Shenduning Granule Attenuates Renal Injury from Oxidative Stress through the Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway.

BACKGROUND: Systemic oxidative stress has been reported to play a central role in the pathogenesis of kidney function decline. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is one of the important endogenous antioxidant stress pathways in cells. This study aims to investigate whether shenduning granule can ameliorate oxidative stress in kidney tissues by activating the Nrf2/ARE pathway, and explores the detailed underlying mechanism. METHODS: A total of 120 male Sprague-Dawley rats were randomly assigned to the sham-operated and operation groups. Rats in the operation group underwent 5/6 nephrectomy. Two weeks later, rats in the operation group were further randomly divided into 5 groups: model group, low-dose, medium-dose and high-dose shenduning granule groups, and losartan group. Rats in each group were given the same volume of corresponding liquid orally. Serum creatinine (SCr), blood urea nitrogen (BUN), 24-h urinary protein, malondialdehyde (MDA) and superoxide dismutase (SOD), Nrf2, heme oxygenase-1 (HO-1), and γ-glutamyl-cysteine synthetase (γ-GCS) were determined. RESULTS: Shenduning granule could markedly elevate HO-1, NRF2, γ-GCS and SOD (p < 0.05), and significantly decreased MDA, 24-h urinary protein, SCr and BUN in rats (p < 0.05). CONCLUSION: Shenduning granule can improve renal antioxidative stress activity in rats, exhibiting a renoprotective effect. The potential mechanism is likely exerted by the activation of the Nrf2/ARE pathway.

[Treatment of Proteinuria in Chronic Glomerular Disease Patients with Pi-Shen Deficiency Complicated Damp-Heat Syndrome by Yishen Qingre Huashi Recipe: a Clinical Study].

OBJECTIVE: To observe the therapeutic effect of Yishen Qingre Huashi Recipe (YQHR) in treating proteinuria of chronic glomerular disease patients with Pi-Shen deficiency complicated damp-heat syndrome (PSDCDHS). METHODS: Totally 121 stage 1 -2 primary chronic glomerular disease patients with PSDCDHS were randomly assigned to the treated group (85 cases) and the control group (36 cases) according to 2:1. All patients received conventional and symptomatic treatment. Patients in the treated group took YQHR additionally, while those in the control group took Losartan Potassium Tablet (50 mg each time, once per day) additionally. The therapeutic course for all was 6 months. Changes of 24 h urine protein, blood urea nitrogen (BUN), serum creatinine(SCr), and estimated glomerular filtration rate (eGFR) were observed at different time points. And the difference in therapeutic effects were compared between the two groups. RESULTS: Compared with the control group after 6 months of treatment, 24 h urine protein obviously decreased in the treated group (P <0. 05). There was no statistical difference in SCr, BUN, or eGFR between the two groups after 6 months of treatment (P >0. 05). The total effective rate after 2, 4, and 6 months of treatment in the treated group was 77. 6% (66/85 cases), 82. 4% (70/85 cases), and 89. 4% (76/85 cases), respectively. They were 47. 2% (17/36 cases), 55. 6% (20/36 cases), and 61. 1% (22/36 cases) in the control group, respectively. Compared with before treatment in the treated group, the total effective effect after 6 months of treatment was higher than that after 2 months of treatment (χ2=4. 28, P <0. 01). Compared with the control group at the same time points, the total effective rate in the treated group after 2, 4, and 6 months of treatment was higher (χ2=10. 87, 9. 53, 13.16, P <0. 01). CONCLUSION: YQHR could significantly lower proteinuria in chronic glomerular disease patients with PSDCDHS, improve the clinical effect, thereby providing clinical evidence for treating chronic glomerular disease proteinuria from resolving dampness and clearing heat.

[Multi-center randomized control study on the effects of syndrome differentiated traditional Chinese medicine therapy on CKD 1-2 with chronic nephritis proteinuria].

