Biodirected Screening and Preparation of Larimichthys crocea Angiotensin-I-Converting Enzyme-Inhibitory Peptides by a Combined In Vitro and In Silico Approach.

Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the Larimichthys crocea protein (LCP) and had low IC50 values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of Larimichthys crocea.

Nomogram for predicting preoperative axillary lymph node status in male breast carcinoma: a SEER population-based study.

Background: Sentinel lymph node biopsy (SLNB) has been recommended as a replacement for axillary lymph node dissection (ALND) in male breast carcinoma (MBC) with clinical axillary lymph node-negative (ALN-negative) as in the case of female. However, the morbidity after SLNB may also have short-term or long-term complications. To avoid unnecessary surgery, building a model which is able to assess the risk of lymph node metastasis is vitally significant. Methods: A retrospective review of the clinical and pathology data were carried out for patients diagnosed with MBC between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation cohorts. A logistic regression model was used to construct the nomogram in the training cohort and then verified in the validation cohort. The receiver operating characteristic (ROC) curve, C-index, and calibration were used to evaluate the predictive ability of the nomogram. Results: Overall, 2,610 patients diagnosed with MBC were included in the study, of which 1,740 were in the training cohort and 870 were in the validation cohort. Logistic regression analysis indicated age at diagnosis, tumor location, tumor stage, pathological type, and histologic grade, were significantly related to axillary lymph node metastasis (ALNM). The area under the curve (AUC) of the nomogram was 0.846 (95% CI: 0.825-0.867) and C-index was 0.848 (95% CI: 0.807-0.889), demonstrating a notable prediction performance. The calibration curve for the nomogram was plotted and the slope was close to 1. The prognostic value of the nomogram was further validated in the validation cohort, with an AUC of 0.848 (95% CI: 0.819-0.877). Conclusions: A nomogram to predict ALNM was successfully established, especially for those who were of advanced age at diagnosis, had small tumor size, displayed low malignancy, and showed clinical ALN-negative, to avoid unnecessary axillary operation. The quality of life for patients is enhanced without conceding the overall survival rate.

The hard problem of consciousness-A perspective from holistic philosophy.

Based on a material view and reductionism, science has achieved great success. These cognitive paradigms treat the external as an objective existence and ignore internal consciousness. However, this cognitive paradigm, which we take for granted, has also led to some dilemmas related to consciousness in biology and physics. Together, these phenomena reveal the interaction and inseparable side of matter and consciousness (or body and mind) rather than the absolute opposition. However, a material view that describes matter and consciousness in opposition cannot explain the underlying principle, which causes a gap in interpretation. For example, consciousness is believed to be the key to influencing wave function collapse (reality), but there is a lack of a scientific model to study how this happens. In this study, we reveal that the theory of scientific cognition exhibits a paradigm shift in terms of perception. This tendency implies that reconciling the relationship between matter and consciousness requires an abstract theoretical model that is not based on physical forms. We propose that the holistic cognitive paradigm offers a potential solution to reconcile the dilemmas and can be scientifically proven. In contrast to the material view, the holistic cognitive paradigm is based on the objective contradictory nature of perception rather than the external physical characteristics. This cognitive paradigm relies on perception and experience (not observation) and summarizes all existence into two abstract contradictory perceptual states (Yin-Yang). Matter and consciousness can be seen as two different states of perception, unified in perception rather than in opposition. This abstract perspective offers a distinction from the material view, which is also the key to falsification, and the occurrence of an event is inseparable from the irrational state of the observer's conscious perception. Alternatively, from the material view, the event is random and has nothing to do with perception. We hope that this study can provide some new enlightenment for the scientific coordination of the opposing relationship between matter and consciousness.

Association of TGF-ß Canonical Signaling-Related Core Genes With Aortic Aneurysms and Aortic Dissections.

