Multiscale structure changes and mechanism of polyphenol-amylose complexes modulated by polyphenolic structures.

This study was designed to investigate the effect of polyphenolic structure on the interaction strength and process between polyphenols (gallic acid (GA), epigallocatechin gallate (EGCG) and tannic acid (TA)) and amylose (AM). The results of Fourier transform infrared spectroscopy, isothermal titration calorimetry, X-ray photoelectron spectroscopy and molecular dynamic simulation (MD) suggested that the interactions between the three polyphenols and AM were noncovalent, spontaneous, low-energy and driven by enthalpy, which would be enhanced with increasing amounts of pyrogallol groups in the polyphenols. The results of turbidity, particle size and appearance of the complex solution showed that the interaction process between polyphenols and AM could be divided into three steps and would be advanced by increasing the number of pyrogallol groups in the polyphenols. At the same time, MD was intuitively employed to exhibit the interaction process between amylose and polyphenols, and it revealed that the interaction induced the aggregation of amylose and that the agglomeration degree of amylose increased with increasing number of pyrogallol groups at polyphenols. Last, the SEM and TGA results showed that TA/AM complexes had the tightest structure and the highest thermal stability (TA/AM˃EGCG/AM˃GA/AM), which could be attributed to TA having five pyrogallol groups.

Dietary sinensetin and polymethoxyflavonoids: Bioavailability and potential metabolic syndrome-related bioactivity.

Sinensetin is among the most ubiquitous polyphenols in citrus fruit and recently has been extensively studied for its ability to prevent or treat diseases. The current literature on the bioavailability of sinensetin and its derivatives was reviewed and the potential ameliorative effects of metabolic syndrome in humans were evaluated. Sinensetin and its derivatives mainly aggregated in the large intestine and extensively metabolized through gut microbiota (GM) and the liver. So intestinal microorganisms had a significant influence on the absorption and metabolism of sinensetin. Interestingly, not only GM acted on sinensetin to metabolize them, but sinensetin also regulated the composition of GM. Thus, sinensetin was metabolized as methyl, glucuronide and sulfate metabolites in the blood and urine. Furthermore, sinensetin was reported to have the beneficial effect of ameliorating metabolic syndromes, including disorders of lipid metabolism (obesity, NAFLD, atherosclerosis), glucose metabolism disorder (insulin resistant) and inflammation, in terms of improving the composition of intestinal flora and modulating metabolic pathway factors in relevant tissues. The present work strongly elucidated the potential mechanism of sinensetin in improving metabolic disorders and supported the contribution of sinensetin to health benefits, thus offering a better perspective in understanding the role played by sinensetin in human health.

Biological Activities and Solubilization Methodologies of Naringin.

Naringin (NG), a natural flavanone glycoside, possesses a multitude of pharmacological properties, encompassing anti-inflammatory, sedative, antioxidant, anticancer, anti-osteoporosis, and lipid-lowering functions, and serves as a facilitator for the absorption of other drugs. Despite these powerful qualities, NG's limited solubility and bioavailability primarily undermine its therapeutic potential. Consequently, innovative solubilization methodologies have received considerable attention, propelling a surge of scholarly investigation in this arena. Among the most promising solutions is the enhancement of NG's solubility and physiological activity without compromising its inherent active structure, therefore enabling the formulation of non-toxic and benign human body preparations. This article delivers a comprehensive overview of NG and its physiological activities, particularly emphasizing the impacts of structural modification, solid dispersions (SDs), inclusion compound, polymeric micelle, liposomes, and nanoparticles on NG solubilization. By synthesizing current research, this research elucidates the bioavailability of NG, broadens its clinical applicability, and paves the way for further exploration and expansion of its application spectrum.

Novel Umami-, Salty-, and Kokumi-Enhancing γ-Glutamyl Tripeptides Synthesized with the Bitter Dipeptides from Defatted Peanut Meal Protein Hydrolysate.

