Huanglian Decoction treats Henoch-Schonlein purpura nephritis by inhibiting NF-κB/NLRP3 signaling pathway and reducing renal IgA deposition.

Henoch-Schonlein purpura nephritis (HSPN) is a systemic vascular inflammatory disease. Huanglian Decoction (HLD) ameliorates renal injury in nephritis; however, the mechanism of action of HLD on HSPN has not been investigated. This study aimed to investigate the protective mechanism of HLD treatment in HSPN. The effects of HLD on HSPN biochemical indices, kidney injury and NF-κB/NLRP3 signaling pathway were analyzed by biochemical analysis, ELISA, HE and PAS staining, immunohistochemistry, immunofluorescence, and Western Blot. In addition, the effects of HLD on HSPN cells were analyzed. We found that HLD treatment significantly reduced renal tissue damage, decreased the levels of IL-17, IL-18, TNF-α, and IL-1ß, and increased the levels of TP and ALB in HSPN mice. It also inhibited the deposition of IgA, IgG, and C3 in kidney tissues and significantly decreased the expression of IκBα, p-IκBα, NLRP3, caspase-1, and IL-1ß in kidney tissues and cells. In addition, PMA treatment inhibited the above-mentioned effects of HLD. These results suggested that HLD attenuates renal injury, IgA deposition, and inflammation in HSPN mice and its mechanism of action may be related to the inhibition of the NF-κB/NLRP3 pathway.

[Expression changes of RNA m6A regulators in mouse cerebellum affected by hypobaric hypoxia stimulation].

Objective: To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment. Methods: Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella. Results: Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced (P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella (P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice (P<0.05). Conclusions: Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

Propagation of extended fractures by local nucleation and rapid transverse expansion of crack-front distortion.

Fractures are ubiquitous and can lead to the catastrophic material failure of materials. Although fracturing in a two-dimensional plane is well understood, all fractures are extended in and propagate through three-dimensional space. Moreover, their behaviour is complex. Here we show that the forward propagation of a fracture front occurs through an initial rupture, nucleated at some localized position, followed by a very rapid transverse expansion at velocities as high as the Rayleigh-wave speed. We study fracturing in a circular geometry that achieves an uninterrupted extended fracture front and use a fluid to control the loading conditions that determine the amplitude of the forward jump. We find that this amplitude correlates with the transverse velocity. Dynamic rupture simulations capture the observations for only a high transverse velocity. These results highlight the importance of transverse dynamics in the forward propagation of an extended fracture.

Rapid and accurate identification of bacteria utilizing laser-induced breakdown spectroscopy.

Timely and accurate identification of harmful bacterial species in the environment is paramount for preventing the spread of diseases and ensuring food safety. In this study, laser-induced breakdown spectroscopy technology was utilized, combined with four machine learning methods - KNN, PCA-KNN, RF, and SVM, to conduct classification and identification research on 7 different types of bacteria, adhering to various substrate materials. The experimental results showed that despite the nearly identical elemental composition of these bacteria, differences in the intensity of elemental spectral lines provide crucial information for identification of bacteria. Under conditions of high-purity aluminum substrate, the identification rates of the four modeling methods reached 74.91%, 84.05%, 85.36%, and 96.07%, respectively. In contrast, under graphite substrate conditions, the corresponding identification rates reached 96.87%, 98.11%, 98.93%, and 100%. Graphite is found to be more suitable as a substrate material for bacterial classification, attributed to the fact that more characteristic spectral lines are excited in bacteria under graphite substrate conditions. Additionally, the emission spectral lines of graphite itself are relatively scarce, resulting in less interference with other elemental spectral lines of bacteria. Meanwhile, SVM exhibited the highest precision rate and recall rate, reaching up to 1, making it the most effective classification method in this experiment. This study provides a valuable approach for the rapid and accurate identification of bacterial species based on LIBS, as well as substrate selection, enhancing efficient microbial identification capabilities in fields related to social security and military applications.

Predictive effect of net water uptake on futile recanalisation in patients with acute large-vessel occlusion stroke.