OBJECTIVE: To determine the effects of Syndrome Differentiated Chinese Medicine (TCM) Therapy on (CKD) 1-2 stage chronic kidney disease with proteinuria. METHODS: A prospective randomized control study was undertaken in 11 centers. A total of 396 chronic nephritis patients were divided into a treatment group (n=297) and a control group (n=99). Their TCM syndrome was classified as "Qi and Yin Deficiency of spleen and kidney" or "Qi and Yang Deficiency of spleen and kidney", with accompanying syndromes showing as "water and dampness", "damp-heat", and "blood stasis". Patients in the treatment group took a dose of Chinese medicine daily in response to their syndromes, while the controls took 50 mg/d losartan. The course of treatment was 24 weeks. Changes of 24-hour urinary protein excretion and glomerular filtration rate (eGFR) before and after treatments (4, 8, 12, 16, 20, 24 weeks), as well as clinical efficacy (after 4, 16, 24 weeks treatments) were measured. RESULTS: 361 patients were included in the final program participants comply analysis (PPS). Patients in the treatment group showed gradual decreased 24-hour urinary protein excretion, whereas the controls remained unchanged. Significant differences in 24-hour urinary protein excretion appeared between the experimental and control group at week 20 and 24 (P<0.05). eGFR decreased in all of the patients after treatments (P=0.0014). At three follow-up points, patients in the treatment group had higher eGFR than the controls, but without statistical significance (P>0.05). Significant differences in clinical remission rate, marked effect rate and total effective rate were observed between the treatment and control groups at week 24 (P<0.001). CONCLUSION: Syndrome differentiated TCM therapy can reduce the level of proteinuria in CKD 1-2 nephritis patients, promoting clinical effectiveness and protecting renal functions.

Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum.

BACKGROUND: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.

[Clinical and mechanism research on functional erectile dysfunction treated with moxibustion and qiangshen shugan qiwei decoction].

OBJECTIVE: To observe the clinical therapeutic effect on functional erectile dysfunction (FED) of kidney deficiency and liver stagnation treated by Baixiao moxibustion and qiangshen shugan qiwei decoction. METHODS: A total of 120 patients with FED were randomized into an observation group (60 cases, 2 cases dropped off) and a control group (60 cases, 4 cases dropped off). In the control group, the patients were treated with oral qiangshen shugan qiwei decoction (Radix Rehmanniae Praeparata, Rhizoma Dioscoreae, Rhizoma Curculiginis, Herba Epimedii, etc.), one dose daily. In the observation group, on the base of the treatment as the control group, Baixiao moxibustion was exerted along the distribution of governor vessel on the back, 30 min each time, once a week. The treatment duration was 4 weeks in the two groups. Before and after treatment, the scores of international index of erectile function-5 (IIEF5), erectile hardness scale (EHS), erectile dysfunction inventory of treatment satisfaction (EDITS) and TCM symptoms were observed in the patients of the two groups. Before and after treatment, the levels of serum sex hormones (testosterone [T], luteinizing hormone [LH], estradiol [E2], prolactin [PRL]) and the expressions of relevant proteins (matrix metalloproteinase-3 [MMP-3], matrix metalloproteinase-9 [MMP-9] and vascular endothelial growth factor [VEGF]) were determined in the patients of the two groups separately. The penile vascular function (peak systolic velocity [PSV], end-diastolic velocity [EDV], resistance index [RI]) was compared before and after treatment. Besides, the clinical therapeutic effect was evaluated. RESULTS: After treatment, the scores of IIEF5, EHS and EDITS were all increased as compared with the values before treatment (P<0.05), and the scores of TCM symptoms were reduced as compared with the values before treatment in the patients of the two groups (P<0.05). After treatment, the scores of IIEF5, EHS and EDITS in the observation group were higher than those in the control group (P<0.05), and the score of TCM symptoms was lower than the control group (P<0.05). After treatment, the levels of T and LH in serum of the two groups and the expressions of serum MMP-3 and MMP-9 in the observation group were all increased as compared with those before treatment (P<0.05), the levels of E2 and PRL in the observation group and VEGF expressions in the two groups were all reduced as compared with those before treatment (P<0.05). The levels of serum T and LH and the expressions of MMP-3 and MMP-9 in the observation groups were all higher than those in the control group (P<0.05), and the levels of E2 and PRL and VEGF expression were lower than the control group (P<0.05). After treatment, PSV was increased and EDV was reduced as compared with those before treatment in the patients of the two groups (P<0.05), RI in the observation group was reduced as compared with that before treatment (P<0.05). After treatment, PSV in the observation group was higher and EDV and RI were lower than the control group (P<0.05). The total effective rate was 87.9% (51/58) in the observation group, higher than 76.8% (43/56) in the control group (P<0.05). CONCLUSION: The combined therapy of Baixiao moxibustion and qiangshen shugan qiwei decoction effectively increases erectile function, erectile hardness and treatment satisfaction in the patients with functional erectile dysfunction of kidney deficiency and liver stagnation, as well as improves penile vascular function. The effect mechanism of this therapy may be related to the regulation of serum sex hormones and relevant proteins.

