Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling

BackgroundZanthoxylum nitidum (Roxb.) DC., also named Liang Mianzhen (LMZ), one kind of Chinese herb characterized with anti-inflammatory and relieving pain potency, which is widely used to treat injuries, rheumatism, arthralgia, stomach pain and so on in China. But its mechanism related to the anti-hyperalgesic has not been reported. The aim of this study was to investigate the analgesic activity of Liang Mianzhen on mice with Complete Freund adjuvant (CFA)-induced chronic inflammatory pain. Meanwhile, the peripheral and central mechanisms of analgesic effect of Liang Mianzhen were further examined via observing the effects of Liang Mianzhen on the signal pathway associated with inflammatory induced hyperalgesia.MethodsThe inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After 1 day of CFA injection, the mice were treated with LMZ (100 mg/kg) for seven consecutive days, and the behavioral tests were measured after the daily intragastric administration of LMZ. The morphological changes on inflamed paw sections were determined by hematoxylin eosin (HE) staining. Changes in the mRNA expression levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor κB p65 (NF-κBp65) were measured on day seven after CFA injection by using real-time quantitative PCR analysis and enzyme linked immunosorbent assay (ELISA) method, respectively. Moreover, immunohistochemistry and western blotting were used to detect extracellular regulated protein kinases 1/2 (ERK1/2) and NF-κB signal pathway activation.ResultsThe extract of LMZ (100 mg/kg) showed a significant anti-inflammatory and analgesic effect in the mice model. The paw edema volume was significantly reduced after the administration of LMZ compared to CFA group, as well as the paw tissues inflammatory damage was relived and the numbers of neutrophils in mice was reduced significantly. The CFA-induced mechanical threshold and thermal hyperalgesia value were significant improved with LMZ treatment at day three to day seven. We also found the mRNA levels of TNF-α, IL-1β, IL-6 and NF-κBp65 were down-regulate after 7 days from the LMZ treatment compared to CFA group. Meanwhile, LMZ significantly suppressed over-expression of the phosphorylation of ERK1/2 and NF-κBp65 in peripheral and central.ConclusionThe present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level

The ecological and etiological investigation of ticks and rodents in China: results from an ongoing surveillance study in Zhejiang Province

ObjectivesThis study aimed to analyze the population density of vector ticks and reservoir hosts rodents, and to investigate the relevant pathogen infection in Zhejiang Province, China.MethodsIn this surveillance study, the data of ticks density were collected with the tick picking method on animal body surface and the drag-flag method, while the rodent density with the night trapping method. The samples of ticks were examined for the severe fever with thrombocytopenia syndrome virus (SFTSV), and blood serum and organs from rodents were subjected for SFTSV, hantavirus, Leptospira, Orientia tsutsugamushi (O. tsutsugamushi) and Yersinia pestis (Y. pestis) screening in the laboratory.ResultsFrom 2017 to 2022 in Zhejiang Province, 16,230 parasitic ticks were found in 1848 positive animals, with the density of parasitic ticks of 1.29 ticks per host animal, and a total of 5,201 questing ticks were captured from 1,140,910 meters of vegetation distance with the questing tick density of 0.46 ticks/flag·100 m. Haemaphysalis longicornis (H. longicornis) was the major species. A total of 2,187,739 mousetraps were distributed and 12,705 rodents were trapped, with the density of 0.58 per 100 trap-nights. Rattus norvegicus was the major species. For SFTSV screening, two groups nymphal ticks of H. longicornis were tested to be positive. For the rodents samples, the Leptospira had a positive rate of 12.28% (197/1604), the hantavirus was 1.00% (16/1604), and the O. tsutsugamushi was 0.15% (2/1332). No positive results were found with SFTSV and Y. pestis in the rodents samples.ConclusionFindings from this study indicated that the ticks and rodents were widely distributed in Zhejiang Province. Particularly, the positive detection of SFTSV, Leptospira, hantavirus and O. tsutsugamushi in ticks or rodents from this area suggested that more attention should be paid to the possibilities of relevant vector-borne diseases occurrence

Development and field evaluation of a novel sugar bait device for controlling residential vector mosquitoes in Zhejiang Province, China

BackgroundMosquito-borne diseases pose serious public health threats in Zhejiang Province, China, and vector control is believed to be the primary method for reducing transmission. Due to severe resistance problems, effective and sustainable methods without chemical insecticides are urgently required to control mosquito vectors. Attractive toxic sugar baits (ATSB) are newly developed methods to control mosquitoes in recent decades with the core element sugar bait, which was invented according to the sugar-feeding behavior of mosquitoes. In this study, we developed a Novel Sugar Bait Device (NSBD) trap by combining sugar bait and physical adhesive capture technology. The study aimed to evaluate the effect of the NSBD trap on controlling mosquitoes in residential environments and to identify the optimal sugar solution concentration in the sugar bait of the NSBD for real use.MethodsFour residential villages in Ningbo City with similar geographic environments and mosquito densities were selected for field trials in 2022. One village (site 1) was designated as the control group, and three villages (sites 2–4) served as the test groups to assess the effectiveness of NSBD traps with different sugar solution concentrations (6, 8, and 10%) in the sugar bait. Larval and adult mosquito densities were monitored monthly before and semi-monthly after the trials using the CDC light trap and larval pipette method.ResultsBefore the trials, we monitored mosquito density for 3 months to confirm the baseline mosquito density among the four sites, and no statistical differences in adult and larval mosquitoes were found (adult, F = 3.047, p > 0.05; larvae, F = 0.436, p > 0.05). After the trials, all NCBD traps effectively controlled larval and adult mosquito densities, with the highest standard decrease rates of larval and adult mosquito densities at 57.80 and 86.31%, respectively, observed in site 4. The most suitable sugar solution concentration in the sugar bait was 10%.ConclusionNSBD traps effectively controlled mosquitoes in residential environments during field trials. Without the use of insecticides, this may be a promising choice for mosquito vector control to prevent mosquito-borne diseases

