Developing industry-scale microfluidization for cell disruption, biomolecules release and bioaccessibility improvement of Chlorella pyrenoidosa.

To facilitate biomolecules extraction and bioaccessibility of Chlorella pyrenoidosa, a novel industry-scale microfluidization (ISM) was used to disrupt cells effectively. Microscope images showed ISM damaged cell integrity, disorganized cell wall structure, pulverized cell membrane and promoted the release of intracellular components. The decrease of particle size and the increase of ζ-potential also confirmed the cell disruption. The cell breakage ratio of sample treated at 120 MPa was 98%. Compared with untreated samples, total soluble solid content and protein extraction rate of the sample treated at 120 MPa increased by 2 °Brix and 12%. Protein was degraded by ISM, the release of intracellular protein and the reduction of molecular weight increased protein digestibility by 20% in in vitro gastric phase. Lipid yield and chlorophyll b content were also increased by ISM. These results provided a new solution to cell disruption of microalgae and expanded the application field of ISM.

The Status Quo and Influencing Factors of Care Activities and Support Behaviors of the Main Caregivers of Stroke Patients During the Transition Period from Discharge.

Objective: This study investigated stroke patients and their primary caregivers, examining the impact of stroke events on caregivers and families, identifying factors affecting burden levels, and proposing measures to improve caregivers' quality of life and reduce family burden. Methods: This study adopted a questionnaire method, which includes a general information questionnaire, a patient self-care ability evaluation scale (Barthel index), a caregiver needs evaluation scale, and a social support evaluation scale (SSRS). Results: A total of 163 primary caregivers, mostly spouses or children of the patients, participated with an average age of 55.99 ± 11.92 years. A significant portion (36.81%) provided care alone for an average of 6.06 years. Social support received by caregivers was generally low, with only 1.84% reporting high support. 90.13% of caregivers experienced varying levels of burden, with 61.35% experiencing mild burden, 25.15% moderate burden, and 3.68% severe burden. Conclusion: The study concluded that China's nursing system for stroke patients is inadequate, relying heavily on family members for rehabilitation.

2-phenylacetamide Separated from the seed of Lepidium apetalum Willd. inhibited renal fibrosis via MAPK pathway mediated RAAS and oxidative stress in SHR Rats.

BACKGROUND: Renal fibrosis with Renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress are one of the major complications in hypertension. 2-phenylacetamide (PA), a major active component of Lepidium apetalum Willd. (L.A), has numerous pharmacological effects. Its analogues have the effect of anti-renal fibrosis and alleviating renal injury. This study aims to explore the underlying mechanism of PA for regulating the renal fibrosis in SHR based on the MAPK pathway mediated RAAS and oxidative stress. METHODS: The SHR rats were used as the hypertension model, and the WKY rats were used as the control group. The blood pressure (BP), urine volume were detected every week. After PA treatment for 4 weeks, the levels of RAAS, inflammation and cytokines were measured by Enzyme-Linked Immunosorbnent Assay (ELISA). Hematoxylin-Eosin staining (HE), Masson and Immunohistochemistry (IHC) were used to observe the renal pathology, collagen deposition and fibrosis. Western blot was used to examine the MAPK pathway in renal. Finally, the SB203580 (p38 MAPK inhibitor) antagonism assay in the high NaCl-induced NRK52e cells was used, together with In-Cell Western (ICW), Flow Cytometry (FCM), High Content Screening (HCS) and ELISA to confirm the potential pharmacological mechanism. RESULTS: PA reduced the BP, RAAS, inflammation and cytokines, promoted the urine, and relieved renal pathological injury and collagen deposition, repaired renal fibrosis, decreased the expression of NADPH Oxidase 4 (NOX4), transforming growth factor-ß (TGF-ß), SMAD3 and MAPK signaling pathway in SHR rats. Meanwhile,,the role of PA could be blocked by p38 antagonist SB203580 effectively in the high NaCl-induced NRK52e cells. Moreover, molecular docking indicated that PA occupied the ligand binding sites of p38 MAPK. CONCLUSION: PA inhibited renal fibrosis via MAPK signalling pathway mediated RAAS and oxidative stress in SHR Rats.

Effects of cell wall polysaccharides on the bioaccessibility of carotenoids, polyphenols, and minerals: an overview.

