Yishen Huashi granule modulated lipid metabolism in diabetic nephropathy via PI3K/AKT/mTOR signaling pathways.

Aim: Diabetic nephropathy (DN) is the primary cause of end-stage renal disease worldwide. Although etiology for DN is complex and still needs to be fully understood, lipid metabolism disorder is found to play a role in it. Previously, we found Yishen Huashi (YSHS) granule could inhibit diabetic damage and reduce level of microalbuminuria (mALB) in DN animals. To explore its role and mechanism in lipid metabolism under DN settings, this study was designed. Materials and methods: DN rats were induced by streptozotocin (STZ), HepG2 and CaCO2 cells were applied for in vitro study. Hematoxylin-Eosin (HE), periodic acid-Schiff (PAS) staining, and Transmission Electron Microscopy (TEM) were applied for histological observation; 16s Sequencing was used for intestinal microbiota composition analysis; western blotting (WB) and immunofluorescence were carried out for molecular biological study, and enzyme-linked immunosorbent assay (ELISA) was used for lipid determination. Results: YSHS administration significantly reduced levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL-C), while increased level of high-density lipoprotein (HDL-C); meanwhile, histological changes and steatosis of the liver was ameliorated, integrity of the intestinal barrier was enhanced, and dysbacteriosis within intestinal lumen was ameliorated. Mechanism study found that YSHS modulated mitophagy within hepatocytes and inhibited mTOR/AMPK/PI3K/AKT signaling pathway. Conclusion: In conclusion, we found in the present study that YSHS administration could ameliorate lipid metabolism disorder in DN animals, and its modulation on intestinal-liver axis played a significant role in it.

The Protective Effect of the Asystasia chelonoides Extracts on Hypertensive Nephropathy Rats.

BACKGROUND: Hypertensive nephropathy (HN) is one kind of kidney disorders caused by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In recent years, nephropathy accompanied by hypertension is becoming one of the main causes for kidney replacement therapy, but few effective treatments have been reported for HN treatment. Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear. METHODS: To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying mechanisms of AC extracts treatment in the HN rat model. RESULTS: AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFß1 and NF-кB in HN rats. CONCLUSION: The finding of the article demonstrated that AC extracts had the better therapeutic effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.

The Protective Effect of Bajijiasu on the Treatment of Hypertensive Nephropathy in Rats.

BACKGROUNDS: Hypertensive nephropathy (HN) is a kind of renal disease caused by essential hypertension that eventually worsens into end-stage renal disease (ESRD). HN could damage the renal tubules, induce kidney damage and renal failure, and increase the risk of stroke, heart disease or death, but there are few ideal drugs for HN treatment. METHODS: In this study, we explored the therapeutic effect of bajijiasu (a compound from Morinda officinalis how and a common traditional Chinese medicine for tonifying the kidney) on the HN rat model. Biochemical analysis, HE staining, and PAS staining were used to assess the effects of bajijiasu on HN rat model. Western blotting was used to analyze the potential mechanisms. RESULTS: The results of HE staining and PAS staining showed that bajijiasu could alleviate the pathological changes in HN rat models; biochemical analysis found that the concentration of Malondialdehyde (MDA), total protein (TP), albumin (ALB), microalbuminuria (MALB), blood urea nitrogen (BUN), creatinine (Cr), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) were significantly decreased compared with the model group after bajijiasu treatment; and bajijiasu could regulate the expression of TNF-α, IL-6, MDA, SOD1 and AGEs in HN rats; the result of western blotting demonstrated that bajijiasu could down-regulate the expression of TGFß1, NOX4, JNK, p- JNK and up-regulate the expression PPARγ and SOD 1 in HN rats. CONCLUSION: Those results demonstrated that bajijiasu could alleviate the pathological changes and physiological and biochemical symptoms of HN rat models by regulating the expression of TGFß1, PPARγ, JNK, p-JNK, NOX4 and SOD1 but could not lower the blood pressure of HN rats. Those pieces of evidence may provide a new therapeutic method for HN treatment.

Transforming growth factor-ß signaling: From tissue fibrosis to therapeutic opportunities.

Fibrosis refers to the excessive deposition of extracellular matrix components in the processes of wound repair or tissue regeneration after tissue damage. Fibrosis occurs in various organs such as lung, heart, liver, and kidney tissues, resulting in the failure of organ structural integrity and its functional impairment. It has long been thought to be relentlessly progressive and irreversible process, but both preclinical models and clinical trials in multiorgans have shown that fibrosis is a highly dynamic process. Transforming growth factor-beta (TGF-ß) is a superfamily of related growth factors. Many studies have described that activation of profibrotic TGF-ß signaling promotes infiltration and/or proliferation of preexisting fibroblasts, generation of myofibroblasts, extracellular matrix deposition, and inhibition of collagenolysis, which leads to fibrosis in the pathological milieu. This review describes the effect of TGF-ß signaling in fibrotic-associate lung, heart, liver, and kidney tissues, followed by a detailed discussion of canonical and non-canonical TGF-ß signaling pathway. In addition, this review also discusses therapeutic options by using natural products and chemical agents, for targeting tissue fibrosis via modulating TGF-ß signaling to provide a more specific concept-driven therapy strategy for multiorgan fibrosis.

