Divergent and Compensatory Effects of BMP2 and BMP4 on the VSMC Phenotype and BMP4's Role in Thoracic Aortic Aneurysm Development.

Vascular smooth muscle cells (VSMCs) play a key role in aortic aneurysm formation. Bone morphogenetic proteins (BMPs) have been implicated as important regulators of VSMC phenotype, and dysregulation of the BMP pathway has been shown to be associated with vascular diseases. The aim of this study was to investigate for the first time the effects of BMP-4 on the VSMC phenotype and to understand its role in the development of thoracic aortic aneurysms (TAAs). Using the angiotensin II (AngII) osmotic pump model in mice, aortas from mice with VSMC-specific BMP-4 deficiency showed changes similar to AngII-infused aortas, characterised by a loss of contractile markers, increased fibrosis, and activation of matrix metalloproteinase 9. When BMP-4 deficiency was combined with AngII infusion, there was a significantly higher rate of apoptosis and aortic dilatation. In vitro, VSMCs with mRNA silencing of BMP-4 displayed a dedifferentiated phenotype with activated canonical BMP signalling. In contrast, BMP-2-deficient VSMCs exhibited the opposite phenotype. The compensatory regulation between BMP-2 and BMP-4, with BMP-4 promoting the contractile phenotype, appeared to be independent of the canonical signalling pathway. Taken together, these results demonstrate the impact of VSMC-specific BMP-4 deficiency on TAA development.

Metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion/Caco-2 cell transport, and their prebiotic effects during colonic fermentation.

The health-promoting activities of polyphenols and their metabolites originating from germinated quinoa (GQ) are closely related to their digestive behavior, absorption, and colonic fermentation; however, limited knowledge regarding these properties hinder further development. The aim of this study was to provide metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion and Caco-2 cell transport, whilst also investigating the changes in the major polyphenol metabolites and the effects of prebiotics during colonic fermentation. It was found that germination treatment increased the polyphenol content of quinoa by 21.91%. Compared with RQ group, 23 phenolic differential metabolites were upregulated and 47 phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after simulated digestion, 7 kinds of phenolic differential metabolites were upregulated and 17 kinds of phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after cell transport, 7 kinds of phenolic differential metabolites were upregulated and 9 kinds of phenolic differential metabolites were downregulated in GQ group. In addition, GQ improved the bioaccessibilities and transport rates of various polyphenol metabolites. During colonic fermentation, GQ group can also increase the content of SCFAs, reduce pH value, and adjust gut microbial populations by increasing the abundance of Actinobacteria, Bacteroidetes, Verrucomicrobiota, and Spirochaeota at the phylum level, as well as Bifidobacterium, Megamonas, Bifidobacterium, Brevundimonas, and Bacteroides at the genus level. Furthermore, the GQ have significantly inhibited the activity of α-amylase and α-glucosidase. Based on these results, it was possible to elucidate the underlying mechanisms of polyphenol metabolism in GQ and highlight its beneficial effects on the gut microbiota.

Assessment of pulmonary physiological changes caused by aging, cigarette smoking, and COPD with hyperpolarized 129Xe magnetic resonance.