Carotenoids, polyphenols, and minerals (CPMs) are representative bioactive compounds and micronutrients in plant-based foods, showing many potentially positive bioactivities. Bioaccessibility is a prerequisite for bioactivities of CPMs. Cell wall polysaccharides (CWPs) are major structural components of plant cell wall, and they have been proven to affect the bioaccessibility of CPMs in different ways. This review summarizes recent literatures about the effects of CWPs on the bioaccessibility of CPMs and discusses the potential mechanisms. Based on the current findings, CWPs can inhibit the bioaccessibility of CPMs in gastrointestinal tract. The effects of CWPs on the bioaccessibility of polyphenols and minerals mainly attributes to bind between them, while CWPs affect the bioaccessibility of carotenoids by changing the digestive environment. Further, this review overviews the factors (environmental conditions, CWPs properties and CPMs characteristics) affecting the interactions between CWPs and CWPs. This review may help to better design healthy and nutritious foods precisely.

Metabolomic strategies and biochemical analysis of the effect of processed Rehmanniae radix extract on a blood-deficient rat model.

BACKGROUND: Rehmanniae Radix (RR), an herb with numerous pharmacological effects, is widely used in traditional Chinese medicine for the treatment of blood deficiency syndrome, either alone or in combination with other herbs. However, the mechanism by which processed Rehmanniae Radix (PRR) improves blood enrichment efficacy has not been clearly defined. METHODS: Ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) and biochemical methods were combined to explore the hematopoietic functional mechanisms of PRR on blood deficiency in a rat model, as well as the potential active ingredient for blood enrichment efficacy. The pharmacological effects of PRR were evaluated on a rat blood deficiency model induced by cyclophosphamide in combination with 1-acetyl-2-phenylhydrazine. The blood routine index, including white blood cell (WBC), red blood cell (RBC), and platelet (PLT) counts, as well as hemoglobin (HGB) level, and the changing metabolite profile based on urine and serum were assessed. Nontargeted metabolomic studies, combined with biochemical analyses, were employed to clarify pharmacological mechanisms. RESULTS: PRR significantly increased the blood routine index levels and reversed the levels of SOD, GSH, and ATP. The PRR group was similar to the control group, as determined from the metabolic profile. All of the 60 biomarkers, representing the typical metabolic characteristics of the blood-deficient rat model, mainly involved energy metabolism dysfunction, the peripheral circulation system, and oxidative damage in the body. This improvement may be attributed to changes in polysaccharide and sixteen non-polysaccharide compounds in PRR, which were caused by processing RR with rice wine. CONCLUSIONS: The strategies of integrated metabolomic and biochemical analyses were combined, revealing the biological function and effective mechanism of PRR.

Mutation of Beclin1 acetylation site at K414 alleviates high glucose-induced podocyte impairment in the early stage of diabetic nephropathy by inhibiting hyperactivated autophagy.

BACKGROUND: Our group recently reported that a mutation of the novel Beclin1 K414R acetylation site impacts the stability of Beclin1 protein, which decreases autophagy in adipocytes and further impedes adipocyte differentiation and lipolysis. This study was to explore whether Beclin1 acetylation plays a role in the early renal injury induced by high glucose and to further investigate the K414R mutation site in podocytes. METHODS: Male Sprague-Dawley rats were randomized to con (control) and diabetic nephropathy (DN) groups. The DN group was induced by a single 55 mg/kg intraperitoneal injection of streptozotocin and fed a high-fat and high-sugar diet (the con group received an equal volume of the vehicle and fed a plain diet), after 3 days of induction, blood glucose levels were measured to confirm the onset of diabetes. Then, at weeks 0 and 4, the biochemical index was assayed and renal cortex tissues were harvested. MPC5 podocytes were cultured in vitro. Beclin1 (K414R)-pLVX-ZsGreen1-N1(wild-type or mutant) lentiviral plasmids were transfected into podocytes. Western blot or immunoprecipitation was used to test proteins or the acetylation levels respectively, and immunohistochemistry was used to analyze morphological changes of podocytes. Immunofluorescence was used to detect the aggregation of LC3 puncta. RESULTS: The acetylation level of Beclin1 was upregulated with podocyte injury exacerbated in high glucose at 24 h and that a mutation at K414R could inhibit hyperactivated autophagy, which ameliorated podocyte impairment. CONCLUSION: These findings suggest that the acetylation site at K414 is a critical molecule and drug target and that further research into this area is warranted.

