Clinical study of enhanced recovery after surgery in laparoscopic appendectomy for acute appendicitis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a comprehensive management modality that promotes patient recovery, especially in the patients undergoing digestive tumor surgeries. However, it is less commonly used in the appendectomy. AIM: To study the application value of ERAS in laparoscopic surgery for acute appendicitis. METHODS: A total of 120 patients who underwent laparoscopic appendectomy due to acute appendicitis were divided into experimental group and control group by random number table method, including 63 patients in the experimental group and 57 patients in the control group. Patients in the experimental group were managed with the ERAS protocol, and those in the control group were received the traditional treatment. The exhaust time, the hospitalization duration, the hospitalization expense and the pain score between the two groups were compared. RESULTS: There was no significant difference in age, gender, body mass index and Sunshine Appendicitis Grading System score between the experimental group and the control group (P > 0.05). Compared to the control group, the patients in the experimental group had earlier exhaust time, shorter hospitalization time, less hospitalization cost and lower degree of pain sensation. The differences were statistically significant (P < 0.01). CONCLUSION: ERAS could significantly accelerate the recovery of patients who underwent laparoscopic appendectomy for acute appendicitis, shorten the hospitalization time and reduce hospitalization costs. It is a safe and effective approach.

Newcastle Disease Virus (NDV)-based vaccine candidate against SARS-CoV-2 Omicron by intranasal immunization.

Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Currently, the development of affordable vaccine against Omicron variant of concern (VOC) is necessary. Here, we assessed the safety and immunogenicity of a SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing the spike (S) protein of Omicron BA.1 administrated intranasally (IN) or intramuscularly (IM) in Golden Syrian hamster model. Immunogenicity studies showed that the prime-boost regimen elicited high antibody titers and the modified S antigen (Sm-F) could induce robust antibody response in low dosage immunization through IN route. Sera of the immunized hamsters provided effective cross-neutralizing activity against different Omicron variants, the prototype and delta strains of SARS-CoV-2. Moreover, the vaccine could provide complete immunoprotection in hamsters against the Omicron BA.1 challenge by either intranasal or intramuscular immunization. Overall, our study provides an alternative nasal vaccine against the SARS-CoV-2 Omicron variants.

[Analysis of Prognosis and Therapeutic Effect of Patients with Thrombotic Thrombocytopenic Purpura].

OBJECTIVE: To summarize the features of clinical and laboratory parameters of thrombotic thrombocytopenic purpura (TTP), and to analyze the factors affecting the prognosis and therapeutic effect during the acute phase of the disease. METHODS: The etiology, clinical features, laboratory parameters, treatment regimens and other data of 59 TTP patients admitted to Hunan Provincial People's Hospital were retrospectively analyzed. And the differences of each variable between the death group and the survival group were compared, the correlations between each variable and prognosis, as well as the therapeutic effect of the acute phase patients were analyzed. RESULTS: Among the 59 cases of TTP, one 4-year-old boy was inherited TTP, the other 58 cases were acquired TTP (39 cases were idiopathic TTP and 19 were secondary TTP), including 27 males and 31 females, with a median age of 54 (11-84) years old. 36 patients were tested for von Willebrand factor cleaving protease (ADAMTS13) activity, and 34 patients (94.44%) had decreased ADAMTS13 activity. There was a statistical difference in the activity of ADAMTS13 between idiopathic and secondary TTP patients (P<0.001). There were statistical differences in factors such as age (64 vs 51 years), ALT/AST ratio (0.61 vs 0.36), therapeutic plasma exchange (TPE) times (3 times vs 8 times), and TPE duration (3 d vs 9 d) between the death and survival groups. Multivariate analysis showed that total times of TPE (OR=5.175,95%CI: 1.169-22.914, P=0.030), ALT/AST ratio (OR=4.387, 95%CI: 1.019-18.891, P=0.047) were associated with mortality. COX regression analysis showed that degree of neuropsychiatric disorder (HR=0.200, 95%CI: 0.084-0.474, P<0.001), days from onset to initiation of TPE (HR=0.288, 95%CI: 0.114-0.726, P=0.008), treatment regimen (HR=0.336, 95%CI: 0.125-0.902, P=0.030) were associated with platelet recovery and therapeutic effect in the acute phase of the patients. CONCLUSION: TTP patients with high ALT/AST ratio have a higher mortality rate. Patients with enough times and full course of TPE have lower mortality rate. Poor therapeutic effect were found in TTP patients with severe neuropsychiatric disorders, delayed diagnosis and treatment, and who added rituximab when TPE was ineffective.

ent-Atisane Diterpenoids from Euphorbia helioscopia and Their Anti-inflammatory Activities.

