(-)-α-Bisabolol inhibits D-Gal-induced HSF cellular senescence in vitro and prevents skin aging in vivo by reducing SASP.

Objectives: To study the anti-aging effect of (-)-α-bisabolol ((-)-α-bis) on the skin and preliminarily clarify its mechanism. Materials and Methods: Human skin fibroblasts (HSF) were induced senescence by D-Galactose. Senescence ß-galactosidase staining was utilized to evaluate the senescence of HSF. TNF-α, IL-6, IL-8, IL-1ß, CCL-2, CCL-5, and MMP-9 in senescence-as-sociated secretory phenotype (SASP) were detected by RT-qPCR. Meanwhile, aged BALB/c mice were applied topically with 0.5% and 2%(-)-α-bis gel for 30 days continuously to evaluate anti-aging parameters on the skin such as surface measurement, the Trans Epidermal Water Loss (TEWL), and skin barrier index of dorsal skin. Then, HE staining, Masson staining, and IHC were applied to measure epidermal thickness, collagen fiber content in the dermis, and content of dermal collagen I, respectively. Last, SOD, MDA, and HYP contents of the back skin tissue of mice were also detected. Results: (-)-α-Bis reduced the expression of senescence-associated ß-galactosidase (SA-ß-gal) and expression levels of SASP in HSF cells stimulated by D-Gal (P<0.05). Mice aged 9 months were applied locally with (-)-α-bis gel to improve skin aging, the TEWL and skin barrier index of dorsal skin, and ameliorate the epidermal thickness and contents of dermal collagen fibers and collagen I (P<0.05). Furthermore, (-)-α-bis up-regulated the mRNA expression levels of elastin and collagen III effectively (P<0.05). Conclusion: (-)-α-Bis can delay the senescence of HSF cells by reducing the expression of SA-ß-gal and SASP factors in vitro. Improved skin barrier function as well as SASP is responsible for the delay of skin aging in vivo.

Cross-domain microbiomes: the interaction of gut, lung and environmental microbiota in asthma pathogenesis.

Recent experimental and epidemiological studies underscore the vital interaction between the intestinal microbiota and the lungs, an interplay known as the "gut-lung axis". The significance of this axis has been further illuminated following the identification of intestinal microbial metabolites, such as short-chain fatty acids (SCFA), as key mediators in setting the tone of the immune system. Through the gut-lung axis, the gut microbiota and its metabolites, or allergens, are directly or indirectly involved in the immunomodulation of pulmonary diseases, thereby increasing susceptibility to allergic airway diseases such as asthma. Asthma is a complex outcome of the interplay between environmental factors and genetic predispositions. The concept of the gut-lung axis may offer new targets for the prevention and treatment of asthma. This review outlines the relationships between asthma and the respiratory microbiome, gut microbiome, and environmental microbiome. It also discusses the current advancements and applications of microbiomics, offering novel perspectives and strategies for the clinical management of chronic respiratory diseases like asthma.

Metabolite Profiling Analysis of the Tongmai Sini Decoction in Rats after Oral Administration through UHPLC-Q-Exactive-MS/MS.

Tongmai Sini decoction (TSD), the classical prescriptions of traditional Chinese medicine, consisting of three commonly used herbal medicines, has been widely applied for the treatment of myocardial infarction and heart failure. However, the absorbed components and their metabolism in vivo of TSD still remain unknown. In this study, a reliable and effective method using ultra-performance liquid chromatography coupled with hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Exactive-MS/MS) was employed to identify prototype components and metabolites in vivo (rat plasma and urine). Combined with mass defect filtering (MDF), dynamic background subtraction (DBS), and neutral loss filtering (NLF) data-mining tools, a total of thirty-two major compounds were selected and investigated for their metabolism in vivo. As a result, a total of 82 prototype compounds were identified or tentatively characterized in vivo, including 41 alkaloids, 35 phenolic compounds, 6 saponins. Meanwhile, A total of 65 metabolites (40 alkaloids and 25 phenolic compounds) were tentatively identified. The metabolic reactions were mainly hydrogenation, demethylation, hydroxylation, hydration, methylation, deoxylation, and sulfation. These findings will be beneficial for an in-depth understanding of the pharmacological mechanism and pharmacodynamic substance basis of TSD.

Identification of rBlo t 41 with a chitin-binding type-2 domain: A novel major allergen from Blomia tropicalis.