OBJECTIVE: To comprehensively assess the impact of aging, cigarette smoking, and chronic obstructive pulmonary disease (COPD) on pulmonary physiology using 129Xe MR. METHODS: A total of 90 subjects were categorized into four groups, including healthy young (HY, n = 20), age-matched control (AMC, n = 20), asymptomatic smokers (AS, n = 28), and COPD patients (n = 22). 129Xe MR was utilized to obtain pulmonary physiological parameters, including ventilation defect percent (VDP), alveolar sleeve depth (h), apparent diffusion coefficient (ADC), total septal wall thickness (d), and ratio of xenon signal from red blood cells and interstitial tissue/plasma (RBC/TP). RESULTS: Significant differences were found in the measured VDP (p = 0.035), h (p = 0.003), and RBC/TP (p = 0.003) between the HY and AMC groups. Compared with the AMC group, higher VDP (p = 0.020) and d (p = 0.048) were found in the AS group; higher VDP (p < 0.001), d (p < 0.001) and ADC (p < 0.001), and lower h (p < 0.001) and RBC/TP (p < 0.001) were found in the COPD group. Moreover, significant differences were also found in the measured VDP (p < 0.001), h (p < 0.001), ADC (p < 0.001), d (p = 0.008), and RBC/TP (p = 0.032) between the AS and COPD groups. CONCLUSION: Our findings indicate that pulmonary structure and functional changes caused by aging, cigarette smoking, and COPD are various, and show a progressive deterioration with the accumulation of these risk factors, including cigarette smoking and COPD. CLINICAL RELEVANCE STATEMENT: Pathophysiological changes can be difficult to comprehensively understand due to limitations in common techniques and multifactorial etiologies. 129Xe MRI can demonstrate structural and functional changes caused by several common factors and can be used to better understand patients' underlying pathology. KEY POINTS: Standard techniques for assessing pathophysiological lung function changes, spirometry, and chest CT come with limitations. 129Xe MR demonstrated progressive deterioration with accumulation of the investigated risk factors, without these limitations. 129Xe MR can assess lung changes related to these risk factors to stage and evaluate the etiology of the disease.

Fungal metabolite altersolanol a exhibits potent cytotoxicity against human placental trophoblasts in vitro via mitochondria-mediated apoptosis.

Altersolanol A, a fungus-derived tetrahydroanthraquinone, has shown cytotoxic effects on multiple cancer cells. However, its reproductive toxicity in humans has not been well-addressed. The present study was aimed at investigating the cytotoxicity of altersolanol A on human placental trophoblasts including choriocarcinoma cell line JEG-3 and normal trophoblast cell line HTR-8/SVneo in vitro. The results showed that altersolanol A inhibited proliferation and colony formation of human trophoblasts, and the choriocarcinoma cells were more sensitive to the compound than the normal trophoblasts. Altersolanol A induced cell cycle arrest at G2/M phase in JEG-3 cells and S phase in HTR-8/SVneo cells, downregulated the expression of cell cycle-related checkpoint proteins, and upregulated the p21 level. Altersolanol A also promoted apoptosis in human trophoblasts via elevating the Bax/Bcl-2 ratio and decreasing both caspase-3 and caspase-9 levels. Meanwhile, altersolanol A suppressed the mitochondrial membrane potential and induced ROS production and cytochrome c release, which activated the mitochondria-mediated intrinsic apoptosis. Moreover, migration and invasion were inhibited upon altersolanol A exposure with downregulation of matrix metalloproteinase (MMP)-2 in JEG-3 cells and MMP-9 in HTR-8/SVneo cells. Mechanically, altersolanol A supplement decreased the phosphorylation of JNK, ERK, and p38, manifesting the inactivation of MAPK signaling pathway in the human trophoblasts. In conclusion, altersolanol A exhibited potential reproductive cytotoxicity against human trophoblasts via promoting mitochondrial-mediated apoptosis and inhibiting the MAPK signaling pathway.

The impact of provider-patient communication skills on primary healthcare quality and patient satisfaction in rural China: insights from a standardized patient study.

OBJECTIVES: In middle-income countries, poor physician-patient communication remains a recognized barrier to enhancing healthcare quality and patient satisfaction. This study investigates the influence of provider-patient communication skills on healthcare quality and patient satisfaction in the rural primary healthcare setting in China. METHODS: Data were collected from 504 interactions across 348 rural primary healthcare facilities spanning 21 counties in three provinces. Using the Standardized Patient method, this study measured physician-patient communication behaviors, healthcare quality, and patient satisfaction. Communication skills were assessed using the SEGUE questionnaire framework. Multivariate linear regression models and multivariate logistic regression models, accounting for fixed effects, were employed to evaluate the impact of physicians' communication skills on healthcare quality and patient satisfaction. RESULTS: The findings indicated generally low provider-patient communication skills, with an average total score of 12.2 ± 2.8 (out of 24). Multivariate regression models, which accounted for physicians' knowledge and other factors, demonstrated positive associations between physicians' communication skills and healthcare quality, as well as patient satisfaction (P < 0.05). Heterogeneity analysis revealed stronger correlations among primary physicians with lower levels of clinical knowledge or more frequent training. CONCLUSION: This study emphasizes the importance of prioritizing provider-patient communication skills to enhance healthcare quality and patient satisfaction in rural Chinese primary care settings. It recommends that the Chinese government prioritize the enhancement of provider-patient communication skills to improve healthcare quality and patient satisfaction.