Transforming growth factor-beta (TGF-ß) signaling is essential for the maintenance of the normal structure and function of the aorta. It includes SMAD-dependent canonical pathways and noncanonical signaling pathways. Accumulated genetic evidence has shown that TGF-ß canonical signaling-related genes have key roles in aortic aneurysms (AAs) and aortic dissections and many gene mutations have been identified in patients, such as those for transforming growth factor-beta receptor one TGFBR1, TGFBR2, SMAD2, SMAD3, SMAD4, and SMAD6. Aortic specimens from patients with these mutations often show paradoxically enhanced TGF-ß signaling. Some hypotheses have been proposed and new AA models in mice have been constructed to reveal new mechanisms, but the role of TGF-ß signaling in AAs is controversial. In this review, we focus mainly on the role of canonical signaling-related core genes in diseases of the aorta, as well as recent advances in gene-mutation detection, animal models, and in vitro studies.

Stochastic model predictive control framework for resilient cyber-physical systems: review and perspectives.

In the era of Industrial 4.0, the next-generation control system regards the cyber-physical system (CPS) as the core ingredient thanks to the comprehensive integration of physical systems, online computation, networking and control. A reliable, stable and resilient CPS should pledge robustness and safety. A significant concern in CPS development arises from security issues since the CPS is vulnerable to physical constraints, ubiquitous uncertainties and malicious cyber attacks. The integration of the stochastic model predictive control (MPC) framework and the resilient mechanism is a possible approach to guarantee robustness in the presence of stochastic uncertainties and enable resilience against cyber attacks. This review paper aims to offer a detailed overview of existing stochastic MPC algorithms and their CPS applications. More specifically, we first review existing stochastic MPC algorithms for both linear and nonlinear systems subject to probabilistic constraints. We then discuss how to extend the stochastic MPC framework to incorporate resilience mechanisms for constrained CPS under various malicious attacks. Finally, we present an architectural stochastic MPC-based framework for resilient CPS and identify future research challenges. This article is part of the theme issue 'Towards symbiotic autonomous systems'.

Integral-Type Event-Triggered Model Predictive Control of Nonlinear Systems With Additive Disturbance.

This article studies integral-type event-triggered model predictive control (MPC) of continuous-time nonlinear systems. An integral-type event-triggered mechanism is proposed by incorporating the integral of errors between the actual and predicted state sequences, leading to reduced average sampling frequency. Besides, a new and improved robustness constraint is introduced to handle the additive disturbance, rendering the MPC problem with a potentially enlarged initial feasible region. Furthermore, the feasibility of the designed MPC and the stability of the closed-loop system are rigorously investigated. Several sufficient conditions to guarantee these properties are established, which is related to factors, such as the prediction horizon, the disturbance bound, the triggering level, and the contraction rate for the robustness constraint. The effectiveness of the proposed algorithm is illustrated by numerical examples and comparisons.

Erchen Decoction Mitigates Lipid Metabolism Disorder by the Regulation of PPARγ and LPL Gene in a High-Fat Diet C57BL/6 Mice Model.

Erchen decoction (ECD) is a common treatment prescribed in traditional Chinese medicine (TCM) clinics, which has remarkable efficacy in the treatment of obesity, fatty liver, hyperlipidemia, diabetes, and other diseases caused by phlegm. In this study, we investigated the effect that ECD had on the lipid metabolism induced by high-fat diet in C57BL/6 mice. Body weight, body length, and abdominal circumference were detected. Blood lipid content was measured via biochemical assay kit. The gene and protein expression of PPARγ and LPL in visceral fat and skeletal muscle of mice was measured by real-time PCR and western blot. The research discovered that the phlegm-resolving effect that ECD had on high-fat diet mice was mainly manifested as reduced body weight, Lee's index, abdominal circumference, and level of TG and TC. Meanwhile, we observed significantly increased PPARγ mRNA and protein level in visceral fat and PPARγ and LPL protein level in skeletal muscle in the ECD group. Contrarily, a decrease in PPARγ mRNA level in skeletal muscle in the ECD group was observed. Therefore, we speculate that ECD regulates the lipid metabolic disorder by decreasing the blood lipid level. Moreover, the potential molecular mechanism of ECD is to promote the expression of PPARγ in visceral fat and skeletal muscle and the expression of LPL in skeletal muscle.

Effect of roasting and in vitro digestion on phenolic profiles and antioxidant activity of water-soluble extracts from sesame.

