Patients' Perceptions of Barriers and Facilitators to the Adoption of E-Hospitals: Cross-Sectional Study in Western China.

BACKGROUND: As an innovative approach to providing web-based health care services from physical hospitals to patients at a distance, e-hospitals (ie, extended care hospitals through the internet) have been extensively developed in China. This closed health care delivery chain was developed by combining e-hospitals with physical hospitals; treatment begins with web-based consultation and registration, and then, patients are diagnosed and treated in a physical hospital. This approach is promising in its ability to improve accessibility, efficiency, and quality of health care. However, there is limited research on end users' acceptance of e-hospitals and the effectiveness of strategies aimed to prompt the adoption of e-hospitals in China. OBJECTIVE: This study aimed to provide insights regarding the adoption of e-hospitals by investigating patients' willingness to use e-hospitals and analyzing the barriers and facilitators to the adoption of this technology. METHODS: We used a pretested self-administered questionnaire and performed a cross-sectional analysis in 1032 patients across three hierarchical hospitals in West China from June to August 2019. Patients' sociodemographic characteristics, medical history, current disease status, proficiency with electronic devices, previous experience with web-based health services, willingness to use e-hospitals, and perceived facilitators and barriers were surveyed. Multiple significance tests were employed to examine disparities across four age groups, as well as those between patients who were willing to use e-hospitals and those who were not. Multivariate logistic regression was also performed to identify the potential predictors of willingness to use e-hospitals. RESULTS: Overall, it was found that 65.6% (677/1032) of participants were willing to use e-hospitals. The significant predictors of willingness to use e-hospitals were employment status (P=.02), living with children (P<.001), education level (P=.046), information technology skills (P<.001), and prior experience with web-based health care services (P<.001), whereas age, income, medical insurance, and familiarity with e-hospitals were not predictors. Additionally, the prominent facilitators of e-hospitals were convenience (641/677, 94.7%) and accessibility to skilled medical experts (489/677, 72.2%). The most frequently perceived barrier varied among age groups; seniors most often reported their inability to operate technological devices as a barrier (144/166, 86.7%), whereas young participants most often reported that they avoided e-hospital services because they were accustomed to face-to-face consultation (39/52, 75%). CONCLUSIONS: We identified the variables, facilitators, and barriers that play essential roles in the adoption of e-hospitals. Based on our findings, we suggest that efforts to increase the adoption of e-hospitals should focus on making target populations accustomed to web-based health care services while maximizing ease of use and providing assistance for technological inquiries.

Insight into the multi-scale structure and retrogradation of corn starch by partial gelatinization synergizing with epicatechin/epigallocatechin gallate.

Starch retrogradation is of great importance to the quality of starch-based food. This study investigated the effect of partial gelatinization (PG) synergizing with polyphenol (epicatechin, EC; epigallocatechin gallate, EGCG) on the multi-scale structure and short/long-term retrogradation of corn starch (CS). The PG synergizing with EC/EGCG substantially suppressed the short/long-term retrogradation properties of CS. These could be confirmed by the decreased storage modulus and viscosity, the relative crystallinity (1.54%, 3.56%), and the retrogradation degree (9.99%, 20.18%) of CS during storage for 1, 14 days after PG synergizing with EGCG and EC, respectively. This is because PG treatment promoted the hydrogen bond interaction between disordered starch molecules and EC/EGCG. These were proven by the larger aggregation, more and brighter fluorescents, and the reduced long/short-range order structures in CS after PG synergizing with EC/EGCG. This study is helpful for the development of foods with enhanced nutrition and low-retrogradation.

Improving access to primary health care through financial innovation in rural China: a quasi-experimental synthetic difference-in-differences approach.

