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.

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.

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.

Low Calf Circumference Predicts Nutritional Risks in Hospitalized Patients Aged More Than 80 Years.

OBJECTIVE: The aim of this study was to determine whether low calf circumference (CC) could predict nutritional risk and the cutoff values of CC for predicting nutritional risk in hospitalized patients aged ⪖ 80 years. METHODS: A total of 1,234 consecutive patients aged ⪖ 80 years were enrolled in this study. On admission, demographic data, CC, and laboratory parameters were obtained. Patients with Nutritional Risk Screening 2002 (NRS-2002) total score ⪖ 3 were considered as having nutritional risk. RESULTS: CC values were significantly lower in patients with nutritional risk compared to those in patients without nutritional risk [27.00 (24.50-31.00) vs. 31.00 (29.00-33.50], P < 0.001]. CC was negatively correlated with age and nutritional risk scores. Logistic regression analysis of nutritional risk revealed that body mass index, albumin level, hemoglobin level, cerebral infarction, neoplasms, and CC (OR, 0.897; 95% confidence interval, 0.856-0.941; P < 0.001) were independent impact factors of nutritional risk. Nutritional risk scores increased with a decrease in CC. In men, the best CC cutoff value for predicting nutritional risk according to the NRS-2002 was 29.75 cm. In women, the cutoff value was 28.25 cm. CONCLUSION: CC is a simple, noninvasive, and valid anthropometric measure to predict nutritional risk for hospitalized patients aged ⪖ 80 years.

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.

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.

The development and issues of nursing education in China: a national data analysis.

BACKGROUND: The development of and the issues arising in the nursing educational sector as the provider for nursing workforce have drawn increasing attention. OBJECTIVES: To describe the development of nursing education in mainland China and to analyze related issues. DESIGN: A retrospective, descriptive study with secondary data analysis. METHODS: The scale and composition of nursing education programs from 2006 to 2012 in mainland China were analyzed, and changes in the scale of the nursing workforce from 2002 to 2013 were compared to facilitate an interpretation of nursing education. RESULTS: The scale of initial nursing education was large and expanded rapidly. In 2012, the total recruitment was 515,710, including 39,747 (7.71%) students training for a baccalaureate degree, 143,726 (27.87%) students training for an advanced diploma, and 332,237 (64.42%) students training in secondary diploma programs. The nursing workforce in China grew dramatically, with an increase of 120,000 to 286,000 nurses each year since 2006, but the nurse shortage remained existed (there were only 2.05 nurses per 1000 population, and the nurse to doctor ratio was 1:1 in 2013). The recruitment of nursing students per 1000 population was greater in the west (0.51) and middle (0.40) regions than in the east region (0.28), while the number of nurses per 1000 population had the opposite pattern (1.71, 1.75, and 2.02 nurses per 1000 population in the west, middle, and east regions, respectively) in 2012. CONCLUSIONS: Nursing education in China has developed rapidly, and some issues require attention. We suggest that initial nursing education be improved by increasing the recruitment to advanced diploma and baccalaureate programs and decreasing the recruitment to secondary diploma programs and by ensuring the quality of education. Multiple strategies should be taken to effectively raise the social status and prestige of the nursing profession and to ease the nurse shortage.

A new kaempferol trioside from Silphium perfoliatum.

A new apiose-containing kaempferol trioside, kaempferol-3-O-α-L-rhamnosyl-(1‴ → 6″)-O-ß-D-galactopyranosyl-7-O-ß-D-apiofuranoside, along with 16 known compounds, were isolated from 50% acetone extract of Silphium perfoliatum L. Their structures were elucidated by acid hydrolysis and spectroscopic techniques including UV, IR, MS, ¹H, ¹³C, and 2D-NMR. In addition, the pharmacological activity of compound 1 was tested with HepG2 and Balb/c mice (splenic lymphocytes and thymic lymphocytes) in vitro, and it exhibited inhibitory effect on the proliferation of HepG2 cells and showed the immunosuppressive activity.

Antihyperlipidaemic and antioxidant effect of the total flavonoids in Selaginella tamariscina (Beauv.) Spring in diabetic mice.

OBJECTIVES: To investigate the antidiabetic, antihyperlipidaemic and antioxidant activity of total flavonoids in Selaginella tamariscina (Beauv.) Spring (TFST) in a mouse model of diabetes. METHODS: Normal mice, mice fed with a high-fat emulsion diet and streptozotocin (STZ)-induced diabetic mice were treated with TFST for 6 weeks. Serum glucose, insulin and lipid, hepatic steatosis, production of the protein visfatin and antioxidant indices were evaluated. KEY FINDINGS: TFST significantly decreased the concentration of fasting blood glucose, total cholesterol, triglycerides and low-density-lipoprotein cholesterol, while it increased the levels of insulin and high-density-lipoprotein cholesterol in diabetic mice. TFST also improved the results of the oral glucose tolerance test to a certain degree. Furthermore, both the free fatty acid levels in the liver and hepatic steatosis were ameliorated by TFST treatment. These changes may be be associated with decreased production of visfatin. Administration of TFST also significantly decreased the levels of malondialdehyde, nitric oxide and inducible nitric oxide synthase and increased the content of glutathione and the activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the liver. No change in blood glucose levels were observed in the normal mice treated with TFST. CONCLUSIONS: TFST showed an excellent effect in reducing the high blood glucose level but had no effect on normal blood glucose level. The antidiabetic activity of TFST could be explained by its antioxidant and antihyperlipidaemic activity, which finally elevated the insulin sensitivity of liver.