Phytochemical investigation on the anti-inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent-atisane diterpenoids (1-3) and five known analogues (4-8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X-ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent-atisane diterpenoid featuring a hydroxyl group at C-9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.

Lanatoside C decelerates proliferation and induces apoptosis through inhibition of STAT3 and ROS-mediated mitochondrial membrane potential transformation in cholangiocarcinoma.

Introduction: The incidence of cholangiocarcinoma (CCA) has increased worldwide in recent years. Given the poor prognosis associated with the current management approach of CCA, new therapeutic agents are warranted to improve the prognosis of this patient population. Methods: In this study, we extracted five cardiac glycosides (CGs) from natural plants: digoxin, lanatoside A, lanatoside C, lanatoside B, and gitoxin. Follow-up experiments were performed to assess the effect of these five extracts on cholangiocarcinoma cells and compounds with the best efficacy were selected. Lanatoside C (Lan C) was selected as the most potent natural extract for subsequent experiments. We explored the potential mechanism underlying the anticancer activity of Lan C on cholangiocarcinoma cells by flow cytometry, western blot, immunofluorescence, transcriptomics sequencing, network pharmacology and in vivo experiments. Results: We found that Lan C time-dependently inhibited the growth and induced apoptosis of HuCCT-1 and TFK-1 cholangiocarcinoma cells. Besides Lan C increased the reactive oxygen species (ROS) content in cholangiocarcinoma cells, decreased the mitochondrial membrane potential (MMP) and resulted in apoptosis. Besides, Lan C downregulated the protein expression of STAT3, leading to decreased expression of Bcl-2 and Bcl-xl, increased expression of Bax, activation of caspase-3, and initiation of apoptosis. N-acetyl-L-cysteine (NAC) pretreatment reversed the effect of Lan C. In vivo, we found that Lan C inhibited the growth of cholangiocarcinoma xenografts without toxic effects on normal cells. Tumor immunohistochemistry showed that nude mice transplanted with human cholangiocarcinoma cells treated with Lan C exhibited decreased STAT3 expression and increased caspase-9 and caspase-3 expression in tumors, consistent with the in vitro results. Conclusion: In summary, our results substantiates that cardiac glycosides have strong anti-CCA effects. Interestingly the biological activity of Lan C provides a new anticancer candidate for the treatment of cholangiocarcinoma.

Anti-inflammatory ent-cleistanthane-type diterpenoids from Phyllanthus rheophyticus.

A bioactivity-guided isolation from the aerial parts of Phyllanthus rheophyticus obtained 17 undescribed ent-cleistanthane-type diterpenoids, namely phyllarheophols A-Q, as well as 12 known analogs. Their structures were characterized by a combination of spectroscopic data interpretation, single-crystal X-ray diffraction and ECD analysis. The anti-inflammatory activities of these compounds were evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW264.7 macrophages, and their preliminary structure-activity relationships were also discussed. Further study showed that promising compounds phyllarheophol D and phyacioid B significantly suppressed the expressions of cytokines and nitric oxide synthase through the NF-κB signaling pathway.

Diterpenoids with an unusual tricyclo[10.3.0.02,9]pentadecane skeleton from Pedilanthus tithymaloides as multidrug resistance modulators.

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.

Predictive Value of Eosinophil Cationic Protein in Nasal Secretions in Eosinophilic Chronic Rhinosinusitis.

OBJECTIVES: To investigate the value of secretions Eosinophilic cationic protein (ECP) detection in the diagnosis of endotypes of Chronic rhinosinusitis (CRS) and its correlation with clinical symptoms, so as to provide guidance for the clinical application of EOS and ECP detection in secretions. METHODS: Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their EOS% and ECP levels were measured. Correlation analysis was performed for EOS% and ECP levels in secretions and tissues, respectively. The correlation between secretions EOS% and ECP and clinical symptom scores (symptomatic visual analog scale (VAS) scores, Lanza-kennedy scores from nasal endoscopy and Lund-Mackay scores from sinus CT) was further analyzed. Receiver operating characteristic curves were used to assess the predictive potential of EOS% and ECP in nasal secretions. RESULTS: Eosinophilic chronic rhinosinusitis (ECRS) patients had higher concentrations of ECP in nasal secretions than healthy subjects and NECRS (non-eosinophilic CRS) (p < 0.0001;0.0001); EOS% in nasal secretions was higher in ECRS than healthy subjects (p = 0.0055), but the differences between ECRS and NECRS were not statistically significant (p = 0.0999). Correlation analysis showed that tissue EOS% was correlated with ECP concentration and EOS% in nasal secretions (R = 0.5943;0.2815). There was a correlation between EOS% in secretions with a total LM score (R = 0.3131); ECP concentration in secretions with a total LK score (R = 0.3792). To diagnose ECRS, the highest area under the curve (0.8230) was determined for ECP in secretions; the highest area under the curve (0.6635) was determined for EOS% in secretions. CONCLUSION: Measurement of ECP in nasal secretions is useful for non-invasive diagnosis of ECRS. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3304-3312, 2023.

