Icariin restrains NLRP3 inflammasome-mediated Th2 immune responses and ameliorates atopic dermatitis through modulating a novel lncRNA MALAT1/miR-124-3p axis.

CONTEXT: Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases. OBJECTIVE: The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development. MATERIALS AND METHODS: BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin. RESULTS: Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses. DISCUSSION AND CONCLUSIONS: The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.

Morinda officinalis extract exhibits protective effects against atopic dermatitis by regulating the MALAT1/miR-590-5p/CCR7 axis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a genetic predisposition, and the traditional Chinese medicine Morinda officinalis and its roots are characterized with anti-inflammatory effects and have been used for the treatment of various disease. However, it is still largely unknown whether Morinda officinalis extract (MOE) can be used for the treatment of AD. OBJECTIVES: In our study we aimed to determine whether MOE could ameliorate 2,4-dinitrochlorobenzene (DNCB)-induced AD and elucidate molecular mechanisms. METHODS: We established an AD mouse model by using DNCB. Skin pathological analysis and ELISA assay were used to detect the effect of MOE on the inflammation of AD model mouse skin and the expression changes of inflammatory factors, and further functional verification was performed in TNF-α/IFN-γ-induced HaCaT cells. RESULTS: Our in vivo experiments confirmed that MOE remarkably reduced DNCB-induced AD lesions and symptoms, such as epidermal and dermal thickness and mast cell infiltration and inflammatory cytokines secretion in the mice models. In addition, the underlying mechanisms by which MOE ameliorated AD had been uncovered, and we verified that MOE inhibited MALAT1 expression in AD, resulting in attenuated expression of C-C chemokine receptor type 7 (CCR7) regulated by MALAT1-sponge miR-590-5p in a competing endogenous RNA (ceRNA) mechanisms-dependent manner, thereby inhibiting TNF-α/IFN-γ-induced cellular proliferation and inflammation.

[Effect mechanism of pricking and cupping therapy combined with Chinese herbal wet compress in treatment of herpes zoster based on Th1/Th2 imbalance and serum substance P].

OBJECTIVE: To observe the effects of pricking and cupping therapy combined with Chinese herbal wet compress on Th1/Th2 balance and the concentration of substance P (SP) in treatment of patients with herpes zoster at acute stage and explore the mechanism of clinical efficacy of this combined therapeutic method. METHODS: The patients of herpes zoster at acute stage were randomly divided into a treatment group (58 cases), a control group No.1 (57 cases), a control group No.2 (58 cases) and a control group No.3 (59 cases). In the treatment group, the therapeutic regimen was pricking and cupping+Chinese herbal wet compress+basic treatment. In the control group No.1, pricking and cupping + basic treatment were administered. In the control group No.2, Chinese herbal wet compress+basic treatment were provided. In the control group No.3, only basic treatment was delivered. The treatment duration was 9 days in each group. The score of pain degree, the score of sleep quality and the rehabilitation conditions of pain and herpes were observed in 4 groups. The concentration of serum interleukin 4 (IL-4), interferon gamma (IFN-γ) and SP were detected by ELISA. The clinical efficacy was evaluated. The occurrence of adverse reaction during treatment was observed. RESULTS: After treatment, the score of pain degree and the concentrations of serum IL-4 and SP were all lower than those before treatment in 4 groups (P<0.05); and the score of subjective sleep quality, the concentrations of serum IFN-γ and IFN-γ/IL-4 were all increased in comparison with those before treatment (P<0.05). In the treatment group and the control groups No.1 and No.2, the score of pain degree and the concentrations of serum IL-4 and SP were all lower than those in the control group No.3 (P<0.05); and the score of subjective sleep quality, the concentrations of serum IFN-γ and IFN-γ/IL-4 were higher than those in the control group No.3, respectively (P<0.05). Besides, every indicator in the treatment group was improved more significantly than that either in the control group No.1 or the control group No.2 (P<0.05). After treatment, compared with the control group No.3, the time of pain relief and disappearance, and the time of blister termination, incrustation and decrustation were all shorter in the treatment group, the control group No.1 and the control group No.2 separately (P<0.05); and every indicator in the treatment group was reduced more significantly in comparison with either the control group No.1 or the control group No.2 (P<0.05). The total effective rate in the treatment group (96.55%, 56/58), the control group No.1 (92.98%, 53/57) and the control group No.2 (91.38%, 53/58) was higher than that in the control group No.3 (74.58%, 44/59, P<0.05). No any adverse reaction occurred in the 4 groups. CONCLUSION: The pricking and cupping therapy combined with Chinese herbal wet compress effectively promotes the recovery of Th1/Th2 balance and reduces the concentration of serum SP in patients with herpes zoster at acute stage. This combined therapeutic regimen is conductive to the recovery of patients, the improvement of therapeutic effects and the decrease of the risk of pos-therpetic neuralgia.

The Impact of Climate Change on the Resistance of Rice Near-Isogenic Lines with Resistance Genes Against Brown Planthopper.