The effects of roasting and in vitro digestion on total phenolic content (TPC), total flavonoid content (TFC), phenolic profiles, and antioxidant activity of water-soluble extracts from six varieties of sesame were investigated in this study. Our results showed that the major phenolic compounds in raw, roasted and digested sesame were gallic acid (GA), protocatechuic acid (PA), 4-hydroxybenzoic acid (4 HBA), ferulic acid (FA) and quercetin (Quer). Roasting significantly increased the TPC, pinoresinol diglucoside (PD), sesamol, as well as the content of phenolic compounds (especially GA, PA, 4 HBA and Quer) in sesame, but kept or reduced the TFC, sesamin and sesamolin. After roasting, the antioxidant potency composite index (ACI) of six varieties of sesame was significantly increased by 29.8%-216.6%. Additionally, the ACI of gastric digestion was significantly higher than that of oral and intestinal digestion during the in vitro digestion of the roasted-sesame, except for the varieties of Ganzhi 9 and Ganzhi 17. This study showed that five phenolic compounds (GA, PA, 4 HBA, p-coumaric acid, Quer) and sesamol of the water-soluble extracts contributed to the antioxidant activities of the digestive products of sesame.

Fabrication of Ligusticum chuanxiong polylactic acid microspheres: A promising way to enhance the hepatoprotective effect on bioactive ingredients.

Ligusticum chuanxiong extract-polylactic acid sustained-release microspheres (LCE-PLA) are fabricated in this study for enhancing both duration and hepatoprotective efficacy of the main bioactive ingredients. LCE-PLA in vitro release, cytotoxicity and in vivo hepatoprotective effect were discussed to evaluate its efficiency and functionality. Results demonstrated that the optimal drug-loading rate and encapsulation efficiency of tetramethylpyrazine (TMP, the main active ingredient) were 8.19%, 83.72%, respectively. The LCE-PLA in vitro release of TMP showed prolong 5-fold and in vitro cytotoxicity declined 25.00% compared with naked LCE. After 6 weeks of in vivo intervention in high fat diet mice, both liver aspartate aminotransferase and alanine aminotransferase levels were higher in LCE-PLA group than LCE group. The above results indicated that TMP had a higher bioavailability of hepatoprotection when encapsulation of LCE-PLA was applied. The current study has provided a promising novel way to enhance the efficacy of short half-life ingredients.

Minimally invasive management of acute ureteral obstruction and severe infection caused by upper urinary tract calculi.

PURPOSETo evaluate therapeutic efficacy of two minimally invasive surgical methods in managing acute ureteral obstruction and severe infection caused by upper urinary tract calculi (UUTC).PATIENTS AND METHODSData of 47 patients diagnosed with acute upper urinary tract obstruction and severe infection caused by ureteral calculus using X-ray CT between September 2014 and January 2019 were retrospectively analyzed. All patients were treated with immediate renal drainage and, after infection and ureteral obstruction were relieved, UUTC removal. Renal drainage was performed by ultrasound-guided percutaneous nephrostomy and retrograde ureteral catheterization was performed using cystoscopy. Kidney and ureteral stones were removed; renal function and the urinary tract were examined by X-ray during follow-up.RESULTSPercutaneous nephrostomy was performed in 29 patients in a critical condition including intolerance to surgery, high-grade hydronephrosis, or failure of retrograde ureteric stent placement. In other 18 patients diagnosed with small stones (≤10 mm) and low-grade hydronephrosis, indwelling double-J ureteral stents were temporally installed by a cystoscope. Acute infection and ureteral obstruction were relieved; white blood cell counts returned to normal values within 3 to 7 days after drainage in all patients. In the second-stage treatment, percutaneous nephrolithotomy (PCNL), ureteroscopic lithotripsy, extracorporeal shock wave lithotripsy and nephrectomy were performed in 24, 10, 8 and 5 patients, respectively. No patients developed severe complication after stone removal surgery. All patients were followed up for 3 months to 4.5 years. Renal function was significantly recovered; 17/29 (59%) patients with elevated serum creatinine returned to normal and serum creatinine in 12/29 (41%) patients improved significantly after drainage, with a pre-operation level of 285±169µM vs 203±91µM post-operation (P = 0.014). Five patients were lost during follow-up.CONCLUSIONThis study demonstrated an optimal approach for relieving upper urinary tract obstruction and acute infection in which percutaneous nephrostomy drainage is preferred for patients with severe pyonephrosis, large stones (>10 mm) with high-grade hydronephrosis, steinstrasse, or failure in retrograde ureteric stent placement, while retrograde ureteral catheterization using cystoscopy is suitable for patients diagnosed with small stones (≤10 mm) and low-grade hydronephrosis.

