Study on effects and relevant mechanisms of Mudan granules on renal fibrosis in streptozotocin-induced diabetes rats.

AIMS: The effects and relevant mechanisms of Mudan granules in the renal fibrosis of diabetic rats were explored through in vivo experiments, which provided a scientific basis for expanding their clinical indications. METHODS: Male SD rats were given a single intraperitoneal injection of STZ (65 mg/kg) to induce diabetes rat models. After treatment with Mudan granules, the general condition of rats was recorded. Blood glucose, blood lipids, and renal function-related indicators were detected, renal tissue morphological changes and fibrosis-related indicators were observed, and the expression of pathway-related proteins were examined. RESULTS: The general condition of diabetes rats was improved after the treatment of Mudan granules, the 24-h urinary protein and urinary albumin to creatinine ratio were reduced, and the renal function and lipid results were modified. The tissue damage to the rat kidney has been repaired. Expression of TGF-ß1/Smad-related pathway proteins was suppressed in kidney tissues, and the fibrosis factor CO-IV, FN, and LN were reduced in serum. CONCLUSION: Mudan granules may inhibit of TGF-ß1/Smad pathway, inhibit the production of ECM, reduce the levels of fibrosis factors CO-IV, FN, and LN, to have a protective effect on kidney in diabetes rats.

Molecular evolutionary and antigenic characteristics of newly isolated H9N2 avian influenza viruses in Guangdong province, China.

Four new H9N2 avian influenza viruses (AIVs) were isolated from domestic birds in Guangdong between December 2015 and April 2016. Nucleotide sequence comparisons indicated that most of the internal genes of these four strains were highly similar to those of human H7N9 viruses. Amino acid substitutions and deletions found in the HA and NA proteins indicated that all four of these new isolates may have an enhanced ability to infect humans and other mammals. A cross-hemagglutinin-inhibition assay, conducted with two vaccine strains that are broadly used in China, suggested that antisera against vaccine candidates could not provide complete inhibition of the new isolates.

Next-generation molecular diagnosis: single-cell sequencing from bench to bedside.

Single-cell sequencing (SCS) is a fast-growing, exciting field in genomic medicine. It enables the high-resolution study of cellular heterogeneity, and reveals the molecular basis of complicated systems, which facilitates the identification of new biomarkers for diagnosis and for targeting therapies. It also directly promotes the next generation of genomic medicine because of its ultra-high resolution and sensitivity that allows for the non-invasive and early detection of abnormalities, such as aneuploidy, chromosomal translocation, and single-gene disorders. This review provides an overview of the current progress and prospects for the diagnostic applications of SCS, specifically in pre-implantation genetic diagnosis/screening, non-invasive prenatal diagnosis, and analysis of circulating tumor cells. These analyses will accelerate the early and precise control of germline- or somatic-mutation-based diseases, particularly single-gene disorders, chromosome abnormalities, and cancers.

Rosuvastatin pretreatment suppresses distant organ injury following unilateral renal ischemia-reperfusion in hypertensive Dahl salt-sensitive rats.

AIM: Ischaemia-reperfusion (I/R) induces distant organ injury (DOI) via inflammation and oxidative stress. Statins have anti-inflammatory and anti-oxidant effects independent of their cholesterol-lowering properties. To clarify whether statins could suppress DOI, we investigated the effect of rosuvastatin (RO) on the contralateral kidney following unilateral renal I/R. METHODS: Dahl salt-sensitive rats (6 weeks old) were randomly divided into four groups: sham, sham with RO, I/R, and I/R with RO. All rats were fed a high-salt (8%) diet for 6 weeks. RO (10 mg/kg per day) was pre-administered by supplementation to the drinking water for 2 weeks before I/R. The rats then underwent unilateral renal I/R (ischemia for 45 min). Three days after I/R, laboratory data, histological changes and protein expression levels of the contralateral kidney were assessed. RESULTS: I/R significantly elevated serum creatinine and malondialdehyde levels and induced a significantly higher glomerular sclerosis index and tubular dilation area of the contralateral kidney, with about 2-fold infiltration of ED-1-positive cells. In the I/R group, protein expression of superoxide dismutase (SOD) of the contralateral kidney was reduced to about 50% of the sham group. RO-pretreatment significantly suppressed all of these changes following I/R. CONCLUSION: RO-pretreatment diminished contralateral kidney injury with the suppression of ED-1-positive cell infiltration and SOD reduction after I/R. RO appears to have a protective effect on DOI by its anti-inflammatory and anti-oxidant effects.

