Changes in gut microbiota linked to a prevention of cardiac remodeling induced by hypertension in spontaneously hypertensive rats fed a pawpaw fruit diet.

Objective: Dietary intake of fruit is associated with lower incidence of hypertension and cardiovascular risk. Papaya is a kind of delicious fruit and reported has dietary therapeutic effects, such as digestive stimulation and hypotensive efficacy. However, the mechanism of pawpaw involved have not been elucidated. Here, we illustrate that the effect of pawpaw on the gut microbiota and the prevention of cardiac remodeling. Methods: Gut microbiome, cardiac structure/function, and blood pressure were examined in SHR and WKY groups. The intestinal barrier was tested with histopathologic; immunostaining and Western blot were used to measure the tight junction protein level; Gpr41 was tested by RT-PCR, and inflammatory factors were detected with ELISA. Results: We observed a significant decrease in microbial richness, diversity, and evenness is the spontaneously hypertensive rat (SHR), in addition to an increased Firmicutes/Bacteroidetes (F/B) ratio. These changes were accompanied by decreased in acetate and butyrate-producing bacteria. Compared with SHR, treatment with pawpaw at the dosage of 10 g/kg for 12 weeks significantly reduced the blood pressure, cardiac fibrosis and cardiac hypertrophy, while the ratio of F/B decreased. We also found that the concentration of short-chain fatty acids (SCFAs) was increased in SHR fed with pawpaw compared with that in control group, while the gut barrier was restored and level of proinflammatory cytokines in the serum were decreased. Conclusions: Pawpaw, rich of high fiber, led to changes in the gut microbiota that played a protective role in the development of cardiac remodeling. The potential mechanism of pawpaw may explained by the generation of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate, increasing tight junction protein level occluding to enhance the gut barrier for less releasing the inflammation cytokines, and upregulating G-protein-coupled receptor 41 (GPR41) to reduce blood pressure.

Research on Seawater Intrusion Suppression Scheme of Minjiang River Estuary.

Seawater intrusion in the Minjiang River estuary has gravely endangered the water security of the surrounding area in recent years. Previous studies mainly focused on exploring the mechanism of intrusion, but failed to provide a scheme for suppressing seawater intrusion. The three most relevant determinants to chlorine level, which represented the strength of seawater intrusion, were determined using Pearson correlation analysis as being the daily average discharge, daily maximum tidal range, and daily minimum tidal level. Considering the lower requirement of sample data and the ability to handle high-dimensional data, the random forest algorithm was used to construct a seawater intrusion suppression model and was combined with a genetic algorithm. The critical river discharge for suppressing estuary seawater intrusion determined using this model. The critical river discharge was found to gradually increase with the maximum tidal range, which in three different tide scenarios was 487 m3/s, 493 m3/s, and 531 m3/s. The practicable seawater intrusion suppression scheme was built up with three phases to make it easier to regulate upstream reservoirs. In the scheme, the initial reading of river discharge was 490 m3/s, and it rose to 650 m3/s over six days, from four days before the high tide's arrival to two days following it, and before falling down to 490 m3/s at the end. Verified with the 16 seawater intrusion events in the five dry years, this scheme could eliminate 75% of the seawater intrusion risk and effectively reduce the chlorine level for the remaining 25% of events.

Salvianolic acid D: A potent molecule that protects against heart failure induced by hypertension via Ras signalling pathway and PI3K/Akt signalling pathway.

Ethnopharmacological relevance: Salvianolic acid D (Sal D) is a natural substance extracted from Radix Salviae that performs a cardiovascular benefit. However, the protective mechanism of Sal-D for heart failure remains uncertain. Aim of the study: In this study, we aim to evaluate the effect of Sal D on heart failure and elucidate its underlying mechanisms. Materials and methods: Using the spontaneously hypertensive rats (SHR) as a cardiac remodelling model, the cardioprotective effect of Sal D was evaluated. Employing bioinformatics analysis, the related mechanisms of Sal D treatment on heart failure were identified and validated by Western blot and polymerase chain reaction. Results: The results showed that Sal D significantly improved cardiac function and attenuated cardiac hypertrophy. Besides, Sal D impaired mitochondrial structure and restored the energy charge of cardiomyocytes managed by angiotensin II. Bioinformatics analysis suggested that Sal D might improve heart failure by modulating the Ras and PI3K/AKT signalling pathways verified in vitro and in vivo. Conclusion: In summary, Sal D can improve the heart function of SHR by inhibiting the Ras signalling pathway and activating the PI3K/AKT signalling pathway.