[Spatial and temporal variation in normalized difference vegetation index of vegetation in Liaoning Province from the perspective of ecogeographic zoning]. / 生态地理分区视角下的辽宁省植被归一化植被指数的时空变化.

Normalized difference vegetation index (NDVI) is an important indicator reflecting vegetation cover and growth status. It is of significance for regional ecological conservation and natural resource management to investigate its spatial and temporal variation trends and response to ecological factors. We divided Liaoning Province into three ecological geographical regions, including northwest agro-pastoral zone, central agricultural zone, and eastern agroforestry zone. Based on remote sensing, vegetation, climate, topography and human activities, we used trend analysis and geographic probe model to examine the spatial and temporal trends of NDVI in Liaoning Province, and analyzed the intensity and interaction mechanism of each driver on the spatial distribution pattern of NDVI. The results showed that the annual average NDVI in Liaoning Province from 2001 to 2020 was 0-0.92, showing a distribution pattern of high in the east and low in the west, high in the inland and low in the coastal land. The overall trend of vegetation cover was increasing, and the NDVI increasing areas were mainly concentrated in the northwest agro-pastoral zone and the eastern agroforestry zone, the NDVI reduction areas were mainly concentrated at the border between the central agricultural zone and the eastern agroforestry zone, as well as in the coastal area of the eastern agroforestry zone. The annual average NDVI change varied among the three ecological-geographic zones. The NDVI of the northwest agro-pastoral zone from 2001 to 2020 were generally low, but showed a fluctuating trend of slow increase. The NDVI of the eastern agroforestry zone was high overall, and the interannual variation of NDVI was generally stable. The distribution of high and low NDVI in the central agricultural zone was staggered, and the interannual variation of NDVI showed a decreasing trend. Natural factors were the key drivers of NDVI changes in the three ecogeographic zones, with cumulative temperature and precipitation having the greatest influence. The interactions between the factors were all mutually and nonlinearly enhanced.

Yishen Huashi Granules Ameliorated the Development of Diabetic Nephropathy by Reducing the Damage of Glomerular Filtration Barrier.

Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes and the primary cause of end-stage renal disease. At present, renin-angiotensin-aldosterone system (RAAS) blockers have been applied as first-class drugs to restrain development of DN; however, its long-term effect is limited. Recent evidence has shown definite effects of Chinese medicine on DN. Yishen Huashi (YSHS) granule is a traditional Chinese Medicine prescription that has been used in the clinic to treat DN, but its mechanism is not understood. Methods: In the present study, both in vitro and in vivo studies were carried out. The DN model was induced by STZ in Wistar rats, and GEnC and HPC cell lines were applied in the in vitro study. Quality of YSHS was evaluated by LC-MS/MS. A metabolomic study of urine was carried out by LC-MS; influence of YSHS on composition of DN was analyzed by network pharmacology. Mechanism of the YSHS on DN was analyzed by Q-PCR, Western Blot, and multi-immunological methods. Results: We found YSHS administration significantly reduced levels of HbA1c and mALB. Histopathological analysis found that YSHS preserved integrity of glomerular filtration barrier by preserving viability of glomerular endothelial cells and podocytes, inhibiting glomerular fibrosis, reducing oxidative stress damage, and enhancing cross-talk among glomerular endothelial cells and podocytes. Network pharmacology, differential metabolite analysis, as well as intracellular pathway experimental study demonstrated that the PI3K/AKT/mTOR signaling pathway played a pivotal role in it. Conclusion: Our present findings supplied new understanding toward the mechanism of YSHS on inhibiting DN.

Intake of flavonoids from Astragalus membranaceus ameliorated brain impairment in diabetic mice via modulating brain-gut axis.

BACKGROUND: Brain impairment is one of a major complication of diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus is a herbal medicine commonly used to relieve the complications of diabetes. Flavonoids is one of the major ingredients of Astragalus membranaceus, but its function and mechanism on diabetic encepholopathy is still unknown. METHODS: Type 2 diabetes mellitus (T2DM) model was induced by high fat diet and STZ in C57BL/6J mice, and BEnd.3 and HT22 cell lines were applied in the in vitro study. Quality of flavonoids was evaluated by LC-MS/MS. Differential expressed proteins in the hippocampus were evaluated by proteomics; influence of the flavonoids on composition of gut microbiota was analyzed by metagenomics. Mechanism of the flavonoids on diabetic encepholopathy was analyzed by Q-PCR, Western Blot, and multi-immunological methods et al. RESULTS: We found that flavonoids from Astragalus membranaceus (TFA) significantly ameliorated brain damage by modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose and food intake, repaired blood brain barrier, protected hippocampus synaptic function; improved hippocampus mitochondrial biosynthesis and energy metabolism; and enriched the intestinal microbiome in high fat diet/STZ-induced diabetic mice. In the in vitro study, we found TFA increased viability of HT22 cells and preserved gut barrier integrity in CaCO2 monocellular layer, and PGC1α/AMPK pathway participated in this process. CONCLUSION: Our findings demonstrated that flavonoids from Astragalus membranaceus ameliorated brain impairment, and its modulation on gut-brain axis plays a pivotal role. Our present study provided an alternative solution on preventing and treating diabetic cognition impairment.