Review of biomimetic ordered microstructures in advancing synergistic integration of adhesion and microfluidics.

Many ordered arrangements are observable in the natural world, serving not only as pleasing aesthetics but also as functional improvements. These structured arrangements streamline cohesion while also facilitating the spontaneous drainage of liquids in microfluidics, resulting in effective separation and signal enhancement. Nevertheless, there is a substantial challenge when handling microstructured chips with microfluidic detection and adhesion. The arrangement of the adhesive interface's microstructure affects the liquid flow in the microfluidic chip, impacting the detection's sensitivity and accuracy. Additionally, the liquid in the microfluidic chip corrodes the adhesive material and structure, reducing the adhesion strength due to the hydration layer between the material and the contact interface. Therefore, this review explores the application of ordered structures in the integration of adhesion and microfluidics. We discussed the standard preparation method, appropriate materials, and the application of ordered structures in biomimetic adhesion and microfluidics. Furthermore, the paper discusses the major challenges in this field and provides opinions on its future developments.

RNF20 Reduces Cell Proliferation and Warburg Effect by Promoting NLRP3 Ubiquitination in Liver Cancer.

The present study explored that the effects and its possible mechanisms of ring finger protein 20 (RNF20) in Postoperative survival rate of liver cancer in clinical. All the serum samples were collected from our hospital. Quantitative polymerase chain reaction (PCR) and microarray analysis, and RNA pull down assay were used in this study. We found that the serum RNF20 mRNA expression level in patients with liver cancer were down-regulated. Postoperative survival rate of RNF20 high expression was higher than that of RNF20 low expression. Then, over-expression of RNF20 diminished liver cancer cell proliferation and metastasis. RNF20 reduced Warburg effect of liver cancer. RNF20 expression regulated NOD-like receptor protein 3 (NLRP3) expression and increased NLRP3 Ubiquitination. NLRP3 participated in the effects of RNF20 on cell proliferation, and not affected on Warburg effect of liver cancer. Our study demonstrated that the serum RNF20 expression level was down-regulated in liver cancer, and promoted postoperative survival rate. RNF20 can reduce cancer progression of liver cancer by NLRP3 signal pathway, suggesting that it may prove to be a potential therapeutic target for postoperative survival rate of liver cancer.

Microscopic Mechanism for Further NO Heterogeneous Reduction by Potassium-Doped Biochar: A DFT Study.

Biomass reburning is an efficient and low-cost way to control nitric oxide (NO), and the abundant potassium (K) element in biomass affects the heterogeneous reaction between NO and biochar. Due to the incomplete simulation of the NO heterogeneous reduction reaction pathway at the molecular level and the unclear catalytic effect of K element in biochar, further research is needed on the possible next reaction and the influencing mechanism of the element. After the products of the existing reaction pathways are referenced, two reasonably simplified biochar structural models are selected as the basic reactants to study the microscopic mechanism for further NO heterogeneous reduction on the biochar surface before and after doping with the K atom based on density functional theory. In studying the two further NO heterogeneous reduction reaction pathways, we find that the carbon monoxide (CO) molecule fragment protrudes from the surface of biochar models with the desorption of N2 at the TS4 transition state, and the two edge types of biochar product models obtained by simulation calculation are Klein edge and ac56 edge observed in the experiment. In studying the catalytic effect of potassium in biochar, we find that the presence of K increases the heat release of adsorption of NO molecules, reduces the energy barrier of the rate-determining step in the nitrogen (N2) generation and desorption process (by 50.88 and 69.97%), and hinders the CO molecule from desorbing from the biochar model surface. Thermodynamic and kinetic analyses also confirm its influence. The study proves that the heterogeneous reduction reaction of four NO molecules on the surface of biochar completes the whole reaction process and provides a basic theoretical basis for the emission of nitrogen oxides (NOx) during biomass reburning.