A low follicle-stimulating hormone level is a protective factor for non-alcoholic fatty liver disease in older men aged over 80.

PURPOSE: Recent studies have suggested the significant relationship between follicle-stimulating hormone (FSH) and non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. However, it is unknown whether FSH impacts the risk of NAFLD in men. This study aimed to investigate the association between serum FSH levels and NAFLD in elderly Chinese men aged 80-98, a particular group with worse outcomes of NAFLD. PATIENTS AND METHODS: A cross-sectional analysis was performed in 444 subjects in a geriatric health center. The highest quartile of serum FSH was used as reference. Hepatic steatosis was defined according to the results of liver ultrasound. Fibrosis-4 (FIB-4) Index > 2.67 was defined as advanced fibrosis. RESULTS: Based on liver ultrasound, 108 (24.3%) subjects had NAFLD. FSH level were negatively correlated with total testosterone, estradiol, nutritional risk, and the prevalence of high education level (all P < 0.01), and positively correlated with age, luteinizing hormone, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The correlation between FSH and body mass index or antihypertensive drug usage was marginally significant (P = 0.057; P = 0.066, respectively). The percentage of subjects with NAFLD had a trend to increase following the quartiles of serum FSH (20.0% in quartile 1, 18.2% in quartile 2, 27.3% in quartile 3, and 31.6% in quartile 4). After adjustment for common pathogenic risk factors, nutritional risk, and other sex hormones, serum FSH were progressively associated with odds ratios for NAFLD. The adjusted odds ratios and 95% CIs for quartile 1, quartile 2, and quartile 3, compared with quartile 4 were 0.132 (0.034-0.516), 0.190 (0.052-0.702), and 0.404 (0.139-1.173), respectively. Obesity was not involved in the potential negative role of circulating FSH on the risk of NAFLD in our population. Furthermore, our results revealed no significant association between FSH and advance fibrosis, the OR (95% CI) for advanced fibrosis was 1.018 (0.983-1.054) (P = 0.316) after adjusting for the potential covariates, although a positive correlation of FSH and FIB-4 score was observed (r = 0.325, P = 0.001). CONCLUSION: Low FSH level may decrease the risk of NAFLD in elderly Chinese men. These findings warrant replication in more extensive studies.

The nephroprotective effects and mechanisms of rehmapicrogenin include ROS inhibition via an oestrogen-like pathway both in vivo and in vitro.

BACKGROUND: The root of Rehmannia glutinosa (R. glutinosa) is commonly used in various traditional Chinese herbal formulae to ameliorate nephropathy; however, little is known about its active component(s) and mechanisms. AIM: In the present study, we examined the protective effect and potential mechanism of rehmapicrogenin, a monomeric compound extracted from R. glutinosa, against Adriamycin (ADR)-induced nephropathy (AN) in vivo and in vitro. METHODS: In this study, an ADR-induced kidney injury model was employed to investigate the nephroprotective effects of rehmapicrogenin in mice. In vivo, ELISA kits, flow cytometry, haematoxylin-eosin staining, immunofluorescence techniques, and western blotting were used to evaluate the effect of rehmapicrogenin on kidney injury in mice. In vitro, the effects of rehmapicrogenin on NRK-52E cellular damage induced by ADR were determined using the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The mechanism was investigated using ELISA kits, flow cytometry and In-Cell Western™ blotting. RESULTS: In vivo, rehmapicrogenin treatment significantly attenuated the pathological changes in the kidney induced by ADR; rescued weight, serum creatinine (Scr), blood urea nitrogen (BUN) and urine albumin (U-ALB) levels; reduced reactive oxygen species (ROS) accumulation; and decreased oxidative stress, the apoptosis rate, and cell survival in ADR-treated mice. Importantly, both in vivo and in vitro experimental results demonstrated that rehmapicrogenin regulates the Nrf2/ARE signalling pathway, the most important pathway for oxidative stress. Rehmapicrogenin attenuated ADR-induced kidney damage by reducing oxidative stress through the oestrogen receptor pathway. Moreover, after treatment with ICI 182780 (the oestrogen receptor-nonspecific antagonist Faslodex), the improvement induced by rehmapicrogenin was significantly reversed. CONCLUSIONS: In conclusion, rehmapicrogenin attenuates kidney damage by reducing inflammatory factor release through the oestrogen signalling pathway.

