosystem and its native counterpart according to Bray Curtis Distance Algorithm. The results showed that after 20-23 years of succession, thirty-five ecosystem functions differed among plots and eight highest ecosystem functions were found in RPT and RPM (P < 0.05). In scenarios of biomass productivity, carbon sequestration, general biodiversity conservation and nutrient accumulation scenarios, RPM scored 0.645, 0.470, 0.467 and 0.578, respectively. Accordingly, RPT scored 0.458, 0.447, 0.405 and 0.515, respectively. Consequently, RPT and RPM had the highest scores in the four management objectives compared to other plots. With regard to the ecosystem affinities, RPT was analogous to RPM. Similarly, RUA and PPH resembled PM and RM, respectively. Overall, the pioneer tree species determined the reclamation quality in the dump in the long term, which could be referred as the "trigger effect" in the succession trajectory in reclaimed ecosystem, and the reclaimed coal mine ecosystem diverged from the surrounding ecosystem and reached a new self-sustaining state after 20-23 years of succession.

Spinal GRPR and NPRA Contribute to Chronic Itch in a Murine Model of Allergic Contact Dermatitis.

Recurrent and intractable chronic itch is a worldwide problem, but mechanisms, especially the neural mechanisms, underlying chronic itch still remain unclear. In this study, we investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis induced by squaric acid dibutylester. We found that repeated exposure of mice to squaric acid dibutylester evoked persistent spontaneous scratching and significantly aberrant cutaneous and systemic immune responses lasting for weeks. Squaric acid dibutylester-induced itch requires both nonhistaminergic and histaminergic pathways, which are likely relayed by GRPR and NPRA in the spinal cord, respectively. Employing genetic, pharmacologic, RNAscope assay, and cell-specific ablation methods, we dissected a neural circuit for prolonged itch formed as Grpr+ neurons act downstream of Npr1+ neurons in the spinal cord. Taken together, our data suggested that targeting GRPR and NPRA may provide effective treatments for allergic contact dermatitis-associated chronic pruritus.