Real-world evidence of combined treatment of biologics and exclusive enteral nutrition in patients with ileum-dominant Crohn's disease: A multicenter study.

BACKGROUND & AIMS: Although biologics were prescribed to achieve and maintain clinical remission of active Crohn's disease (CD), almost half of patients experienced a loss of response or intolerance. Here, we investigated the efficacy of combined treatment of biologics and 16-weeks exclusive enteral nutrition (EEN) in moderate-to-severe CD patients with small intestine lesions. METHODS: This was a real-world, multicenter retrospective study, from October 2016 to March 2023, medical records of patients registered at three IBD centers were reviewed for patients with ileal or ileocolonic CD in moderate-to-severe activity. All patients received treatment of biologics with concomitant 16-week EEN (BioEEN) or biologics alone (Bio). The clinical outcomes and endoscopic outcomes were assessed at week 16 and 52. RESULTS: There was no statistically significant difference between Bio (97 patients) and BioEEN group (100 patients) at baseline for demographic and clinical characteristics. Compared to treatment with biologics alone, patients with BioEEN treatment achieved higher rates of clinical response (95.0% vs. 66.0%), clinical remission (87.0% vs. 52.6%), endoscopic response (91.4% vs. 47.4%) including mucosal healing (85.7% vs. 23.7%) at week 16. The superiority of BioEEN sustained in maintenance, with 84.7% (vs. 49.1%) clinical response, 77.8% (vs. 38.6%) clinical remission, 69.2% (vs. 32.6%) endoscopic response and 51.9% (vs. 18.6%) mucosal healing at week 52. CONCLUSIONS: Combined treatment of biologics and 16-week EEN was an efficient therapeutic strategy with affirmative effectiveness for small intestine diseases of active CD.

The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study.

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.

KSNP: a fast de Bruijn graph-based haplotyping tool approaching data-in time cost.

Long reads that cover more variants per read raise opportunities for accurate haplotype construction, whereas the genotype errors of single nucleotide polymorphisms pose great computational challenges for haplotyping tools. Here we introduce KSNP, an efficient haplotype construction tool based on the de Bruijn graph (DBG). KSNP leverages the ability of DBG in handling high-throughput erroneous reads to tackle the challenges. Compared to other notable tools in this field, KSNP achieves at least 5-fold speedup while producing comparable haplotype results. The time required for assembling human haplotypes is reduced to nearly the data-in time.

Comparison of Alternative Protein Hydrogels for Delivering Myricetin: Interaction Mechanism and Stability Evaluation.

Food protein carriers from different sources might have distinct stabilizing and enhancing effects on the same small molecule. To elucidate the molecular mechanism, five different sourced proteins including soy protein isolates (SPIs), whey protein isolates (WPIs), edible dock protein (EDP), Tenebrio molitor protein (TMP), and yeast protein (YP) were used to prepare protein hydrogels for delivering myricetin (Myr). The results suggested that the loading capacity order of Myr in different protein hydrogels was EDP (11.5%) > WPI (9.3%) > TMP (8.9%) > YP (8.0%) > SPI (7.6%), which was consistent with the sequence of binding affinity between Myr and different proteins. Among five protein hydrogels, EDP had an optimum loading ability since it possessed the highest hydrophobic amino acid content (45.52%) and thus provided a broad hydrophobic cavity for loading Myr. In addition, these protein-Myr composite hydrogels displayed the core-shell structure, wherein hydrogen bonding and hydrophobic interaction were the primary binding forces between proteins and Myr. Moreover, the thermal stability, storage stability, and sustained-release properties of Myr were significantly enhanced via these protein delivery systems. These findings can provide scientific guidance for deeper utilization of food alternative protein sources.

Effects of proprioceptive neuromuscular facilitation combined with threshold inspiratory muscle training on respiratory function in neurocritical patients with weaning failure: a randomized controlled trial.