RETRACTED: Residual pomegranate affecting the nonspecific immunity of juvenile Darkbarbel catfish.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Editors-in-Chief and first Author. The article duplicates significant parts of a paper that had already appeared in Fish & Shellfish Immunology, Volume 93 (2019) 726-731, https://doi.org/10.1016/j.fsi.2019.06.052. One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. The first author informed the journal that the article was published without the knowledge of the co-authors.

Effect of organic loading rate on the removal of DMF, MC and IPA by a pilot-scale AnMBR for treating chemical synthesis-based antibiotic solvent wastewater.

This study focuses on the effects of organic loading rate (OLR) on the removal of N,N-Dimethylformamide(DMF), m-Cresol (MC) and isopropyl alcohol (IPA) by a pilot-scale anaerobic membrane bioreactor (AnMBR) for treating chemical synthesis-based antibiotic solvent wastewater at period of improved influent COD concentration with decreased HRT. The whole process was divided into five stages in terms of the variation of OLR ranging from 3.9 to 12.7 kg COD/(m3·d). During 249 days of operating time, the average DMF, MC, IPA removal efficiency were 96.9%,98.2% and 96.4%, respectively. Cake layer was accumulated on the membrane surface acted as a dynamic secondary biofilm which lead to the increase of physical removal rate. In addition, mathematical statistical models was built on the linear regression techniques for exploring the inner relationship between EPS and the performance of the AnMBR.

[Effects of climate and grazing on the vegetation cover change in Xilinguole League of Inner Mongolia, North China].

Based on the monthly temperature and precipitation data of 15 meteorological stations and the statistical data of livestock density in Xilinguole League in 1981-2007, and by using ArcGIS, this paper analyzed the spatial distribution of the climate aridity and livestock density in the League, and in combining with the ten-day data of the normalized difference vegetation index (NDVI) in 1981-2007, the driving factors of the vegetation cover change in the League were discussed. In the study period, there was a satisfactory linear regression relationship between the climate aridity and the vegetation coverage. The NDVI and the livestock density had a favorable binomial regression relationship. With the increase of NDVI, the livestock density increased first and decreased then. The vegetation coverage had a complex linear relationship with livestock density and climate aridity. The NDVI had a positive correlation with climate aridity, but a negative correlation with livestock density. Compared with livestock density, climate aridity had far greater effects on the NDVI.

[A services value of different landscape types in Longitudinal Range-Gorge Region].

Based on the RS image of Longitudinal Range-Gorge Region (LRGR) in 2001, the study area was classified into seven first-class landscape types (forestland, grassland, farmland, wetland, water body, urban land, and glacier), and 26 second-class landscape types in consideration of climate belt, vegetation, and topography. By using GIS technology, the services value of different landscape types of LRGR were studied in regards to the study results on services value of Chinese terrestrial ecosystems. The results indicated that the total services value of LRGR was 5 302.35 x 10(8) yuan x a(-1), accounting for 9.47% of the whole country. The service value of soil conservation was the highest, which occupied 18.05% of the total services value, while the service values of gas adjustability and biodiversity protection ranked the second and third. Due to its distribution extent and services intensity per unit area, the forest landscape, which covered 66.11% of the total area, contributed most (85.34%) to the total service value of LRGR, followed by grassland and farmland landscapes.

[Spatial analysis on land use in Xishuangbanna].

Based on remote image and GIS technology, this paper analyzed the relationships between land use system and natural topographic factors such as elevation, slope, and river system in Xishuangbanna. The results showed that the land use system in the study region was dominated by forestland, cropland and grassland. The area of forestland was 13 420 km, accounting for 74% of the total, and that of cropland and grassland was 3 251 km2 and 2 332 km2, accounting for 13% and 18% of the total, respectively. The areas of these three land use types varied with elevation in single-peaked curve. Forestland mainly distributed around the elevation of 1 000 - 1 200 m, while cropland and grassland centralized at the elevation of 900 m. Urban land and cropland, which were greatly influenced by human activity, had lower slope index than forestland and grassland. Besides elevation and slope, river system in valley had effects on land use condition. With increasing buffer distance in valley, a strong spatial pattern of land use type was presented, i. e. , cropland, urban land and unused land concentrated greatly adjacent to water, while forestland and grassland were far away from valley. A landscape with relatively primary status, which was comprised of forestland as matrix, river as corridor, and cropland as patch, would come into being.