Construction and analysis of a conjunctive diagnostic model of HNSCC with random forest and artificial neural network.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous tumor that is highly aggressive and ranks fifth among the most common cancers worldwide. Although, the researches that attempted to construct a diagnostic model were deficient in HNSCC. Currently, the gold standard for diagnosing head and neck tumors is pathology, but this requires a traumatic biopsy. There is still a lack of a noninvasive test for such a high-incidence tumor. In order to screen genetic markers and construct diagnostic model, the methods of random forest (RF) and artificial neural network (ANN) were utilized. The data of HNSCC gene expression was accessed from Gene Expression Omnibus (GEO) database; we selected three datasets totally, and we combined 2 datasets (GSE6631 and GSE55547) for screening differentially expressed genes (DEGs) and chose another dataset (GSE13399) for validation. Firstly, the 6 DEGs (CRISP3, SPINK5, KRT4, MMP1, MAL, SPP1) were screened by RF. Subsequently, ANN was applied to calculate the weights of 6 genes. Besides, we created a diagnostic model and nominated it as neuralHNSCC, and the performance of neuralHNSCC by area under curve (AUC) was verified using another dataset. Our model achieved an AUC of 0.998 in the training cohort, and 0.734 in the validation cohort. Furthermore, we used the Cell-type Identification using Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm to investigate the difference in immune cell infiltration between HNSCC and normal tissues initially. The selected 6 DEGs and the constructed novel diagnostic model of HNSCC would make contributions to the diagnosis.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Euphohelides A-C, ent-Abietane-Type Norditerpene Lactones from Euphorbia helioscopia and Their Anti-Inflammatory Activities.

Three unreported ent-abietane-type norditerpene lactones, euphohelides A-C (1-3), and 11 known analogs (4-14) were isolated from the whole plants of Euphorbia helioscopia L. Euphohelide A (1) is an unprecedented 2-nor-ent-abietane lactone bearing a unique 5/6/6/5 tetracyclic system. Euphohelides B (2) and C (3) possess 2-nor-6/6/6/5 and 2,3-dinor-5/6/6/5 dilactone tetracyclic moieties, respectively. Their structures were established by spectroscopic methods, computational ECD, and X-ray crystallographic analyses. A biomimetic synthesis of 1 was achieved from precursor 4 based on the speculative biogenetic pathway. Compounds 1 and 5 significantly alleviated the release of LPS-induced NO with IC50 values of 32.98 ± 1.13 and 33.82 ± 3.25 µM, which might be related to the regulation of the NF-κB signaling pathway.

Tryptophan metabolism as bridge between gut microbiota and brain in chronic social defeat stress-induced depression mice.

Backgrounds: Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to explore the relationships between gut microbiota and host's metabolism in depression. Methods: Chronic social defeat stress (CSDS) model of depression was established using C57BL/6 male mice. Fecal samples were collected from CSDS group and control group to measure gut microbiota and microbial metabolites. Meanwhile, tryptophan metabolism-related metabolites in hippocampus were also analyzed. Results: CSDS successfully induced depressive-like behaviors in CSDS group. The 24 differential bacterial taxa between the two groups were identified, and 14 (60.87%) differential bacterial taxa belonged to phylum Firmicutes. Functional analysis showed that tryptophan metabolism was significantly affected in CSDS mice. Meanwhile, 120 differential microbial metabolites were identified, and two key tryptophan metabolism-related metabolites (tryptophan and 5-hydroxytryptophan (5-HTP)) were significantly decreased in feces of CSDS mice. The correlation analysis found the significant relationships between tryptophan and differential bacterial taxa under Firmicutes, especially genus Lactobacillus (r=0.801, p=0.0002). In addition, the significantly decreased 5-hydroxytryptamine (5-HT) in hippocampus of depressed mice was also observed. Conclusions: Our results showed that tryptophan metabolism might have an important role in the crosstalk between gut microbioa and brain in depression, and phylum Firmicutes, especially genus Lactobacillus, might be involved in the onset of depression through regulating tryptophan metabolism.