BACKGROUND: The impact of climate change on insect resistance genes is elusive. Hence, we investigated the responses of rice near-isogenic lines (NILs) that carry resistance genes against brown planthopper (BPH) under different environmental conditions. RESULTS: We tested these NILs under three environmental settings (the atmospheric temperature with corresponding carbon dioxide at the ambient, year 2050 and year 2100) based on the Intergovernmental Panel on Climate Change prediction. Comparing between different environments, two of nine NILs that carried a single BPH-resistant gene maintained their resistance under the environmental changes, whereas two of three NILs showed gene pyramiding with two maintained BPH resistance genes despite the environmental changes. In addition, two NILs (NIL-BPH17 and NIL-BPH20) were examined in their antibiosis and antixenosis effects under these environmental changes. BPH showed different responses to these two NILs, where the inhibitory effect of NIL-BPH17 on the BPH growth and development was unaffected, while NIL-BPH20 may have lost its resistance during the environmental changes. CONCLUSION: Our results indicate that BPH resistance genes could be affected by climate change. NIL-BPH17 has a strong inhibitory effect on BPH feeding on phloem and would be unaffected by environmental changes, while NIL-BPH20 would lose its ability during the environmental changes.

Transcriptomics identifies key defense mechanisms in rice resistant to both leaf-feeding and phloem feeding herbivores.

BACKGROUND: Outbreaks of insect pests in paddy fields cause heavy losses in global rice yield annually, a threat projected to be aggravated by ongoing climate warming. Although significant progress has been made in the screening and cloning of insect resistance genes in rice germplasm and their introgression into modern cultivars, improved rice resistance is only effective against either chewing or phloem-feeding insects. RESULTS: In this study, the results from standard and modified seedbox screening, settlement preference and honeydew excretion tests consistently showed that Qingliu, a previously known leaffolder-resistant rice variety, is also moderately resistant to brown planthopper (BPH). High-throughput RNA sequencing showed a higher number of differentially expressed genes (DEGs) at the infestation site, with 2720 DEGs in leaves vs 181 DEGs in sheaths for leaffolder herbivory and 450 DEGs in sheaths vs 212 DEGs in leaves for BPH infestation. The leaf-specific transcriptome revealed that Qingliu responds to leaffolder feeding by activating jasmonic acid biosynthesis genes and genes regulating the shikimate and phenylpropanoid pathways that are essential for the biosynthesis of salicylic acid, melatonin, flavonoids and lignin defensive compounds. The sheath-specific transcriptome revealed that Qingliu responds to BPH infestation by inducing salicylic acid-responsive genes and those controlling cellular signaling cascades. Taken together these genes could play a role in triggering defense mechanisms such as cell wall modifications and cuticular wax formation. CONCLUSIONS: This study highlighted the key defensive responses of a rarely observed rice variety Qingliu that has resistance to attacks by two different feeding guilds of herbivores. The leaffolders are leaf-feeder while the BPHs are phloem feeders, consequently Qingliu is considered to have dual resistance. Although the defense responses of Qingliu to both insect pest types appear largely dissimilar, the phenylpropanoid pathway (or more specifically phenylalanine ammonia-lyase genes) could be a convergent upstream pathway. However, this possibility requires further studies. This information is valuable for breeding programs aiming to generate broad spectrum insect resistance in rice cultivars.

[Fire needling stripping after local anesthesia for verruca vulgaris: a multi-center randomized controlled trial].

OBJECTIVE: To compare the clinical therapeutic effect of fire needling stripping after local anesthesia, simple fire needling and liquid nitrogen cryotherapy on verruca vulgaris. METHODS: A total of 900 patients with verruca vulgaris were randomized into a fire needling stripping group (300 cases, 2 cases dropped off), a fire needling group (300 cases, 4 cases dropped off) and a liquid nitrogen cryotherapy group (300 cases, 5 cases dropped off). After local anesthesia of compound lidocaine cream, fire needling therapy was adopted, and the necrotic tissue of verruca was stripped in the fire needling stripping group. Simple fire needling therapy was adopted in the fire needling group, without local anesthesia and stripping. Liquid nitrogen cryotherapy was adopted in the liquid nitrogen cryotherapy group. The treatment was given once a week, and totally 3 weeks were required in the 3 groups. The skin lesion scores of number, area, thickness, color, pruritus, isomorphism and the level of T lymphocyte (CD+3、CD+4、CD+8、CD+4/ CD+8) in peripheral blood were observed before and after treatment, and the adverse reaction was recorded in the 3 groups. Five weeks after treatment, the therapeutic effect was evaluated. RESULTS: Compared before treatment, the skin lesion scores were decreased (P<0.05), the levels of T lymphocyte in peripheral blood were increased in the 3 groups (P<0.05). After treatment, all the items of the skin lesion score in the fire needling stripping group were lower than those in the fire needling group and the liquid nitrogen cryotherapy group (P<0.05), the levels of T lymphocyte in peripheral blood were higher than those in the fire needling group and the liquid nitrogen cryotherapy group (P<0.05); all the items of the skin lesion score in the liquid nitrogen cryotherapy group were lower than those in the fire needling group (P<0.05). At the follow-up, the total effective rate was 88.6% (264/298) in the fire needling stripping group, which was superior to 81.4% (241/296) in the fire needling group and 81.4% (240/295) in the liquid nitrogen cryotherapy group (P<0.05). The cases of infection, causalgia and cicatrix in the liquid nitrogen cryotherapy group were more than those in the fire needling stripping group and the fire needling group (P<0.05). CONCLUSION: Fire needling stripping after local anesthesia can effectively treat the verruca vulgaris, improve the skin lesion and immunity, its therapeutic effect is superior to simple fire needling and liquid nitrogen cryotherapy.