Defatted peanut meal protein hydrolysates (DPMHs) usually have a bitter taste. γ-Glutamylation by Bacillus amyloliquefaciens l-glutaminase was introduced to DPMH to reduce its bitterness and generated a γ-glutamylated product (DPMH-G). Extra l-glutamine (l-Gln) (5% w/w) was added to DPMH, and the mixture was then γ-glutamylated (DPMH-G-Q). Results showed that γ-glutamylation decreased the bitterness of the products and also enhanced their kokumi, umami, and salty taste, especially for DPMH-G-Q. Bitter amino acids and bitter peptides were found to be substrates (acceptors) of the synthesized γ-[Glu](1,2)-AAs and γ-Glu-AA-AAs, respectively. The production yield of γ-[Glu](1,2)-AAs was only 0.69/100 g for DPMH-G and 2.30/100 g for DPMH-G-Q, which was much lower than that of γ-Glu-AA-AAs (5.73/100 g for DPMH-G and 18.72/100 g for DPMH-G-Q). The improvement in taste attributes of DPMH might mainly be due to the consumption of bitter dipeptides and the production of γ-Glu-AA-AAs. In DPMH-G-Q, eight γ-Glu-AA-AAs were identified, including γ-Glu-Ile-Lys, γ-Glu-Ala-Ile, γ-Glu-Leu-Leu, γ-Glu-Phe-Leu, γ-Glu-Thr-Leu, γ-Glu-Ile-Met, γ-Glu-Val-Leu, and γ-Glu-Ser-Tyr, which were first time reported. They all can enhance umami, salty, and kokumi taste with a threshold value between 1.61 ± 0.21-2.16 ± 0.19, 1.65 ± 0.19-2.23 ± 0.20, and 0.67 ± 0.21-1.00 ± 0.22 mM, respectively. Insufficient l-Gln restricted the formation of γ-glutamyl peptides, and this was why DPMH-G had a lower yield and variety than DPMH-G-Q. This also suggested that l-glutaminase is selective to different substrates. Overall, this study provides a new method to reduce the bitterness of protein hydrolysates and also improve the taste by synthesizing γ-glutamyl tripeptides.

Effect of polyphenolic structure and mass ratio on the emulsifying performance and stability of emulsions stabilized by polyphenol-corn amylose complexes.

O/W emulsions stabilized by polyphenol/amylose (AM) complexes with several polyphenol/AM mass ratios and different polyphenols (gallic acid (GA), epigallocatechin gallate (EGCG) and tannic acid (TA)) were prepared by a high-intensity ultrasound emulsification technique. The effect of the pyrogallol group number of polyphenols and the mass ratio of polyphenols/AM on polyphenol/AM complexes and emulsions was studied. The soluble and/or insoluble complexes gradually formed upon adding polyphenols into the AM system. However, insoluble complexes were not formed in the GA/AM systems because GA has only one pyrogallol group. In addition, the hydrophobicity of AM could also be improved by forming polyphenol/AM complexes. The emulsion size decreased with increasing pyrogallol group number on the polyphenol molecules at a fixed ratio, and the size could also be controlled by the polyphenol/AM ratio. Moreover, all emulsions presented various degrees of creaming, which was restrained by decreasing emulsion size or the formation of a thick complex network. The complex network was enhanced by increasing the ratio or pyrogallol group number on the polyphenol molecules, which was because the increasing number of complexes was adsorbed onto the interface. Altogether, compared to GA/AM and EGCG/AM, the TA/AM complex emulsifier had the best hydrophobicity and emulsifying properties, and the TA/AM emulsion had the best emulsion stability.

Pulmonary veno-occlusive disease in Sjogren's syndrome: a case report.