Association Between Serum Follicle-Stimulating Hormone and Sarcopenia and Physical Disability Among Older Chinese Men: Evidence From a Cross-Sectional Study.

Background: Sarcopenia is a geriatric syndrome characterized by progressive loss of muscle mass, function and quality and associated with a range of adverse health outcomes including disability. Despite a negative correlation between muscle mass and follicle-stimulating hormone (FSH) levels in postmenopausal women, it is unclear if FSH is associated with sarcopenia and its poor outcomes, especially in older men. Methods: We used cross-sectional data from 360 men aged over 80 who participated in health check-ups to investigate correlations between serum FSH and sarcopenia, individual sarcopenia components, low physical performance (gait speed ≤ 0.8 m/s) and instrumental activities of daily living (IADL) disability. Sarcopenia and severe sarcopenia were diagnosed according to the revised definition of the European Working Group on Sarcopenia in Old People (EWGSOP2). Results: The prevalence of sarcopenia was 17.8% in this population. In binary logistic regression analysis, compared with higher FSH group, lower FSH group showed a significant reduction in the risk of low calf circumference (a surrogate for muscle mass; OR 0.308, 95% CI 0.109-0.868, P = 0.026) after adjusting potential confounders including age, waist circumference, education, exercise, associated biochemical parameters, other sex hormones and high-sensitivity C-reactive protein. The correlation between FSH and low handgrip strength was marginally significant (OR 0.390, 95% CI 0.151-1.005, P = 0.051). No associations were observed between FSH and sarcopenia, severe sarcopenia, and disability in adjusted models. Conclusion: In older men, circulating FSH was not associated with sarcopenia, sarcopenia severity, the majority of its components and adverse health outcome (IADL disability), with the exception of low calf circumference. Further work is needed to better elucidate the association of FSH and low muscle quantity by adopting more accurate measurement method of appendicular skeletal muscle mass such as DXA, CT or MRI.

Oligosaccharides composition of Descurainiae sophia exerts anti-heart failure by improving heart function and water-liquid metabolism in rats with heart failure.

PURPOSE: To investigate the protective effect of Oligosaccharides composition of Descurainiae sophia on doxorubicin-induced heart failure in rats, and to study its mechanism. METHOD: A rat model of heart failure was established in 180-220 g male Sprague-Dawley rats by low-dose intraperitoneal injection of doxorubicin for 6 weeks. Four weeks after continuous administration, echocardiography was used to detect left ventricular end diastolic diameter (LVEDD) and end systolic diameter (LVESD) in each group, and left ventricular short axis shortening rate (LVFS) and ejection fraction (LVEF) were calculated. ELISA method was used to detecte the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), troponin I (cTnI), creatine kinase (CK), angiotensin II (Ang II), aldosterone (ALD), arginine pressurization AVP, Renin, Endothelin (ET-1), Nitric Oxide (NO), AQP2 in urine. 6 h cumulative urine output was measured by metabolic cage method after administration for 3 weeks. The urine osmotic pressure was measured by freezing point method. The expression of AQP2 protein in kidney was detected by Western blot method. The changes of myocardial morphology were observed. RESULTS: Compared with the normal control group, the heart rate of the model group was significantly increased (P < 0.01). LVESD and LVEDD were significantly increased (P < 0.01), LVEF and LVFS were significantly decreased (P < 0.01). The levels of CK, cTnI, NO, ET-1, BNP, ANP, ALD, AngII, Renin, AQP2, AVP and osmotic pressure were significantly increased (P < 0.01). Urine output was significantly decreased (P < 0.01). The heart HE showed obvious lesions. Compared with the model group, the Oligosaccharides composition of Descurainiae sophia significantly reduced the heart rate (P < 0.05), decreased LVESD and LVEDD (P < 0.01 or P < 0.05), and increased LVFS and LVEF values (P < 0.01). Oligosaccharides composition of Descurainiae sophia could significantly improve pathological damage of the heart, decrease the levels of cTnI, BNP, AngII, ALD, Renin, AVP in the serum, osmotic pressure and AQP2in the urine (P < 0.01 or P < 0.05), down-regulate the expression of AQP2 protein in the renal(P < 0.01), increase urine volume (P < 0.05). CONCLUSION: Oligosaccharides composition of Descurainiae sophia can significantly improve cardiac function and the disorder of water metabolism in rats with heart failure. Oligosaccharides composition of Descurainiae sophia exerts anti- heart failure through the RAAS system and the arginine vasopressin system.