BACKGROUND: Inadequate financing constrains primary healthcare (PHC) capacity in many low- and middle-income countries, particularly in rural areas. This study evaluates an innovative PHC financing reform in rural China that aimed to improve access to healthcare services through supply-side integration and the establishment of a designated PHC fund. METHODS: We employed a quasi-experimental synthetic difference-in-differences (SDID) approach to analyze county-level panel data from Chongqing Province, China, spanning from 2009 to 2018. The study compared the impact of the reform on PHC access and per capita health expenditures in Pengshui County with 37 other control counties (districts). We assessed the reform's impact on two key outcomes: the share of outpatient visits at PHC facilities and per capita total PHC expenditure. RESULTS: The reform led to a significant increase in the share of outpatient visits at PHC facilities (14.92% points; 95% CI: 6.59-23.24) and an increase in per capita total PHC expenditure (87.30 CNY; 95% CI: 3.71-170.88) in Pengshui County compared to the synthetic control. These effects were robust across alternative model specifications and increased in magnitude over time, highlighting the effectiveness of the integrated financing model in enhancing PHC capacity and access in rural China. CONCLUSIONS: This research presents compelling evidence demonstrating that horizontal integration in PHC financing significantly improved utilization and resource allocation in rural primary care settings in China. This reform serves as a pivotal model for resource-limited environments, demonstrating how supply-side financing integration can bolster PHC and facilitate progress toward universal health coverage. The findings underscore the importance of sustainable financing mechanisms and the need for policy commitment to achieve equitable healthcare access.

Trilobatin attenuates cerebral ischaemia/reperfusion-induced blood-brain barrier dysfunction by targeting matrix metalloproteinase 9: The legend of a food additive.

BACKGROUND AND PURPOSE: Blood-brain barrier (BBB) breakdown is one of the crucial pathological changes of cerebral ischaemia-reperfusion (I/R) injury. Trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effects against cerebral I/R injury as demonstrated in our previous study. This study was designed to investigate the effect of TLB on BBB disruption after cerebral I/R injury. EXPERIMENTAL APPROACH: Rats with focal cerebral ischaemia caused by transient middle cerebral artery occlusion were studied along with brain microvascular endothelial cells and human astrocytes to mimic BBB injury caused by oxygen and glucose deprivation/reoxygenation (OGD/R). KEY RESULTS: The results showed that TLB effectively maintained BBB integrity and inhibited neuronal loss following cerebral I/R challenge. Furthermore, TLB increased tight junction proteins including ZO-1, Occludin and Claudin 5, and decreased the levels of apolipoprotein E (APOE) 4, cyclophilin A (CypA) and phosphorylated nuclear factor kappa B (NF-κB), thereby reducing proinflammatory cytokines. TLB also decreased the Bax/Bcl-2 ratio and cleaved-caspase 3 levels along with a reduced number of apoptotic neurons. Molecular docking and transcriptomics predicted MMP9 as a prominent gene evoked by TLB treatment. The protective effects of TLB on cerebral I/R-induced BBB breakdown was largely abolished by overexpression of MMP9, and the beneficial effects of TLB on OGD/R-induced loss of BBB integrity in human brain microvascular endothelial cells and astrocyte co-cultures was markedly reinforced by knockdown of MMP9. CONCLUSIONS AND IMPLICATIONS: Our findings reveal a novel property of TLB: preventing BBB disruption following cerebral I/R via targeting MMP9 and inhibiting APOE4/CypA/NF-κB axis.

Trilobatin suppresses aging-induced cognitive impairment by targeting SIRT2: Involvement of remodeling gut microbiota to mediate the brain-gut axis.