BACKGROUND: Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) belongs to Group 1 pulmonary hypertension. Pulmonary veno-occlusive disease (PVOD), which is characterized by venous system aberrations, has been previously reported in CTD-PAH; however, it has rarely been observed in Sjogren's syndrome (SS). CASE PRESENTATION: Our 28-year-old female patient was admitted to the hospital with recurrent shortness of breath even after minimal physical activity. Her chest high-resolution CT scan demonstrated pulmonary artery dilatation and bilateral ground-glass nodules. A subsequent right heart catheterization confirmed pulmonary hypertension because her mean pulmonary arterial pressure was 62 mmHg. Our inquisitive genomic assessment identified a novel EIF2AK4 mutation at c.1021 C > T (p. Gln341*), the dominant causal gene of PVOD. Histological examination demonstrated stenosis and occlusions in the pulmonary veins. Because she presented with features such as dry eyes and Raynaud's phenomenon, we performed a biopsy on the labial salivary gland, which confirmed SS. Her treatment regimen included PAH-targeted therapies (tadalafil and macitentan) in combination with hydroxychloroquine. Although she was hospitalized several times due to acute exacerbation of PAH, her disease progression was under control, and she did not demonstrate any signs of pulmonary edema even after a three-year treatment period. CONCLUSION: Here, we report the case of an SS-PAH patient with PVOD who carried a novel biallelic EIF2AK4 mutation, and PAH-targeted therapies were well tolerated by our patient.

Synergistic Effect of Kokumi-Active γ-Glutamyl Peptides and l-Glutamate on Enhancing Umami Sensation and Stimulating Cholecystokinin Secretion via T1R1/T1R3 Activation in STC-1 Cells.

This study aimed to investigate the synergistic effect of γ-glutamyl peptides (γEL, γEV, and γEγEV) and l-glutamate (MSG) on the activation of the umami receptor (T1R1/T1R3) in relation to enhanced umami taste and promoted cholecystokinin (CCK) secretion. The synergy of γ-glutamyl peptides and MSG (1-15 mM, 1:1) caused a significant increase in both the umami taste score by 0.218 ± 0.015-1.216 ± 0.031 times and the CCK secretion by 41.41 ± 6.46-201.16 ± 12.91% when compared to the group treated with individual MSG. The increase in CCK secretion promoted by γ-glutamyl peptides was only reduced by 11.54 ± 0.01-45.65 ± 3.58% after adding yjr CaSR inhibitor (NPS 2143), implying that there were other receptors besides CaSR involved in the stimulation of CCK secretion. The mixture of γEγEV and MSG synergistically increased the intracellular calcium release by 111.26 ± 11.94-135.28 ± 16.60% in STC-1 and 108.47 ± 7.89-152.33 ± 26.26% in HEK 293 compared to MSG. The protein expression for T1R1/T1R3 was increased, indicating that the mixture can activate T1R1/T1R3. The amino acids V277, S147, and D190 of T1R3 can be critical for the binding of γEγEV to T1R3. This is the first report on the synergistic effect of taste-active substances on taste sensation and hormone release via taste receptor activation.

Genome-Wide Identification and Analysis of the Growth-Regulating Factor Family in Zanthoxylum armatum DC and Functional Analysis of ZaGRF6 in Leaf Size and Longevity Regulation.

Growth-regulating factors (GRFs) are plant-specific transcription factors that play an important role in plant growth and development. In this study, fifteen GRF gene members containing QLQ and WRC domains were identified in Zanthoxylum armatum. Phylogenetic and collinearity analysis showed that ZaGRFs were closely related to CsGRFs and AtGRFs, and distantly related to OsGRFs. There are a large number of cis-acting elements related to hormone response and stress induction in the GRF gene promoter region of Z. armatum. Tissue-specific expression analysis showed that except for ZaGRF7, all the ZaGRFs were highly expressed in young parts with active growth and development, including terminal buds, seeds, and young flowers, suggesting their key roles in Z. armatum growth and development. Eight ZaGRFs were selected to investigate the transcriptional response to auxin, gibberellin and drought treatments. A total of six ZaGRFs in the NAA treatment, four ZaGRFs in the GA3 treatment, and six ZaGRFs in the PEG treatment were induced and significantly up-regulated. Overexpression of ZaGRF6 increased branching and chlorophyll content and delayed senescence of transgenic Nicotiana benthamiana. ZaGRF6 increased the expression of CRF2 and suppressed the expression of ARR4 and CKX1, indicating that ZaGRF6 is involved in cytokinin metabolism and signal transduction. These research results lay a foundation for further analysis of the GRF gene function of Z. armatum and provide candidate genes for growth, development, and stress resistance breeding of Z. armatum.

