Characterization of the potential allergenicity of enzymatically hydrolyzed casein in Balb/c mouse model.

Bovine casein is a major allergen present in cow milk to induce anaphylaxis. In this study, the potential allergenicity of enzymatically hydrolyzed casein (HC) was evaluated based on in vitro and in vivo. The results showed that Alcalase and Protamex treatment (AT, PT) reduced the potential allergenicity of CN, with the greatest reductions of 68.25% and 50.75%, respectively. In addition, in vivo results showed that HC effectively alleviated allergic response symptoms of Balb/c mice; a significant tendency toward decreased serum IgG1 and mast cell tryptase levels was observed, accompanied by a decrease of Th2-associated IL-4, IL-5, and IL-13 and an increase of IFN-γ levels in spleen. Moreover, the inflammation of the lung, jejunum, and ileum was remarkably ameliorated. The findings indicated that HC induced a shift toward Th1 response and maintained the Th1/Th2 immune balance. Importantly, our results provide the basis for the production of hypoallergenic dairy products.

The Effect of "Offline-to-Online" Trust Transfer on the Utilization of Online Medical Consultation Among Chinese Rural Residents: Experimental Study.

BACKGROUND: Online medical consultation can serve as a valuable means for rural residents to access high-quality health care resources, thereby mitigating the geographic and economic disadvantages prevalent in rural areas. Nevertheless, due to lower cognitive abilities, rural residents often face challenges in trusting and making effective use of online medical consultations. More likely, adopting a bounded rational decision-making model that facilitates the "offline-to-online" trust transfer could prove to be a potentially effective approach. This strategy aims to encourage less technologically experienced rural residents to trust and make use of online medical consultations. OBJECTIVE: This study aims to characterize the status of "offline-to-online" trust transfer among rural residents in the context of internet health care, and analyze its direct impact on facilitating the utilization of online medical consultation. Additionally, we investigate the family spillover effect of "offline-to-online" trust transfer in promoting the use of online medical consultation among rural family members, considering its distributional effect across various education levels of the population. METHODS: A multistage stratified random sampling method was used to survey participants in rural areas of China from July to September 2021, encompassing a total of 2597 rural residents from 960 rural households. Propensity score values were estimated using logit regression, and the propensity score matching method, using the K-nearest neighbor matching, radius matching, and kernel matching methods, was applied to create matched treatment and control samples of rural residents based on their experience of "offline-to-online" trust transfer. Subsequently, we calculated average treatment effect scores to compare the differences in utilizing online medical consultation between the treatment and control rural samples. RESULTS: As many as 551/960 (57.4%) rural residents experienced an "offline-to-online" trust transfer, with a higher likelihood observed in the older population with lower levels of education and higher satisfaction with local health care services. Furthermore, rural residents who underwent "offline-to-online" trust transfer were 37%-40% more likely to utilize online medical consultation compared with those who did not experience this trust transfer. Additionally, family members of householders who underwent "offline-to-online" trust transfer were 25%-28% more likely to utilize online medical consultation than those whose householders did not experience this trust transfer. Notably, when compared with populations with high-level education, the "offline-to-online" trust transfer had more significant direct and spillover effects on the utilization of online medical consultation services among rural residents with low-level education. CONCLUSIONS: To enhance the "offline-to-online" trust transfer among rural residents and its facilitation in their utilization of online medical consultation, as well as other mobile health (mHealth) and ubiquitous health (uHealth) services, we recommend that online health care providers adopt a "patient-oriented" service model. This approach aims to elevate rural residents' satisfaction with local health care services and harness the trust-building functions inherent in physician-patient relationships and among family members.

Protective effects of 4-geranyloxy-2,6-dihydroxybenzophenonel on DSS-induced ulcerative colitis in mice via regulation of cAMP/PKA/CREB and NF-κB signaling pathways.

Hypericum sampsonii Hance has traditionally been used to treat enteritis and diarrhea. As one of the main benzophenones isolated from H. sampsonii, 4-geranyloxy-2,6-dihydroxybenzophenonel (4-GDB) has been shown to possess anti-inflammatory effects. However, the therapeutic effect and potential mechanisms of 4-GDB in ulcerative colitis (UC) remain unclear. This study aimed to evaluate the role of 4-GDB in UC using a dextran sulfate sodium-induced colitis mouse model. Intragastric administration of 4-GDB (20 mg/kg/day) for 8 days significantly attenuated colonic injury, reduced the expression of inflammatory mediators, and improved colonic barrier function in mice with colitis. Furthermore, in vivo and in vitro experiments indicated that 4-GDB could activate cAMP/PKA/CREB and inhibit the NF-κB pathway. Collectively, 4-GDB may be a potential agent for treating UC by regulating the cAMP/PKA/CREB and NF-κB pathways.