Diagnostic value of myeloperoxidase and eosinophil cationic protein in nasal secretions for endotypes of chronic rhinosinusitis.

OBJECTIVES: To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions. METHODS: We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions. RESULTS: Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions. CONCLUSIONS: Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.

Multi-omics data reveals the important role of glycerophospholipid metabolism in the crosstalk between gut and brain in depression.

BACKGROUND: Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to observe the characteristics of gut microbiota, lipid metabolism and neurotransmitters in Gut-Liver-Brain axis in depressed mice (DM), and identify some novel perceptions on relationships between gut microbiota and depression. METHODS: A mouse model of depression was built used chronic unpredictable mild stress (CUMS). Fecal samples (measuring gut microbiota compositions, microbial genes and lipid metabolites), liver samples (measuring lipid metabolites), and hippocampus (measuring neurotransmitters) were collected. Both univariate and multivariate statistical analyses were used to identify the differential gut microbiota, metabolic signatures and neurotransmitters in DM. RESULTS: There were significant differences on both microbial and metabolic signatures between DM and control mice (CM): 71 significantly changed operational taxonomic units (OTUs) (60.56% belonged to phylum Firmicutes) and 405 differential lipid metabolites (51.11% belonged to Glycerophospholipid (GP) metabolism) were identified. Functional analysis showed that depressive-like behaviors (DLB)-related differential microbial genes were mainly enriched in GP metabolism. Weighted correlation network analysis (WGCNA) showed that DLB-related differential metabolites mainly belonged to GPs. Meanwhile, seven differential neurotransmitters were identified. Comprehensive analysis found that Lachnospiraceae and gamma-aminobutyric acid (GABA) were significantly correlated with 94.20% and 53.14% differential GPs, respectively, and GABA was significantly correlated with three main DLB phenotypes. CONCLUSION: Our results provided novel perceptions on the role of Gut-Liver-Brain axis in the onset of depression, and showed that GP metabolism might be the bridge between gut microbiota and depression. "Lachnospiraceae-GP metabolism-GABA" held the promise as a potential way between gut microbiota and brain functions in DM.

Azaphilones from the Fungus Penicillium multicolor LZUC-S2 and Their Antibacterial Activity.

Two new azaphilones, penimultiones A and B, together with seven known analogs were isolated from the culture of Penicillium multicolor LZUC-S2. Their structures were elucidated by detailed spectroscopic data analysis and chemical transformation. Penimultiones A and B belong to a rare class of azaphilones possessing a 1,3-dioxolane moiety. In addition, all compounds were evaluated for their antibacterial activity against five clinically bacterial strains in vitro, and three compounds showed potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 12.5 to 50.0 µg/mL.

[Temporal and Spatial Variation Characteristics of Carbon Storage in the Source Region of the Yellow River Based on InVEST and GeoSoS-FLUS Models and Its Response to Different Future Scenarios].

Regional land use change is the main cause of carbon storage changes in ecosystems. Predicting the impact of future land use changes on carbon storage is of great significance for the sustainable development of carbon storage functions. In recent years, under the combined action of natural and human factors, the land use in the source region of the Yellow River has changed significantly, and its carbon storage function has also changed accordingly. This study combined InVEST and GeoSoS-FLUS models to evaluate land use change and its impact on carbon storage in the source region of the Yellow River from 2000 to 2020 and from 2020 to 2040 under different scenarios. The results showed that:① from 2000 to 2020, the carbon storage in the source region of the Yellow River showed an overall upward trend, with a total increase of 11.59×106 t. ② Over the past 20 years, the land use changes in the source region of the Yellow River included mainly the increase in the area of low-coverage grassland, construction land, and wetland and the decrease in the area of high-coverage grassland, medium-coverage grassland, and unused land, as well as the large-scale reduction of unused land and the reduction of grassland. The increase in the area of wetlands was the main reason for the increase in carbon storage. ③ Under the natural change scenario in 2040, the ecosystem carbon storage in the source region of the Yellow River was 871.34×106 t, an increase of 3.92×106 t compared with that in 2020. Under the ecological protection scenario, carbon storage increased significantly, with an increase of 13.53×106 t compared with that in 2020. The results of this study can provide a scientific reference for the decision-making of land use management and the sustainable development of carbon storage function in the source region of the Yellow River.