Challenges in the diagnosis of calyceal diverticulum: A report of two cases and review of the literature.

BACKGROUND: Calyceal diverticula outpouchings that occur rarely in the upper collecting system of the kidney and is often difficult to detect. In this study, we present two cases of calyceal diverticula and discuss their clinical characteristics and radiologic features. PATIENTS AND METHODS: In the presented two cases, we applied several imaging examinations, including delayed intravenous pyelography, retrograde pyelography and axial computerized tomographic (CT) scanning of the kidneys with and without contrast. Serum creatinine levels in fluid withdrawn from the diverticula were found to be significantly higher than the simultaneous serum creatinine levels. Intravenous injection of methylene blue through a ureteral catheter was also aided in the diagnosis. Calyceal diverticulum neck dilatation was performed through a percutaneous nephroscope.ResultsThe two cases were diagnosed preoperatively and the operation was successful performed. The nephrostomy tube was removed seven days after surgery without complications. CT scans of the kidney after six months showed that the size of the calyceal diverticulum of two patients were considerably smaller than pre-surgery. There were no reports of pain in the lumbar region or other discomfort. COMMENTS: Diagnosis of calyceal diverticulum mainly depend on a variety of imaging examinations, including the delayed intravenous pyelography, retrograde pyelography, and kidney CT plain scan plus enhanced scan. If the patient cannot be diagnosed by above methods, cyst fluid can be aspirated percutaneously to measure the preoperative creatinine level. If it is significantly higher than the serum creatinine level, the cyst fluid is considered urine, which can assist in the diagnosis of calyceal diverticulum. A ureteral catheter should also be inserted before operation namely, intravenous injection of methylene blue through a ureteral catheter is helpful for diagnosis. The choice of surgical treatment is based on the size and location of calyceal diverticulum and clinical manifestations.

A potential role of TLR2 in xenograft rejection of porcine iliac endothelial cells: An in vitro study.

BACKGROUND: Porcine vascular endothelial cells are a major participant in xenograft rejection. The Toll-like receptor 2 (TLR2) pathway plays an important role in both innate and adaptive immunity. The specific role of TLR2 in the response to a xenograft has not been reported. Whether the TLR2 pathway in pig vascular endothelial cells is involved in acute rejection needs to be investigated, and the mechanism is explored. METHODS: We used a modified antibody-dependent complement-mediated cytotoxicity (ADCC) assay to conduct in vitro experiments. In porcine iliac artery endothelial cells (PIECs), siRNA was used to knock down the expression of TLR2, CXCL8, and CCL2. The effect of human serum or inactivated human serum on the expression of TLR2 was analyzed by real-time PCR and Western blotting, and transwell assays were used to assess the chemotactic efficiency of PIECs on human monocyte-macrophages (THP-1 cells) and human neutrophils. The downstream signaling pathways activated by human serum were detected by Western blotting, and the regulation of proinflammatory chemokines and cytokines by TLR2 signaling was assessed by real-time PCR and ELISA. RESULTS: TLR2 was significantly upregulated in PIECs after exposure to human serum, and porcine proinflammatory chemokines, CXCL8 and CCL2, were induced, at least partially, in a TLR2-dependent pattern; the upregulated chemokines participated in the chemotaxis of human neutrophils and THP-1 cells across the species barrier. CONCLUSIONS: (i) TLR2 is significantly upregulated in PIECs by human serum, (ii) the elevated TLR2 participates in the chemotaxis of inflammatory cells through the secretion of chemokine CCL2 and CXCL8, and (iii) blockade of TLR2 would be beneficial for xenograft survival.

Effects of thermal preparation and in vitro digestion on lignan profiles and antioxidant activity in defatted-sesame meal.