BACKGROUND: Aging is associated with learning and memory disorder, affecting multiple brain areas, especially the hippocampus. Previous studies have demonstrated trilobatin (TLB), as a natural food additive, can extend the life of Caenorhabditis elegans and exhibit neuroprotection in Alzheimer's disease mice. However, the possible significance of TLB in anti-aging remains elusive. PURPOSE: This study aimed to delve into the physiological mechanism by which TLB ameliorated aging-induced cognitive impairment in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: 6-month-old SAMP8 mice were administrated with TLB (5, 10, 20 mg/kg/day, i.g.) for 3 months. The therapeutic effect of TLB on aging-induced cognitive impairment was assessed in mice using behavioral tests and aging score. The gut microbiota composition in fecal samples was analyzed by metagenomic analysis. The protective effects of TLB on blood-brain barrier (BBB) and intestinal barrier were detected by transmission electron microscope, H&E staining and western blot (WB) assay. The inhibitive effects of TLB on inflammation in brain and intestine were assessed using immunofluorescence, WB and ELISA assay. Molecular docking and surface plasma resonance (SPR) assay were utilized to investigate interaction between TLB and sirtuin 2 (SIRT2). RESULTS: Herein, the findings exhibited TLB mitigated aging-induced cognitive impairment, neuron injury and neuroinflammation in hippocampus of aged SAMP8 mice. Moreover, TLB treatment repaired imbalance of gut microbiota in aged SAMP8 mice. Furthermore, TLB alleviated the damage to BBB and intestinal barrier, concomitant with reducing the expression of SIRT2, phosphorylated levels of c-Jun NH2 terminal kinases (JNK) and c-Jun, and expression of MMP9 protein in aged SAMP8 mice. Molecular docking and SPR unveiled TLB combined with SIRT2 and down-regulated SIRT2 protein expression. Mechanistically, the potential mechanism of SIRT2 in TLB that exerted anti-aging effect was validated in vitro. As expected, SIRT2 deficiency attenuated phosphorylated level of JNK in HT22 cells treated with d-galactose. CONCLUSION: These findings reveal, for the first time, SIRT2-mediated brain-gut barriers contribute to aging and aging-related diseases, and TLB can rescue aging-induced cognitive impairment by targeting SIRT2 and restoring gut microbiota disturbance to mediate the brain-gut axis. Overall, this work extends the potential application of TLB as a natural food additive in aging-related diseases.

[Image quality adapted thoracic diameters in CT coronary artery imaging].

OBJECTIVE: To evaluate the correlation between image quality and thoracic diameters, anteroposterior diameter (AP) and right-left diameter (RL) for the optimization of reducing radiation dose in coronary artery imaging with Dual-source CT. METHODS: 118 patients underwent CT coronary artery imaging (CTCA) were divided into two groups (A and B) according to body mass index (BMI). There were 58 patients in group A with BMI values > or = 25 kg/m2 and < 30 kg/m2; and 60 patients in group B with BMI values < 25 kg/m2. Scan parameters: collimation 64 X 0.6 mm, reconstruction slice thickness 0.75 mm, reconstructin interval 0.7 mm, FOV 150-180 mm, the pitch adjusted according to heart rate automatically. CT imagings were obtained with tube voltage 100 kV, tube current 330 mAs (group A) and 100 kV, tube current 220 mAs (group B). The contrast-noise ratio (CNR), signal to noise ratio (SNR), as well as blind correlation test score values were calculated to establish the relationship among BMI, AP, RL and CNR, SNR. RESULTS: RL of five levels in groups of A, B were correlated to CNRa (P < 0.05). In group A and B (except iii, iv level of Group A), AP were associated with CNRa (P < 0.05). In addition to ii, iv level of group A, v level of group B, BMI were associated with CNRa (P < 0.05). The correlation coefficient of CNRa and RL of group A except ii level was greater than that of CNRa and AP. The correlation coefficient of CNRa, SNRa and RL of group B was greater than that of CNRa, SNRa and AP. Except iii level, the correlation coefficient of CNRa, SNRa and AP of group A was greater than that of CNRa, SNRa and BMI. Except ii level, the correlation coefficient of CNRa and AP of group B was greater than that of CNRa and BMI. CONCLUSION: Thoracic diameter of RL can be used as a guider to select the appropriate scan protocol in the coronary imaging acqusition with dual-source CT.

Receptor Tyrosine Kinase: Still an Interesting Target to Inhibit the Proliferation of Vascular Smooth Muscle Cells.

Vascular smooth muscle cells (VSMCs) proliferation is a critical event that contributes to the pathogenesis of vascular remodeling such as hypertension, restenosis, and pulmonary hypertension. Increasing evidences have revealed that VSMCs proliferation is associated with the activation of receptor tyrosine kinases (RTKs) by their ligands, including the insulin-like growth factor receptor (IGFR), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR). Moreover, some receptor tyrosinase inhibitors (TKIs) have been found and can prevent VSMCs proliferation to attenuate vascular remodeling. Therefore, this review will describe recent research progress on the role of RTKs and their inhibitors in controlling VSMCs proliferation, which helps to better understand the function of VSMCs proliferation in cardiovascular events and is beneficial for the prevention and treatment of vascular disease.

Insight into the improvement in pasting and gel properties of waxy corn starch by critical melting treatments.