AIM: To determine whether net water uptake (NWU) based on automated software evaluation could predict futile recanalisation in patients with acute anterior circulation large-vessel occlusion (LVO). MATERIALS AND METHODS: Patients with acute anterior circulation LVO undergoing mechanical thrombectomy in Jinling Hospital were evaluated retrospectively. NWU and other baseline data were evaluated by performing univariate and multivariate analyses. The primary endpoint was 90-day modified Rankin scale score ≥3. A nomogram to predict poor clinical outcomes was developed based on multivariate logistic regression analysis. RESULTS: Overall, 135 patients who underwent thrombectomy with a TICI grade ≥2b were enrolled. In multivariate logistic regression analysis, the following factors were identified as independent predictors of futile recanalisation: age (odds ratio [OR]: 1.055, 95 % confidence interval [CI]: 1.004-1.110, p=0.035), female (OR: 0.289, 95 % CI: 0.098-0.850, p=0.024), hypertension (OR: 3.182, 95 % CI: 1.160-8.728, p=0.025), high blood glucose level (OR: 1.36, 95 % CI: 1.087-1.701, p=0.007), admission National Institutes of Health Stroke Scale score (OR: 1.082, 95 % CI: 1.003-1.168, p=0.043), and NWU (OR: 1.312, 95 % CI: 1.038-1.659, p=0.023). CONCLUSIONS: NWU based on Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) could be used to predict the occurrence of futile recanalisation in patients with acute anterior circulation LVO ischaemic stroke.

[High expression of CPNE3 correlates with poor long-term prognosis of gastric cancer by inhibiting cell apoptosis via activating PI3K/AKT signaling].

OBJECTIVE: To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer (GC) and the possible mechanism. METHODS: We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February, 2013 to October, 2017. TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients. GO analysis was performed to predict the biological role of CPNE3 in GC. We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown, CPNE3 overexpression and LY294002 (a PI3K/AKT inhibitor) treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting. RESULTS: TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC (P < 0.05). The patients with high CPNE3 expressions had a reduced 5-year survival (P < 0.01), and a high CPNE3 expression, CEA level≥5 µg/L, CA19-9 level ≥37 kU/L, T3-T4 stage, and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery. The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59% and 74.55%, respectively (P < 0.05). GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis. In MGC803 cells, CPNE3 knockdown significantly increased cell apoptosis, enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression, while CPNE3 overexpression produced the opposite results (P < 0.05). The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression (P < 0.05). Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells (P < 0.05). CONCLUSION: CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

The association between periodontitis and hepatitis virus infection: a cross-sectional study utilizing data from the NHANES database (2003-2018).

OBJECTIVES: Periodontitis and hepatitis virus infection significantly impact individuals' well-being and are prevalent public health concerns globally. Given the current scarcity of large-scale cross-sectional epidemiological studies, this study seeks to enrich the evidence base by examining the link between these two conditions. STUDY DESIGN AND METHODS: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2003-2018. A multivariate logistic regression analysis was performed to assess the association between periodontitis and hepatitis virus infection, adjusting for the potential confounding factors. Subsequently, a stratified analysis was conducted to explore the relationship between periodontitis and hepatitis virus infection based on age, gender, race, marital status, alcohol consumption, smoking status, and the presence of chronic diseases. RESULTS: In this study, which included 5755 participants, there was a positive association between hepatitis virus infection and periodontitis (odds ratio [OR]: 2.609 [95% confidence interval (CI): 1.513, 4.499]). Furthermore, a significant association was observed between moderate periodontitis and hepatitis virus infection (OR: 2.136 [95% CI: 1.194, 3.822]), and this association was even stronger for severe periodontitis (OR: 3.583 [95% CI: 1.779, 7.217]). Importantly, this positive association between hepatitis virus infection and periodontitis was consistent across different subgroups. CONCLUSIONS: This study presents evidence of a significant association between periodontitis and hepatitis virus infection. These findings highlight the crucial importance of integrating periodontal health and liver health considerations into public health interventions. Further research is necessary to elucidate the underlying mechanisms and develop targeted interventions for effectively managing periodontitis and hepatitis virus infection.

[Predictive value of net water uptake with respect to early neurological improvement after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke].