Clinical study on Yishen Qufeng Shengshi Recipe () for glomerular proteinuria patients: A randomized controlled trial.

OBJECTIVE: To explore the therapeutic effect of Yishen Qufeng Shengshi Recipe (, YQSR) in patients with glomerular proteinuria METHODS: A total of 145 patients with glomerular proteinuria were selected and randomly assigned to the treatment group (108 cases) and the control group (37 cases) according to a random number table in a ratio of 3:1. All patients received conventional and symptomatic treatment. In addition, patients in the treatment and control groups were given YQSR (200 mL, twice per day, orally) and losartan (50 mg/d orally), respectively for 6 months. The 24-h urine protein quantity, blood urea nitrogen, and serum creatinine in the two groups were measured at multiple time points before and after treatment. RESULTS: At the end of the study, 5 cases were lost to follow-up in the treatment group and 1 in the control group. Finally, the statistical data included 103 cases in the treatment group and 36 cases in the control group. The total effectiveness after 2, 4, and 6 months was 81.6% (84/103), 87.4% (90/103), and 92.2% (95/103), respectively, in the treatment group and 47.2% (17/36), 55.6% (20/36), and 61.1% (22/36), respectively, in the control group, with significant difference between the two groups (P<0.01 at all observation points). In the treatment group, the curative effect after 6 months was better than that after 2 months (P<0.05). The 24-h urine protein quantity was significantly lower in the treatment group at 3, 4, 5, and 6 months than that in the control group (P<0.05 or P<0.01, respectively) CONCLUSION: YQSR could significantly reduce the amount of glomerular proteinuria in the early stage.

[Effect of extract of Gingko biloba on soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in patients with early diabetic nephropathy].

OBJECTIVE: To investigate the effect of extract of Gingko biloba (EGb) on soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with early diabetic nephropathy (DN). METHODS: Sixty-three patients with DN in early stage were randomly assigned to the control group (29 cases) and the treatment group (34 cases). Both groups were treated by routine treatment, and with EGb given to the treatment group additionally. The treatment course was 2 months. Serum sICAM-1 and sVCAM-1 were determined with ELISA before and after treatment, and urinary albumin excretion rate (UAER), fasting plasma glucose (FPG), serum creatinine (SCr) and blood lipids, etc. were examined as well. RESULTS: The levels of serum sICAM-1 and sVCAM-1 were significantly lower in both groups after treatment than those before treatment (P < 0.05 or P < 0.01), and the decrement in the treatment group was more significant than that in the control group (P < 0.01). And the levels of UAER, SCr and blood lipids decreased in the treatment group after treatment (P < 0.05 or P < 0.01). CONCLUSION: EGb could retard the development of early DN through decreasing the levels of serum sICAM-1 and sVCAM-1.

The anti-inflammatory and anti-apoptotic effects of nesfatin-1 in the traumatic rat brain.

Nesfatin-1 has been demonstrated to possess anti-inflammatory and anti-apoptotic effects in the rat brain with subarachnoid hemorrhage. The study was designed to investigate the influence of nesfatin-1 on inflammatory responses and neuronal cell apoptosis after traumatic brain injury. Wistar rats were subjected to 5, 10 or 20 µg/kg of nesfatin-1 at designed time points (0.5, 2, 4 or 8h after head trauma) intraperitoneally. Rats were sacrificed at hours 2, 6 and 12, as well as day 1, 2, 3 and 5 after head trauma. The administration of 10 or 20 µg/kg of nesfatin-1 at hour 0.5 after head trauma could significantly suppress gene expressions of nuclear factor kappa-B, lessen concentrations of tumor necrosis factor-alpha, interleukin-1beta and interleukin-6, diminish caspase-3 activity as well as reduce number of apoptotic neuronal cells in traumatic rat brain tissues (P<0.05), but the administration of 5 µg/kg of nesfatin-1 not (P>0.05). Moreover, 20 µg/kg nesfatin-1 also significantly suppressed the inflammation and neuronal cell apoptosis when applied 2, 4 or 8h after head trauma. However, a clear concentration-response or time-response relationship was not found. These findings suggest that nesfatin-1 may inhibit nuclear factor kappa-B-dependent inflammatory responses, and lessen caspase-3-mediated neuronal cell apoptosis after traumatic brain injury in rats.