To improve the pasting and gel properties of waxy corn starch (WCS), the native starch was modified by critical melting (CM) at the onset temperature (TO), peak temperature (TP), and conclusion temperature (TC) (labeled CMO, CMP, and CMC respectively). CM treatments significantly enhanced the thermal stability of the WCS, as indicated by the increase in the peak gelatinization temperature, pasting temperature, and peak time. In addition, after CMP treatment, the storage modulus, hardness, gumminess, springiness, and chewiness of starch gels significantly increased by 43.29 %, 31.14 %, 23.36 %, 8.26 %, and 61.43 %, respectively, and the syneresis rate significantly decreased by 19.69 % (p < 0.05). These results indicated that CMP treatments significantly improved the gelling ability and freeze-thaw stability of the WCS. These results are ascribed to the partial disruption and enhanced rearrangement of the starch crystalline structure. CMP treatment induced the crystalline structure of starch to be partially disrupted and a hard structure was formed on the surface of starch granules. The hard structure in CMP-treated starch supplied more attachment points for crystalline structure rearrangement during gelatinization. Therefore, the above results indicated that CMP treatments can be used to modify starch to improve the pasting and gel properties of starch-based food products.

Icariside II mitigates myocardial infarction by balancing mitochondrial dynamics and reducing oxidative stress through the activation of Nrf2/SIRT3 signaling pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2)/silent mating type information regulation 2 homolog 3 (SIRT3) signaling pathway plays a pivotal role in regulating mitochondrial dynamics and oxidative stress, which are considered to be the principal pathogenesis of myocardial infarction (MI). Our previous study proved that pretreatment with icariside II (ICS II), a major active ingredient of Herbal Epimedii, exerts cardioprotective effect on MI, however, whether post-treatment with ICS II can alleviate MI and its underlying mechanism are still uncertain. Therefore, the present study was designed to investigate the therapeutic effect and the possible mechanism of ICS II on MI both in vivo and in vitro. The results revealed that post-treatment with ICS II markedly ameliorated myocardial injury in MI-induced mice and mitigated oxygen and glucose deprivation (OGD)-elicited cardiomyocyte injury. Further researches showed that ICS II promoted mitochondrial fusion, and suppressed mitochondrial fission and oxidative stress, which were achieved by facilitating the nuclear translocation of Nrf2 and activation of SIRT3. In summary, our findings indicate that ICS II mitigates MI-induced mitochondrial dynamics disorder and oxidative stress via activating the Nrf2/SIRT3 signaling pathway.

Physical modification of maize starch by gelatinizations and cold storage.

The effects of gelatinization at three selected temperatures (DSC characteristic peaks temperature: TO, TP, and TC) and subsequent cold storage (CS) treatment on structural characteristics, pasting, and rheological properties of maize starch (MS) were investigated. The pasting, rheological properties of MS was changed with the increase of gelatinization temperature from TO to TC, but were not further significantly changed if the gelatinization temperature was higher than TC. Pasting and thermal properties analysis suggested that gelatinization at TC (TC treatment) significantly increased the gelatinization and pasting temperature of MS. Moreover, TC treatment decreased breakdown viscosity by 8.49 times and setback viscosity by 2.53 times. Dynamic rheological measurements revealed that the TC treatment caused the lower G' and G" of MS, and decreased the thickening coefficient by 55.17 %. These results indicated that TC treatment could enhance the thermal stability properties of MS, inhibiting the shear and short-term retrogradation, the shear-thinning behavior of MS. Interestingly, the CS treatment further inhibited the shear and short-term retrogradation and the shear-thinning behavior of MS. The leaked starch molecules aggregate to form a harder structure after gelatinization and starch molecules were further aggregated after CS treatment, these all were hypothesized to be responsible for these results.

Cross-Verification of COVID-19 Information Obtained From Unofficial Social Media Accounts and Associated Changes in Health Behaviors: Web-Based Questionnaire Study Among Chinese Netizens.