Geniposide in Gardenia jasminoides var. radicans Makino modulates blood pressure via inhibiting WNK pathway mediated by the estrogen receptors.

OBJECTIVES: To investigate the effects of geniposide in an iridoid found in Gardenia jasminoides var. radicans Makino (GJRM) in spontaneous hypertensive rat (SHR) and explore the possible mechanisms. METHODS: In this study, we detected the content of geniposide in GJRM by high-performance liquid chromatography (HPLC). Then, we used acute diuretic experiments to determine whether geniposide has diuretic effect. Moreover, we carried out experiments on SHR to further study the mechanism of hypertension, while real-time PCR, Western blot and immunohistochemistry were used for the experiments in vivo test. Hypotonic model was used for in vitro test. KEY FINDINGS: Our data showed that the content of geniposide in the extract of GJRM is 27.54%. Meanwhile, 50 mg/kg geniposide showed the strongest effect on promoting urine volume. Further study indicated that the extract of GJRM and geniposide could significantly reduce blood pressure and promote the excretion of urine and Na+ in SHR. In addition, geniposide significantly inhibited the activation of the with-no-lysine kinase (WNK) signalling pathway and significantly increases the protein expressions of estrogen receptor α (ERα), estrogen receptor ß (ERß) and G protein-coupled receptor 30 (GPR30) in SHR. In hypotonic model, geniposide significantly inhibits the phosphorylation of NKCC and NCC and could be antagonistic to estrogen receptor antagonists. CONCLUSIONS: Collectively, we would suggest that geniposide may potentially be utilized as an adjunct to existing thiazide and thiazide-like diuretics to control hypertension, mainly through inhibiting the activation of the WNK signalling pathway mediated by the estrogen receptor.

Comparison of the value of malnutrition and sarcopenia for predicting mortality in hospitalized old adults over 80 years.

OBJECTIVE: This study aimed to compare the prognostic value of malnutrition and sarcopenia for mortality in old adults over 80 years. METHODS: A prospective analysis was performed in 427 hospitalized old adults. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the revised consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP2). Malnutrition was defined according to the European Society of Clinical Nutrition and Metabolism (ESPEN) criteria. Mortality data were available for up to 32 months of follow-up. RESULTS: The overall prevalence of sarcopenia and malnutrition was 35.1% and 19.4%, respectively. The percentage of coexistence of sarcopenia and malnutrition was 12.2%. Of the 427 participants, 83 deaths were reported during the mean follow-up periods of 24.9 months. Compared with non-sarcopenic subjects with well-nutrition, sarcopenic subjects with well-nutrition and non-sarcopenic subjects with well-nutrition had higher mortality risk (Hazard Ratio (HR), 2.36; 95% confidence interval (CI), 1.31-4.24, P < 0.001; HR, 4.33; 95% CI, 2.12-8.85, P = 0.004; respectively). The patients who coexisted with sarcopenia and malnutrition had the highest risk of mortality (HR, 7.31; 95% CI, 4.21-12.69, P < 0.001). Both sarcopenia and malnutrition could predict mortality separately. Still, from the components of the Cox regression multivariate models, the malnutrition was one of the independent factors influencing the death, sarcopenia was not. CONCLUSION: When malnutrition and sarcopenia were compared together in a longitude cohort, malnutrition was an independent risk factor for mortality, while sarcopenia was not. The coexistence of malnutrition and sarcopenia showed a synergistically accumulated risk for death.

Comparison of the efficacy of Nutritional Risk Screening 2002 and Mini Nutritional Assessment Short Form in recognizing sarcopenia and predicting its mortality.