Kaempferol inhibits renal fibrosis by suppression of the sonic hedgehog signaling pathway.

BACKGROUND: Most chronic kidney diseases (CKDs) develop to end-stage renal disease (ESRD), which is characterized by fibrosis and permanent tissue and function loss. As a result, better and more effective remedies are essential. Kaempferol (KAE) is a common flavonoid extracted from plants. It can control the progression of kidney fibrosis and the epithelial-to-mesenchymal transition (EMT) of the renal tubular system. PURPOSE: We aim to investigate the effect of KAE therapy on extracellular matrix deposition and stimulation of EMT in vitro and in vivo to elucidate the treatment mechanisms regulating these effects. STUDY DESIGN: Chronic hypertension-induced kidney fibrosis was studied in spontaneously hypertensive rats with chronic kidney disease. Biochemical analysis, histological staining, and the expression level of relative proteins were used to assess the effect of KAE on renal function and fibrosis. The direct impact of KAE on proliferation and migration was evaluated using human renal tubular epithelial cells (HK-2) induced by transforming growth factor-ß1 (TGF-ß1), which can then induce EMT. The molecular mechanism of KAE was verified using co-IP assay and immunofluorescence. RESULTS: KAE could reduce blood pressure and decrease the extracellular matrix (ECM) components (including collagen I and collagen Ш), TGF-ß1, and α-SMA in the kidneys of hypertension-induced rats with chronic kidney disease. Moreover, in HK-2 cell treated with TGF-ß1, KAE administration significantly suppressed proliferation, migration, and EMT via increasing the expression of E-cadherin, while reducing the N-cadherin and α-SMA. Sufu was exceedingly repressed in HK-2 cells treated with TGF-ß1. KAE inhibited the activation of Shh and Gli through increasing the expression of Sufu, thereby blocking the nuclear translocation of Gli1 in vitro. CONCLUSION: KAE ameliorated kidney fibrosis and EMT by inhibiting the sonic hedgehog signaling pathway, thereby to attenuate the pathological progression of hypertensive kidney fibrosis.

Modulation of transforming growth factor-beta signaling pathway mediates the effects of Kangxian Formula on cardiac remodeling.

ETHNOPHARMACOLOGICAL RELEVANCE: Kangxian formula (KXF) is a traditional Chinese medicine which shows effective outcomes in treating cardiac remodeling induced by hypertension. However, the exact effects and the mechanisms involved remain obscure. AIM OF THE STUDY: In this study, we aimed to identify the therapeutic role of KXF in vivo and in vitro, and investigate the mechanism of KXF on hypertension induced cardiac remodeling. MATERIALS AND METHODS: After quality control of KXF using fingerprint, blood pressure, cardiac structure/function indexes, and degree of myocardial collagen were measured in vivo. Moreover, the proliferation, migration, and fibroblast-to-myofibroblast transformation (FMT) of cardiac fibroblasts (CFBs) were determined. Using gene chip, the related mechanisms of KXF treatment on cardiac remodeling were identified and further validated by western blot and polymerase chain reaction. RESULTS: A stable quality control standard of KXF was established in this study. KXF administration ameliorated systolic/diastolic blood pressure, cardiac damages, and cardiac fibrosis in vivo. The proliferation, migration, and FMT of CFBs were also inhibited by the treatment of KXF medicated serum. Furthermore, KXF reduced the protein level of transforming growth factor-beta (TGF-ß) receptors Ⅰ, Ⅱ, Tak1, p38, Smad2/3, and Smad4 and the expression of mRNA, which are the hub proteins in the TGF-ß signaling pathway. CONCLUSION: Our findings suggest that KXF attenuates cardiac remodeling by improving cardiac damages, attenuating cardiac fibrosis, and inhibiting the activity of CFBs. In addition, KXF ameliorates cardiac remodeling partially through modulating the TGF-ß signaling pathway. These data provide insights and mechanisms into the wide application of KXF in clinical practice.

Data-Driven Modeling and the Influence of Objective Function Selection on Model Performance in Limited Data Regions.