BACKGROUND: As social media platforms have become significant sources of information during the pandemic, a significant volume of both factual and inaccurate information related to the prevention of COVID-19 has been disseminated through social media. Thus, disparities in COVID-19 information verification across populations have the potential to promote the dissemination of misinformation among clustered groups of people with similar characteristics. OBJECTIVE: This study aimed to identify the characteristics of social media users who obtained COVID-19 information through unofficial social media accounts and were (1) most likely to change their health behaviors according to web-based information and (2) least likely to actively verify the accuracy of COVID-19 information, as these individuals may be susceptible to inaccurate prevention measures and may exacerbate transmission. METHODS: An online questionnaire consisting of 17 questions was disseminated by West China Hospital via its official online platforms, between May 18, 2020, and May 31, 2020. The questionnaire collected the sociodemographic information of 14,509 adults, and included questions surveying Chinese netizens' knowledge about COVID-19, personal social media use, health behavioral change tendencies, and cross-verification behaviors for web-based information during the pandemic. Multiple stepwise regression models were used to examine the relationships between social media use, behavior changes, and information cross-verification. RESULTS: Respondents who were most likely to change their health behaviors after obtaining web-based COVID-19 information from celebrity sources had the following characteristics: female sex (P=.004), age ≥50 years (P=.009), higher COVID-19 knowledge and health literacy (P=.045 and P=.03, respectively), non-health care professional (P=.02), higher frequency of searching on social media (P<.001), better health conditions (P<.001), and a trust rating score of more than 3 for information released by celebrities on social media (P=.005). Furthermore, among participants who were most likely to change their health behaviors according to social media information released by celebrities, female sex (P<.001), living in a rural residence rather than first-tier city (P<.001), self-reported medium health status and lower health care literacy (P=.007 and P<.001, respectively), less frequent search for COVID-19 information on social media (P<.001), and greater level of trust toward celebrities' social media accounts with a trust rating score greater than 1 (P≤.04) were associated with a lack of cross-verification of information. CONCLUSIONS: The findings suggest that governments, health care agencies, celebrities, and technicians should combine their efforts to decrease the risk in vulnerable groups that are inclined to change health behaviors according to web-based information but do not perform any fact-check verification of the accuracy of the unofficial information. Specifically, it is necessary to correct the false information related to COVID-19 on social media, appropriately apply celebrities' star power, and increase Chinese netizens' awareness of information cross-verification and eHealth literacy for evaluating the veracity of web-based information.

Icariin and its metabolites as potential protective phytochemicals against cardiovascular disease: From effects to molecular mechanisms.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among all types of diseases in the world, affecting many millions of individuals every year. CVD includes hypertension, atherosclerosis, pulmonary hypertension, heart failure, cardiomyopathy, coronary heart disease, etc., which are involved in complex etiology, pathogenesis and many risk factors. Modern pharmacological studies have revealed that Epimedium possesses a variety of beneficial effects in regulating cardiovascular inflammation and other biological activities, which provides a therapeutic value for the prevention and treatment of these cardiovascular diseases. In this review, we discuss the cardiovascular protective effects of icariin, an active component from Epimedium, and its metabolites. We summarize a range of studies showing that the modes of action of icariin on CVD relate to its inhibition of myocardial apoptosis and prevention of inflammation on endothelial cell injury, emphasizing the multiple effects of icariin and its metabolites in the repair of common heart failure and myocardial infarction, as well as the formation of neointima. In particular, an emphasis is placed on the discussion of the action mechanism of icariin in combination with new advances in the understanding of the pathology of CVD with potential application of icariin in the treatment of this human disorder.

Readiness of healthcare providers for e-hospitals: a cross-sectional analysis in China before the COVID-19 period.