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity.

BACKGROUND: Peritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H2) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H2 on the peritoneal membrane of experimental PD rats. METHOD: Eight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8-11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and H2PD group (PD solution with dissolved H2 at 400 ppb). Furthermore, the influence of iron (FeCl3: 5 µM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H2PD groups). The H2PD solution was manufactured by bathing a PD bag in H2-oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis. RESULTS: In the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the H2PD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-H2PD group. CONCLUSION: H2-dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H2 in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.

Avian influenza H9N2 seroprevalence among swine farm residents in China.

In parts of southern China, some large-scale swine farms are adjacent to lakes and ponds that are home to many types of birds. Some swine farms will also raise poultry for consumption and sale. Swine farms in rural China may be the source of the AIV outbreak. A seroepidemiological study was conducted among swine farm residents to understand the prevalence of antibodies against avian influenza virus (AIV) H9N2 in southern China. A total of 2,006 swine farm residents were sampled. Serum samples were tested for the presence of antibodies against H9N2 AIV by hemagglutination inhibition (HI) and microneutralization assays. A total of 37 serum samples from swine farm residents were HI positive for A/chicken/Guangdong/V/2008(H9N2), and 24 serum samples (all of which were also HI positive) were microneutralization assays positive for A/chicken/Guangdong/V/2008(H9N2). Due to the special pig farming model in southern China, the residents are in close contact with different kinds of birds. Thus, controlling bird-to-human transmission of AIV in swine farms with poultry may be an important means of preventing widespread AIV infection in humans.

Ischemia/reperfusion of unilateral kidney exaggerates aging-induced damage to the heart and contralateral kidney.

AIMS: We aimed to determine the impact of aging on ischemic acute kidney injury, especially in terms of the pathological mechanisms of kidney and heart crosstalk. METHOD: The effects of 45 min of unilateral ischemic reperfusion (IR) of the renal artery on the contralateral kidney and heart were histologically assessed in 7- and 40-week-old SD rats after 7 days. RESULTS: Glomerular sclerosis, interstitial fibrosis and numbers of ED1 cells were significantly increased in the contralateral kidneys of the 40-, but not the 7-week-old rats. The numbers of ED1 cells in the heart significantly and similarly increased in both groups, but reactive fibrosis after IR was significant only in the 40-week-old rats. The exaggerated profibrotic response induced by aging seemed to be closely associated with the increased number of ED1 cells in the affected area. CONCLUSION: Aging could play a major role in exaggerating the pathological processes of inflammation to fibrosis in remote organs including the heart and the nonischemic kidney after IR stimulation of the unilateral kidney.

Characteristics of patients with longer treatment period of lenvatinib for unresectable hepatocellular carcinoma: A post-hoc analysis of post-marketing surveillance study in Japan.

Patient profiles suitable for long-term lenvatinib treatment for unresectable hepatocellular carcinoma (uHCC) are yet to be fully understood. This post-hoc analysis aimed to identify such patient characteristics and explore the impact of treatment duration and relative dose intensity (RDI) on treatment outcomes. The data were obtained from 703 patients in a multicenter, prospective cohort study in Japan. Lenvatinib-naïve patients with uHCC were enrolled between July 2018 and January 2019 and were followed up for 12 months. Moreover, patients were dichotomized using the median treatment duration into the longer- (≥177 days; n = 352) or shorter-treatment (<177 days; n = 351) groups. The longer-treatment group often had better performance status, lower Child-Pugh score and better modified albumin-bilirubin grade than the shorter treatment group (p<0.05 for all). The objective response rate (47.6% vs. 28.2%; p<0.001) and disease control rate (92.4% vs. 60.2%; p<0.001) were both significantly higher in the longer-treatment groups than in the shorter-treatment groups. The proportion of patients with any adverse drug reactions was generally similar between the two treatment groups. Within the longer-treatment group, the disease control rate was high regardless of dose modification (i.e., RDI <100% vs. ≥100% during the initial 177 days) (91.2% vs. 98.0%). In conclusion, patients with longer treatment tended to have better overall conditions. Lenvatinib dose modifications at the physician's discretion, considering the balance between effectiveness and safety, may contribute to the long-term treatment.