Objective: To investigate the value of net water uptake (NWU) for predicting early neurological improvement (ENI) after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke. Methods: A case-control study. A total of 132 patients (80 men, 52 women, median age 68 years) with acute anterior circulation large vessel occlusive stroke receiving endovascular treatment were retrospectively analyzed at Jinling Hospital from October 2014 to September 2019. Patients were divided into two groups based on the occurrence of ENI, which was defined as either an improvement of NIHSS score of ≥4 points, or an NIHSS score of 0 or 1 at 24 hours after endovascular treatment. The rank sum test, Chi square test, and other methods were used to compare differences in baseline characteristics between the two groups. Logistic regression analysis was used to investigate independent predictors of postoperative ENI. Receiver operating characteristic curve analysis used to assess the capacity of NWU to predict ENI. Results: Of the 132 patients in the study, ENI occurred in 47 and did not occur in 85. In multivariate logistic regression analysis age [odds ratio (OR)=0.940, 95% confidence interval (CI) 0.903-0.979, P=0.003], time from stroke onset to puncture (OR=0.995, 95%CI 0.991-0.999, P=0.025), time from puncture to recanalization/end of operation (OR=0.985, 95%CI 0.974-0.996, P=0.007), NWU (OR=0.762, 95%CI 0.620-0.937, P=0.010), and mTICI (OR=1.644, 95%CI 1.043-2.590, P=0.032) were predictive factors for ENI. Receiver operating characteristic curve analysis indicated that NWU could effectively predict ENI (area under the curve=0.642, 95%CI 0.543-0.741, P=0.007), and prediction accuracy was improved when it was combined with other clinical parameters. Conclusion: NWU is an independent predictor of ENI in patients with acute anterior circulation large vessel occlusive stroke undergoing endovascular treatment.

Application of aptamer-based viral detection in animals.

Viral infections are common causes of diseases in animals and appropriate methods are increasingly being required to detect viral pathogens in animals. In this regard, similar to antigen- -antibody interactions, aptamers have high affinity and specificity for their respective target molecules, and can be selected using the Systematic Evolution of Ligands by EXponential enrichment (SELEX) technique. Recently, significant progress has been made in the development of aptamer selection and aptamer-based sensors for viral detection, and here we review some of the recent advances in aptamer-based detection of viral infections in animals. This review will serve as a comprehensive resource for aptamer-based strategies in viral diagnostics.

[Analysis of the predictive value of plateletcrit for the degree of liver fibrosis in patients with chronic HBV infection with ALT less than two times the upper limit of normal].

Objective: Plateletcrit (PCT) is considered a new potential index to predict the degree of liver fibrosis in patients with chronic hepatitis B (CHB). This study aimed to explore the predictive value of PCT for the degree of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection with alanine aminotransferase (ALT) < 2× upper limit of normal (ULN). Measurement data were compared using the t-test, ANOVA, or non-parametric test (Mann-Whitney U test). Categorical variables were compared using χ (2) test or Fisher's exact test. Methods: 140 cases with chronic HBV infection who underwent liver biopsy and ALT < 2×ULN were enrolled from January 2016 to March 2021. Univariate and multivariate logistic regression and the area under the receiver operating characteristic curve (AUC) were used to determine the predictive value of PCT for the degree of liver fibrosis. The likelihood ratio (LR) was used to optimize the selection of the diagnostic cut-off. Results: (1) Among the 140 cases, there were 34 (24.3%) cases in the S0 stage, 47 (33.6%) cases in the S1 stage, 16 (11.4%) cases in the S2 stage, 19 (13.6%) cases in the S3 stage, and 24 (17.1%) cases in the S4 stage. The overall mean PCT level was 0.19 ± 0.06%. (2) Univariate analysis revealed that PCT between patients with stages of liver fibrosis was S(0-1) and S(2-4) (0.20% ± 0.05% vs. 0.16% ± 0.06%, t = 3.955, P < 0.001), S(0 -2) and S(3-4) (0.20% ± 0.05% vs. 0.15% ± 0.06%, t = 5.631, P < 0.001) and S(0-3) and S4 (0.20% ± 0.05% vs. 0.12% ± 0.05%, t = 7.113, P < 0.001), respectively, and the differences were statistically significant. Multivariate logistic regression analysis showed that PCT was an independent risk factor for liver fibrosis stages S(2-4), S(3-4), and S4 (OR = 0.925, 95% CI: 0.859 - 0.997, P = 0.042; OR = 0.867, 95% CI: 0.789 - 0.954, P = 0.003; OR = 0.708, 95% CI: 0.593 - 0.846; P < 0.001). (3) The AUCs of PCT were 0.702, 0.777, and 0.885 for diagnosing liver fibrosis stages S(2-4), S(3-4), and S4 in patients with chronic HBV infection with ALT < 2×ULN. PCT was superior for the cirrhosis (S4) diagnosis. 92 (65.7%) cases were diagnosed as cirrhosis or non-cirrhosis according to the LR optimized diagnostic and exclusion diagnostic cut-offs (≤0.09%, ≤0.17%), with an accuracy of 97.8%. Conclusion: PCT has a high diagnostic and exclusion value for cirrhotic patients with chronic HBV infection with ALT < 2×ULN. Furthermore, it can be used as a non-invasive diagnostic index for determining and assisting the diagnosis of cirrhosis in resource-constrained areas, reducing the need for pathological examination of liver biopsies, and it has the advantage of being simple and intuitive without complex calculations.