Integrative Analysis of Metabolomics and Transcriptomics Reveals Molecular Mechanisms of Anthocyanin Metabolism in the Zikui Tea Plant (Camellia sinensis cv. Zikui).

In this study, we performed an association analysis of metabolomics and transcriptomics to reveal the anthocyanin biosynthesis mechanism in a new purple-leaf tea cultivar Zikui (Camellia sinensis cv. Zikui) (ZK). Three glycosylated anthocyanins were identified, including petunidin 3-O-glucoside, cyanidin 3-O-galactoside, and cyanidin 3-O-glucoside, and their contents were the highest in ZK leaves at 15 days. This is the first report on petunidin 3-O-glucoside in purple-leaf tea. Integrated analysis of the transcriptome and metabolome identified eleven dependent transcription factors, among which CsMYB90 had strong correlations with petunidin 3-O-glucoside, cyanidin 3-O-galactoside, and cyanidin 3-O-glucoside (PCC > 0.8). Furthermore, we also identified key correlated structural genes, including two positively correlated F3'H (flavonoid-3'-hydroxylase) genes, two positively correlated ANS (anthocyanin synthase) genes, and three negatively correlated PPO (polyphenol oxidase) genes. Overexpression of CsMYB90 in tobacco resulted in dark-purple transgenic calluses. These results showed that the increased accumulation of three anthocyanins in ZK may promote purple-leaf coloration because of changes in the expression levels of genes, including CsMYB90, F3'Hs, ANSs, and PPOs. These findings reveal new insight into the molecular mechanism of anthocyanin biosynthesis in purple-leaf tea plants and provide a series of candidate genes for the breeding of anthocyanin-rich cultivars.

pH-driven-assembled soy peptide nanoparticles as particulate emulsifier for oil-in-water Pickering emulsion and their potential for encapsulation of vitamin D3.

Pickering emulsions prepared by food-grade particles have gained growing attention due to their promising application in functional food and pharmaceutical industries. In this study, we successfully fabricated soy peptide-based nanoparticles (SPN) through pH-driven process. Obtained particles with small particle size were surface active and shared intermediate wettability, and they could be well applied as an efficient particulate emulsifier for stabilizing oil-in-water Pickering emulsions at SPN concentration above 0.25 wt%. Furthermore, formed emulsions stabilized with SPN exhibited good protection towards Vitamin D3 against UV irradiation and oxidative deterioration, where controlled release of Vitamin D3in vitro could also be well achieved by modulating particle concentration. The whole process can contribute to a sustainable development of low-value peptide byproducts as functional food ingredients.

Efficacy and safety of pulsed dye laser for the treatment of surgical scars: a systematic review and meta-analysis.

Various clinical trials have explored whether the pulsed dye laser (PDL) method is safe to treat scars, especially surgical scars. However, comprehensive evidence confirming the exact outcomes of PDL for treating surgical scars is lacking. The efficacy and safety of PDL in the treatment of surgical scars were determined through a review of several studies. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched, and the main clinical outcomes were Vancouver Scar Scale (VSS) scores in terms of pigmentation, vascularity, pliability, and height. Review Manager 5.4 software was used for statistical analyses of the data; we chose a standardized mean difference (SMZ) to present the results with 95% confidence interval (CI). Overall, seven randomized controlled trials were used for this meta-analysis, all of these papers used 585 nm or 595 nm PDL with 7 mm or 10 mm spot size and a fluence of 3.5 to 10 J/cm2 for treating surgical scars; besides, the pulse duration ranged from 450 µs to 10 ms. We found that PDL significantly resulted in decreased VSS scores (P = 0.02) in four aspects: pigmentation (P = 0.0002), vascularity (P < 0.00001), pliability (P = 0.0002), and height (P = 0.0002). Moreover, scar improvement was similar when using 585 nm and 595 nm PDL in terms of pigmentation (P = 0.76), vascularity (P = 0.34), pliability (P = 0.64), and height (P = 0.57). Furthermore, our review indicated that PDL has no obvious adverse effects for most people, except transitory erythema and purpura. The meta-analysis showed that both 585 nm and 595 nm PDL therapy can effectively reduce the VSS score, suggesting that PDL can be a safe and effective method for the treatment of surgical scars.