Tangningtongluo Tablet ameliorates pancreatic damage in diabetic mice by inducing autophagy and inhibiting the PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Diabetes is a metabolic disease characterized by hyperglycaemia. Tangningtongluo Tablet (TNTL) is an inpatient formula extensively utilized to treat diabetes mellitus (DM), but the protective mechanism is not clear. This study aimed to investigate the relevant mechanisms by which TNTL affects pancreatic damage in diabetic mice and autophagy. METHODS: The impact of TNTL on pancreatic damage in diabetic mice in vitro and in vivo was investigated via glucose and lipid metabolism analyses, HE staining, CCK-8, TUNEL staining, Annexin V/PI, and Western blotting. Molecular docking and Western blotting were used to verify the results of network pharmacological analysis, which was carried out to explore the mechanism by which TNTL affects DM. The autophagosome levels were visualized via RFP-GFP-LC3 and transmission electron microscopy, and lysosomal function was evaluated via Lysotracker red staining. Western blot, immunohistochemistry and immunofluorescence staining were used to detect the expression of the autophagy proteins LC3, p62 and LAMP2. RESULTS: Compared with the model group, TNTL protected pancreas from oxidative stress, decreased the level of MDA, increased the levels of SOD and GSH-px, induced the occurrence of autophagy and decreased the levels of apoptotic factors. Moreover, TNTL inhibited the protein expression of p-PI3K, p-Akt and p-mTOR, increased the levels of LC3 and LAMP2 and decreased the level of p62, and the autophagy inhibitor CQ blocked the protective effect of TNTL on pancreatic damage in diabetic mice. CONCLUSION: These results demonstrated that TNTL ameliorated pancreatic damage in diabetic mice by inhibiting the PI3K/Akt/mTOR signaling and regulating autophagy.

Protective Effect and Related Mechanism of Modified Danggui Buxue Decoction on Retinal Oxidative Damage in Mice based on Network Pharmacology.

INTRODUCTION: Age-related macular degeneration (AMD) is one of the common diseases that cause vision loss in the elderly, and oxidative stress has been considered a major pathogenic factor for AMD. Modified Danggui Buxue Decoction (RRP) has a good therapeutic effect on non-proliferatic diabetic retinopathy and can improve the clinical symptoms of patients. METHODS: The key ingredients and core targets of RRP protecting retinal oxidative damage were obtained by Network pharmacology analysis. A mouse retinal oxidative damage model induced by tail vein injection of 1% NaIO3 solution (25 mg/kg) was treated with RRP for 4 weeks and used to verify the pharmacodynamics and related mechanism. AIM: This study aimed to predict and verify the protective effect and mechanism of RRP on retinal oxidative damage in mice based on network pharmacology and animal experiments. RESULTS: A total of 15 key active components included in RRP interacted with 57 core targets related to retinal oxidative damage (such as AKT1, NFE2L2, HMOX1), mainly involved in the AGE-RAGE signaling pathway in diabetic complications, PI3K-AKT signaling pathway and so on. Further studies in vivo found that RRP improved the retinal oxidative damage, increased the content of SOD and GSH, decreased the content of MDA in mouse serum, promoted the expression of p-PI3K, p-AKT, Nrf2, HO-1 and NQO1 proteins in the mouse retina, and inhibited the expression of Nrf2 in the cytoplasm. CONCLUSION: This study revealed that RRP had a protective effect on oxidative damage of the retina in mice, and might exert anti-oxidative effect by activating the PI3K/Akt/Nrf2 signal pathway. This study provided scientific data for the further development of hospital preparations of RRP, and a good theoretical basis for the clinical application of RRP.