[Application of TIGIT combined with interleukin-6 detection in the evaluation of Crohn's disease status].

To explore the application of IL-6, PCT, T lymphocyte subsets and TIGIT expression on T lymphocytes in the evaluation of Crohn's disease status. Using a cross-sectional study, total of 119 confirmed patients with Crohn's disease who were treated in the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from June 2020 to December 2022 were selected. The age range was 18-59 years old, and the median age (interquartile range) was 37 (29, 45) years old, including 57 cases in active disease group (30 males, 27 females), 62 cases in disease remission group (33 males, 29 females); 50 healthy control groups (27 males, 23 females), the age range was 19-60 years old, and the median age (interquartile range) was 38 (31, 46) years old. The level of IL-6 was detected by flow fluorescence microsphere method, the concentration of PCT was detected by immunochromatography, and the levels of T lymphocyte subsets and TIGIT were detected by flow cytometry. The differences and correlations between the detection indicators in each group were compared, logistic regression was used to analyze the factors influencing the progression of Crosne's disease and the clinical value of each detection indicator was analyzed by ROC curve. The results showed that there were no statistically significant differences in age and gender among the control group, the remission group, and the active group (H=1.422,χ2=0.020;P=0.491, P=0.990); in the active group, IL-6 was 17.55(9.67, 21.72)pg/ml, PCT was 0.38(0.14, 0.43)ng/ml, CD3+CD4+ was 35.47%±6.01%, CD3+CD8+ was 30.50%±5.20%, TIGIT was 25.08%±6.30%; in the remission group, IL-6 was 8.46(5.21, 10.04) pg/ml, PCT was 0.26(0.11, 0.35) ng/ml, CD3+CD4+ was 37.62%±4.86%, CD3+CD8+ was 28.30%±5.28%, TIGIT was 34.22%±5.45%; in the control group, IL-6 was 6.13(3.57, 8.12)pg/ml, PCT was 0.17(0.10, 0.21)ng/m, CD3+CD4+ was 39.74%±3.94%, CD3+CD8+ was 26.59%±4.50%, and TIGIT was 37.64%±6.22%.There were significant differences in IL-6, PCT, CD3+CD4+%, CD3+CD8+%, and TIGIT among the three groups(H=58.688, H=18.003, F=9.600, F=8.124, F=65.059;P<0.001, P<0.001, P<0.001, P<0.001, P<0.001), Among them, IL-6 and TIGIT in the active group were significantly different from those in the remission group (P<0.001, P<0.001), and only TIGIT was significantly different between the remission group and the control group (P=0.007);Spearman correlation analysis showed that the expression of TIGIT on T lymphocytes was negatively correlated with the levels of IL-6; the results of Logistic regression analysis showed that IL-6, PCT and TIGIT were independent factors affecting the progression of Crohn's disease;Comparing the ROC curves of the active group and the remission group, found that TIGIT was significantly different from PCT, CD3+CD4+, CD3+CD8+(Z=4.011, Z=4.091, Z=4.157; P<0.001, P<0.001, P<0.001), no statistical difference with IL-6 (Z=1.193, P=0.233). Selected the combined detection of IL-6 and TIGIT with the best AUC area and Youden index, which shows that the clinical value is improved, the AUC area of IL-6+TIGIT was significantly different from that of IL-6 (Z=2.674, P=0.008). In summary, TIGIT of T lymphocytes and IL-6 detection may be valuable in the diagnosis and treatment of Crohn's disease, and the combined detection of TIGIT and IL-6 may be meaningful for evaluating the status of Crohn's disease.