BACKGROUND: Blomia tropicalis (B. tropicalis) has been reported to impose an increased risk of allergic diseases. However, few characteristics of the unknown allergen components responsible for B. tropicalis allergy and clinical relevance have been fully identified. METHODS: We synthesized and characterized the physicochemical properties and cross-reactivity of the newly discovered recombinant B. tropicalis group 41 allergen (rBlo t 41). Subsequently, sera were collected from 107 B. tropicalis allergic subjects to evaluate the prevalence of the rBlo t 41. Lastly, its allergenicity was tested in humans by basophil activation assays, and in mice by a model of allergic asthma. RESULTS: The mature protein of rBlo t 41 was described as 104 amino acids long and 15.8 kDa, and its limited cross-reactivity was observed between allergens of house dust mites (HDM). Sensitization rate of rBlo t 41 (56.07 %) was lower than rBlo t 2 (76.29 %) and rBlo t 5 (69.07 %) in our study. Besides, rBlo t 41 elicited CD63 upregulation in basophils, whereas rBlo t 41-sensitized mice generated rBlo t 41-IgE and developed allergic airway inflammation after allergen exposure. Of note, component-based tests showed a high area under curve value (AUC = 0.75) of rBlo t 41, displaying its favorable diagnostic potential in B. tropicalis allergy. CONCLUSIONS: rBlo t 41 was identified as a candidate novel major allergen with good diagnostic potential in B. tropicalis sensitization. Additionally, we provided strong evidence about rBlo t 41 on the clinically relevant manifestations in B. tropicalis allergies, conducive to facilitating the development of component-resolved diagnosis.

Developing and validating clinical models to identify candidates for allergic rhinitis pre-exposure prophylaxis.

PURPOSE: Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire. METHODS: This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively. RESULTS: This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models. CONCLUSION: Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Patterns of aeroallergen sensitization in asthma patients identified by latent class analysis: A cross-sectional study in China.

BACKGROUND: This cross-sectional study aimed to identify latent sensitization profiles of asthma patients in mainland China, unveiling the association between regional differences and sensitization patterns. METHODS: 1056 asthma participants from 10 medical centers divided into eastern and western cohorts were clustered into four individual sensitization patterns, respectively, by using an unsupervised statistical modeling method, latent class analysis (LCA), based on the levels of 12 aeroallergens specific IgE reactivities. Moreover, differences in clinical characteristics and environmental exposures were compared in different sensitization patterns. RESULTS: Four distinct sensitization patterns in the two cohorts were defined as follows, respectively. Eastern cohort: Class 1: "High weed pollen and house dust mites (HDMs) sensitization" (8.87%), Class 2: "HDMs dominated sensitization" (38.38%), Class 3: "High HDMs and animal dander sensitization" (6.95%), Class 4: "Low/no aeroallergen sensitization" (45.80%). Western cohort: Class 1: "High weed pollen sensitization" (26.14%), Class 2: "High multi-pollen sensitization" (15.02%), Class 3: "HDMs-dominated sensitization" (10.33%), Class 4: "Low/no aeroallergen sensitization" (48.51%). Of note, the significant statistical difference in age, asthma control test score (ACT) and comorbidities were observed within or between different sensitization patterns. Exposure factors in different sensitization patterns were pointed out. CONCLUSIONS: Asthmatic patients with distinct sensitization patterns were clustered and identified through the LCA method, disclosing the relationship between sensitization profiles of multiple aeroallergens and geographical differences, providing novel insights and potential strategies for atopic disease monitoring, management and prevention in clinical practice.

Evolution of the newest diagnostic methods for COVID-19: a Chinese perspective. / ä¸­å›½è§†è§’ä¸‹çš„æ–°å† è‚ºç‚Žæœ€æ–°è¯Šæ–­æ–¹æ³•æ¼”è¿›.

Coronavirus disease 2019 (COVID-19) has continued to spread globally since late 2019, representing a formidable challenge to the world's healthcare systems, wreaking havoc, and spreading rapidly through human contact. With fever, fatigue, and a persistent dry cough being the hallmark symptoms, this disease threatened to destabilize the delicate balance of our global community. Rapid and accurate diagnosis of COVID-19 is a prerequisite for understanding the number of confirmed cases in the world or a region, and an important factor in epidemic assessment and the development of control measures. It also plays a crucial role in ensuring that patients receive the appropriate medical treatment, leading to optimal patient care. Reverse transcription-polymerase chain reaction (RT-PCR) technology is currently the most mature method for detecting viral nucleic acids, but it has many drawbacks. Meanwhile, a variety of COVID-19 detection methods, including molecular biological diagnostic, immunodiagnostic, imaging, and artificial intelligence methods have been developed and applied in clinical practice to meet diverse scenarios and needs. These methods can help clinicians diagnose and treat COVID-19 patients. This review describes the variety of such methods used in China, providing an important reference in the field of the clinical diagnosis of COVID-19.