Triterpenoids from the genus Ilex attenuate free fatty acid-induced lipid accumulation in HepG2 cells by regulating lipid metabolism disorder and the AMPK signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Various traditional Chinese medicines from the genus Ilex (Aquifoliaceae) have been reported to have excellent hypolipidaemic effects. Although triterpenoids have been found to be the main active components, the underlying mechanisms have not been clarified. AIM OF THE STUDY: This study aimed to investigate the lipid-lowering effect, structure-activity relationship and action mechanism of triterpenoids from the genus Ilex. MATERIALS AND METHODS: FFA was used to induce HepG2 cells to establish a classical lipid-lowering activity screening model for the activities of 31 triterpenoids, and the contents of intracellular lipids, TC, and TG were measured. Furthermore, the structure-activity relationship was discussed. Mechanistically, UPLC-Q/TOF-MS-based metabolomics and lipidomics studies were performed, and metabolic pathways were analysed to investigate the lipid-lowering mechanism. Moreover, western blotting was performed to analyse the expression of key proteins of lipid metabolism and predict the targets of action. RESULTS: Thirteen triterpenoids significantly reduced intracellular lipid accumulation and decreased the levels of TG and TC. Among them, rotundic acid (RA) showed stronger lipid-lowering activity than the simvastatin-positive group, and structure-activity relationship analysis indicated that the hydroxyl groups at C-3 and C-19, hydroxymethyl groups at C-23, and carboxyl groups at C-28 may be the key groups for biological activity. Twenty-two metabolites in the metabolomics study and 19 metabolites in the lipidomics study were identified. The identified biomarkers were primarily glycerophosphocholine, LysoPCs, PCs, TAGs, LysoPEs, LysoPIs and sphingolipids, which are involved in glycerophospholipid and sphingolipid metabolism. Moreover, western blotting analysis showed that the expression of SREBP-1 and HMGCR decreased, while AMPK and ACC phosphorylation and the expression of CPT1A and CYP7A1 increased in the RA-treated group. CONCLUSION: The results suggested that triterpenoids from the genus Ilex showed significant lipid-lowering effects and that RA may be a novel hypolipidaemic drug candidate. Moreover, the underlying mechanism indicated that RA showed a lipid-lowering effect by regulating glycerophospholipid and sphingolipid metabolism and activating the AMPK pathway.

Impacts of Internet Use on Chinese Patients' Trust-Related Primary Healthcare Utilization.

Background: The internet has greatly improved the availability of medical knowledge and may be an important avenue to improve patients' trust in physicians and promote primary healthcare seeking by reducing information asymmetry. However, very few studies have addressed the interactive impacts of both patients' internet use and trust on primary healthcare-seeking decisions. Objective: To explore the impact of internet use on the relationship between patients' trust in physicians and primary healthcare seeking among Chinese adults 18 years of age and older to understand the varieties of effects in different cities. Methods: Generalized linear mixed models were applied to investigate the interactive impacts of internet use and patients' trust in physicians on primary healthcare seeking using pooled data from the China Family Panel Study of 2014 to 2018. We also compared these effects based on different levels of urbanization, ages, and PHC services. Results: Overall, a higher degree of patients' trust (p < 0.001) was able to directly predict better primary healthcare seeking, and internet use significantly increased the positive effect of patients' trust on primary healthcare seeking (p < 0.001). However, the marginal effect analysis showed that this effect was related to the level of patients' trust and that internet use could reduce the positive effect of patients' trust on primary healthcare seeking when the individual had a low level of trust (≤ 3 units). Further, the heterogeneity analysis indicated that the benefits from internet use were higher in cities with high urbanization, high aging, and high PHC service levels compared to cities with low levels of these factors. Conclusions: The internet use may enhance patients' trust-related PHC utilization. However, this impact is effective only if patients' benchmark trust remains at a relatively high level. Comparatively, the role of internet use is more effective in areas with high urbanization, high aging and high PHC level. Thus, with increasing accessibility to the internet, the internet should be regulated to disseminate correct healthcare information. Moreover, in-depth integration of the internet and PHC should be promoted to provide excellent opportunities for patient participation, and different strategies should be set according to each city's characteristics.

Butyrolactone and sesquiterpene derivatives as inhibitors of iNOS from the roots of Lindera glauca.

Nine previously undescribed butyrolactone and sesquiterpene derivatives, named cyclopentanone A (1), subamolides F and G (2 and 3), secosubamolide F (4), rupestonic acids J - L (5-7), linderaguaianols A and B (8 and 9), together with six known ones 10-15 were isolated from the roots of Lindera glauca. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and Mo2(AcO)4-induced circular dichroism. Compound 1 that possessed a unique five-membered cyclopentane skeleton with a side chain was rarely found from natural sources. The biogenetic pathway for 1-4 was postulated. Secosubamolide F (4) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with IC50 value of 1.73 ± 0.18 µM and also significantly suppressed the production of iNOS. The binding interactions between 4 and iNOS were investigated using docking analyses.

Upregulation of heat shock protein 32 with hemin alleviates acute heat-induced hepatic injury in mice.

Heat shock protein 32 (HSP32) is a stress response protein that can be induced by heat stress in the liver, and its induction can act as an important cellular defence mechanism against heat-induced liver injury. To investigate the functional role of HSP32 in protecting liver tissue against heat stress in mice and the mechanism by which it achieves this protective effect, HSP32 expression and carbon monoxide (CO) contents in a model of mice subjected to acute, transient heat exposure were examined. Furthermore, functional and histological parameters of liver damage and the possible involvement of oxidative stress to induce oxidative deterioration of liver functions and caspase-3 expression were also investigated in this study. We found that heat treatment of mice produced severe hepatic injury, whereas upregulation of HSP32 with hemin pretreatment prevented mice from liver damage. In contrast, addition of Sn-protoporphyrin (SnPP) to inhibit HSP32 expression completely reversed its hepatoprotective effect. It is concluded that upregulation of HSP32 by hemin could alleviate acute heat-induced hepatocellular damage in mice, and its by-product CO seems to play a more important role in hepatoprotective mechanism.