[Performance of exhaled carbon monoxide measurement in smoking cessation clinics and its influence on patients' willingness and behavior for smoking cessation].

Objective: To evaluate the performance of exhaled carbon monoxide measurement in smoking cessation clinics and its influence on patients' willingness and behavior for smoking cessation in China. Methods: Data of 41 566 patients who visited 257 smoking cessation clinics equipped with exhaled carbon monoxide detectors from 2019 to 2021 were selected to study the relationship between exhaled carbon monoxide measurement and patients' willingness to quit smoking as well as smoking cessation rate in those who completed follow up. Results: Only 21 470 (51.7%) of the patients received exhaled carbon monoxide measurement in the first visit. Patients who had exhaled carbon monoxide measurement were 1.87 (95%CI: 1.78-1.96) times more likely to have stronger willingness to quit smoking. The follow up results indicated that the patients with exhaled carbon monoxide measurement in the first visit were 1.10 (95%CI: 1.05-1.16) times more likely to quit smoking one month later than those without the measurement, and 1.22 (95%CI: 1.17-1.29) times more likely to quit smoking three months later than those without measurement. Conclusions: Exhaled carbon monoxide measurement can improve patients' willingness to quit smoking and increase smoking cessation rate. However, the testing rate is low in smoking cessation clinics at present. It's important to promote the equipment and utilization of exhaled carbon monoxide detector in smoking cessation clinics.

[Acetylcorynoline inhibits microglia activation by regulating EGFR/MAPK signaling to promote functional recovery of injured mouse spinal cord].

OBJECTIVE: To investigate the effect of acetylcorynoline (Ace) for promoting functional recovery of injured spinal cord in rats and explore the underlying mechanism. METHODS: Rat models of spinal cord injury (SCI) were treated with intraperitoneal injection of different concentrations of Ace, with the sham-operated rats as the control group. After the treatment, the changes in motor function of the rats and the area of spinal cord injury were assessed with BBB score and HE staining, and the changes in pro-inflammatory cytokine levels and microglial activation were determined using PCR, ELISA and immunofluorescence staining. In a lipopolysaccharide (LPS)-treated BV2 cell model, the effects of different concentrations of Ace or DMSO on microglial activation and inflammatory cytokine production were observed. Network pharmacology analysis was performed to predict the target protein and signaling mechanism that mediated the inhibitory effect of Ace on microglia activation, and AutoDock software was used for molecular docking between Ace and the target protein. A signaling pathway blocker (Osimertinib) was used to verify the signaling mechanism in rat models of SCI and LPS-treated BV2 cell model. RESULTS: In rat models of SCI, Ace treatment significantly increased the BBB score, reduced the area of spinal cord injury, and lowered the number of activated microglia cells and the levels of pro-inflammatory cytokines (P < 0.05). The cell experiments showed that Ace treatment significantly lower the level of cell activation and the production of inflammatory cytokines in LPS-treated BV2 cells (P < 0.05). Network pharmacology analysis suggested that EGFR was the main target of Ace, and they bound to each other via hydrogen bonds as shown by molecular docking. Western blotting confirmed that Ace inhibited the activation of the EGFR/MAPK signaling pathway in injured mouse spinal cord tissue and in LPS-treated BV2 cells, and its inhibitory effect was comparable to that of Osimertinib. CONCLUSION: In rat models of SCI, treatment with Ace can inhibit microglia-mediated inflammatory response by regulating the EGFR/MAPK pathway, thus promoting tissue repair and motor function recovery.

Anti-diabetic effect of quercetin in type 2 diabetes mellitus by regulating the microRNA-92b-3p/EGR1 axis.

Insulin resistance (IR) is predominantly causal for type 2 diabetes mellitus (T2DM). To solve this problem, this study particularly determined the role of quercetin (Que) in controlling IR in T2DM mice. The T2DM mouse model was established, and given 20 mg/kg/d Que by gavage for 6 weeks, and the lentiviral vector that interfered with microRNA-92b-3p (miR-92b-3p) or early growth response 1 (EGR1) expression was injected into the tail vein of T2DM mice. Blood glucose homeostasis and histopathological changes in the pancreas were observed after the corresponding treatment. miR-92b-3p and EGR1 expressions were assessed in T2DM mice, as well as their interlink. In results we found that Que could improve IR and pancreatic histopathological changes in T2DM mice. Low miR-92b-3p and high EGR1 were expressed in T2DM mice, while Que could upregulate miR-92b-3p to target EGR1. Enhancing miR-92b-3p or reducing EGR1 could further improve IR and pancreatic histopathological changes in T2DM mice after Que administration. Nevertheless, silencing miR-92b-3p or overexpressing EGR1 contributed to the opposite results. We concluded that Que exerted anti-diabetic effects in T2DM mice by regulating the miR-92b-3p/EGR1 axis.