Cocrystal of phloretin with isoniazid: preparation, characterization, and evaluation.

Phloretin (Phl) is a natural flavonoid compound with wide range of biological activities but demonstrates poor water solubility and limited pharmacological effects. In this study, one cocrystal of phloretin-isoniazid (Phl-Inz) was prepared successfully using the solvent evaporation method. The physical properties of cocrystal were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TG), powder X-ray diffraction (PXRD), Fourier-transform infrared (FT-IR) and single crystal X-ray diffraction (SCXRD). The Hirshfeld surface analysis explained further interactions in the cocrystal. The solubility test showed that the solubility of the cocrystal was increased at pH 1.2 and pH 6.8 compared to that of the pure drug. The test in vitro simulated gastrointestinal digestion showed that the release of phloretin in the cocrystal was better than that in the pure phloretin. The results of the DPPH and ABTS scavenging activity showed that the in vitro antioxidant activity of the cocrystal was improved. The anticancer assay exhibited improved cytotoxicity in the Phl-Inz cocrystal as compared with the pure Phl.

The relationship of D. pteronyssinus allergic component sIgE and sIgG4 in house dust mite allergic rhinitis or/and allergic asthma patients.

Objective: House-dust mite sensitization is an important cause of allergic asthma and/or rhinitis in southern China. This study aimed to analyze the immune effect and relationship between the Dermatophagoides pteronyssinus components specific immunoglobulin E (sIgE) and sIgG4. Methods: The serum levels of sIgE and sIgG4 to D. pteronyssinus allergen components Der p 1, 2, 3, 5, 7, 10, and 23 were detected in 112 patients with allergic rhinitis (AR) and/or allergic asthma (AA). Results: Overall, Der p 1 had the highest positive rate of sIgE (72.3%), followed by Der p 2 (65.2%) and Der p 23 (46.4%). Meanwhile, the highest positive rates of sIgG4 were for Der p 2 (47.3%), Der p 1 (33.0%), and Der p 23 (25.0%). The patients with AR and AA had a higher positive rate (43.4%) of sIgG4 than that in the patients with AR (42.4%) and the patients with AA (20.4%; p = 0.043). In patients with AR, the positive rate of sIgE in Der p 1 (84.8%) was higher than that in sIgG4 (42.4%; p = 0.037), but the positive rate of sIgG4 in Der p 10 (21.2%) was higher than that in sIgE (18.2%; p < 0.001). Most of the patients were positive for sIgE and sIgG4 of Der p 2 and Der p 10 at the same time. However, positive results for sIgE alone were just found in Der p 7 and Der p 21. Optimal scale analysis showed that Der p 2, Der p 7, and Der p 21 sIgG4 were closely related to AR and AA (Cronbach α = 0.917). Conclusion: Herein, the D. pteronyssinus allergen components showed different characteristics among the patients with AR, patients with AA, and patients with AR and AA in southern China. Thus, sIgG4 may be play an important role in allergic reactions.

Characteristics of Allergen Components of Dermatophagoides pteronyssinus in Shrimp and Mite Co-Sensitized Patients in Southern China.

INTRODUCTION: Dermatophagoides pteronyssinus (Dp) and shrimp are common air allergens and allergenic food sources, respectively, in southern China. This study aimed to analyze the specific immunoglobulin E (sIgE) characteristics and relationships of Dp components among co-sensitized patients with Dp and shrimp. MATERIALS AND METHODS: Serum samples were collected from 112 patients with Dp sensitization (61 with shrimp sensitization and 51 without) from southern China. The sIgE concentrations of Dp and shrimp crude extracts were determined by ImmunoCAP, and the sIgE of Dp allergen components (Der p 1, Der p 2, Der p 5, Der p 7, Der p 10, Der p 21, and Der p 23) was detected by protein chip. RESULTS: Overall, in the Dp-allergic patients, Der p 1 had the highest positive rate (72.3%), followed by Der p 2 (65.2%), Der p 23 (46.4%), Der p 7 (32.14%), Der p 21 (29.46%), Der p 5 (22.32%), and Der p 10 (17.86%). Compared with that in the shrimp nonsensitized group, the positive rate of sIgE for Der p 10 (27.87% vs. 5.88%, p = 0.002) in the shrimp sensitization group was significantly higher; however, the positive rate of sIgE for Der p 7 (22.95% vs. 43.14%, p = 0.023) was significantly lower. Moreover, the concentration of sIgE for Der p 10 increased statistically in the shrimp-sensitized group. The correlation analysis also showed that shrimp sensitization was significantly correlated with Der p 10. CONCLUSION: Among patients with Dp sensitization, Der p 1 had the highest positive rate, followed by Der p 2 and Der p 23. Meanwhile, Der p 10 may play an important role in patients with shrimp sensitization, while Der p 7 may be the meaningful allergen component in patients with Dp sensitization alone. In general, component-resolved diagnosis technology in clinical practice can effectively guide patients with polysensitization to avoid allergic substances.