Defatted-sesame meal (DSM), a byproduct of sesame oil, has attracted considerable interest in the food industry because of its strong antioxidant activity. The aim of this study was to measure the content and distribution of lignans in DSM and evaluate their antioxidant activity after thermal processing and in vitro digestion. The results showed that the sesame lignans (SL) content and antioxidant activity were significantly influenced by the temperature and time during thermal preparation, and the maximum antioxidant potency composite index (ACI) was obtained after roasting the samples at 240 °C for 20 min. As sesame seed was processed with longer time and higher temperature, more pinoresinol diglucoside (PD) and sesamol were measured in DSM. According to the correlation matrix under thermal preparation, a significant contribution to the antioxidant potency of DSM was discovered. After in vitro digestion, the release amount of lignans increased by 19.6%, and the values of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and ACI gradually declined after digestion, with a 40% decrease in both the DPPH radical scavenging activity and the ACI from oral to intestinal phase. These results could be used to help improve the bioavailability of SL and obtaining high quality sesame byproducts.

Enhanced functional properties of biopolymer film incorporated with curcurmin-loaded mesoporous silica nanoparticles for food packaging.

Curcumin loaded mesoporous silica nanoparticle (SBA-15) was incorporated into chitosan (CS) film to improve the functional properties of pure CS film. Curcumin was loaded into SBA-15 (SBA-15-Cur) through a rotavapor method. The structural properties of SBA-15-Cur were characterised in detail by small-angle X-ray scattering, fourier transform-infrared (FT-IR) spectroscopy, transmission electron microscopy and N2 adsorption-desorption analyses. The CS/SBA-15-Cur bionanocomposite film was prepared by solvent casting. The mechanical properties of the bionanocomposite film were improved by the addition of the SBA-15-Cur nanofiller, as revealed by the FT-IR analysis of the biocomposite film. However, the water vapour permeability of the films was not significantly influenced by the filler. Release studies suggested that the CS/SBA-15-Cur bionanocomposite film exhibited pH-responsive and sustained release behaviour of curcumin. The CS/SBA-15-Cur film demonstrated efficient antimicrobial activity against Staphylococcus aureus and Escherichia coli. These data indicated that the CS/SBA-15-Cur bionanocomposite film could be a promising active food packaging material.

Drug repurposing: Ibrutinib exhibits immunosuppressive potential in organ transplantation.

Long-term administration of classic immunosuppressants can induce severe adverse effects. The development of novel immunosuppressants confronts great challenges and opportunities. Ibrutinib, an approved drug for B-cell lineages and chronic graft versus host disease (cGVHD), exhibits immunosuppressive efficacy in autoimmune diseases. Ibrutinib's potential as an immunosuppressant in organ transplantation has not been investigated to date. In a xeno-artery patch model ex vivo, ibrutinib inhibited the proliferation of PBMCs (POD 14-42), mainly CD3+CD4+ and CD3+CD8+ T cells ex vivo. The secretion of cytokines (IL-6, IL-2 and IFN-γ) was suppressed in response to ibrutinib. In allo-skin transplantation models, ibrutinib delayed the rejection of grafted skins. Ibrutinib decreased the amount of T/B cells and lymphocyte infiltration. Altogether, ibrutinib exhibited immunosuppressive potential through cytokine regulation and T cell inhibition ex vivo and in vitro. Repositioning of ibrutinib as an immunosuppressant will greatly facilitate novel immunosuppressant development.

Porcine IL-6, IL-1ß, and TNF-α regulate the expression of pro-inflammatory-related genes and tissue factor in human umbilical vein endothelial cells.

Whether porcine cytokines are induced after pig-to-primate xenotransplantation and activate human cells remains unknown. First, we investigated the regulation of porcine IL-6, IFN-γ, IL-1ß, and TNF-α in xenotransplantation using an in vitro model in which porcine aortic endothelial cells (PAECs) and porcine peripheral blood mononuclear cells (PBMCs) were stimulated with human serum. Downstream cytokines/chemokines were monitored. Pro-inflammatory cytokines (IL-6, IFN-γ, and IL-1ß) and chemokines (IL-8, MCP-1, and CXCL2) were upregulated in the both cell types. TNF-α was induced 10-fold in PAECs, but not in PBMCs. Then, we assessed the role of porcine IL-6, IFN-γ, IL-1ß, and TNF-α in xenotransplantation using western blotting and real-time PCR. Human umbilical vein endothelial cells (HUVECs) were selected as the target cells. Signaling pathways and downstream genes, such as those related to adhesion, inflammation, and coagulation, and chemokines were investigated. Porcine IL-1ß and TNF-α significantly activated NF-κB and P38, and STAT3 was activated by porcine IL-6 in HUVECs. The adhesion genes (E-selectin, VCAM-1, and ICAM-1), inflammatory cytokines (IL-6, IL-1ß, and TNF-α), chemokines (MCP-1 and IL-8), and the pro-coagulation gene (tissue factor) were upregulated by porcine IL-1ß and TNF-α. Porcine IL-6 increased the expression of ICAM-1, IL-6, MCP-1, and tissue factor, but decreased IL-8 expression slightly. Surprisingly, porcine IFN-γ could not activate STAT1 or regulate the expression of any of the above genes in HUVECs. In conclusion, these findings suggest that porcine IL-6, IL-1ß, and TNF-α activate HUVECs and regulate downstream genes expression, which may promote inflammation and coagulation response after xenotransplantation.