OBJECTIVES: The growth and development of smartphones and eHealth technologies have enabled the potential for extended care hospitals (e-hospitals) in China in order to facilitate the success of a primary healthcare centre (PHC)-based integrated delivery model. Although the adoption of e-hospitals is essential, few studies have directed their research towards understanding the perspectives of healthcare providers. This study aims to identify the current readiness of healthcare providers to adopt e-hospital technologies, determine the factors influencing this adoption and describe the perceived facilitators and barriers in regard to working at e-hospitals. DESIGN: A cross-sectional study conducted in Sichuan, China, between June and September 2019. SETTINGS: Information was collected from healthcare providers who have more than 3 years of work experience from a tertiary hospital, secondary hospital, PHCs and private hospital. PARTICIPANTS: 2298 medical professionals were included in this study. OUTCOME MEASURE: This study included a self-administered questionnaire that was used to assess participants' sociodemographic characteristics, online medical practices, willingness to use e-hospitals and perceived facilitators/barriers to working at e-hospitals. Multivariate regression analysis was performed in order to evaluate the independent factors associated with e-hospital work. RESULTS: Overall, 86.3% had a positive response towards working at e-hospitals. Age (p<0.05), familiarity with e-hospitals (p<0.001) and prior work practices in online healthcare settings (p<0.001) were associated with participants' readiness to work at e-hospitals. Gender, education level, professional level, the tier of their affiliated hospital and workload were not statistically associated. Healthcare providers who had positive attitudes towards e-hospitals considered improved efficiency, patient satisfaction, communication among physicians, increased reputation and income, and alleviated workload to be advantages of adoption. The participants who were unwilling to work at e-hospitals perceived lack of time, insufficient authenticity/reliability and underdeveloped policies as potential barriers. CONCLUSION: Improving operative proficiency in electronic devices, accommodating to work schedules, increasing familiarity with e-hospitals and regulating practices will improve the readiness of healthcare providers to work at e-hospitals.

Characteristics of inflammation process in monocrotaline-induced pulmonary arterial hypertension in rats.

OBJECTIVE: A growing evidence demonstrates that inflammation is a major contributor to the pathogenesis of pulmonary arterial hypertension (PAH). However, blocking inflammation has only been shown to be of minor clinical benefit due to a lack of understanding of the precise inflammation present in PAH. Thus, the present study aimed to investigate characteristics of inflammatory process in PAH induced by monocrotaline (MCT) in rats. METHODS: Adult male Sprague-Dawley rats received a single dose of MCT (50 mg/kg, ip), and the occurrence of PAH and inflammation biomarkers were measured at 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 days after MCT injection. RESULTS: From the 6th day after the injection of MCT, the mean pulmonary artery pressure gradually increased and doubled on the 30th day, accompanied by right ventricular hypertrophy and pulmonary arterial remodeling in a time-dependent manner. In the first 6 days after MCT treatment, only pro-inflammatory cytokines TNF-α, IL-1ß increased, which was defined as acute inflammatory phase, after that, both pro-inflammatory factors TNF-α, IL-1ß, IL-6, IL-12 and anti-inflammatory factors Arg1, IL-10, TGF-ß increased, which was defined as chronic inflammatory phase. The M1/M2 macrophage ratios in lung and alveolar lavage fluid were elevated on the 6th and 30th day, moreover, which were higher on the 6th than 30th day, and the PI3K/Akt signaling pathway increased along with the progression of PAH and correlated with pro-inflammatory proteins, which revealed also to some extent the characteristics of inflammation of PAH induced by MCT. CONCLUSION: The course of PAH induced by MCT injection is progressive with persistent inflammation, which is defined as acute inflammatory phase within 6 days after MCT treatment, after that, is defined as chronic inflammatory phase.

Long-term trends and regional variations of hypertension incidence in China: a prospective cohort study from the China Health and Nutrition Survey, 1991-2015.

OBJECTIVE: The aim is to explore the trends of hypertension incidence and regional variations in China from 1991 to 2015. DESIGN: A dynamic prospective cohort study. SETTING: China Health and Nutrition Survey 1991-2015. PARTICIPANTS: 12 952 Chinese adults aged 18+ years. PRIMARY OUTCOME MEASURES: Incident hypertension from 1993 to 2015. RESULTS: Age-standardised hypertension incidence increased from 40.8 per 1000 person-years (95% CI 38.3 to 43.4) between 1993 and 1997 to 48.6 (95% CI 46.1 to 51.0) between 2011 and 2015. The increasing trends were further supported by results from subsequent extended Cox proportional hazard model. In addition, results from the modelling analysis showed that individuals in eastern, central and northeastern China had greater risks of hypertension occurrence in comparison with their counterparts in western China. CONCLUSION: Hypertension incidence increased during the study period. The growth called for more attention on the health education and health promotion of individuals with great risks.

Synergistic effects of plant protein hydrolysates and xanthan gum on the short- and long-term retrogradation of rice starch.