Rhinitis symptom in patients with self-reported allergic rhinitis is influenced by sensitization pattern: A cross-sectional study of China.

BACKGROUND: Allergic rhinitis (AR) is characterized by distinct clinical heterogeneity and allergic sensitization patterns. We aimed to quantify rhinitis symptoms in patients with self-reported allergic rhinitis according to the potential sensitization patterns for relevant allergens in China. METHODS: We used latent class analysis (LCA; a subset of structural equation modeling) to independently cluster patients into different patterns of atopic sensitization in an unsupervised manner, based on specific immunoglobulin E tests. AR symptom severity was assessed by the visual analogue scale. We evaluated the association between the severity of AR and the allergen sensitization patterns. RESULTS: LCA revealed four phenotypes of atopic sensitization among 967 patients with self-report AR. We labeled latent classes as: Class 1, weed pollens and indoor sensitization (n = 74 [7.7%]); Class 2, weed pollen with low indoor sensitization (n = 275 [28.4%]); Class 3, low or no sensitization (n = 350 [36.2%]); and Class 4, house dust mite-dominated sensitization (n = 268 [27.7%]). AR was more severe in Class 2 compared to the other 3 classes, indicating that upper respiratory symptoms are more severe among patients with isolated seasonal rhinitis. CONCLUSION: We have identified four sensitization patterns in patients with self-reported AR, which were associated with different clinical symptoms and comorbidities.

Three patterns of sensitization to mugwort, timothy, birch and their major allergen components revealed by Latent class analysis.

BACKGROUND: Mugwort, timothy, and birch are commonly spread pollen allergens across China. Although several studies have described the rates of sensitization to mugwort, timothy, and birch in China, most of them just on specific whole-allergen extracts but little was known about the co-sensitization characteristics of its allergen components. This study aimed to explore the patterns of sensitization to mugwort, timothy, birch, and their major allergen components. METHOD: Serum specific IgE (sIgE) levels of allergen components of mugwort, timothy, birch, and cross-reactive carbohydrate determinants (CCD) were detected in 160 patients whose serum showed positive results to at least one of mugwort, timothy, and birch allergens via EUROBlotMaster system. Skin prick testing was utilized to assess the allergic reaction of grass, weed, and tree allergens. Latent class analysis was used to identify underlying patterns of sensitization to a series of allergen components and their corresponding extracts. RESULTS: 88.8% of patients with allergic rhinitis and/or asthma were positive for mugwort-sIgE, 30% for timothy-sIgE, and 32.5% for birch-sIgE. By using the LCA model, three sensitization patterns as "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized", "Timothy, mugwort, and CCD co-sensitized", "Mugwort and Art v 1 co-sensitized" were revealed based on optimal statistical fit in this study. Compared with other clusters, participants in "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized" pattern were associated with higher sensitization rates of common grass and tree pollens allergen. The spearman's coefficient between CCD and timothy was larger than the corresponding values of CCD with mugwort or birch. CONCLUSION: CCD and profilin, as minor allergens in pollens, were associated with other pollen sIgE false positives presumably due to cross-reactivity. Patients sensitized with profilin had a significantly higher risk of sensitization to other pollens.

SAHA Alleviates Diarrhea-Predominant Irritable Bowel Syndrome Through Regulation of the p-STAT3/SERT/5-HT Signaling Pathway.