Upregulation of a novel LncRNA AC104958.2 stabilized by PCBP2 promotes proliferation and microvascular invasion in hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) were reported to be involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). Microvascular invasion (MVI) is an independent predictor for early recurrence and overall survival in postoperative patients with HCC. However, the mechanisms how lncRNAs affect HCC and MVI remain elusive. By RNA sequencing (RNA-seq) in a series of 65 HCC samples and 30 paired adjacent non-tumor liver tissue, we identified a novel lncRNA AC104958.2 that was significantly upregulated in HCC tissues and associated with MVI. Overexpression of AC104958.2 obviously elevated cell viability, metastasis, invasion and epithelial-mesenchymal transition (EMT), while knockout of AC104958.2 mediated by CRISPR/Cas9 technique showed the opposite effects. In addition, the interaction between AC104958.2 and Poly (rC) binding protein 2 (PCBP2) was identified by RNA pull down and mass spectrometry (MS), which was further validated by RNA immunoprecipitation (RIP). PCBP2 was also upregulated in HCC and associated with MVI. High expression of both AC104958.2 and PCBP2 was correlated with tumor size, TNM stage and MVI in HCC. Overexpression of PCBP2 greatly increased the cell viability, metastasis, invasion and EMT. Moreover, actinomycin D assay showed that overexpression of PCBP2 enhanced the RNA stability of AC104958.2. In conclusion, our study showed that a novel lncRNA AC104958.2 exerted oncogenic roles in HCC and might be a promising biomarker and therapeutic target.

Potential carcinogenic heterocyclic aromatic amines (HAAs) in foodstuffs: Formation, extraction, analytical methods, and mitigation strategies.

During the heat treatment of proteinaceous food, heterocyclic aromatic amines (HAAs), a kind of strong mutagens/carcinogens are formed. HAAs can be classified into two major groups based on the heating temperature, which are thermic HAAs generally formed in 150 to 300 °C and pyrolytic HAAs produced above 300 °C. This review focuses on the formation mechanisms of HAAs and identifies different mechanisms of the formation of HAAs in foodstuffs. Moreover, an overview of the available extraction, purification methods, and instrumental analytical methods in the last two decades is shown to determine the HAAs in various foodstuffs. Finally, based on the factors that affect the formation of HAAs in heat-processed foodstuffs, such as the cooking method, food type, the recipe, and the content of substances with enhancing or inhibiting effects on the formation of HAAs, this review also highlights the most promising strategies for mitigating HAAs, which include adjusting cooking methods or process conditions, adding natural product extracts, antioxidants or other compounds, or reasonable selection of types of foodstuff. The review intends to provide a broad but comprehensive understanding of the formation, extraction, purification, analytical methods, and possible mitigation strategies for isolated and identified HAAs.

Cost-effectiveness of second-line nivolumab for platinum-treated advanced non-small-cell lung cancer.

Aim: To analyze the economic impact of nivolumab and chemotherapy in patients with non-small-cell lung cancer (NSCLC) who developed disease progression after platinum-containing dual-drug chemotherapy. Materials & methods: The partitioned survival model was used to analyze the cost-utility of two NSCLC treatments by nivolumab and docetaxel. The clinical data resulted from the Phase III clinical trial. The cost parameters were derived from our previous studies, and the utility parameters were derived from the literature. Results: The quality-adjusted life-years of nivolumab and docetaxel were 0.778 and 0.336. The lifetime direct medical expenses of nivolumab and docetaxel were US$44,707.17 and US$12,826.72. The incremental cost-effectiveness ratio was $72,127.71/quality-adjusted life-year. Conclusion: The combination of chemotherapy, nivolumab is not a cost-effective choice in the second-line treatment of NSCLC.