AIM2 inflammasome activation may mediate high mobility group box 1 release in murine allergic rhinitis / Ativação do inflamassoma AIM2 pode mediar a liberação da proteína do grupo Box-1 de alta mobilidade no modelo murino de rinite alérgica

Abstract Introduction: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. Objective: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. Methods: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. Results: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. Conclusions: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

Resumo Introdução: A proteína do grupo Box-1 de alta mobilidade participa da patogênese da rinite alérgica. A ativação do inflamassoma pode mediar a liberação de proteína do grupo Box-1 de alta mobilidade. O papel do inflamassoma ausente no melanoma 2 na rinite alérgica permanece incerto. Objetivo: Investigar a função do inflamassoma ausente no melanoma 2 em um modelo murino de rinite alérgica e a interação entre a proteína do grupo Box-1 de alta mobilidade e o inflamassoma ausente no melanoma 2. Método: Um modelo murino de rinite alérgica foi estabelecido com 20 camundongos Balb/c. A expressão dos componentes do inflamassoma ausente no melanoma 2, da proteína speck-like associada à apoptose com CARD (Asc), da caspase-1 p20 e do domínio de pirina da família NLR adicional com 3 (Nlrp3) foi detectada por western blotting durante a rinite alérgica. Alterações de inflamassoma ausente no melanoma 2, na caspase-1 e na proteína do grupo Box-1 de alta mobilidade após o teste de provocação com ovalbumina foram demonstradas por imuno-histoquímica. O ensaio dUTP Nick-End Labeling mediado por TdT, TUNEL e clivagem de caspase-3 e PARP-1 foram usados para a observação de piroptose. Resultados: Eosinofilia e infiltração de células caliciformes foram observadas na mucosa nasal de camundongos do grupo rinite alérgica. Inflamassoma ausente no melanoma 2, Asc e caspase-1 p20 aumentou após a exposição à ovalbumina, enquanto Nlrp3 não aumentou. A proteína do grupo Box-1 de alta mobilidade foi liberada na mucosa nasal de camundongos com rinite alérgica. As células TUNEL-positivas aumentaram no epitélio e na lâmina própria, enquanto a clivagem da caspase-3 e a PARP-1 não foram observadas. Conclusão: O inflamassoma ausente no melanoma 2 foi ativado e pode ocorrer piroptose na mucosa nasal após o tratamento com ovalbumina. Esses fatores podem contribuir para a translocação de proteína do grupo Box-1 de alta mobilidade e o desenvolvimento de rinite alérgica.

Jatrophane diterpenoids with cytotoxic activity from the whole plant of Euphorbia heliosocpia L.

Eight undescribed jatrophane diterpenoids, euphohelinoids A-H, along with 11 known analogues were isolated from the whole plant of Euphorbia heliosocpia L. Among them, euphohelinoids A and B contain a rare type of jatrophane diterpenoid skeleton with a 7,8-seco scaffold. To the best of our knowledge, only two such jatrophane diterpenoids have been reported. In addition, euphohelinoids G and H belong to a rare class of jatrophane diterpene possessing a ß-hydroxy group at C-11. Structure elucidation of these undescribed diterpenoids was performed by spectroscopic analysis, including NMR, HRESIMS, IR, electronic circular dichroism (ECD) and DP4+ analysis. The cytotoxicity of 17 abundant jatrophane diterpenes was evaluated against HepG2, HeLa, HL-60, and SMMC-7721 cell lines. Seven compounds presented potent cytotoxicity against the four tested cell lines with IC50 values from 8.1 to 29.7 µM. Moreover, preliminary structure-activity relationships for these jatrophane diterpenoids were discussed.

Two New Eremophilane-Type Sesquiterpenoids from Ligularia sagitta.

Two new eremophilane-type sesquiterpenoids, sagittacins F and G (1 and 2), together with one known isomer of sagittacin F (3) were isolated from the leaves and stems of Ligularia sagitta. Their structures were elucidated by interpretation of spectroscopic data and the absolute configurations of 1 and 3 were determined by X-ray spectroscopy. Compound 1 belongs to a rare class of eremophilane-type sesquiterpenoid featuring an α-oriented hydroxy group at C-1. A nitric oxide (NO) production inhibitory assay was applied to evaluate their anti-inflammatory activities by using LPS-induced RAW 264.7 cells. Compounds 2 and 3 exhibited modest NO production inhibitions with IC50 values of 45.15±2.72 and 49.83±2.34 µM, respectively.