Objective: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and stool irregularity. However, its pathophysiological mechanisms, which trigger intestinal motility disorders and diarrhea leading to diarrhea-predominant IBS (D-IBS), remain largely unknown. Methods: In the present study, we established a D-IBS rat model by mother-infant separation combined with restraint stress. Then we exposed the modelled rats to suberoylanilide hydroxamic acid (SAHA) treatment, followed by determination of their visceral sensitivity. Toluidine blue staining served to reveal the effects of SAHA treatment on mast cells of D-IBS model rats. Then we measured the expression of serotonin (5-hydroxytryptamine; 5-HT) and its receptors by ELISA. Results: Construction of short hairpin RNA (sh)-serotonin transporter (SERT) lentivirus vectors verified the regulation of the 5-HT signaling pathway by phosphorylated (p)-STAT/SERT. SAHA treatment of D-IBS model rats reduced the fecal water content, electromyography integral change rate, abdominal withdrawal reflex score, and number of mast cells, as well as the expression of 5-HT type 3A (5-HT3AR), 3B receptor (5-HT3BR), and 4 receptor (5-HT4R) receptors. The treatment also elevated the expression of signal transducer and activator for transcription 3 (STAT3) and SERT. Activation of p-STAT3 may reverse the inhibitory effect of SAHA on the elevated visceral sensitivity of D-IBS model rats. Moreover, SAHA promoted the transcription of SERT through repression of the p-STAT3/5-HT signaling, thereby inhibiting the visceral sensitivity of D-IBS model rats. Conclusion: This study highlights that SAHA treatment can alleviate D-IBS through regulation of the p-STAT3/SERT/5-HT signaling pathway.

A Multicenter Study Assessing Risk Factors and Aeroallergens Sensitization Characteristics in Children with Self-Reported Allergic Rhinitis in China.

BACKGROUND: Up to now, epidemiological studies on allergy rhinitis (AR) have primarily focused on determining the risk of disease in Chinese adults, with the majority of them designed by single centers, while cross-sectional and epidemiological data describing allergic sensitization in children with self-reported AR are scarce. OBJECTIVE: This study was estimating of the latest information about the sensitization patterns and risk factors of clinical AR to develop effective strategies for the prevention and treatment of AR. METHODS: We conducted a cross-sectional survey between January 2020 and June 2021 involving children from seven cities in China who reported AR. A total of 762 children participated in this survey. To evaluate the risk factors and specific sensitization patterns of clinical AR through questionnaires and specific immunoglobulin E to 11 aeroallergens. RESULTS: Of the 762 patients, 593 (77.8%) had at least one positive IgE level. Aged 7-14 years (OR 1.503, (95% CI 1.058-2.136), P = 0.023); With allergic conjunctivitis (OR 1.843, (95% CI 1.297-2.620), P = 0.001) and living in the Eastern (OR 1.802, (95% CI 1.263-2.573), P = 0.001) all elevated the risk of clinical AR associated with aeroallergens. The sensitization rates of D. pteronyssinus and D. farinae were higher than those of other allergens in the 0-6 and 7-14 years old age groups. The most common aeroallergens among self-reported children with AR in the eastern were D. farinae (74.9%) and D. pteronyssinus (74.3%), while in the western were mugwort (60.0%) and marguerite (56.6%). Majority of sIgE-positive subjects were sensitized to three or more of the tested pollen allergens in the Western (52.1%), compared with 5.7% in the Eastern. CONCLUSION: There was an apparent geographic variation in childhood allergies in China. Age factors also had strong impacts on the allergen sensitization rate of children, but these impacts differed across regions.

Regulating effect of baicalin on IKK/IKB/NF-kB signaling pathway and apoptosis-related proteins in rats with ulcerative colitis.

OBJECTIVE: This study was aimed to explore effect of baicalin on IKK/IKB/NF-kB signaling pathway and apoptosis-related proteins in rats with ulcerative colitis (UC). METHODS: Histopathological observation and scores of colon tissue were performed in the UC rat model. IKK/IKB/NF-kB signaling pathway and apoptosis-related proteins were measured by Western blotting. RESULTS: Baicalin significantly increased the activity of SOD, CAT and GSH-Px in colon tissue of rats with UC, but significantly decreased the content of MDA, IL-1ß, MPO, PEG2 and TNF-α in colon tissue of rats with UC. In the molecular mechanism, baicalin significantly decreased the expression of cleaved-caspase3, cleaved-caspase9, Bcl-2/Bax, cyt-c, NF-kB p-65, p-IKKß/IKKß and p-IKBα/IKBα. Baicalin could significantly inhibit p-IKBα/IKBα content change, but had no significant effect on p-IKKß/IKKß. CONCLUSION: Baicalin may have a regulating effect on IKK/IKB/NF-kB signaling pathway and apoptosis-related proteins in UC rats.