The identification of unit hydrographs and component flows from rainfall, evapotranspiration and streamflow data (IHACRES) model has been proven to be an efficient yet basic model to simulate rainfall-runoff processes due to the difficulty in obtaining the comprehensive data required by physical models, especially in data-scarce, semi-arid regions. The success of a calibration process is tremendously dependent on the objective function chosen. However, objective functions have been applied largely in over daily and monthly scales and seldom over sub-daily scales. This study, therefore, implements the IHACRES model using 'hydromad' in R to simulate flood events with data limitations in Zhidan, a semi-arid catchment in China. We apply objective function constraints by time aggregating the commonly used Nash-Sutcliffe efficiency into daily and hourly scales to investigate the influence of objective function constraints on the model performance and the general capability of the IHACRES model to simulate flood events in the study watershed. The results of the study demonstrated the advantage of the finer time-scaled hourly objective function over its daily counterpart in simulating runoff for the selected flood events. The results also indicated that the IHACRES model performed extremely well in the Zhidan watershed, presenting the feasibility of the use of the IHACRES model to simulate flood events in data scarce, semi-arid regions.

Application of hybrid ANN-whale optimization model in evaluation of the field capacity and the permanent wilting point of the soils.

Field capacity (FC) and permanent wilting point (PWP) are two important properties of the soil when the soil moisture is concerned. Since the determination of these parameters is expensive and time-consuming, this study aims to develop and evaluate a new hybrid of artificial neural network model coupled with a whale optimization algorithm (ANN-WOA) as a meta-heuristic optimization tool in defining the FC and the PWP at the basin scale. The simulated results were also compared with other core optimization models of ANN and multilinear regression (MLR). For this aim, a set of 217 soil samples were taken from different regions located across the West and East Azerbaijan provinces in Iran, partially covering four important basins of Lake Urmia, Caspian Sea, Persian Gulf-Oman Sea, and Central-Basin of Iran. Taken samples included portion of clay, sand, and silt together with organic matter, which were used as independent variables to define the FC and the PWP. A 80-20 portion of the randomly selected independent and dependent variable sets were used in calibration and validation of the predefined models. The most accurate predictions for the FC and PWP at the selected stations were obtained by the hybrid ANN-WOA models, and evaluation criteria at the validation phases were obtained as 2.87%, 0.92, and 2.11% respectively for RMSE, R2, and RRMSE for the FC, and 1.78%, 0.92, and 10.02% respectively for RMSE, R2, and RRMSE for the PWP. It is concluded that the organic matter is the most important variable in prediction of FC and PWP, while the proposed ANN-WOA model is an efficient approach in defining the FC and the PWP at the basin scale.

The Combination of Scutellaria baicalensis Georgi and Sophora japonica L. ameliorate Renal Function by Regulating Gut Microbiota in Spontaneously Hypertensive Rats.

Chronic kidney disease (CKD) is becoming a notable health concern globally. The combination of Scutellaria baicalensis Georgi (SB) and Sophora japonica L. (SJ) has been demonstrated to have anti-hypertensive effects and improve kidney injury clinically. This study aimed to explore the renal protective effect of the combination of SB and SJ against CKD and clarify the potential mechanisms. Male spontaneously hypertensive rats (SHR) were used to induce hypertensive nephropathy and were treated with SB or SJ separately or in combination for 15 weeks, and an antibiotic group was used for a rescue experiment. Blood pressure, serum or urine biochemical markers, serum inflammation factors, short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and oxidative stress indicators were assessed. Western blot analysis was performed to determine the expression of intestinal tight junction proteins, including occludin and ZO-1. The mRNA expression of the SCFAs receptors olfactory 78 (Olfr78) and G protein-coupled receptor 41 (GPR41) was determined by quantitative real-time PCR. Gut microbiota profiles were established via high-throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene. SB and SJ significantly ameliorated the severity of renal injury induced by hypertension. The combination also decreased the ratio of Firmicutes/Bacteroidetes, increased the relative abundance of Lactobacillus, and reduced that of Clostridiaceae. The intestinal barrier was improved, and the change in dominant bacteria reduced IS accumulation and further inhibited oxidative stress activation in kidneys. SB and SJ increased SCFAs production, inhibited inflammatory factor release, and regulated blood pressure by decreasing the expression of Olfr78 and increasing that of GPR41, then alleviated kidney damage. This research demonstrated the positive effects of SB and SJ in a rat model of hypertensive nephropathy, indicated that the treatment of SB and SJ by improving the intestinal barrier function, increasing SCFAs, reducing inflammation, decreasing IS, and inhibiting oxidative stress reactions.

Identification of lncRNA NEAT1/miR-21/RRM2 axis as a novel biomarker in breast cancer.