OBJECTIVE: This study aimed to examine the efficacy of Nutritional Risk Screening 2002 (NRS2002) and Mini Nutritional Assessment Short Form (MNA-SF) in recognizing sarcopenia and predicting its mortality in Chinese geriatric hospitalized patients. METHODS: A prospective analysis was performed in 430 hospitalized geriatric patients. Nutrition status was assessed using the NRS2002 and MNA-SF scales. Anthropometric measures and biochemical parameters were carried out for each patient. Sarcopenia was defined according to the revised consensus definition of the European Working Group on Sarcopenia in Older People (EWGSOP2). Patients were follow-up for up to 26 months. RESULTS: The overall prevalence of sarcopenia was 35.3% in this population. In the sarcopenic patients, 53 (34.9%) were malnutrition/nutritional risk according to NRS2002 assessment and 101 (66.4%) patients were malnutrition/nutritional risk according to MNA-SF assessment. NRS2002 vs MNA-SF showed moderate agreement (κ = 0.460, P < 0.001). Receiver operating characteristic analysis showed that the area under the curve of MNA-SF was larger than NRS2002 in recognizing sarcopenia (0.763 vs 0.649, P = 0.001). During a median follow-up time of 20.22 months, 48 (31.6%) sarcopenic patients died. The Kaplan-Meier curve demonstrated that malnutrition/nutritional risk patients according to whether NRS2002 or MNA-SF assessment had a higher risk of death than the normal nutrition patients (χ2 = 15.728, P < 0.001; χ2 = 7.039, P = 0.008, respectively). Age, serum albumin levels, and NRS2002 score were independent factors influencing the mortality. CONCLUSION: MNA-SF score may be better than the NRS2002 score to recognize sarcopenia in Chinese geriatric population. Both NRS2002 and MNA-SF scores could predict mortality, but NRS2002 score was the independent predict factor.

Predictive Value of Nutritional Risk Screening 2002 and Mini Nutritional Assessment Short Form in Mortality in Chinese Hospitalized Geriatric Patients.

BACKGROUND AND AIM: The presence of malnutrition in hospitalized geriatric patients is associated with an increased risk of mortality. This study aimed to examine the performance of Nutritional Risk Screening 2002 (NRS2002) and Mini Nutritional Assessment Short Form (MNA-SF) in predicting mortality for hospitalized geriatric patients in China. METHODS: A prospective analysis was performed in 536 hospitalized geriatric patients aged ≥65 years. Nutrition status was assessed using the MNA-SF and NRS2002 scales within 24 hrs of admission. Anthropometric measures and biochemical parameters were carried out for each patient. Patients were follow-up for up to 2.5 years. RESULTS: At baseline, 161 (30.04%) patients had malnutrition/nutritional risk according to NRS2002 assessment. According to MNA-SF, 284 (52.99%) patients had malnutrition/nutritional risk. Malnutrition/nutritional risk patients had lower anthropometric and biochemical parameters (P<0.05). NRS2002 and MNA-SF had a strong correlation with classical nutritional markers (P<0.05). NRS2002 versus MNA-SF showed moderate agreement (kappa=0.493, P<0.001). During a median follow-up time of 795 days (range 10-947 days), 118 (22%) participants died. The Kaplan-Meier curve demonstrated that malnutrition/nutritional risk patients according to NRS2002 or MNA-SF assessment had a higher risk of mortality than the normal nutrition patients (χ 2=17.67, P<0.001; χ 2=28.999, P<0.001, respectively). From the components of the Cox regression multivariate models, only the NRS2002 score was an independent risk factor influencing the mortality. CONCLUSION: Both NRS2002 and MNA-SF scores could predict mortality in Chinese hospitalized geriatric patients. But only NRS2002 score was the independent predictor for mortality.

Antidiabetic Activity and Potential Mechanism of Amentoflavone in Diabetic Mice.

AIM: To investigate the anti-diabetic activity of amentoflavone (AME) in diabetic mice, and to explore the potential mechanisms. METHODS: Diabetic mice induced by high fat diet and streptozotocin were administered with amentoflavone for 8 weeks. Biochemical indexes were tested to evaluate its anti-diabetic effect. Hepatic steatosis, the histopathology change of the pancreas was evaluated. The activity of glucose metabolic enzymes, the expression of Akt and pAkt, and the glucose transporter type 4 (GLUT4) immunoreactivity were detected. RESULTS: AME decreased the level of glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and glucagon, and increased the levels of high density lipoprotein cholesterol (HDL-C) and insulin. Additionally, AME increased the activity of glucokinase (GCK), phosphofructokinase-1 (PFK-1), and pyruvate kinase (PK), and inhibited the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G-6-Pase). Mechanistically, AME increased superoxide dismutase (SOD), decreased malondialdehyde (MDA), activation of several key signaling molecules including pAkt (Ser473), and increased the translocation to the sedimenting membranes of GLUT4 in skeletal muscle tissue. CONCLUSIONS: AME exerted anti-diabetic effects by regulating glucose and lipid metabolism, perhaps via anti-oxidant effects and activating the PI3K/Akt pathway. Our study provided novel insight into the role and underlying mechanisms of AME in diabetes.