The effects of the DASH dietary pattern on clinical outcomes and quality of life in adults with uncontrolled asthma: Design and methods of the ALOHA Trial.

BACKGROUND: Poor diet quality is an important risk factor for increased asthma prevalence and poor asthma control. To address the question of whether adults with asthma can benefit from following a healthy diet, this trial will test the efficacy and mechanisms of action of a behavioral intervention promoting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern with sodium reduction among patients with uncontrolled asthma. METHODS: In this 2-arm randomized clinical trial, 320 racially/ethnically and socioeconomically diverse adults with uncontrolled asthma on standard controller therapy will be randomized to either a control or an intervention group and assessed at baseline, 3, 6 and 12 months. Control and intervention participants will receive education on lung health, asthma, and other general health topics; additionally, the intervention group will receive DASH behavioral counseling over 12 months. The primary hypothesis is that the DASH behavioral intervention, compared with the education-only control, will lead to significantly more participants with minimum clinically important improvement (responders) in asthma-specific quality of life at 12 months. Secondary hypotheses will test the intervention effects on other asthma (e.g., asthma control, lung function) and non-asthma outcomes (e.g., quality of life). Additionally, therapeutic (e.g., short chain fatty acids, cytokines) and nutritional biomarkers (e.g., dietary inflammatory index, carotenoids) will be assessed to understand the mechanisms of the intervention effect. CONCLUSION: This trial can substantially advance asthma care by providing rigorous evidence on the benefits of a behavioral dietary intervention and mechanistic insights into the role of diet quality in asthma. CLINICALTRIALS: gov #: NCT05251402.

Dietary alpha-ketoglutarate enhances intestinal immunity by Th17/Treg immune response in piglets after lipopolysaccharide challenge.

Alpha-ketoglutarate (AKG) is important for improving intestinal and systemic immune function. This study aimed to explore whether AKG enhances gut immunity in lipopolysaccharide (LPS)-challenged piglets by modulating the immune-related helper T cells 17 (Th17)/regulatory T cells (Treg) balance pathway. A 2 × 2 factor design was used on 24 pigs, with the major factors being diet (basal diet or 1% AKG diet) and immunological challenge (saline or LPS). Piglets were fed with a basal or AKG diet for 21 d and then received intraperitoneal injection of LPS or saline. The results demonstrated that AKG supplementation enhanced growth performance compared with the control group (P < 0.05). AKG improved the ileal morphological structure (P < 0.01). Finally, AKG supplementation increased interleukin (IL)-10, transforming growth factor beta-1, forkhead box P3, and signal transducer and activator of transcription 5 genes expression whereas decreasing IL-6, IL-8, IL-1ß, tumor necrosis factor-α, IL-17, IL-21, signal transducer and activator of transcription 3 and rar-related orphan receptor c genes expression (P < 0.05). These findings suggested that dietary AKG can improve the growth performance of piglets. Meanwhile, dietary AKG can alleviate LPS-induced intestinal inflammation through Th17/Treg immune response signaling pathway.

Immature digestive and immune systems cause a variety of problems. The balance of helper Tcells 17 (Th17) and regulatory T cells (Treg) is critical in maintaining normal immune function in animals. Piglets' growth performance and immune function are all influenced by alpha-ketoglutarate (AKG). However, how AKG exerts its effect on intestinal immunity in piglets through modulating the immune signaling of Th17/Treg biology has not been explored. In this study, an inflammation model was established by lipopolysaccharide (LPS) injection. This study was to test the hypothesis that AKG can enhance growth performance and attenuate LPS-challenged intestinal inflammation by modulating Th17/Treg response. We concluded that dietary AKG can improve the growth performance of piglets. Dietary AKG alleviated intestinal inflammation induced by LPS through the Th17/Treg response, thereby improving intestinal immunity. These findings can provide a theoretical foundation for utilizing AKG in weaned piglet diets for the regulation of intestinal immune activity through nutrition.