Controlling and delaying the retrogradation of gelatinized rice starch (GRS) can improve the quality of GRS-based foods during storage. Here, we evaluated the influence of corn protein hydrolysates (CPHs), rice protein hydrolysates (RPHs), wheat protein hydrolysates (WPHs), and soybean protein hydrolysates (SPHs) on inhibiting the short- and long- term retrogradation of RS-xanthan gum mixtures. Compared with WPHs, RPHs, CPHs, the SPHs cooperating with xanthan gum (SPHs-XT) showed the highest inhibitory effect. The increased loss tangent (tan δ) in the dynamic viscoelastic measurement suggested that SPHs-XT enhanced the liquid-like properties of GRS gel. The decreased storage modulus (G') and the reduced setback value indicated that the short-term retrogradation of GRS was restrained by SPHs-XT. Meanwhile, during a 14-day storage at 4 °C, the hardness of GRS gel was significantly decreased from 1382.5 g to 201.4 g after the addition of SPHs-XT before storage determined by using a texture profile analysis (TPA), and the relative crystallinity of the retrograded GRS was decreased from 18.18% to 8.15% determined by using a X-ray diffraction (XRD) with a corresponding decrease of the retrogradation enthalpy determined by using a differential scanning calorimetry (DSC). These results suggested that SPHs-XT could inhibit the the long-term retrogradation of GRS. Moreover, the water molecules were determined to be locked in GRS gel after the addition of SPHs-XT by using a low-field nuclear magnetic resonance (LF-NMR). In addition, thin membranes and filaments formed by the addition of SPHs-XT in GRS gel were observed by using a scanning electron microscopy (SEM), suggesting a decreased cross-linking of GRS molecules by the addition of SPHs-XT to form ordered structures. These results indicated that the addition of SPHs-XT is a potential to inhibit the short- and long-term retrogradation of GRS and further to improve the nutrition of the GRS based products.

Ginsenoside Rg1 prevents vascular intimal hyperplasia involved by SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in a rat balloon injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Mey. is a traditional tonic that has been used for thousands of years, and has positive effects on vascular diseases. Ginsenoside Rg1 (GS-Rg1) is one of the active ingredients of Panax ginseng C. A. Mey. and has been shown to have beneficial effects against ischemia/reperfusion injury. Our previously study has found that GS-Rg1 can mobilize bone marrow stem cells and inhibit vascular smooth muscle proliferation and phenotype transformation. However, pharmacological effects and mechanism of GS-Rg1 in inhibiting intimal hyperplasia is still unknown. AIM OF THE STUDY: This study was aimed to investigate whether GS-Rg1 prevented vascular intimal hyperplasia, and the involvement of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1 axes. MATERIALS AND METHODS: Rats were operated with carotid artery balloon injury. The treatment groups were injected with 4, 8 and 16 mg/kg of GS-Rg1 for 14 days. The degree of intimal hyperplasia was evaluated by histopathological examination. The expression of α-SMA (α-smooth muscle actin) and CD133 were detected by double-label immunofluorescence. Serum levels of SDF-1α, SCF and soluble FKN (sFKN) were detected by enzyme linked immunosorbent assay (ELISA). The protein expressions of SCF, SDF-1α and FKN, as well as the receptors c-kit, CXC chemokine receptor type 4 (CXCR4) and CX3C chemokine receptor type 1 (CX3CR1) were detected by immunochemistry. RESULTS: GS-Rg1 reduced intimal hyperplasia by evidence of the values of NIA, the ratio of NIA/MA, and the ratio of NIA/IELA and the ratio of NIA/LA, especially in 16 mg/kg group. Furthermore, GS-Rg1 8 mg/kg group and 16 mg/kg group decreased the protein expressions of the SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in neointima, meanwhile GS-Rg1 8 mg/kg group and 16 mg/kg group also attenuated the expressions of SDF-1α, SCF and sFKN in serum. In addition, the expression of α-SMA and CD133 marked smooth muscle progenitor cells (SMPCs) was decreased after GS-Rg1 treatment. CONCLUSIONS: GS-Rg1 has a positive effect on inhibiting vascular intimal hyperplasia, and the underlying mechanism is related to inhibitory expression of SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes.

METTL3 and ALKBH5 oppositely regulate m6A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes.