Combination of Dichloroacetate and Atorvastatin Regulates Excessive Proliferation and Oxidative Stress in Pulmonary Arterial Hypertension Development via p38 Signaling.

Pulmonary arterial hypertension (PAH) is a lethal disease generally characterized by pulmonary artery remodeling. Mitochondrial metabolic disorders have been implicated as a critical regulator of excessively proliferative- and apoptosis-resistant phenotypes in pulmonary artery smooth muscle cells (PASMCs). Dichloroacetate (DCA) is an emerging drug that targets aerobic glycolysis in tumor cells. Atorvastatin (ATO) is widely used for hyperlipemia in various cardiovascular diseases. Considering that DCA and ATO regulate glucose and lipid metabolism, respectively, we hypothesized that the combination of DCA and ATO could be a potential treatment for PAH. A notable decrease in the right ventricular systolic pressure accompanied by reduced right heart hypertrophy was observed in the DCA/ATO combination treatment group compared with the monocrotaline treatment group. The DCA/ATO combination treatment alleviated vascular remodeling, thereby suppressing excessive PASMC proliferation and macrophage infiltration. In vitro, both DCA and ATO alone reduced PASMC viability by upregulating oxidative stress and lowering mitochondrial membrane potential. Surprisingly, when combined, DCA/ATO was able to decrease the levels of reactive oxygen species and cell apoptosis without compromising PASMC proliferation. Furthermore, suppression of the p38 pathway through the specific inhibitor SB203580 attenuated cell death and oxidative stress at a level consistent with that of DCA/ATO combination treatment. These observations suggested a complementary effect of DCA and ATO on rescuing PASMCs from a PAH phenotype through p38 activation via the regulation of mitochondrial-related cell death and oxidative stress. DCA in combination with ATO may represent a novel therapeutic strategy for PAH treatment.

Rapid disease progress in a PVOD patient carrying a novel EIF2AK4 mutation: a case report.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary arterial hypertension (PAH) share an overlapping disease phenotype. Hence it is necessary to distinguish them. CASE PRESENTATION: Our 14-year-old female patient admitted with progressive shortness of breath, dizziness, and fatigue even after minimal physical activity was clinically suspected for PAH, based on her previous history. Her chest computed tomography artery reported the presence of PVOD triad features - subpleural thickened septal lines, ground-glass nodules/opacities and mediastinal lymphadenopathy. Because of her weak physical stature, a lung biopsy was not performed; however, the genetic testing identified a novel heterozygous EIF2AK4 mutation at c.4833_4836dup (p.Q1613Kfs*10) - the dominant susceptible factor driving PVOD. Combination of genetic testing and computed tomography artery facilitated us to distinguish PVOD from PAH. Her disease symptoms advanced aggressively so that she died even before the lung transplantation, which was less than 6 months from the onset of disease symptoms. CONCLUSION: This case report highlights that novel EIF2AK4 mutation at [c.4833_4836dup (p.Q1613Kfs*10)] would predict an aggressive phenotype of PVOD. Hence, we conclude that a genetic test identifying EIF2AK4 mutation would serve as a tool for the early diagnosis of PVOD, circumventing lung biopsy.

In vivo reflectance confocal microscopy for evaluating common facial hyperpigmentation.