Single-cell RNA sequencing highlights the role of PVR/PVRL2 in the immunosuppressive tumour microenvironment in hepatocellular carcinoma

IntroductionThe conflict between cancer cells and the host immune system shapes the immune tumour microenvironment (TME) in hepatocellular carcinoma (HCC). A deep understanding of the heterogeneity and intercellular communication network in the TME of HCC will provide promising strategies to orchestrate the immune system to target and eradicate cancers.MethodsHere, we performed single-cell RNA sequencing (scRNA-seq) and computational analysis of 35786 unselected single cells from 3 human HCC tumour and 3 matched adjacent samples to elucidate the heterogeneity and intercellular communication network of the TME. The specific lysis of HCC cell lines was examined in vitro using cytotoxicity assays. Granzyme B concentration in supernatants of cytotoxicity assays was measured by ELISA.ResultsWe found that VCAN+ tumour-associated macrophages (TAMs) might undergo M2-like polarization and differentiate in the tumour region. Regulatory dendritic cells (DCs) exhibited immune regulatory and tolerogenic phenotypes in the TME. Furthermore, we observed intensive potential intercellular crosstalk among C1QC+ TAMs, regulatory DCs, regulator T (Treg) cells, and exhausted CD8+ T cells that fostered an immunosuppressive niche in the HCC TME. Moreover, we identified that the TIGIT-PVR/PVRL2 axis provides a prominent coinhibitory signal in the immunosuppressive TME. In vitro, antibody blockade of PVR or PVRL2 on HCC cell lines or TIGIT blockade on immune cells increased immune cell-mediated lysis of tumour cell. This enhanced immune response is paralleled by the increased secretion of Granzyme B by immune cells.DiscussionCollectively, our study revealed the functional state, clinical significance, and intercellular communication of immunosuppressive cells in HCC at single-cell resolution. Moreover, PVR/PVRL2, interact with TIGIT act as prominent coinhibitory signals and might represent a promising, efficacious immunotherapy strategy in HCC

Role of Nrf2 and Its Activators in Respiratory Diseases

Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidant response element- (ARE-) driven cytoprotective protein expression. The activation of Nrf2 signaling plays an essential role in preventing cells and tissues from injury induced by oxidative stress. Under the unstressed conditions, natural inhibitor of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), traps Nrf2 in the cytoplasm and promotes the degradation of Nrf2 by the 26S proteasome. Nevertheless, stresses including highly oxidative microenvironments, impair the ability of Keap1 to target Nrf2 for ubiquitination and degradation, and induce newly synthesized Nrf2 to translocate to the nucleus to bind with ARE. Due to constant exposure to external environments, including diverse pollutants and other oxidants, the redox balance maintained by Nrf2 is fairly important to the airways. To date, researchers have discovered that Nrf2 deletion results in high susceptibility and severity of insults in various models of respiratory diseases, including bronchopulmonary dysplasia (BPD), respiratory infections, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and lung cancer. Conversely, Nrf2 activation confers protective effects on these lung disorders. In the present review, we summarize Nrf2 involvement in the pathogenesis of the above respiratory diseases that have been identified by experimental models and human studies and describe the protective effects of Nrf2 inducers on these diseases

Analysis of prognostic value of lactate metabolism-related genes in ovarian cancer based on bioinformatics

Abstract Background Recent studies have provided evidence supporting the functional role and mechanism of lactate in suppressing anticancer immunity. However, there is no systematic analysis of lactate metabolism-related genes (LMRGs) and ovarian cancer (OV) prognosis. Results Six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) were selected as prognostic genes and a prognostic model was utilized. Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) analyses were further performed and indicated that the prognostic model was effective. Subsequently, the neoplasm_cancer_status and RiskScore were determined as independent prognostic factors, and a nomogram was established with relatively accurate forecasting ability. Additionally, 2 types of immune cells (Central memory CD8 T cell and Immature B cell), 4 types of immune functions (APC co inhibition, DCs, Tfh and Th1 cells), 9 immune checkpoints (BTLA, CTLA4, IDO1, LAG3, VTCN1, CXCL10, CXCL9, IFNG, CD27) and tumor immune dysfunction and exclusion (TIDE) scores were significantly different between risk groups. The expression of 6 genes were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the expression of 6 genes were higher in the high-grade serous carcinoma (HGSC) samples. Conclusion A prognostic model related to lactate metabolism was established for OV based on six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) that could provide new insights into therapy