The purpose of this study was to determine the effects of combining proprioceptive neuromuscular facilitation (PNF) with threshold inspiratory muscle training (TIMT), compared with TIMT alone, on respiratory function in neurocritical patients who experienced a weaning failure. Forty-seven participants (mostly after a stroke), were randomly divided into the experimental group (n = 24) and the control group (n = 23). The control group received usual care and TIMT, whereas the experimental group, in addition, underwent four 90-s periods of manual PNF. Both groups performed training in the ICU twice a day for 5 consecutive days. The main outcome measures included maximum inspiratory pressure, diaphragmatic excursions, diaphragm thickening fraction, oxygenation index, and forced expiratory volume in 1 s/forced vital capacity. The results showed a significant group-by-time interaction effect for maximum inspiratory pressure [F (1, 45) = 17.84, η2 = 0.328, P < 0.001] and oxygenation index [F [1, 45) = 5.58, η2 = 0.11, P = 0.023]. When compared with the control group, the experimental group showed overall significantly higher maximum inspiratory pressure [mean difference = 4.37 cm H2O, 95% confidence interval (CI) 0.25-8.50, P = 0.038]. No other significant group differences were found. Combining PNF with TIMT may improve respiratory function in neurocritical patients with weaning failure. This combination approach may increase the likelihood of survival of neurocritical patients in the ICU.

Exenatide reduces atrial fibrillation susceptibility by inhibiting hKv1.5 and hNav1.5 channels.

Exenatide, a promising cardioprotective agent, protects against cardiac structural remodeling and diastolic dysfunction. Combined blockade of sodium and potassium channels is valuable for managing atrial fibrillation (AF). Here, we explored whether exenatide displayed anti-AF effects by inhibiting human Kv1.5 and Nav1.5 channels. We used the whole-cell patch-clamp technique to investigate the effects of exenatide on hKv1.5 and hNav1.5 channels expressed in human embryonic kidney 293 cells and studied the effects of exenatide on action potential (AP) and other cardiac ionic currents in rat atrial myocytes. Additionally, an electrical mapping system was used to explore the effects of exenatide on electrical properties and AF activity in isolated rat hearts. Finally, a rat AF model, established using acetylcholine and calcium chloride, was employed to evaluate the anti-AF potential of exenatide in rats. Exenatide reversibly suppressed IKv1.5 with IC50 of 3.08 µM, preferentially blocked hKv1.5 channel in its closed state, and positively shifted the voltage-dependent activation curve. Exenatide also reversibly inhibited INav1.5 with IC50 of 3.30 µM, negatively shifted the voltage-dependent inactivation curve, and slowed its recovery from inactivation with significant use-dependency at 5 and 10 Hz. Furthermore, exenatide prolonged AP duration and suppressed the sustained K+ current (Iss) and transient outward K+ current (Ito), but without inhibition of L-type Ca2+ current (ICa,L) in rat atrial myocytes. Exenatide prevented AF incidence and duration in rat hearts and rats. These findings demonstrate that exenatide inhibits IKv1.5 and INav1.5in vitro and reduces AF susceptibility in isolated rat hearts and rats.

The nutritional profile of chia seeds and sprouts: tailoring germination practices for enhancing health benefits-a comprehensive review.

Chia seeds have gained significant attention due to their unique composition and potential health benefits, including high dietary fibers, omega-3 fatty acids, proteins, and phenolic compounds. These components contribute to their antioxidant, anti-inflammatory effects, as well as their ability to improve glucose metabolism and dyslipidemia. Germination is recognized as a promising strategy to enhance the nutritional value and bioavailability of chia seeds. Chia seed sprouts have been found to exhibit increased essential amino acid content, elevated levels of dietary fiber and total phenols, and enhanced antioxidant capability. However, there is limited information available concerning the dynamic changes of bioactive compounds during the germination process and the key factors influencing these alterations in biosynthetic pathways. Additionally, the influence of various processing conditions, such as temperature, light exposure, and duration, on the nutritional value of chia seed sprouts requires further investigation. This review aims to provide a comprehensive analysis of the nutritional profile of chia seeds and the dynamic changes that occur during germination. Furthermore, the potential for tailored germination practices to produce chia sprouts with personalized nutrition, targeting specific health needs, is also discussed.

BcABF1 Plays a Role in the Feedback Regulation of Abscisic Acid Signaling via the Direct Activation of BcPYL4 Expression in Pakchoi.