BACKGROUND: In clinical settings, atypical facial hyperpigmentation such as nevus of Ota, acquired bilateral nevus of Ota-like macules (ABNOM), melasma, and café-au-lait spots are often missed and misdiagnosed. Summarizing in vivo reflectance confocal microscopy (RCM) features of the hyperpigmentation is helpful in the diagnosis of ambiguous lesions. METHODS: We recruited 196 patients referred for unequivocal facial hyperpigmentation, including 55 patients with nevus of Ota, 45 patients with ABNOM, 62 patients with melasma, and 34 patients with café-au-lait spots. The RCM images were evaluated at the epidermis, the dermis-epidermis junction (DEJ), and the upper papillary dermis from both hyperpigmented patches and normal skin. RESULTS: In the superficial and middle dermis, 41 of 55 patients (74.5%) with nevus of Ota were characterized by a cord-like or lumpy structure between the collagen fibers. And there was no melanin deposition detected in the dermis in 14 of 55 (25.5%) patients. In ABNOM, 37 of 45 (82.2%) patients were characterized by a cord-like or lumpy structure in the superficial dermis and 8 of 45 patients (17.8%) was no melanin deposition detected in the dermis. The epidermis was no difference between nevus of Ota, ABNOM, and the normal skin. Melasma was detected increased cobblestone pattern in the epidermis of all patients, branching architecture in 21 of 62 patients (33.9%), and focally aggregated round to triangular cells in the upper dermis of 18 of 62 patients (29.0%). In all patients with afé-au-lait spots, increased cobblestone pattern in the epidermis and regular and increased density of ringed pattern in the DEJ were visualized. CONCLUSIONS: Our findings indicate that RCM may be useful in the auxiliary diagnosis of nevus of Ota, ABNOM, melasma, and café-au-lait spots.

γ-[Glu](n=1,2)-Phe/-Met/-Val stimulates gastrointestinal hormone (CCK and GLP-1) secretion by activating the calcium-sensing receptor.

This study was conducted to discover the effectiveness of dietary peptides (γ-[Glu](n=1,2)-Phe/-Met/-Val) as stimulators of cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1) secretion. The kokumi-active γ-[Glu](n=1,2)-Phe/-Met/-Val at concentrations of 2.5-10 mM would trigger the release of CCK and GLP-1 by activating the calcium-sensing receptor (CaSR). The CaSR-mediated Ca2+/CaM/CaMK pathway was proposed in γ-[Glu](n=1,2)-Phe/-Met/-Val-induced CCK and GLP-1 secretion based on the following results: the exposure to γ-Glu-Phe increased the protein expression level (western blot analysis), the intracellular calcium ([Ca2+]i) mobilization in response to γ-[Glu](n=1,2)-Phe/-Met/-Val was strongly enhanced, and the inhibitors of signaling pathway proteins (NPS-2143, BAPTA-AM, and KN62) abolished partially γ-[Glu](n=1,2)-Phe/-Met/-Val-induced CCK and GLP-1 secretion.

Increased Risk of Hypertension in Young Adults in Southwest China: Impact of the 2017 ACC/AHA High Blood Pressure Guideline.

PURPOSE OF REVIEW: To examine the impact of the new 2017 ACC/AHA hypertension guideline on the prevalence of hypertension, its constituent ratio, and their associated factors in southwest China. RECENT FINDINGS: A total of 14,220 permanent residents ≥ 18 years were enrolled in this survey. According to the 2017 ACC/AHA hypertension guideline, the hypertension prevalence was substantially increased (46.9% vs. 24.5%); consistent across different age and gender groups, while the hypertension awareness (23.8% vs. 45.6%); treatment (18.6% vs. 35.5%); control (2.3% vs. 11.2%); and control among treatment (9.6% vs. 24.0%) patients were decreased in southwest of China. In our cohort, 31.1% participants were newly diagnosed as hypertension. Young adults accounted considerable proportion in this newly diagnosed hypertension population. The proportion of young hypertensive individuals substantially increased, whereas those of the older hypertensive subjects decreased. Among the hypertensive subjects aged ≥ 65 years undergoing treatment, 90% of the elderly subjects were not eligible for hypertension control and 32.5% have systolic blood pressure control at 130-149 mmHg, and thus need to intensify antihypertensive treatment according to 2017 ACC/AHA hypertension guideline. Smoking, drinking, body fat percentage, and body mass index were considered the factors associated with hypertension according to the Chinese hypertension guideline but not in the 2017 ACC/AHA hypertension guideline. The adoption of the 2017 ACC/AHA hypertension guideline will substantially increase hypertension prevalence in southwest of China. The new definition of hypertension implies that more young adults will likely suffer from high cardiovascular risks, while additional one third of elder hypertensive subjects will likely need intensified antihypertension treatments.