Integrating strategies of chemistry, biochemistry and metabolomics for characterization of the medication principle of "treating cold/heat syndrome with hot/cold herbs".

ETHNOPHARMACOLOGICAL RELEVANCE: "Treating cold syndrome with hot herbs & treating heat syndrome with cold herbs" is a fundamental medication principle of Chinese medicine. Scientists have been working hard to explore the scientific essence of this medication principle. However, researchers only focused on the herbs or syndrome individually, the intrinsic relationship between the cold/hot herbs and cold/heat syndrome received little attention. Consequently, the medication principle still lacked a scientific explanation. AIM OF THE STUDY: The aim of present study was to explore the scientific essence involved in the medication principle. MATERIALS AND METHODS: First, extracts of cold and hot herb1-7 were analyzed using UPLC-Q-TOF/MS to research the chemical composition. Second, expression of enzymes relating glucose aerobic oxidation and respiratory chain were detected to assess the metabolic state of rats in cold herb, hot herb, cold syndrome and heat syndrome groups. Lastly, metabolomic approach was utilized to screen out biomarkers and related pathways shared between the cold and hot herb groups, the cold and heat syndrome groups, as well as the herb and syndrome groups. RESULTS: The integrated results of chemistry, biochemistry and metabolomics study indicated that the cold (hot) herbs could remedy heat (cold) syndrome through inhibiting (promoting) arginine and proline metabolism and tryptophan metabolism, and the associated excessive (sluggish) material metabolism, ATP storage and generation in heat (cold) syndrome. The fundamental reason behind the differential efficacies of cold and hot herbs was the chemical composition and different contents of shared components. CONCLUSIONS: The medication principle was scientifically elucidated from perspective of material and energy metabolism. Moreover, this integrated novel strategy provides a feasible approach for future research of Chinese medicinal herb.

Concurrent Hearing, Genetic, and Cytomegalovirus Screening in Newborns, Taiwan.

OBJECTIVE: To evaluate the feasibility and potential benefits of incorporating genetic and cytomegalovirus (CMV) screenings into the current newborn hearing screening (NHS) programs. STUDY DESIGN: Newborns were recruited prospectively from a tertiary hospital and a maternity clinic between May 2016 and December 2016 and were subjected to hearing screening, CMV screening, and genetic screening for 4 common mutations in deafness genes (p.V37I and c.235delC of GJB2 gene, c.919-2A>G of SLC26A4 gene, and the mitochondrial m.1555A>G). Infants with homozygous nuclear mutations or homoplasmic/heteroplasmic mitochondrial mutation (referred to as "conclusively positive genotypes") and those who tested positive for CMV received diagnostic audiologic evaluations. RESULTS: Of the total 1716 newborns enrolled, we identified 20 (1.2%) newborns with conclusively positive genotypes on genetic screening, comprising 15 newborns (0.9%) with GJB2 p.V37I/p.V37I and 5 newborns (0.3%) with m.1555A>G. Three (0.2%) newborns tested positive on CMV screening. Twelve of the 20 newborns (60%) with conclusively positive genotypes and all 3 newborns who tested positive for CMV (100%) passed NHS at birth. Diagnostic audiologic evaluations conducted at 3 months confirmed hearing impairment in 6 of the 20 infants (30%) with conclusively positive genotypes. CONCLUSIONS: This study confirms the feasibility of performing hearing, genetic, and CMV screenings concurrently in newborns and provides evidence that the incorporation of these screening tests could potentially identify an additional subgroup of infants with impaired hearing that might not be detected by the NHS programs.

Estrogenic Effects of the Extracts from the Chinese Yam (Dioscorea opposite Thunb.) and Its Effective Compounds in Vitro and in Vivo.