Abscisic acid-responsive element-binding factor 1 (ABF1), a key transcription factor in the ABA signal transduction process, regulates the expression of downstream ABA-responsive genes and is involved in modulating plant responses to abiotic stress and developmental processes. However, there is currently limited research on the feedback regulation of ABF1 in ABA signaling. This study delves into the function of BcABF1 in Pakchoi. We observed a marked increase in BcABF1 expression in leaves upon ABA induction. The overexpression of BcABF1 not only spurred Arabidopsis growth but also augmented the levels of endogenous IAA. Furthermore, BcABF1 overexpression in Arabidopsis significantly decreased leaf water loss and enhanced the expression of genes associated with drought tolerance in the ABA pathway. Intriguingly, we found that BcABF1 can directly activate BcPYL4 expression, a critical receptor in the ABA pathway. Similar to BcABF1, the overexpression of BcPYL4 in Arabidopsis also reduces leaf water loss and promotes the expression of drought and other ABA-responsive genes. Finally, our findings suggested a novel feedback regulation mechanism within the ABA signaling pathway, wherein BcABF1 positively amplifies the ABA signal by directly binding to and activating the BcPYL4 promoter.

[Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments].

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1ß in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

Glutathione Induces Keap1 S-Glutathionylation and Mitigates Oscillating Glucose-Induced ß-Cell Dysfunction by Activating Nrf2.

Glutathione (GSH), a robust endogenous antioxidant, actively participates in the modulation of the redox status of cysteine residues in proteins. Previous studies have indicated that GSH can prevent ß-cell failure and prediabetes caused by chronic oscillating glucose (OsG) administration. However, the precise mechanism underlying the protective effect is not well understood. Our current research reveals that GSH is capable of reversing the reduction in Nrf2 levels, as well as downstream genes Grx1 and HO-1, in the islet ß-cells of rats induced by chronic OsG. In vitro experiments have further demonstrated that GSH can prevent ß-cell dedifferentiation, apoptosis, and impaired insulin secretion caused by OsG. Additionally, GSH facilitates the translocation of Nrf2 into the nucleus, resulting in an upregulation of Nrf2-targeted genes such as GCLC, Grx1, HO-1, and NQO1. Notably, when the Nrf2 inhibitor ML385 is employed, the effects of GSH on OsG-treated ß-cells are abrogated. Moreover, GSH enhances the S-glutathionylation of Keap1 at Cys273 and Cys288, but not Cys151, in OsG-treated ß-cells, leading to the dissociation of Nrf2 from Keap1 and facilitating Nrf2 nuclear translocation. In conclusion, the protective role of GSH against OsG-induced ß-cell failure can be partially attributed to its capacity to enhance Keap1 S-glutathionylation, thereby activating the Nrf2 signaling pathway. These findings provide novel insights into the prevention and treatment of ß-cell failure in the context of prediabetes/diabetes, highlighting the potential of GSH.

Purple rice starch in wheat: Effect on retrogradation dependent on addition amount.

While individual starch types may not possess the ideal gelatinization and retrogradation properties for specific applications, the amalgamation of multiple starch varieties might bestow desirable physicochemical properties upon resulting starch-based products. This study explored the impact of incorporating purple rice starch (PRS), as a novel starch variant (up to 15 % PRS), on the gelatinization and retrogradation (within 14 days) of regular wheat starch (WS). Rheological and texture assessments demonstrated that the introduction of PRS diminished the viscoelasticity and hardness of fresh WS paste. Additionally, in the case of retrograded WS pastes stored at 4 °C for 1-14 days, the incorporation of 10 % or 15 % PRS effectively retarded the reduction in transparency and significantly reduced hardness, retrogradation degree, the ratio of absorbance at 1047/1017 cm-1, and relative crystallinity. Notably, 10 % PRS results in a more pronounced effect. Conversely, 5 % PRS induced an opposing impact on retrograded WS post-storage. Moreover, scanning electron microscopy revealed that as the proportion of PRS increased, the microstructure of gelatinized WS-PRS closely resembled that of pure PRS. In conclusion, the diverse effects of varying PRS proportions on WS alter the texture and characteristics of starch-based foods, underscoring the potential of starch blending for improved applications.