Simultaneous determination of four sesame lignans and conversion in Monascus aged vinegar using HPLC method.

A simple, accurate and specific high-performance liquid chromatography (HPLC) method has been developed and validated for simultaneous determination of sesamol, sesamin, asarinin and sesamolin in Monascus aged vinegar. The effects of acid hydrolysis and four heating treatments on the components content in Monascus aged vinegar were discussed. The results showed that the isomerisation of sesamin to asarinin, and decomposition of sesamolin to sesamol significantly increased, regardless of heating or acid hydrolysis. Thermal processes and acid hydrolysis increased the content of sesamol and asarinin, respectively, but severe thermal processes resulted in the loss of total sesame lignans. Sesamol and asarinin reached the highest (2.720 ±â€¯0.202 µg/mL and 2.064 ±â€¯0.075 µg/mL) for autoclaving (125 °C, 15 min) and acid hydrolysis (25 °C, 15 min, nature pH), respectively. Therefore, autoclaving and acid hydrolysis were considered as the optimal way to obtain higher content of sesamol and asarinin.

Evaluation of antioxidant activities of ethanol extract from Ligusticum subjected to in-vitro gastrointestinal digestion.

The Rhizome of Ligusticum chuanxiong Hort, a traditional Chinese medicine, is widely used to treat cardiovascular diseases and attenuate oxidative stress. The main bioactive compounds including tetramethylpyrazine (TMP), polyphenols, ferulic acid have been reported to be responsible for these effects. This study was to evaluate the influence of Ligusticum chuanxiong extraction (LCE) in mimic gastrointestinal tract on antioxidant activity. The effects of gastric digestion group metabolic liquid on free radical scavenging followed as DPPH > ·O2- > ·OH, while the clearance effects of intestine digestion group expressed as ·O2-> ·OH > DPPH. Furthermore, the digested extraction promoted lower cellular antioxidant activity (CAA) with dose-response correlations. Gastrointestinal digestion increased the release of bound ferulic acids and polyphenols. Content of ferulic acid in gastric and intestinal metabolic solution increased from 6.07 mg/g to 9.33 mg/g and 14.17 mg/g. The free phenolic before and after digestion were 177.38 mg/g, 179.69 mg/g and 194.99 mg/g, respectively. The simulated gastrointestinal digestion of LCE promoted a significant increase in the free phenolic acids content, antioxidant activity and CAA.

TRPM8 activation improves energy expenditure in skeletal muscle and exercise endurance in mice.

Skeletal muscle serving as the major organ is responsible for energy expenditure and exercise endurance, which directly influence cardiometabolic risk factors. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the energy metabolism of adipocytes. However, the involvement of TRPM8 in the energy metabolism of skeletal muscle remains unexplored. Our data revealed that TRPM8 was expressed in cultured C2C12 myocytes. Menthol treatment increased uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) expression in C2C12 myotubes through TRPM8 activation. Moreover, dietary menthol upregulated the expression of UCP1 and PGC1α in skeletal muscle of mice. In addition, dietary menthol enhanced exercise endurance and reduced blood lactic acid and triglycerides through TRPM8 activation. It is concluded that dietary menthol improves energy metabolism and exercise endurance by increasing UCP1 and PGC1α in skeletal muscles, suggesting dietary menthol might be a novel therapeutic approach for cardiometabolic diseases management and prevention.