BACKGROUND: The aim of this study was to explore the estrogenic effects of the extracts from Chinese yam and its effective compounds. METHODS: The activity of the yam was investigated by the uterine weight gain of mice and a proliferation assay of breast cancer cell lines (MCF-7 cell); the estrogenic activity was comprehensively evaluated by a serum pharmacology experiment. The levels of estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were also measured. Western blot analysis and antagonist assays with faslodex (ICI182,780), methylpiperidino-pyrazole (MPP), Delta (9) -tetrahydrocannabinol (THC), and G-15 were used to explore the mechanism of the effects of the yam. To find the effective compounds of the yam which play a role in its estrogen-like effects, we used the same methods to study the effects of adenosine and arbutin. RESULTS: The Chinese yam and two main compounds, adenosine and arbutin, have estrogen-like effects. The mechanism of the yam which plays a role in its estrogen-like effects was mainly mediated by the estrogen receptors ERα, ERß, and GPR30; that of adenosine was mainly mediated by estrogen receptors ERα and ERß, and that of arbutin was mainly mediated by estrogen receptors ERß and GPR30. CONCLUSIONS: The Chinese yam has estrogen-like effects; adenosine and arbutin are two of the effective compounds in the yam which play a role in its estrogen-like effects.

Two Sulfur Glycoside Compounds Isolated from Lepidium apetalum Willd Protect NRK52e Cells against Hypertonic-Induced Adhesion and Inflammation by Suppressing the MAPK Signaling Pathway and RAAS.

Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺-K⁺ ATP content in renal medulla. After treatment with cis-DG and trans-DG, expression of calcineurin (CAN) and Ca/calmodulin-dependent protein kinase II (CaMK II) was decreased in renal tissue and Ca2+ influx was inhibited, thereby reducing the secretion of transforming growth factor-ß (TGFß), reversing the increase in adhesion and inflammatory factor E-selectin and monocyte chemotactic protein 1 (MCP-1) induced by high NaCl, while reducing oxidative stress status and decreasing the expression of cyclooxygenase-2 (COX2). Furthermore, inhibition of protein kinase C (PKC) expression also contributed to these improvements. The cis-DG and trans-DG reduced the expression of p-p44/42 MAPK, p-JNK and p-p38, inhibited the phosphorylation of the MAPK signaling pathway in NRN52e cells induced by high salt, decreased the overexpression of p-p38 and p-HSP27, and inhibited the overactivation of the p38-MAPK signaling pathway, suggesting that the p38-MAPK pathway may play a vital role in the hypertonic-induced adhesion and inflammatory response. From the results of this study, it can be concluded that the mechanism of cis-DG and trans-DG may mainly be through inhibiting the p38-MAPK signaling pathway, inhibiting the excessive activation of the RAAS system, and thereby reducing adhesion and inflammatory factors.

Phenolic constituents from the root bark of Morus alba L. and their cardioprotective activity in vitro.

A flavanone C-glycoside, steppogenin-5'-C-ß-D-glucopyranoside, six prenylated 2-arylbenzofuran derivatives, moracin O-3″-O-ß-D-glucopyranoside, moracin O-3'-O-ß-D-xylopyranoside, moracin P-2″-O-ß-D-glucopyranoside, moracin P-3'-O-ß-D-glucopyranoside, moracin P-3'-O-α-L-arabinopyranoside and moracin P-3'-O-[ß-D-glucopyranosyl-(1 â†’ 2)]-α-L-arabinopyranoside, two phenolic acids, 2,4-dihydroxy-5-(4-hydroxybenzyl) benzoic acid and 2,4-dihydroxy-5-(3,4-dihydroxybenzyl) benzoic acid, as well as three known compounds, moracinoside C, moracin O, and moracin P were isolated from the root bark of Morus alba L. Their structures were ascertained on the basis of spectroscopic evidence. The protective effects of the compounds against doxorubicin-induced cardiomyopathy in H9c2 cells was investigated in vitro. Of all of the isolated compounds, moracin P-3'-O-ß-D-glucopyranoside, moracin O and moracin P had a strong protective influence against doxorubicin-induced cell death with EC50 values of 9.5 ± 2.6, 4.5 ± 1.3, and 8.8 ± 2.4 µM, respectively.