As a major disease that threatens the health of women worldwide, breast cancer (BC) lacks effective molecular markers in the clinic at the same time. We aim at finding a new biomarker of BC. In our study, through the Gene Expression Omnibus database chip, a total of 1393 pairs of microRNA-messenger RNA (miRNA-mRNA) networks and 35754 pairs of long noncoding RNA-miRNA networks were obtained. We found out that NEAT1/miR-21/RRM2 axis may play a role in BC diagnosis and prognosis. The real-time quantitative reverse transcription-polymerase chain reaction test was used to analyze the mRNA level of NEAT1, miR-21, and RRM2. Western blot was used to detect the protein level of RRM2. Through the 5-ethynyl-2'-deoxyuridine assay, the proliferation of MDA-MB-231 cells was detected. Through wound healing and transwell assay, the migration of MDA-MB-231 cells was detected. Altogether, our data indicated that NEAT1, miR-21, and RRM2 were upregulated in several BC cell lines. Overexpressed of miR-21 in MDA-MB-231 cells promote proliferation and migration. Besides, our results demonstrated that overexpressed of miR-21 upregulated the level of RRM2. Accordingly, miR-21/RRM2 might be a new diagnosis and treatment target of BC.

Danshenol A Alleviates Hypertension-Induced Cardiac Remodeling by Ameliorating Mitochondrial Dysfunction and Suppressing Reactive Oxygen Species Production.

Current therapeutic approaches have a limited effect on cardiac remodeling, which is characteristic of cardiac fibrosis and myocardial hypertrophy. In this study, we examined whether Danshenol A (DA), an active ingredient extracted from the traditional Chinese medicine Radix Salviae, can attenuate cardiac remodeling and clarified the underlying mechanisms. Using the spontaneously hypertensive rat (SHR) as a cardiac remodeling model, DA ameliorated blood pressure, cardiac injury, and myocardial collagen volume and improved cardiac function. Bioinformatics analysis revealed that DA might attenuate cardiac remodeling through modulating mitochondrial dysfunction and reactive oxygen species. DA repaired the structure/function of the mitochondria, alleviated oxidative stress in the myocardium, and restored apoptosis of cardiomyocytes induced by angiotensin II. Besides, DA inhibited mitochondrial redox signaling pathways in both the myocardium and cardiomyocytes. Thus, our study suggested that DA attenuates cardiac remodeling induced by hypertension through modulating mitochondrial dysfunction and reactive oxygen species.

An epididymis-specific secretory protein Clpsl2 critically regulates sperm motility, acrosomal integrity, and male fertility.

The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. Here we report that Clpsl2, a novel colipase homology, is exclusively expressed in the caupt epididymis and conserved in mammalian. Clpsl2 was secreted into the lumen and covered the acrosome region and principal piece of spermatozoa tail. And during epididymal transit, the binding rate between Clpsl2 protein and the spermatozoa gradually decreased. Though Clpsl2 had the highest identifies with pancreatic colipase (Clps), Clpsl2 lacked those conserved amino acids in pancreatic Clps that interacting with lipase, correspondingly, the recombinant Clpsl2 protein did not possess the Clps function such as promoting the hydrolysis of lipase to its substrate glycerine trioleate. However, sequence analysis showed that Clpsl2 has the potency to bind with lipid. Knockdown expression of Clpsl2 by lentivirus-mediated RNAi in vivo caused an attenuation of spermatozoa motility, a suppressed acrosomal reaction, a decrease of cauda spermatozoa number, and subfertility. This study identified a novel and conserved molecule, Clpsl2, was specifically expressed in epididymis and involved in the regulation of spermatozoa motility, acrosomal integrity, and male fertility.

To identify the important soil properties affecting dinoseb adsorption with statistical analysis.

Investigating the influences of soil characteristic factors on dinoseb adsorption parameter with different statistical methods would be valuable to explicitly figure out the extent of these influences. The correlation coefficients and the direct, indirect effects of soil characteristic factors on dinoseb adsorption parameter were analyzed through bivariate correlation analysis, and path analysis. With stepwise regression analysis the factors which had little influence on the adsorption parameter were excluded. Results indicate that pH and CEC had moderate relationship and lower direct effect on dinoseb adsorption parameter due to the multicollinearity with other soil factors, and organic carbon and clay contents were found to be the most significant soil factors which affect the dinoseb adsorption process. A regression is thereby set up to explore the relationship between the dinoseb adsorption parameter and the two soil factors: the soil organic carbon and clay contents. A 92% of the variation of dinoseb sorption coefficient could be attributed to the variation of the soil organic carbon and clay contents.