N6-methyladenosine (m6A) mRNA modifications play critical roles in various biological processes. However, no study addresses the role of m6A in macroautophagy/autophagy. Here, we show that m6A modifications are increased in H/R-treated cardiomyocytes and ischemia/reperfusion (I/R)-treated mice heart. We found that METTL3 (methyltransferase like 3) is the primary factor involved in aberrant m6A modification. Silencing METTL3 enhances autophagic flux and inhibits apoptosis in H/R-treated cardiomyocytes. However, overexpression of METTL3 or inhibition of the RNA demethylase ALKBH5 has an opposite effect, suggesting that METTL3 is a negative regulator of autophagy. Mechanistically, METTL3 methylates TFEB, a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3'-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. Further experiments show that autophagic flux enhanced by METTL3 deficiency is TFEB dependent. In turn, TFEB regulates the expression levels of METTL3 and ALKBH5 in opposite directions: it induces ALKBH5 and inhibits METTL3. TFEB binds to the ALKBH5 promoter and activates its transcription. In contrast, inhibition of METTL3 by TFEB does not involve transcriptional repression but rather downregulation of mRNA stability, thereby establishing a negative feedback loop. Together, our work uncovers a critical link between METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease. Abbreviations: ACTB, actin beta; ALKBH5, alkB homolog 5, RNA demethylase; ANXA5, annexin A5; ATG, autophagy-related; BafA, bafilomycin A1; CASP3, caspase 3; ELAVL1, ELAV like RNA binding protein 1; FTO, FTO, alpha-ketoglutarate dependent dioxygenase; GFP, green fluorescent protein; GST, glutathione S-transferase; HNRNPD, heterogeneous nuclear ribonucleoprotein D; H/R, hypoxia/reoxygenation; I/R, ischemia/reperfusion; LAD, left anterior descending; m6A, N6-methyladenosine; MEFs, mouse embryo fibroblasts; Mer, mutated estrogen receptor domains; METTL3, methyltransferase like 3; METTL14, methyltransferase like 14; mRFP, monomeric red fluorescent protein; MTORC1, mechanistic target of rapamycin kinase complex 1; NMVCs, neonatal mouse ventricular cardiomyocytes; PCNA, proliferating cell nuclear antigen; PE, phosphatidylethanolamine; PI, propidium iodide; PTMs, post-translational modifications; PVDF, polyvinylidenedifluoride; RIP, RNA-immunoprecipitation; siRNA, small interfering RNA; SQSTM1, sequestosome 1; TFEB, transcription factor EB; TUBA: tublin alpha; WTAP, WT1 associated protein; YTHDF, YTH N6-methyladenosine RNA binding protein.

Trabid inhibits hepatocellular carcinoma growth and metastasis by cleaving RNF8-induced K63 ubiquitination of Twist1.

TRAF-binding domain (Trabid), one of deubiquitination enzymes, was recently reported to activate Wnt/ ß-catenin signaling pathway. However, the role of Trabid in tumors including hepatocellular carcinoma (HCC) and the underlying mechanisms controlling its activity remain poorly understood. Here, we report that Trabid is significantly downregulated in HCC tumor samples and cell lines compared with normal controls and that its expression level is negatively correlated with HCC pathological grading, recurrence, and metastasis. The reintroduction of Trabid expression in tumor cells significantly decreases HCC progression as well as pulmonary metastasis. The effect of Trabid on HCC development occurs at least partially through regulation of Twist1 activity. Mechanistically, Trabid forms a complex with Twist1 and specifically cleaves RNF8-induced K63-linked poly-ubiquitin chains from Twist1, which enhances the association of Twist1 with ß-TrCP1 and allows for subsequent K48-linked ubiquitination of Twist1. Knockdown of Trabid increases K63-linked ubiquitination, but abrogates K48-linked ubiquitination and degradation of Twist1, thus enhancing HCC growth and metastasis. Interestingly, Twist1 negatively regulates the promoter activity of Trabid, indicating that a double-negative feedback loop exists. Our findings also identify an essential role for activation of Trabid by AKT-mediated phosphorylation at Ser78/Thr117 in negatively regulating Twist1 signaling, which further provides insights into the mechanisms by which Trabid regulates Twist1 ubiquitination. Our results reveal that Trabid is a previously unrecognized inhibitor of HCC progression and metastasis, which sheds light on new strategies for HCC treatment.